An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

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Bisht Surendra S

2006-12-01

Full Text Available Abstract Background Tetramic acids with polyenyl substituents are an important class of compounds in medicinal chemistry. Both solid and solution phase syntheses of such molecules have been reported recently. Thiolactomycin, a clinical candidate for treatment of tuberculosis has led to further explorations in this class. We have recently developed an efficient synthesis of tetramic acids derivatives from L- ascorbic acid. In continuation of this work, we have synthesised dienyl tetramic acid derivatives. Results 5,6-O-Isopropylidene-ascorbic acid on reaction with DBU led to the formation of tetronolactonyl allyl alcohol, which on oxidation with pyridinium chlorochromate gave the respective tetranolactonyl allylic aldehydes. Wittig olefination followed by reaction of the resulting tetranolactonyl dienyl esters with different amines resulted in the respective 5-hydroxy lactams. Subsequent dehydration of the hydroxy lactams with p-toluene sulphonic acid afforded the dienyl tetramic acid derivatives. All reactions were performed at ambient temperature and the yields are good. Conclusion An efficient and practical method for the synthesis of dienyl tetramic acid derivatives from inexpensive and easily accessible ascorbic acid has been developed. The compounds bear structural similarities to the tetramic acid based polyenic antibiotics and thus this method offers a new and short route for the synthesis of tetramic acid derivatives of biological significance.

Toxicological and biochemical characterizations of AChE in phosalone-susceptible and resistant populations of the common pistachio psyllid, Agonoscena pistaciae

Science.gov (United States)

Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad

2014-01-01

Abstract The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity ( KM ) and hydrolyzing efficiency ( Vmax ) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed

Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

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Zheng, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Li, Juan [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Qiu, Zhuibai [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Xia, Zheng [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Li, Wei [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Yu, Lining; Chen, Hailin; Chen, Jianxing [NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, 2140 Xietu Road, Shanghai 200032 (China); Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China); Xie, Qiong, E-mail: xiejoanxq@gmail.com [Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 200032 (China); Chen, Hongzhuan, E-mail: yaoli@shsmu.edu.cn [Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025 (China)

2012-10-01

The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

International Nuclear Information System (INIS)

Zheng, Wei; Li, Juan; Qiu, Zhuibai; Xia, Zheng; Li, Wei; Yu, Lining; Chen, Hailin; Chen, Jianxing; Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao; Xie, Qiong; Chen, Hongzhuan

2012-01-01

The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC 50 values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC 50 values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

Laulvad kirjanikud Prima Vistal

Index Scriptorium Estoniae

2008-01-01

Kirjandusfestivalist Prima Vista 8.-11. maini Tartus ja laulvate kirjanike kontsertidest: 9. mail Tõnu Trubetsky kontsert ansambliga The Flovers of Romance, 10. mail Villu Tamme, Mathura, Lauri Sommer, Kaarel B. Väljamäe, Andreas Kalkuni, Kauksi Ülle, Merca ja Aapo Ilves

Regulation of ACh release from guinea pig bladder urothelial cells: potential role in bladder filling sensations.

Science.gov (United States)

McLatchie, L M; Young, J S; Fry, C H

2014-07-01

The aim of this study was to quantify and characterize the mechanism of non-neuronal ACh release from bladder urothelial cells and to determine if urothelial cells could be a site of action of anti-muscarinic drugs. A novel technique was developed whereby ACh could be measured from freshly isolated guinea pig urothelial cells in suspension following mechanical stimulation. Various agents were used to manipulate possible ACh release pathways in turn and to study the effects of muscarinic receptor activation and inhibition on urothelial ATP release. Minimal mechanical stimulus achieved full ACh release, indicating a small dynamic range and possible all-or-none signal. ACh release involved a mechanism dependent on the anion channel CFTR and intracellular calcium concentration, but was independent of extracellular calcium, vesicular trafficking, connexins or pannexins, organic cation transporters and was not affected by botulinum-A toxin. Stimulating ACh receptors increased ATP production and antagonizing them reduced ATP release, suggesting a link between ACh and ATP release. These results suggest that release of non-neuronal ACh from the urothelium is large enough and well located to act as a modulator of ATP release. It is hypothesized that this pathway may contribute to the actions of anti-muscarinic drugs in reducing the symptoms of lower urinary tract syndromes. Additionally the involvement of CFTR in ACh release suggests an exciting new direction for the treatment of these conditions. © 2014 The British Pharmacological Society.

Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

Science.gov (United States)

Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

2015-10-01

Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

THE ROLES OF DETOXIFYING ENZYMES AND AChE INSENSITIVITY IN METHAMIDOPHOS RESISTANCE DEVELOPMENT AND DECLINE IN NILAPARVATA LUGENS

Institute of Scientific and Technical Information of China (English)

Ze-wenLiu; Zhao-junHan; Ling-chunZhang

2003-01-01

Methamidophos resistance of brown planthopper (Nilaparvata lugens Stal, BPH) was selected in laboratory. After successive selection for 9 generations, the selection was ceased by rearing BPH without contact with any insecticide for 9 generations. In the full course, the successive changes of esterase activity, MFO activity, GSTs activity and AChE insensitivity were analyzed. The results showed that the change of esterase activity was high correlated with that of methamidophos in the full course, which indicated that esterase played very important role both in the resistance development and in the resistance decline. However, the change of AChE insensitivity only significantly correlated with that of resistance in the development stage, and the change of MFO activity or GSTs activity only significantly correlated with that of the resistance in the decline stage, which indicated the changes of AChE insensitivity, MFO activity or GSTs activity only played some roles in different stages of the resistance change.

The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure

Directory of Open Access Journals (Sweden)

Qing Ren

2017-01-01

Full Text Available The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM and methomyl (MT was investigated. The behavior responses of D. magna in DM (13.36 μg/L and 33.40 μg/L and MT (19.66 μg/L and 49.15 μg/L suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.

Perturbation of the Monomer-Monomer Interfaces of the Benzoylformate Decarboxylase Tetramer

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Andrews, Forest H.; Rogers, Megan P.; Paul, Lake N.; McLeish, Michael J. [IUPUI; (Purdue)

2014-08-14

The X-ray structure of benzoylformate decarboxylase (BFDC) from Pseudomonas putida ATCC 12633 shows it to be a tetramer. This was believed to be typical of all thiamin diphosphate-dependent decarboxylases until recently when the structure of KdcA, a branched-chain 2-keto acid decarboxylase from Lactococcus lactis, showed it to be a homodimer. This lent credence to earlier unfolding experiments on pyruvate decarboxylase from Saccharomyces cerevisiae that indicated that it might be active as a dimer. To investigate this possibility in BFDC, we sought to shift the equilibrium toward dimer formation. Point mutations were made in the noncatalytic monomer–monomer interfaces, but these had a minimal effect on both tetramer formation and catalytic activity. Subsequently, the R141E/Y288A/A306F variant was shown by analytical ultracentrifugation to be partially dimeric. It was also found to be catalytically inactive. Further experiments revealed that just two mutations, R141E and A306F, were sufficient to markedly alter the dimer–tetramer equilibrium and to provide an ~450-fold decrease in k_cat. Equilibrium denaturation studies suggested that the residual activity was possibly due to the presence of residual tetramer. The structures of the R141E and A306F variants, determined to <1.5 Å resolution, hinted that disruption of the monomer interfaces will be accompanied by movement of a loop containing Leu109 and Leu110. As these residues contribute to the hydrophobicity of the active site and the correct positioning of the substrate, it seems that tetramer formation may well be critical to the catalytic activity of BFDC.

Dual functionality of β-tryptase protomers as both proteases and cofactors in the active tetramer.

Science.gov (United States)

Maun, Henry R; Liu, Peter S; Franke, Yvonne; Eigenbrot, Charles; Forrest, William F; Schwartz, Lawrence B; Lazarus, Robert A

2018-04-16

Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of the allergic inflammatory responses in asthma. During acute hypersensitivity reactions, mast cells degranulate, releasing active tetramer as a complex with proteoglycans. Extensive efforts have focused on developing therapeutic β-tryptase inhibitors, but its unique activation mechanism is less well explored. Tryptase is active only after proteolytic removal of the pro-domain followed by tetramer formation via two distinct symmetry-related interfaces. We show that the cleaved I16G mutant cannot tetramerize, likely due to impaired insertion of its N-terminus into its 'activation pocket', indicating allosteric linkage at multiple sites on each protomer. We engineered cysteines into each of the two distinct interfaces (Y75C for small or I99C for large) to assess the activity of each tetramer and disulfide-locked dimer. Using size-exclusion chromatography and enzymatic assays, we demonstrate that the two large tetramer interfaces regulate enzymatic activity, elucidating the importance of this protein-protein interaction for allosteric regulation. Notably, the I99C large interface dimer is active, even in the absence of heparin. We show that a monomeric β-tryptase mutant (I99C*:Y75A:Y37bA where C* is cysteinylated Cys99) cannot form a dimer or tetramer, yet is active, but only in the presence of heparin. Thus heparin both stabilizes the tetramer and allosterically conditions the active site. We hypothesize that each β-tryptase protomer in the tetramer has two distinct roles, acting both as a protease and as a cofactor for its neighboring protomer, to allosterically regulate enzymatic activity, providing a rationale for direct correlation of tetramer stability with proteolytic activity. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

TDDFT investigation of excitation of water tetramer under femtosecond laser pulse irradiation

Science.gov (United States)

Wang, Zhiping; Xu, Xuefen; Zhang, Fengshou; Qian, Chaoyi

2018-04-01

We study the static properties of water tetramer in ground state, the optical absorption spectra and ultrafast nonadiabatic dynamical response of water tetramer to short and intense laser pulses with different intensities by a real-space, real-time implementation of time-dependent density functional theory coupled to molecular dynamics (TDDFT-MD) nonadiabatically. The calculated results are in good agreement with available values in literature. Four typical irradiated scenarios of water tetramer in laser field, which are “normal vibration,” “break and reorganization,” “fragmentation and new formation” and “pure fragmentation”, are explored by discussing the ionization, the bond lengths of OH bonds and hydrogen bonds and the kinetic energy of ions. The dynamic simulation shows that the reaction channel of water tetramer can really be controlled by choosing appropriate laser parameters referring to the optical absorption spectra and hydrogen ions play an important role in the reaction channel. Furthermore, it is found that the laser intensity affects the kinetic energy of ejected protons more than that of the remaining fragments and all dynamic processes are somehow directly related to the velocity of departing protons.

Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement

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Cristiano Chiapinotto Spiazzi

2015-01-01

Full Text Available Alzheimer’s disease (AD is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25–35; 3 nmol/3 μL or distilled water was administered via intracerebroventricular (i.c.v. injection. Selenofuranoside (5 mg/kg or vehicle (canola oil was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM and step-down passive-avoidance (SDPA tests. Antioxidant defenses along with reactive species (RS were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

Design, synthesis and evaluation of some N-methylenebenzenamine derivatives as selective acetylcholinesterase (AChE) inhibitor and antioxidant to enhance learning and memory.

Science.gov (United States)

Shrivastava, Sushant K; Srivastava, Pavan; Upendra, T V R; Tripathi, Prabhash Nath; Sinha, Saurabh K

2017-02-15

Series of some 3,5-dimethoxy-N-methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N-methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC 50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4. The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

大白鼠海马神经元NOS与AChE活性的研究%Study on the NOS and AChE Activity in the Hippocampus Neurons of Rat

Institute of Scientific and Technical Information of China (English)

夏保芦; 杨荣; 杨友华; 杨敏; 黄丹

2005-01-01

目的:观察大白鼠海马不同亚区一氧化氮合酶(NOS)与乙酰胆碱酯酶(AChE)阳性神经元的活性.方法:分别采用还原型尼克酰胺嘌呤二核苷酸脱氢酶(NADPH-d)和乙酰胆碱酯酶(AChE)组织化学方法对大白鼠海马不同亚区NOS和AChE阳性神经元的分布以及活性进行研究.结果:海马不同亚区均含有NOS和AChE阳性神经元,其中CA2区NOS呈强阳性反应,CA3区AChE呈强阳性反应.结论:实验表明,NOS和AChE阳性神经元广泛分布于大白鼠海马不同亚区,为进一步探讨海马的学习记忆功能机制提供了形态学佐证.

Statistics and Title VII Proof: Prima Facie Case and Rebuttal.

Science.gov (United States)

Whitten, David

1978-01-01

The method and means by which statistics can raise a prima facie case of Title VII violation are analyzed. A standard is identified that can be applied to determine whether a statistical disparity is sufficient to shift the burden to the employer to rebut a prima facie case of discrimination. (LBH)

Theory vs. experiment for molecular clusters: Spectra of OCS trimers and tetramers

Energy Technology Data Exchange (ETDEWEB)

Evangelisti, Luca [Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, Virginia 22904 (United States); Dipartimento di Chimica “G. Ciamician,” University of Bologna, Via Selmi 2, Bologna 40126 (Italy); Perez, Cristobal; Seifert, Nathan A.; Pate, Brooks H. [Department of Chemistry, University of Virginia, McCormick Road, Charlottesville, Virginia 22904 (United States); Dehghany, M.; Moazzen-Ahmadi, N. [Department of Physics and Astronomy, University of Calgary, 2500 University Drive North West, Calgary, Alberta T2N 1N4 (Canada); McKellar, A. R. W. [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

2015-03-14

All singly substituted {sup 13}C, {sup 18}O, and {sup 34}S isotopomers of the previously known OCS trimer are observed in natural abundance in a broad-band spectrum measured with a chirped-pulse Fourier transform microwave spectrometer. The complete substitution structure thus obtained critically tests (and confirms) the common assumption that monomers tend to retain their free structure in a weakly bound cluster. A new OCS trimer isomer is also observed, and its structure is determined to be barrel-shaped but with the monomers all approximately aligned, in contrast to the original trimer which is barrel-shaped with two monomers aligned and one anti-aligned. An OCS tetramer spectrum is assigned for the first time, and the tetramer structure resembles an original trimer with an OCS monomer added at the end with two sulfur atoms. Infrared spectra observed in the region of the OCS ν{sub 1} fundamental (≈2060 cm{sup −1}) are assigned to the same OCS tetramer, and another infrared band is tentatively assigned to a different tetramer isomer. The experimental results are compared and contrasted with theoretical predictions from the literature and from new cluster calculations which use an accurate OCS pair potential and assume pairwise additivity.

From chemistry to consciousness the legacy of Hans Primas

CERN Document Server

Müller-Herold, Ulrich

2016-01-01

This book reflects on the significant and highly original scientific contributions of Hans Primas. A professor of chemistry at ETH Zurich from 1962 to 1995, Primas continued his research activities until his death in 2014. Over these 50 years and more, he worked on the foundations of nuclear magnetic resonance spectroscopy, contributed to a number of significant issues in theoretical chemistry, helped to clarify central topics in quantum theory and the philosophy of physics, suggested innovative ways of addressing interlevel relations in the philosophy of science, and introduced cutting-edge approaches in the flourishing young field of scientific studies of consciousness. His work in these areas of research and its continuing impact is described by noted experts, colleagues, and collaborators of Primas. All authors contextualize their contributions to facilitate the mutual dialog between these fields.

Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT

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Morse Michael A

2005-07-01

Full Text Available Abstract Background Cryopreservation of PBMC and/or overnight shipping of samples are required for many clinical trials, despite their potentially adverse effects upon immune monitoring assays such as MHC-peptide tetramer staining, cytokine flow cytometry (CFC, and ELISPOT. In this study, we compared the performance of these assays on leukapheresed PBMC shipped overnight in medium versus cryopreserved PBMC from matched donors. Results Using CMV pp65 peptide pool stimulation or pp65 HLA-A2 tetramer staining, there was significant correlation between shipped and cryopreserved samples for each assay (p ≤ 0.001. The differences in response magnitude between cryopreserved and shipped PBMC specimens were not significant for most antigens and assays. There was significant correlation between CFC and ELISPOT assay using pp65 peptide pool stimulation, in both shipped and cryopreserved samples (p ≤ 0.001. Strong correlation was observed between CFC (using HLA-A2-restricted pp65 peptide stimulation and tetramer staining (p Conclusion We conclude that all three assays show concordant results on shipped versus cryopreserved specimens, when using a peptide-based readout. The assays are also concordant with each other in pair wise comparisons using equivalent antigen systems.

Promoting effect of ethanol on dewetting transition in the confined region of melittin tetramer

International Nuclear Information System (INIS)

Ren Xiuping; Zhou Bo; Wang Chunlei

2012-01-01

To study the influence of ethanol molecules on the melittin tetramer folding, we investigated the dewetting transition of the melittin tetramer immersed in pure water and 8% aqueous ethanol solution (mass fraction) by the molecular dynamics simulations. We found that the marked dewetting transitions occurred inside a nanoscale channel of the melittin tetramer both in pure water and in aqueous ethanol solution. Also, ethanol molecules promoted this dewetting transition. We attributed this promoting effect to ethanol molecules which prefer to locate at the liquid-vapor interface and decrease the liquid-vapor surface energy. The results provide insight into the effect of ethanol on the water dewetting phenomena. (authors)

Hypoxic resistance of KRAS mutant tumor cells to 3-Bromopyruvate is counteracted by Prima-1 and reversed by N-acetylcysteine.

Science.gov (United States)

Orue, Andrea; Chavez, Valery; Strasberg-Rieber, Mary; Rieber, Manuel

2016-11-18

The metabolic inhibitor 3-bromopyruvate (3-BrPA) is a promising anti-cancer alkylating agent, shown to inhibit growth of some colorectal carcinoma with KRAS mutation. Recently, we demonstrated increased resistance to 3-BrPA in wt p53 tumor cells compared to those with p53 silencing or mutation. Since hypoxic microenvironments select for tumor cells with diminished therapeutic response, we investigated whether hypoxia unequally increases resistance to 3-BrPA in wt p53 MelJuso melanoma harbouring (Q61L)-mutant NRAS and wt BRAF, C8161 melanoma with (G12D)-mutant KRAS (G464E)-mutant BRAF, and A549 lung carcinoma with a KRAS (G12S)-mutation. Since hypoxia increases the toxicity of the p53 activator, Prima-1 against breast cancer cells irrespective of their p53 status, we also investigated whether Prima-1 reversed hypoxic resistance to 3-BrPA. In contrast to the high susceptibility of hypoxic mutant NRAS MelJuso cells to 3-BrPA or Prima-1, KRAS mutant C8161 and A549 cells revealed hypoxic resistance to 3-BrPA counteracted by Prima-1. In A549 cells, Prima-1 increased p21CDKN1mRNA, and reciprocally inhibited mRNA expression of the SLC2A1-GLUT1 glucose transporter-1 and ALDH1A1, gene linked to detoxification and stem cell properties. 3-BrPA lowered CAIX and VEGF mRNA expression. Death from joint Prima-1 and 3-BrPA treatment in KRAS mutant A549 and C8161 cells seemed mediated by potentiating oxidative stress, since it was antagonized by the anti-oxidant and glutathione precursor N-acetylcysteine. This report is the first to show that Prima-1 kills hypoxic wt p53 KRAS-mutant cells resistant to 3-BrPA, partly by decreasing GLUT-1 expression and exacerbating pro-oxidant stress.

Effects of EGCG and Chlorpyrifos on the Mortality, AChE and GSH of Adult Zebrafish: Independent and Combination

Science.gov (United States)

Zhang, Rong; Zhang, Jian; Gao, Qian; Guo, Nichun

2018-01-01

Chlorpyrifos is a neurotoxic agent and also causes oxidative stress in the body. EGCG is a typical strong antioxidant and has been reported to be neuroprotective. Our study investigated the mortality, the activity of acetylcholinesterase (AChE) in the brain and glutathione (GSH) in the liver of the adult Zebrafish in present of Chlorpyrifos and EGCG independent and combination. The results indicated that after the addition of EGCG, the mortality of zebrafish induced by Chlorpyrifos was reduced and the activity of AChE and glutathione (GSH) inhibited by Chlorpyrifos in zebrafish was significantly increased, which demonstrated that EGCG inhibited the toxicity Chlorpyrifos to zebrafish. The inhibition was dependent on the concentration of EGCG and Chlorpyrifos, which was not shown a gradual change trend but a complex situation.

PRIMA-X Final Report

Energy Technology Data Exchange (ETDEWEB)

Lorenz, Daniel [German Research School for Simulation Sciences GmbH, Aachen (Germany); Wolf, Felix [German Research School for Simulation Sciences GmbH, Aachen (Germany)

2016-02-17

The PRIMA-X (Performance Retargeting of Instrumentation, Measurement, and Analysis Technologies for Exascale Computing) project is the successor of the DOE PRIMA (Performance Refactoring of Instrumentation, Measurement, and Analysis Technologies for Petascale Computing) project, which addressed the challenge of creating a core measurement infrastructure that would serve as a common platform for both integrating leading parallel performance systems (notably TAU and Scalasca) and developing next-generation scalable performance tools. The PRIMA-X project shifts the focus away from refactorization of robust performance tools towards a re-targeting of the parallel performance measurement and analysis architecture for extreme scales. The massive concurrency, asynchronous execution dynamics, hardware heterogeneity, and multi-objective prerequisites (performance, power, resilience) that identify exascale systems introduce fundamental constraints on the ability to carry forward existing performance methodologies. In particular, there must be a deemphasis of per-thread observation techniques to significantly reduce the otherwise unsustainable flood of redundant performance data. Instead, it will be necessary to assimilate multi-level resource observations into macroscopic performance views, from which resilient performance metrics can be attributed to the computational features of the application. This requires a scalable framework for node-level and system-wide monitoring and runtime analyses of dynamic performance information. Also, the interest in optimizing parallelism parameters with respect to performance and energy drives the integration of tool capabilities in the exascale environment further. Initially, PRIMA-X was a collaborative project between the University of Oregon (lead institution) and the German Research School for Simulation Sciences (GRS). Because Prof. Wolf, the PI at GRS, accepted a position as full professor at Technische Universität Darmstadt (TU

Common SAR Derived from Linear and Non-linear QSAR Studies on AChE Inhibitors used in the Treatment of Alzheimer's Disease.

Science.gov (United States)

Pulikkal, Babitha Pallikkara; Marunnan, Sahila Mohammed; Bandaru, Srinivas; Yadav, Mukesh; Nayarisseri, Anuraj; Sureshkumar, Sivanpillai

2017-11-14

Deficits in cholinergic neurotransmission due to the degeneration of cholinergic neurons in the brain are believed to be one of the major causes of the memory impairments associated with AD. Targeting acetyl cholinesterase (AChE) surfaced as a potential therapeutic target in the treatment of Alzheimer's disease. The present study is pursued to develop quantitative structure activity relationship (QSAR) models to determine chemical descriptors responsible for AChE activity. Two different sets of AChE inhibitors, dataset-I (30 compounds) and dataset-II (20 compounds) were investigated through MLR aided linear and SVM aided non-linear QSAR models. The obtained QSAR models were found statistically fit, stable and predictive on validation scales. These QSAR models were further investigated for their common structure-activity relationship in terms of overlapping molecular descriptors selection. Atomic mass weighted 3D Morse descriptors (MATS5m) and Radial Distribution Function (RDF045m) descriptors were found in common SAR for both the datasets. Electronegativity weighted (MATS5e, HATSe, and Mor17e) descriptors have also been identified in regulative roles towards endpoint values of dataset-I and dataset-II. The common SAR identified in these linear and non-linear QSAR models could be utilized to design novel inhibitors of AChE with improved biological activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

ESPRI: Astrometric planet search with PRIMA at the VLTI

Directory of Open Access Journals (Sweden)

Ségransan D.

2011-07-01

Full Text Available The ESPRI consortium will conduct an astrometric survey for extrasolar planets, using the PRIMA facility at the Very Large Telescope Interferometer. Our scientific goals include determining orbital inclinations and masses for planets already known from radial-velocity surveys, searches for planets around nearby stars of all masses, and around young stars. The consortium has built the PRIMA differential delay lines, developed an astrometric operation and calibration plan, and will deliver astrometric data reduction software.

Crystal structure of Lymnaea stagnalis AChBP complexed with the potent nAChR antagonist DHβE suggests a unique mode of antagonism.

Directory of Open Access Journals (Sweden)

Azadeh Shahsavar

Full Text Available Nicotinic acetylcholine receptors (nAChRs are pentameric ligand-gated ion channels that belong to the Cys-loop receptor superfamily. These receptors are allosteric proteins that exist in different conformational states, including resting (closed, activated (open, and desensitized (closed states. The acetylcholine binding protein (AChBP is a structural homologue of the extracellular ligand-binding domain of nAChRs. In previous studies, the degree of the C-loop radial extension of AChBP has been assigned to different conformational states of nAChRs. It has been suggested that a closed C-loop is preferred for the active conformation of nAChRs in complex with agonists whereas an open C-loop reflects an antagonist-bound (closed state. In this work, we have determined the crystal structure of AChBP from the water snail Lymnaea stagnalis (Ls in complex with dihydro-β-erythroidine (DHβE, which is a potent competitive antagonist of nAChRs. The structure reveals that binding of DHβE to AChBP imposes closure of the C-loop as agonists, but also a shift perpendicular to previously observed C-loop movements. These observations suggest that DHβE may antagonize the receptor via a different mechanism compared to prototypical antagonists and toxins.

Chlorpyrifos and Malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity

Science.gov (United States)

Richendrfer, Holly; Creton, Robbert

2015-01-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. PMID:25983063

Chlorpyrifos and malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity.

Science.gov (United States)

Richendrfer, Holly; Creton, Robbert

2015-07-01

Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. Copyright © 2015 Elsevier Inc. All rights reserved.

[Burden of proof in medical cases--presumption of fact and prima facie evidence. II. Presumption of fact and prima facie evidence].

Science.gov (United States)

Sliwka, Marcin

2004-01-01

The aim of this paper was to present the main rules concerning the burden of proof in polish civil trials, including medical cases. The standard rules were presented with all the important exclusions such as presumption of law and fact or prima facie evidence. The author analyses the effect of these institutions on burden of proof in medical cases. The difference between presumptions of fact and prima facie evidence was analysed and explained. This paper also describes the importance of the res ipsa loquitur rule in United Kingdom and USA. This paper includes numerous High Court sentences on evidential and medical issues.

17 CFR 270.3a-1 - Certain prima facie investment companies.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Certain prima facie investment companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment...

Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

International Nuclear Information System (INIS)

Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M.

2009-01-01

The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro γ-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain.

Siglec-7 tetramers characterize B-cell subpopulations and leukemic blasts.

Science.gov (United States)

Gieseke, Friederike; Mang, Philippa; Viebahn, Susanne; Sonntag, Inga; Kruchen, Anne; Erbacher, Annika; Pfeiffer, Matthias; Handgretinger, Rupert; Müller, Ingo

2012-08-01

Cell surface glycosylation has important regulatory functions in the maturation, activation, and homeostasis of lymphocytes. The family of human sialic acid-binding immunoglobulin-like lectins (siglecs) comprises inhibitory as well as activating receptors intimately involved in the regulation of immune responses. Analyses of the interaction between siglecs and glycans are hampered by the low affinity of this interaction. Therefore, we expressed siglec-7 in eukaryotic cells, allowing for glycosylation, and oligomerized the protein in analogy to MHC tetramers. Using this tool, flow cytometric analysis of lymphocytes became possible. Sialic acid-dependent binding of siglec-7 tetramers was confirmed by glycan array analysis and loss of siglec tetramer binding after neuraminidase treatment of lymphocytes. In contrast to most lymphocyte subpopulations, which showed high siglec-7 ligand expression, B-cell subpopulations could be further subdivided according to different siglec-7 ligand expression levels. We also analyzed blasts from acute lymphoblastic leukemias of the B-cell lineage as well as the T-cell lineage, since malignant transformation is often associated with aberrant cell surface glycosylation. While pediatric T-ALL blasts highly expressed siglec-7 ligands, siglec-7 ligands were barely detectable on cALL blasts. Taken together, oligomerization of recombinant soluble siglec-7 enabled flow cytometric identification of physiologic lymphocyte subpopulations and malignant blasts. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MHC class II tetramers made from isolated recombinant α and β chains refolded with affinity-tagged peptides

DEFF Research Database (Denmark)

Braendstrup, Peter; Justesen, Sune Frederik Lamdahl; Osterbye, Thomas

2013-01-01

Targeting CD4+ T cells through their unique antigen-specific, MHC class II-restricted T cell receptor makes MHC class II tetramers an attractive strategy to identify, validate and manipulate these cells at the single cell level. Currently, generating class II tetramers is a specialized undertaking...... effectively limiting their use and emphasizing the need for improved methods of production. Using class II chains expressed individually in E. coli as versatile recombinant reagents, we have previously generated peptide-MHC class II monomers, but failed to generate functional class II tetramers. Adding...... a monomer purification principle based upon affinity-tagged peptides, we here provide a robust method to produce class II tetramers and demonstrate staining of antigen-specific CD4+ T cells. We also provide evidence that both MHC class II and T cell receptor molecules largely accept affinity-tagged peptides...

Tetramer model of leukoemeraldine-emeraldine electrochemistry in the presence of trihalogenoacetic acids. DFT approach.

Science.gov (United States)

Barbosa, Nuno Almeida; Grzeszczuk, Maria; Wieczorek, Robert

2015-01-15

First results of the application of the DFT computational approach to the reversible electrochemistry of polyaniline are presented. A tetrameric chain was used as the simplest model of the polyaniline polymer species. The system under theoretical investigation involved six tetramer species, two electrons, and two protons, taking part in 14 elementary reactions. Moreover, the tetramer species were interacting with two trihalogenoacetic acid molecules. Trifluoroacetic, trichloroacetic, and tribromoacetic acids were found to impact the redox transformation of polyaniline as shown by cyclic voltammetry. The theoretical approach was considered as a powerful tool for investigating the main factors of importance for the experimental behavior. The DFT method provided molecular structures, interaction energies, and equilibrium energies of all of the tetramer-acid complexes. Differences between the energies of the isolated tetramer species and their complexes with acids are discussed in terms of the elementary reactions, that is, ionization potentials and electron affinities, equilibrium constants, electrode potentials, and reorganization energies. The DFT results indicate a high impact of the acid on the reorganization energy of a particular elementary electron-transfer reaction. The ECEC oxidation path was predicted by the calculations. The model of the reacting system must be extended to octamer species and/or dimeric oligomer species to better approximate the real polymer situation.

Escherichia coli Protein Expression System for Acetylcholine Binding Proteins (AChBPs.

Directory of Open Access Journals (Sweden)

Nikita Abraham

Full Text Available Nicotinic acetylcholine receptors (nAChR are ligand gated ion channels, identified as therapeutic targets for a range of human diseases. Drug design for nAChR related disorders is increasingly using structure-based approaches. Many of these structural insights for therapeutic lead development have been obtained from co-crystal structures of nAChR agonists and antagonists with the acetylcholine binding protein (AChBP. AChBP is a water soluble, structural and functional homolog of the extracellular, ligand-binding domain of nAChRs. Currently, AChBPs are recombinantly expressed in eukaryotic expression systems for structural and biophysical studies. Here, we report the establishment of an Escherichia coli (E. coli expression system that significantly reduces the cost and time of production compared to the existing expression systems. E. coli can efficiently express unglycosylated AChBP for crystallography and makes the expression of isotopically labelled forms feasible for NMR. We used a pHUE vector containing an N-terminal His-tagged ubiquitin fusion protein to facilitate AChBP expression in the soluble fractions, and thus avoid the need to recover protein from inclusion bodies. The purified protein yield obtained from the E. coli expression system is comparable to that obtained from existing AChBP expression systems. E. coli expressed AChBP bound nAChR agonists and antagonists with affinities matching those previously reported. Thus, the E. coli expression system significantly simplifies the expression and purification of functional AChBP for structural and biophysical studies.

Ravynic acid, an antibiotic polyeneyne tetramic acid from Penicillium sp. elucidated through synthesis.

Science.gov (United States)

Myrtle, J D; Beekman, A M; Barrow, R A

2016-09-21

A new antibiotic natural product, ravynic acid, has been isolated from a Penicillium sp. of fungus, collected from Ravensbourne National Park. The 3-acylpolyenyne tetramic acid structure was definitively elucidated via synthesis. Highlights of the synthetic method include the heat induced formation of the 3-acylphosphorane tetramic acid and a selective Wittig cross-coupling to efficiently prepare the natural compounds carbon skeleton. The natural compound was shown to inhibit the growth of Staphylococcus aureus down to concentrations of 2.5 µg mL(-1).

Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.

Science.gov (United States)

Somm, Emmanuel; Guérardel, Audrey; Maouche, Kamel; Toulotte, Audrey; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise; Maskos, Uwe; Hüppi, Petra S; Schwitzgebel, Valérie M

2014-05-01

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase

International Nuclear Information System (INIS)

Li Bin; Duysen, Ellen G.; Poluektova, Larisa Y.; Murrin, L. Charles; Lockridge, Oksana

2006-01-01

Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-associated virus serotype 2 (AAV-2), to deliver murine AChE to AChE-/- mice that have no endogenous AChE activity. The vector encoded the most abundant form of AChE: exons 2, 3, 4, and 6. Two-day old animals, with an immature immune system, were injected. AChE delivered intravenously was expressed up to 5 months in plasma, liver, heart, and lung, at 5-15% of the level in untreated wild-type mice. A few mice formed antibodies, but antibodies did not block AChE activity. The plasma AChE was a mixture of dimers and tetramers. AChE delivered intramuscularly had 40-fold higher activity levels than in wild-type muscle. None of the AChE was collagen-tailed. No retrograde transport through the motor neurons to the central nervous system was detected. AChE delivered intrastriatally assembled into tetramers. In brain, the AAV-2 vector transduced neurons, but not astrocytes and microglia. Vector-treated AChE-/- mice lived longer than saline-treated controls. AChE-/- mice were protected from diisopropylfluorophosphate-induced respiratory failure when the vector was delivered intravenously, but not intrastriatally. Since vector-treated animals had no AChE activity in diaphragm muscle, protection from respiratory failure came from AChE in other tissues. We conclude that AChE scavenged OP and in this way protected the activity of butyrylcholinesterase (BChE, EC 3.1.1.8) in motor endplates

Thymidine kinase 1 regulatory fine-tuning through tetramer formation

DEFF Research Database (Denmark)

Mutahir, Zeeshan; Clausen, Anders R.; Andersson, Karl-Magnus

2013-01-01

in higher vertebrates and was especially pronounced in mammalian and bird TK1s. We suggest that the dimer form is the original form and that the tetramer originated in the animal lineage after the split of Dictyostelium and the lineages leading to invertebrates and vertebrates. The efficient switching...

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

Science.gov (United States)

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

2018-03-01

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

Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle

Directory of Open Access Journals (Sweden)

Andrzej P. Herman

2017-01-01

Full Text Available The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE activity at the periphery by Neostigmine (0.5 mg/animal will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH/luteinising hormone (LH secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal. An immune/inflammatory challenge was induced by peripheral administration of lipopolysaccharide (LPS; 400 ng/kg. Peripheral treatment with Donepezil and Neostigmine prevented the LPS-induced decrease (P<0.05 in LHβ gene expression in the anterior pituitary gland (AP and in LH release. Moreover, Donepezil completely abolished (P<0.05 the suppressory effect of inflammation on GnRH synthesis in the preoptic area, when pretreatment with Neostigmine reduced (P<0.05 the decrease in GnRH content in this hypothalamic structure. Moreover, administration of both AChE inhibitors diminished (P<0.05 the inhibitory effect of LPS treatment on the expression of GnRH receptor in the AP. Our study shows that inflammatory dependent changes in the GnRH/LH secretion may be eliminated or reduced by AChE inhibitors suppressing inflammatory reaction only at the periphery such as Neostigmine, without the need for interfering in the central nervous system.

Presentation and information management server PRIMAS

International Nuclear Information System (INIS)

Gibbert, R.

1998-01-01

An advanced computerized information system, PRIMAS, is presented. Its tasks include legal demands by the Federal government and the EU, environmental data model solutions, multi-sectorial analysis etc. Its structure, an open system architecture makes possible to be integrated and connected to existing standard systems. Its main use is the provision and processing of environmental information. (R.P.)

99mTc-labeling of HYNIC-conjugated cyclic RGDfK dimer and tetramer using EDDA as coligand.

Science.gov (United States)

Wang, Jianjun; Kim, Young-Seung; Liu, Shuang

2008-03-01

In this study, EDDA (ethylenediamine- N, N'-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC-dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC-tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC-dimer was allowed to react with 99mTcO4 (-) in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC-dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC-dimer)(EDDA)] with high yield (>90%) and high specific activity ( approximately 8.0 Ci/micromol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC-tetramer)(EDDA)] was always EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC-dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC-dimer and HYNIC-tetramer. Surprisingly, [99mTc(HYNIC-dimer)(EDDA)] and [99mTc(HYNIC-tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC-tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

Science.gov (United States)

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH 2 -CH=CH-CH 2 -) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies

Science.gov (United States)

Ghosh, Shibaji; Chandar, Nellore Bhanu; Jana, Kalyanashis; Ganguly, Bishwajit

2017-08-01

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than 1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes

International Nuclear Information System (INIS)

Wang Min; Wang Jiquan; Gao Mingzhang; Zheng Qihuang

2008-01-01

Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]8) and (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [ 11 C]CH 3 OTf through N-[ 11 C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/μmol specific activity at EOB

Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

DEFF Research Database (Denmark)

Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

2010-01-01

AChR binding sites in several brain regions, particularly in the prefrontal cortex. The alpha7 nAChR agonists SSR180711 and PNU-282987 also increase [(125)I]-BTX binding, suggesting that this is a general consequence of alpha7 nAChR agonism. Interestingly, the alpha7 nAChR positive allosteric modulators PNU......The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n...

The heterocyst differentiation transcriptional regulator HetR of the filamentous cyanobacterium Anabaena forms tetramers and can be regulated by phosphorylation.

Science.gov (United States)

Valladares, Ana; Flores, Enrique; Herrero, Antonia

2016-02-01

Many filamentous cyanobacteria respond to the external cue of nitrogen scarcity by the differentiation of heterocysts, cells specialized in the fixation of atmospheric nitrogen in oxic environments. Heterocysts follow a spatial pattern along the filament of two heterocysts separated by ca. 10-15 vegetative cells performing oxygenic photosynthesis. HetR is a transcriptional regulator that directs heterocyst differentiation. In the model strain Anabaena sp. PCC 7120, the HetR protein was observed in various oligomeric forms in vivo, including a tetramer that peaked with maximal hetR expression during differentiation. Tetramers were not detected in a hetR point mutant incapable of differentiation, but were conspicuous in an over-differentiating strain lacking the PatS inhibitor. In differentiated filaments the HetR tetramer was restricted to heterocysts, being undetectable in vegetative cells. HetR co-purified with RNA polymerase from Anabaena mainly as a tetramer. In vitro, purified recombinant HetR was distributed between monomers, dimers, trimers and tetramers, and it was phosphorylated when incubated with (γ-(32)P)ATP. Phosphorylation and PatS hampered the accumulation of HetR tetramers and impaired HetR binding to DNA. In summary, tetrameric HetR appears to represent a functionally relevant form of HetR, whose abundance in the Anabaena filament could be negatively regulated by phosphorylation and by PatS. © 2015 John Wiley & Sons Ltd.

AChR-specific immunosuppressive therapy of myasthenia gravis.

Science.gov (United States)

Luo, Jie; Lindstrom, Jon

2015-10-15

Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.

A Green Method for Synthesis of 7H-thiazolo[3,2-b][1,2, 4]-triazin-7-one Derivatives as AChE Inhibitors

Directory of Open Access Journals (Sweden)

Liu Sijie

2015-01-01

Full Text Available The authors study an efficient and green approach for the synthesis of 7H-thiazolo [3, 2-b][1,2,4]triazin-7-one derivatives as AChE inhibitors. The 7H-thiazolo[3,2-b][1,2,4]triazin-7-ones were designed by molecular docking, and readily prepared via a one-pot reaction in morpholine hydrosulfate ([Hnhm]HSO4 lonic liquid as the catalyst and solvent. The study of AChE inhibitory activity was carried out through using the Ellman colorimetric assay. The 7H-thiazolo[3,2-b][1,2,4]triazin-7-ones had been successfully synthesized by green catalyst. Most of the target compounds exhibited more than 50% inhibition at 10μM.

Resveratrol tetramer of hopeaphenol isolated from Shorea johorensis (Dipterocarpaceae)

Science.gov (United States)

Aisha, Farra; Din, Laily B.; Yaacob, W. A.

2014-09-01

Hopeaphenol (1) as a resveratrol tetramer was isolated from the bark of Shorea johorensis collected from Imbak Canyon, Sabah, Malaysia. The structure of this compound was determined by the spectroscopic evidences using 1H- and 13C-NMR assigned with HSQC, HMBC, 1H-1H COSY and 1H-1H NOESY spectra, mass spectrum, and by comparison with reported data.

New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation.

Science.gov (United States)

Landais, Elise; Romagnoli, Pablo A; Corper, Adam L; Shires, John; Altman, John D; Wilson, Ian A; Garcia, K Christopher; Teyton, Luc

2009-12-15

Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examined each parameter critical for the production of pMHCT-2 using the I-A(d)-OVA system as a model. Through this process, the geometry of peptide-MHC display by avidin tetramers was examined, as well as the stability of rMHC molecules. However, we discovered that the most important factor limiting the reactivity of pMHCT-2 was the display of peptides. Indeed, long peptides, as presented by MHC class II molecules, can be bound to I-A/HLA-DQ molecules in more than one register, as suggested by structural studies. This mode of anchorless peptide binding allows the selection of a broader repertoire on single peptides and should favor anti-infectious immune responses. Thus, beyond the technical improvements that we propose, the redesign of pMHCT-2 will give us the tools to evaluate the real size of the CD4 T cell repertoire and help us in the production and testing of new vaccines.

Insect nicotinic acetylcholine receptors (nAChRs): Important amino ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-29

Dec 29, 2008 ... nAChRs within the insect central nervous system has led to the development of insecticides targeting .... binding protein (AChBP), a homopentameric structural and functional homolog of ..... of the honey bee, Apis mellifera.

Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies.

Science.gov (United States)

Lo, Rabindranath; Ganguly, Bishwajit

2014-07-29

Organophosphorus nerve agents are highly toxic compounds which strongly inhibit acetylcholinesterase (AChE) in the blood and in the central nervous system (CNS). Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. The reactivation mechanism of tabun-conjugated AChE with various drugs has been examined with density functional theory and ab initio quantum chemical calculations. The presence of a lone-pair located on the amidic group resists the nucleophilic attack at the phosphorus center of the tabun-conjugated AChE. We have shown that the newly designed drug candidate N-(pyridin-2-yl)hydroxylamine, at the MP2/6-31+G*//M05-2X/6-31G* level in the aqueous phase with the polarizable continuum solvation model (PCM), is more effective in reactivating the tabun-conjugated AChE than typical oxime drugs. The rate determining activation barrier with N-(pyridin-2-yl)hydroxylamine was found to be ∼1.7 kcal mol(-1), which is 7.2 kcal mol(-1) lower than the charged oxime trimedoxime (one of the most efficient reactivators in tabun poisonings). The greater nucleophilicity index (ω(-)) and higher CHelpG charge of pyridinylhydroxylamine compared to TMB4 support this observation. Furthermore, we have also examined the reactivation process of tabun-inhibited AChE with some other bis-quaternary oxime drug candidates such as methoxime (MMB4) and obidoxime. The docking analysis suggests that charged bis-quaternary pyridinium oximes have greater binding affinity inside the active-site gorge of AChE compared to the neutral pyridinylhydroxylamine. The peripheral ligand attached to the neutral pyridinylhydroxylamine enhanced the binding with the aromatic residues in the active-site gorge of AChE through effective π-π interactions. Steered molecular dynamics (SMD) simulations have also been performed with the charged oxime (TMB4) and the neutral hydroxylamine. From protein-drug interaction

Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms.

Directory of Open Access Journals (Sweden)

Janine Spieker

Full Text Available Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS. Here, we first analyzed the expression of acetylcholinesterase (AChE by IHC and of choline acetyltransferase (ChAT by ISH in developing embryonic chicken limbs (stages HH17-37. AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER and zone of polarizing activity (ZPA, respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB and Alizarin red (AR stainings, respectively. Both acetylcholine (ACh- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein.

Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells.

Science.gov (United States)

Qian, Jie; Mummalaneni, Shobha K; Alkahtani, Reem M; Mahavadi, Sunila; Murthy, Karnam S; Grider, John R; Lyall, Vijay

2016-01-01

In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and β nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotine-induced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-β-erythroidine, a α4β2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and β4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a dose- and time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells.

Dual Inhibition of AChE and BChE with the C-5 Substituted Derivative of Meldrum’s Acid: Synthesis, Structure Elucidation, and Molecular Docking Studies

Directory of Open Access Journals (Sweden)

Haroon Mehfooz

2017-07-01

Full Text Available Alzheimer’s disease (AD lies in the category of those diseases which are still posing challenges to medicinal chemists, and the search for super-effective drugs for the treatment of AD is a work in progress. The inhibition of cholinesterase is considered a viable strategy to enhance the level of acetylcholine in the brain. The C-5 substituted derivative of Meldrum’s acid was synthesized and screened against acetylcholinesterase (AChE and butyrylcholinesterase (BChE enzyme inhibition activity. The simple and unique structure of synthesized derivative 3 was found to be good for the dual inhibition of both enzymes (AChE and BChE. 2,2-Dimethyl-5-(([2-(trifluoromethyl phenyl]aminomethylidene-1,3-dioxane-4,6-dione (3 showed significant inhibition against AChE, with an IC50 value of 1.13 ± 0.03 µ M (Standard Neostigmine 22.2 ± 3.2 µM, and moderate inhibition against BChE, with an IC50 value of 2.12 ± 1.22 µM (Standard Neostigmine 49.6 ± 6.11 µM. The structural insights reveal that compound 3 possesses intriguing reactive groups, which can potentially evoke the non-covalent interactions and possibly assist by binding in the active site of the target protein. Docking simulations revealed that the compound 3 showed binding inside the active site gorges of both AChE and BChE. An excellent agreement was obtained, as the best docked poses showed important binding features mostly based on interactions due to oxygen atoms and the aromatic moieties of the compound. The docking computations coupled with the experimental findings ascertained that the compound 3 can serve as a scaffold for the dual inhibitors of the human acetylcholine esterases.

Engineering chimeric human and mouse major histocompatibility complex (MHC) class I tetramers for the production of T-cell receptor (TCR) mimic antibodies

Science.gov (United States)

Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.

2017-01-01

Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627

MRI of hyperacute stroke in the AChA territory

Energy Technology Data Exchange (ETDEWEB)

Hamoir, Xavier L.; Grandin, Cecile B.; Cosnard, Guy; Duprez, Thierry [Department of Medical Imaging, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Peeters, Andre [Department of Neurology, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium); Robert, Annie [Department of Epidemiology, Biostatistics Unit of the Public Health School, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels (Belgium)

2004-03-01

The purpose of our study was to derive from the anatomical literature an easy-to-use map of the brain areas supplied by the anterior choroidal artery (AChA) and to assess the correspondence between damage within the putative AChA areas and clinical symptoms. A thorough review of the literature led to the recognition of 16 anatomical areas which could be delineated on routine diffusion-weighted MR images. A database of 138 consecutive ischemic stroke patients examined with MRI less than 6 h after symptoms onset was thereafter processed in a retrospective way. Patients presenting with at least one damaged AChA area were selected so as to assess the prevalence of AChA infarction and the clinical correlates of the condition. Fifteen patients (11%) had at least one damaged AChA area. Only two of them had ''pure'' AChA-restricted infarction. Contralateral hemiparesis and contralateral hemianesthesia were best predicted by lesions within the tail of the caudate nucleus with a sensitivity of 87% and 83%, respectively. Homonymous hemianopsia best correlated with lesions within the posterior limb of the internal capsule and within the retrolenticular part of the internal capsule, with a sensitivity of 100% and a specificity of 70% for both areas. We concluded that the clinical-radiological correlations did not match the neurophysiological standards, thereby highlighting the limitation of this study, which involved a cohort of acute stroke patients recruited from clinical practice and investigated the clinical impact of these brain lesions, even when documented with the most sensitive imaging modality. (orig.)

MRI of hyperacute stroke in the AChA territory

International Nuclear Information System (INIS)

Hamoir, Xavier L.; Grandin, Cecile B.; Cosnard, Guy; Duprez, Thierry; Peeters, Andre; Robert, Annie

2004-01-01

The purpose of our study was to derive from the anatomical literature an easy-to-use map of the brain areas supplied by the anterior choroidal artery (AChA) and to assess the correspondence between damage within the putative AChA areas and clinical symptoms. A thorough review of the literature led to the recognition of 16 anatomical areas which could be delineated on routine diffusion-weighted MR images. A database of 138 consecutive ischemic stroke patients examined with MRI less than 6 h after symptoms onset was thereafter processed in a retrospective way. Patients presenting with at least one damaged AChA area were selected so as to assess the prevalence of AChA infarction and the clinical correlates of the condition. Fifteen patients (11%) had at least one damaged AChA area. Only two of them had ''pure'' AChA-restricted infarction. Contralateral hemiparesis and contralateral hemianesthesia were best predicted by lesions within the tail of the caudate nucleus with a sensitivity of 87% and 83%, respectively. Homonymous hemianopsia best correlated with lesions within the posterior limb of the internal capsule and within the retrolenticular part of the internal capsule, with a sensitivity of 100% and a specificity of 70% for both areas. We concluded that the clinical-radiological correlations did not match the neurophysiological standards, thereby highlighting the limitation of this study, which involved a cohort of acute stroke patients recruited from clinical practice and investigated the clinical impact of these brain lesions, even when documented with the most sensitive imaging modality. (orig.)

Resveratrol tetramer of hopeaphenol isolated from Shorea johorensis (Dipterocarpaceae)

Energy Technology Data Exchange (ETDEWEB)

Aisha, Farra; Din, Laily B.; Yaacob, W. A. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor (Malaysia)

2014-09-03

Hopeaphenol (1) as a resveratrol tetramer was isolated from the bark of Shorea johorensis collected from Imbak Canyon, Sabah, Malaysia. The structure of this compound was determined by the spectroscopic evidences using {sup 1}H- and {sup 13}C-NMR assigned with HSQC, HMBC, {sup 1}H−{sup 1}H COSY and {sup 1}H−{sup 1}H NOESY spectra, mass spectrum, and by comparison with reported data.

La memoria alla barocca ne L’isola del giorno prima di Umberto Eco

Directory of Open Access Journals (Sweden)

Agnieszka Piwowarska

2012-12-01

Full Text Available In his third novel The Island of the Day Before (L’isola del giorno prima Umberto Eco narrates a story of an unusual castaway named Roberto who – instead of being on a desert island – finishes up on an abandoned (but only at first sight ship. The article aims to analyze how the book’s main character, during his loneliness, reminisces about events from his past. And because the novel is set in the Baroque, Roberto´s memories respect the spirit of that time : numerous flashbacks are evoked by unexpected metaphors that link very distant things. The ship, which is for a young man a cumbersome prison, becomes a real Theatre of Memory, according to Giulio Camillo’s idea.

Al CERN prima fase sistema gestione dati LHC

CERN Multimedia

2003-01-01

"Al via la prima fase per la realizzazione del sistema Lhc computing Grid (LCG), progettato per elaborare le quantita' di dati senza precedenti che, a partire dal 2007, saranno prodotte dagli esperimenti eseguiti con il nuovo grande acceleratore Large Hadron Collider (LHC), presso il Cern di Ginevra" 1 page

Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA tetramer-based flow cytometry: a European multicenter evaluation.

NARCIS (Netherlands)

Heijnen, I.; Barnett, D.; Arroz, M.J.; Barry, S.M.; Bonneville, M.; Brando, B.; D'Hautcourt, J.L.; Kern, F.; Totterman, T.H.; Marijt, E.W.; Bossy, D.; Preijers, F.W.M.B.; Rothe, G.; Gratama, J.W.

2004-01-01

BACKGROUND: HLA class I peptide tetramers represent powerful diagnostic tools for detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the current multicenter study is the critical need to standardize tetramer flow cytometry if it is to be implemented as a routine diagnostic

Radiation-induced tetramer-to-dimer transition of Esterichia coli lactose repressor

Czech Academy of Sciences Publication Activity Database

Goffinont, S.; Davídková, Marie; Spotheim-Maurizot, M.

2009-01-01

Roč. 386, č. 2 (2009), s. 300-304 ISSN 0006-291X R&D Projects: GA MŠk OC09012 Institutional research plan: CEZ:AV0Z10480505 Keywords : protein * DNA * radiation * oxidation * tetramer * dimer * lactose repressor Subject RIV: BO - Biophysics Impact factor: 2.548, year: 2009

One-pot, mix-and-read peptide-MHC tetramers

DEFF Research Database (Denmark)

Leisner, Christian Valdemar Vinge; Loeth, Nina; Lamberth, Kasper

2008-01-01

BACKGROUND: Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL's are of importance for research on CTL immunity, and development...... molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps. CONCLUSIONS/SIGNIFICANCE: We have developed an efficient "one-pot, mix-and-read" strategy for peptide-MHC tetramer generation...

Substituent effects on the excited states of phenyl-capped phenylene vinylene tetramers

NARCIS (Netherlands)

Candeias, L.P.; Gelinck, G.H.; Piet, J.J.; Piris, J.; Wegewijs, B.; Peeters, E.; Wildeman, J.; Hadziioannou, G.; Müllen, K.

2001-01-01

The singlet and triplet excited states of phenyl-capped tetramers of phenylene vinylene with different alkyl, alkoxy or cyano substituents, were investigated in benzene solution. The lowest singlet states were studied by laser flash-photolysis with time-resolved microwave conductivity and

Comparative functional expression of nAChR subtypes in rodent DRG neurons.

Science.gov (United States)

Smith, Nathan J; Hone, Arik J; Memon, Tosifa; Bossi, Simon; Smith, Thomas E; McIntosh, J Michael; Olivera, Baldomero M; Teichert, Russell W

2013-01-01

We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70-80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15-30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca(2) (+) transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.

Study on the Highly Sensitive AChE Electrode Based on Multiwalled Carbon Nanotubes

Directory of Open Access Journals (Sweden)

Shuping Zhang

2014-01-01

Full Text Available Using chitosan (CS as carrier, the method named layer-by-layer (LBL self-assembly modification to modify the glassy carbon electrode (GCE with multiwalled carbon nanotubes (MWNTs and acetylcholine esterase (AChE was proposed to prepare the acetylcholine esterase electrode with high sensitivity and stability. The modified electrode was used to detect pesticide of aldicarb, and the enzyme inhibition rate of the electrode showed good linearity with pesticide concentrations in the range of 10−10 g·L−1 to 10−3 g·L−1. The detection limit was 10−11 g·L−1. The modified electrode was also used to detect the actual sample, and the recovery rate range was from 97.72% to 107.15%, which could meet the rapid testing need of the aldicarb residue. After being stored in the phosphate buffer solution (PBS in 4°C for 30 days, the modified electrode showed good stability with the response current that was 80% of the original current.

Prima facie questions in quantum gravity

Science.gov (United States)

Isham, C. J.

The long history of the study of quantum gravity has thrown up a complex web of ideas and approaches. The aim of this article is to unravel this web a little by analysing some of the {\\em prima facie\\/} questions that can be asked of almost any approach to quantum gravity and whose answers assist in classifying the different schemes. Particular emphasis is placed on (i) the role of background conceptual and technical structure; (ii) the role of spacetime diffeomorphisms; and (iii) the problem of time.

Oligomers Based on a Weak Hydrogen Bond Network: the Rotational Spectrum of the Tetramer of Difluoromethane

Science.gov (United States)

Feng, Gang; Evangelisti, Luca; Caminati, Walther; Cacelli, Ivo; Carbonaro, Laura; Prampolini, Giacomo

2013-06-01

Following the investigation of the rotational spectra of three conformers (so-called ``book'', ``prism'' and ``cage'') of the water hexamer, and of some other water oligomers, we report here the rotational spectrum of the tetramer of a freon molecule. The pulse jet Fourier transform microwave (pj-FTMW) spectrum of an isomer of the difluoromethane tetramer has been assigned. This molecular system is made of units of a relatively heavy asymmetric rotor, held together by a network of weak hydrogen bonds. The search of the rotational spectrum has been based on a high-level reference method, the CCSD(T)/CBS protocol. It is interesting to outline that the rotational spectrum of the water tetramer was not observed, probably because the minimum energy structures of this oligomer is effectively nonpolar in its ground states, or because of high energy tunnelling splittings. The rotational spectra of the monomer, dimer, trimer and tetramer of difluoromethane have been assigned in 1952, 1999, 2007, and 2013 (present work), with a decreasing time spacing between the various steps, looking then promising for a continuous and rapid extension of the size limits of molecular systems accessible to MW spectroscopy. C. Pérez, M. T. Muckle, D. P. Zaleski, N. A. Seifert, B. Temelso, G. C. Shields, Z. Kisiel, B. H. Pate, Science {336} (2012) 897. D. R. Lide, Jr., J. Am. Chem. Soc. {74} (1952) 3548. W. Caminati, S. Melandri, P. Moreschini, P. G. Favero, Angew. Chem. Int. Ed. {38} (1999) 2924. S. Blanco, S. Melandri, P. Ottaviani, W. Caminati, J. Am. Chem. Soc. {129} (2007) 2700.

The earthing system of the PRIMA Neutral Beam Test Facility based on the Mesh Common Bonding Network topology

International Nuclear Information System (INIS)

Pomaro, Nicola; Boldrin, Marco; Lazzaro, Gabriele

2015-01-01

Highlights: • We designed a high performance earthing system for the ITER Neutral Beam Test Facility. • The system is based on the Mesh Common Bonded Network topology. • Careful bonding of all metallic structures allowed to obtain a well meshed system. • Special care was dedicated to improve EMC performance of critical areas like control rooms. • The facility experimental results will be representative also of the ITER situation. - Abstract: PRIMA is a large experimental facility under realization in Padova, aimed at developing and testing the Neutral Beam Injectors for ITER. The operation of these devices involves high RF power and voltage up to 1 MV. Frequent and high voltage electrical breakdowns inside the beam sources occur regularly. The presence of a distributed carefully optimized earthing system is of paramount importance to achieve a satisfying disturbances immunity for equipment and diagnostics. The paper describes the design and the realization of the earthing system of the PRIMA facility, which is based on the MESH-Common Bonding Network (MESH-CBN) topology, as recommended by IEC and IEEE standards for installations with high levels of Electromagnetic Interferences (EMI). The principles of the MESH-CBN approach were adapted to the PRIMA layout, which is composed by several buildings, that are independent for seismic and architectural reasons, but are linked by many electrical conduits and hydraulic pipelines. The availability of huge foundations, with a large number of poles and pillars, was taken into account; building parts dedicated to host control rooms and sensitive equipment were treated with particular care. Moreover, the lightning protection system was integrated and harmonized with the earthing system.

The earthing system of the PRIMA Neutral Beam Test Facility based on the Mesh Common Bonding Network topology

Energy Technology Data Exchange (ETDEWEB)

Pomaro, Nicola, E-mail: nicola.pomaro@igi.cnr.it; Boldrin, Marco; Lazzaro, Gabriele

2015-10-15

Highlights: • We designed a high performance earthing system for the ITER Neutral Beam Test Facility. • The system is based on the Mesh Common Bonded Network topology. • Careful bonding of all metallic structures allowed to obtain a well meshed system. • Special care was dedicated to improve EMC performance of critical areas like control rooms. • The facility experimental results will be representative also of the ITER situation. - Abstract: PRIMA is a large experimental facility under realization in Padova, aimed at developing and testing the Neutral Beam Injectors for ITER. The operation of these devices involves high RF power and voltage up to 1 MV. Frequent and high voltage electrical breakdowns inside the beam sources occur regularly. The presence of a distributed carefully optimized earthing system is of paramount importance to achieve a satisfying disturbances immunity for equipment and diagnostics. The paper describes the design and the realization of the earthing system of the PRIMA facility, which is based on the MESH-Common Bonding Network (MESH-CBN) topology, as recommended by IEC and IEEE standards for installations with high levels of Electromagnetic Interferences (EMI). The principles of the MESH-CBN approach were adapted to the PRIMA layout, which is composed by several buildings, that are independent for seismic and architectural reasons, but are linked by many electrical conduits and hydraulic pipelines. The availability of huge foundations, with a large number of poles and pillars, was taken into account; building parts dedicated to host control rooms and sensitive equipment were treated with particular care. Moreover, the lightning protection system was integrated and harmonized with the earthing system.

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

Science.gov (United States)

Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

2018-01-01

In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted

Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.

Science.gov (United States)

Redka, Dar'ya S; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V; Ellis, John; Ernst, Oliver P; Wells, James W

2014-08-29

G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

PRIMA Platform capability for satellite missions in LEO and MEO (SAR, Optical, GNSS, TLC, etc.)

Science.gov (United States)

Logue, T.; L'Abbate, M.

2016-12-01

PRIMA (Piattaforma Riconfigurabile Italiana Multi Applicativa) is a multi-mission 3-axis stabilized Platform developed by Thales Alenia Space Italia under ASI contract.PRIMA is designed to operate for a wide variety of applications from LEO, MEO up to GEO and for different classes of satellites Platform Family. It has an extensive heritage in flight heritage (LEO and MEO Satellites already fully operational) in which it has successfully demonstrated the flexibility of use, low management costs and the ability to adapt to changing operational conditions.The flexibility and modularity of PRIMA provides unique capability to satisfy different Payload design and mission requirements, thanks to the utilization of recurrent adaptable modules (Service Module-SVM, Propulsion Module-PPM, Payload Module-PLM) to obtain mission dependent configuration. PRIMA product line development is continuously progressing, and is based on state of art technology, modular architecture and an Integrated Avionics. The aim is to maintain and extent multi-mission capabilities to operate in different environments (LEO to GEO) with different payloads (SAR, Optical, GNSS, TLC, etc.). The design is compatible with a wide range of European and US equipment suppliers, thus maximising cooperation opportunity. Evolution activities are mainly focused on the following areas: Structure: to enable Spacecraft configurations for multiple launch; Thermal Control: to guarantee thermal limits for new missions, more demanding in terms of environment and payload; Electrical: to cope with higher power demand (e.g. electrical propulsion, wide range of payloads, etc.) considering orbital environment (e.g. lighting condition); Avionics : AOCS solutions optimized on mission (LEO observation driven by agility and pointing, agility not a driver for GEO). Use of sensors and actuators tailored for specific mission and related environments. Optimised Propulsion control. Data Handling, SW and FDIR mission customization

In defence of moral imperialism: four equal and universal prima facie principles.

Science.gov (United States)

Dawson, A; Garrard, E

2006-04-01

Raanan Gillon is a noted defender of the four principles approach to healthcare ethics. His general position has always been that these principles are to be considered to be both universal and prima facie in nature. In recent work, however, he has made two claims that seem to present difficulties for this view. His first claim is that one of these four principles, respect for autonomy, has a special position in relation to the others: he holds that it is first among equals. We argue that this claim makes little sense if the principles are to retain their prima facie nature. His second claim is that cultural variation can play an independent normative role in the construction of our moral judgments. This, he argues, enables us to occupy a middle ground between what he sees as the twin pitfalls of moral relativism and (what he calls) moral imperialism. We argue that there is no such middle ground, and while Gillon ultimately seems committed to relativism, it is some form of moral imperialism (in the form of moral objectivism) that will provide the only satisfactory construal of the four principles as prima facie universal moral principles.

Prima Vistale tuleb tuntud kirjanikke mitmest Euroopa riigist / Kaarel Kressa

Index Scriptorium Estoniae

Kressa, Kaarel, 1983-

2010-01-01

Prima Vista kirjandusfestivali külalisi: Leonie Swann, Attila Bartis, Dmitri Bõkov, Zinaida Lindén, Mihhail Šiškin, Fay Weldon, Jason Goodwin, Rosa Maria Rodríguez Magda, Inga Gaile, Juris Kronbergs, Guntars Godinš, Liana Langa

Pengaruh Komunikasi Interpersonal dan Iklim Organisasi terhadap Kinerja Karyawan PT. Selatan Prima Sejahtera Jaya Pekanbaru

OpenAIRE

Restu, Restu; Indarti, Sri; Johanes, Johanes

2015-01-01

The purpose of this study was to determine the effect of partial and simultaneous interpersonal communication and organizational climate simultaneously on the performance of employees of PT. South Prima Sejahtera Jaya Pekanbaru. The sample in this study were all employees of PT. South PrimaSejahtera Jaya Pekanbaru totaling 35 people. The technique of collecting data using questionnaires. Data analysis technique is quantitative descriptive method and regression.The results showed that interper...

[Women's approach to childhood toothache, abdominal ache and earache].

Science.gov (United States)

Efe, Emine; Öncel, Selma; Yilmaz, Mualla

2012-01-01

This study was conducted to determine women's about attitudes child's teeth, abdomen and ear ache. Those who had lived in Antalya that 6 number primary health care center between March-May 2004 were enrolled in the study. As data collecting tools. A questionnaire prepared by the authors. This study was determined that 29.2 % of the mothers carried out mixture who had prepared at home to child's abdomen and foot base; 30.3 % were to put breast milk childs' ear; 38.9 % were placed aspirin, salt and salts of lemon to childs' teeth ache. The majority of the women make a wrong practices child that teeth, abdomen and ear ache. This traditional practice effecting factors were the women's educational status and age. The results of the study that education about child care, common health problems and incorrect applications shoud be given to women by nurse.

Structural changes in the water tetramer. A combined Monte Carlo and DFT study

Czech Academy of Sciences Publication Activity Database

Vítek, A.; Kalus, R.; Paidarová, Ivana

2010-01-01

Roč. 12, č. 41 (2010), s. 13657-13666 ISSN 1463-9076 R&D Projects: GA AV ČR IAA401870702 Institutional research plan: CEZ:AV0Z40400503 Keywords : Monte Carlo Study * DFT study * water tetramer Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.454, year: 2010

Penerapan Best Practice IT Service Management dalam Perbaikan IT Service Desk: Studi Kasus PT. Matahari Putra Prima

Directory of Open Access Journals (Sweden)

Hendra Hendra

2011-06-01

Full Text Available Information Technology (IT grows very rapidly and affects every aspect of business life to support competition with other companies that have the same field. PT. Matahari Putra Prima has implemented a computerized system as one of its business strategy in achieving the company's business objectives. With the implementation of IT in the company, the role of Service Desk is indispensable in providing services to users. This study aims to identify and analyze the implementation of IT Service Desk of PT. Matahari Putra Prima to the users. This research is expected to increase and improve the quality of IT Service Desk PT. Matahari Putra Prima based on the IT Service Management (ITSM. 

Relationship between calcium entry and ACh release in K+ -stimulated rat brain synaptosomes

International Nuclear Information System (INIS)

Suszkiw, J.B.; O'Leary, M.E.; Toth, G.P.

1986-01-01

This paper examines the pattern of Ca ++ entry-dependent ACh release in relation to the kinetics of Ca ++ entry, and its inactivation in rat brain synaptosomes exposed to 50 mM K 0 + for short and prolonged durations. Intrasynaptosomal ACh was radiolabeled from tritium-choline in the presence of 20 um Paraoxon to inhibit the acetylcholinesterase activity. The release of tritium-ACh was studied in superfused synaptosomal beds formed on glass microfiber filters and by rapid filtration. The intermittent stimulation of superfused synaptosomal beds by 3-min pulses of 50 mM K + evoked decremental output of tritium-ACh which reached nearly undetectable levels after the fifth stimulus

Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA tetramer-based flow cytometry: a European multicenter evaluation.

Science.gov (United States)

Heijnen, Ingmar A F M; Barnett, David; Arroz, Maria J; Barry, Simon M; Bonneville, Marc; Brando, Bruno; D'hautcourt, Jean-Luc; Kern, Florian; Tötterman, Thomas H; Marijt, Erik W A; Bossy, David; Preijers, Frank W M B; Rothe, Gregor; Gratama, Jan W

2004-11-01

HLA class I peptide tetramers represent powerful diagnostic tools for detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the current multicenter study is the critical need to standardize tetramer flow cytometry if it is to be implemented as a routine diagnostic assay. Hence, the European Working Group on Clinical Cell Analysis set out to develop and evaluate a single-platform tetramer-based method that used cytomegalovirus (CMV) as the antigenic model. Absolute numbers of CMV-specific CD8(+) T cells were obtained by combining the percentage of tetramer-binding cells with the absolute CD8(+) T-cell count. Six send-outs of stabilized blood from healthy individuals or CMV-carrying donors with CMV-specific CD8(+) T-cell counts of 3 to 10 cells/microl were distributed to 7 to 16 clinical sites. These sites were requested to enumerate CD8(+) T cells and, in the case of CMV-positive donors, CMV-specific subsets on three separate occasions using the standard method. Between-site coefficients of variation of less than 10% (absolute CD8(+) T-cell counts) and approximately 30% (percentage and absolute numbers of CMV-specific CD8(+) T cells) were achieved. Within-site coefficients of variation were approximately 5% (absolute CD8(+) T-cell counts), approximately 9% (percentage CMV-specific CD8(+) T cells), and approximately 17% (absolute CMV-specific CD8(+) T-cell counts). The degree of variation tended to correlate inversely with the proportion of CMV-specific CD8(+) T-cell subsets. The single-platform MHC tetramer-based method for antigen-specific CD8(+) T-cell counting has been evaluated by a European group of laboratories and can be considered a reproducible assay for routine enumeration of antigen-specific CD8(+) T cells. (c) 2004 Wiley-Liss, Inc.

31 CFR 363.38 - What happens if my financial institution returns an ACH debit?

Science.gov (United States)

2010-07-01

... TreasuryDirect § 363.38 What happens if my financial institution returns an ACH debit? If your designated financial institution returns an ACH debit, we reserve the right to reinitiate the debit at our option. We.... We are not responsible for any fees your financial institution may charge relating to returned ACH...

Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin.

Science.gov (United States)

Ihara, Makoto; Okajima, Toshihide; Yamashita, Atsuko; Oda, Takuma; Hirata, Koichi; Nishiwaki, Hisashi; Morimoto, Takako; Akamatsu, Miki; Ashikawa, Yuji; Kuroda, Shun'ichi; Mega, Ryosuke; Kuramitsu, Seiki; Sattelle, David B; Matsuda, Kazuhiko

2008-06-01

Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-pi interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.

Ultramicromorphological observation of Usnea longissima Ach ...

African Journals Online (AJOL)

The Usnea longissima Ach. grew as an epiphyte on Abies georgei and was collected at an altitude of 3640 m above sea level from the Pudacuo National Park in the Shangri-La County of the Diqing Tibetan Autonomous Prefecture in the Yunnan Province of China. Scanning electron microscopy revealed the ...

Generation of functional HLA-DR*1101 tetramers receptive for loading with pathogen or tumour derived synthetic peptides

Directory of Open Access Journals (Sweden)

Protti Maria

2005-12-01

Full Text Available Abstract Background MHC class I-peptide tetramers are currently utilised to characterize CD8+ T cell responses at single cell level. The generation and use of MHC class II tetramers to study antigen-specific CD4+ T cells appears less straightforward. Most MHC class II tetramers are produced with a homogeneously built-in peptide, reducing greatly their flexibility of use. We attempted the generation of "empty" functional HLA-DR*1101 tetramers, receptive for loading with synthetic peptides by incubation. No such reagent is in fact available for this HLA-DR allele, one of the most frequent in the Caucasian population. Results We compared soluble MHC class II-immunoglobulin fusion proteins (HLA-DR*1101-Ig with soluble MHC class II protein fused with an optimised Bir site for enzymatic biotynilation (HLA-DR*1101-Bir, both produced in insect cells. The molecules were multimerised by binding fluorochrome-protein A or fluorochrome-streptavidin, respectively. We find that HLA-DR*1101-Bir molecules are superior to the HLA-DR*1101-Ig ones both in biochemical and functional terms. HLA-DR*1101-Bir molecules can be pulsed with at least three different promiscuous peptide epitopes, derived from Tetanus Toxoid, influenza HA and the tumour associated antigen MAGE-3 respectively, to stain specific CD4+ T cells. Both staining temperature and activation state of CD4+ T cells are critical for the binding of peptide-pulsed HLA-DR*1101-Bir to the cognate TCR. Conclusion It is therefore possible to generate a soluble recombinant HLA-DR*1101 backbone that is receptive for loading with different peptides to stain specific CD4+ T cells. As shown for other HLA-DR alleles, we confirm that not all the strategies to produce soluble HLA-DR*1101 multimers are equivalent.

Analisis Faktor-Faktor Penempatan Karyawan Terhadap Kepuasan Kerja Karyawan Di PT Yuniko Asia Prima Di Kota Bandung

Directory of Open Access Journals (Sweden)

Darwis Agustriyana

2015-10-01

Full Text Available The research objective is to be achieved (1 To know how the placement of employees and job satisfaction in a textile factory Yuniko Asia Prima (2 To determine the effect of the placement of employees on the level of job satisfaction in a textile factory Yuniko Asia Prima. The study populations were employees at a textile factory Yuniko Asia Prima and the sample is taken as many as 83 employees by the simple technique of sampling with multiple regression analysis. The results showed that the placement of employees at PT Asia Prima Yuniko already well underway. Employees of the company were placed in accordance with academic achievement as well as its experience, and in accordance with the physical and mental health. Also according to the employees, the company delivers wages in accordance with the number of dependents received, and promotion according to the marital status of an employee owned. Employee satisfaction gets a positive response from employees. It can be seen that the needs of the wages, the work itself, promotion, co-workers and supervisors and supervisor monitoring can fulfill the wishes of employees. Influence simultaneously, variable placement of employees has a significant influence with employee job satisfaction, and the results of the analysis of the coefficient of determination, the variable placement of employees by 69% has an influence on the formation of employee satisfaction. However partially, variable marital status and age did not have influence on job satisfaction of employees at PT Yuniko Asia Prima.

Exploiting pH-Regulated Dimer-Tetramer Transformation of Concanavalin A to Develop Colorimetric Biosensing of Bacteria.

Science.gov (United States)

Xu, Xiahong; Yuan, Yuwei; Hu, Guixian; Wang, Xiangyun; Qi, Peipei; Wang, Zhiwei; Wang, Qiang; Wang, Xinquan; Fu, Yingchun; Li, Yanbin; Yang, Hua

2017-05-03

Gold nanoparticles (AuNPs) aggregation-based colorimetric biosensing remains a challenge for bacteria due to their large size. Here we propose a novel colorimetric biosensor for rapid detection of Escherichia coli O157:H7 (E. coli O157:H7) in milk samples based on pH-regulated transformation of dimer/tetramer of Concanavalin A (Con A) and the Con A-glycosyl recognition. Briefly, antibody-modified magnetic nanoparticles was used to capture and concentrate E. coli O157:H7 and then to label with Con A; pH adjusted to 5 was then applied to dissociate Con A tetramer to release dimer, which was collected and re-formed tetramer at pH of 7 to cause the aggregation of dextran-modified AuNPs. The interesting pH-dependent conformation-transformation behavior of Con A innovated the design of the release from the bacteria surface and then the reconstruction of Con A. Therefore, we realized the sensitive colorimetric biosensing of bacteria, which are much larger than AuNPs that is generally not suitable for this kind of method. The proposed biosensor exhibited a limit of detection down to 41 CFU/mL, short assay time (~95 min) and satisfactory specificity. The biosensor also worked well for the detection in milk sample, and may provide a universal concept for the design of colorimetric biosensors for bacteria and virus.

Genistein, a Phytoestrogen in Soybean, Induces the Expression of Acetylcholinesterase via G Protein-Coupled Receptor 30 in PC12 Cells

Directory of Open Access Journals (Sweden)

Etta Y. L. Liu

2018-02-01

Full Text Available Genistein, 4′,5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs, markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA-linked acetyl-cholinesterase (G4 AChE, a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA. The genistein-induced AChE expression was fully blocked by the pre-treatment of H89 (an inhibitor of protein kinase A, PKA and G15 (a selective G protein-coupled receptor 30 (GPR30 antagonist, which suggested a direct involvement of a membrane-bound estrogen receptor (ER, named as GPR30 in the cultures. In parallel, the estrogen-induced activation of GPR30 induced AChE expression in a dose-dependent manner. The genistein/estrogen-induced AChE expression was triggered by a cyclic AMP responding element (CRE located on the ACHE gene promoter. The binding of this CRE site by cAMP response element-binding protein (CREB induced ACHE gene transcription. In parallel, increased expression levels of miR132 and miR212 were found when cultured PC12 cells were treated with genistein or G1. Thus, a balance between production and destruction of AChE by the activation of GPR30 was reported here. We have shown for the first time that the activation of GPR30 could be one way for estrogen or flavonoids, possessing estrogenic properties, to enhance cholinergic functions in the brain, which could be a good candidate for possible treatment of neurodegenerative diseases.

HLA-DQ-Gluten Tetramer Blood Test Accurately Identifies Patients With and Without Celiac Disease in Absence of Gluten Consumption.

Science.gov (United States)

Sarna, Vikas K; Lundin, Knut E A; Mørkrid, Lars; Qiao, Shuo-Wang; Sollid, Ludvig M; Christophersen, Asbjørn

2018-03-01

Celiac disease is characterized by HLA-DQ2/8-restricted responses of CD4+ T cells to cereal gluten proteins. A diagnosis of celiac disease based on serologic and histologic evidence requires patients to be on gluten-containing diets. The growing number of individuals adhering to a gluten-free diet (GFD) without exclusion of celiac disease complicates its detection. HLA-DQ-gluten tetramers can be used to detect gluten-specific T cells in blood of patients with celiac disease, even if they are on a GFD. We investigated whether an HLA-DQ-gluten tetramer-based assay accurately identifies patients with celiac disease. We produced HLA-DQ-gluten tetramers and added them to peripheral blood mononuclear cells isolated from 143 HLA-DQ2.5 + subjects (62 subjects with celiac disease on a GFD, 19 subjects without celiac disease on a GFD [due to self-reported gluten sensitivity], 10 subjects with celiac disease on a gluten-containing diet, and 52 presumed healthy individuals [controls]). T cells that bound HLA-DQ-gluten tetramers were quantified by flow cytometry. Laboratory tests and flow cytometry gating analyses were performed by researchers blinded to sample type, except for samples from subjects with celiac disease on a gluten-containing diet. Test precision analyses were performed using samples from 10 subjects. For the HLA-DQ-gluten tetramer-based assay, we combined flow-cytometry variables in a multiple regression model that identified individuals with celiac disease on a GFD with an area under the receiver operating characteristic curve value of 0.96 (95% confidence interval [CI] 0.89-1.00) vs subjects without celiac disease on a GFD. The assay detected individuals with celiac disease on a gluten-containing diet vs controls with an area under the receiver operating characteristic curve value of 0.95 (95% CI 0.90-1.00). Optimized cutoff values identified subjects with celiac disease on a GFD with 97% sensitivity (95% CI 0.92-1.00) and 95% specificity (95% CI 0

Pharmacological and immunochemical characterization of α2* nicotinic acetylcholine receptors (nAChRs) in mouse brain

Science.gov (United States)

Whiteaker, Paul; Wilking, Jennifer A; Brown, Robert WB; Brennan, Robert J; Collins, Allan C; Lindstrom, Jon M; Boulter, Jim

2009-01-01

Aim: α2 nAChR subunit mRNA expression in mice is most intense in the olfactory bulbs and interpeduncular nucleus. We aimed to investigate the properties of α2* nAChRs in these mouse brain regions. Methods: α2 nAChR subunit-null mutant mice were engineered. Pharmacological and immunoprecipitation studies were used to determine the composition of α2 subunit-containing (α2*) nAChRs in these two regions. Results: [125I]Epibatidine (200 pmol/L) autoradiography and saturation binding demonstrated that α2 deletion reduces nAChR expression in both olfactory bulbs and interpeduncular nucleus (by 4.8±1.7 and 92±26 fmol̇mg-1 protein, respectively). Pharmacological characterization using the β2-selective drug A85380 to inhibit [125I]epibatidine binding proved inconclusive, so immunoprecipitation methods were used to further characterize α2* nAChRs. Protocols were established to immunoprecipitate β2 and β4 nAChRs. Immunoprecipitation specificity was ascertained using tissue from β2- and β4-null mutant mice, and efficacy was good (>90% of β2* and >80% of β4* nAChRs were routinely recovered). Conclusion: Immunoprecipitation experiments indicated that interpeduncular nucleus α2* nAChRs predominantly contain β2 subunits, while those in olfactory bulbs contain mainly β4 subunits. In addition, the immunoprecipitation evidence indicated that both nuclei, but especially the interpeduncular nucleus, express nAChR complexes containing both β2 and β4 subunits. PMID:19498420

Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

Science.gov (United States)

Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

2014-09-01

Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Optogenetic release of ACh induces rhythmic bursts of perisomatic IPSCs in hippocampus.

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Daniel A Nagode

Full Text Available Acetylcholine (ACh influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2, was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs, and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs of local field potentials (LFPs were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach

Prima facie evidence against spin-two Higgs impostors

OpenAIRE

Ellis, John; Sanz, Veronica; You, Tevong

2013-01-01

The new particle X recently discovered by the ATLAS and CMS Collaborations is widely expected to have spin zero, but this remains to be determined. The leading alternative is that X has spin two, presumably with graviton-like couplings. We show that measurements of the X particle to pairs of vector bosons constrain such scenarios. In particular, a graviton-like Higgs impostor in scenarios with a warped extra dimension of AdS type is prima facie excluded, principally because they predict too s...

Synthesis and Biological Evaluation of Novel Jatrorrhizine Derivatives with Amino Groups Linked at the 3-Position as Inhibitors of Acetylcholinesterase

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Xiaofei Jiang

2017-01-01

Full Text Available Jatrorrhizine was considered as one of the active constituents of Coptis chinensis Franch. Herein, jatrorrhizine derivatives with substituted amino groups linked at the 3-position were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Jatrorrhizine derivatives inhibited the activity of acetylcholinesterase (AChE to a greater extent than the lead compound jatrorrhizine. All these jatrorrhizine derivatives were proved to be potent inhibitors of acetylcholinesterase (AChE with submicromolar IC50 values, but less sensitive to butyrylcholinesterase (BuChE, which suggests that these jatrorrhizine derivatives are selective for AChE/BuChE. Compound 3g gave the most potent inhibitor activity for AChE (IC50 = 0.301 μM, which is greater than the lead compound jatrorrhizine. All these results demonstrated that these jatrorrhizine derivatives are potential inhibitors for AChE.

PRIMA-1 and PRIMA-1Met (APR-246: From Mutant/Wild Type p53 Reactivation to Unexpected Mechanisms Underlying Their Potent Anti-Tumor Effect in Combinatorial Therapies

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Anne Perdrix

2017-12-01

Full Text Available p53 protects cells from genetic assaults by triggering cell-cycle arrest and apoptosis. Inactivation of p53 pathway is found in the vast majority of human cancers often due to somatic missense mutations in TP53 or to an excessive degradation of the protein. Accordingly, reactivation of p53 appears as a quite promising pharmacological approach and, effectively, several attempts have been made in that sense. The most widely investigated compounds for this purpose are PRIMA-1 (p53 reactivation and induction of massive apoptosis and PRIMA-1Met (APR-246, that are at an advanced stage of development, with several clinical trials in progress. Based on publications referenced in PubMed since 2002, here we review the reported effects of these compounds on cancer cells, with a specific focus on their ability of p53 reactivation, an overview of their unexpected anti-cancer effects, and a presentation of the investigated drug combinations.

Getting to First Base: Prima Facie Arguments for Propositions of Value.

Science.gov (United States)

Tuman, Joseph S.

1987-01-01

Argues that few clear standards exist for value debate. Defines values as instrumental or terminal, and identifies four prima facie burdens necessary for affirming a value resolution: value identification; value criteria; value hierarchy; and topicality through relevance. Examines the role of presumption and burden of proof in value debate. (MM)

Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds.

Science.gov (United States)

Guex, A G; Spicer, C D; Armgarth, A; Gelmi, A; Humphrey, E J; Terracciano, C M; Harding, S; Stevens, M M

2017-09-01

Conjugated polymers have been proposed as promising materials for scaffolds in tissue engineering applications. The restricted processability and biodegradability of conjugated polymers limit their use for biomedical applications however. Here we synthesised a block- co -polymer of aniline tetramer and PCL (AT-PCL), and processed it into fibrous non-woven scaffolds by electrospinning. We showed that fibronectin (Fn) adhesion was dependant on the AT-PCL oxidative state, with a reduced Fn unfolding length on doped membranes. Furthermore, we demonstrated the cytocompatibility and potential of these membranes to support the growth and osteogenic differentiation of MC3T3-E1 over 21 days.

Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

Science.gov (United States)

Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

2015-08-01

Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

Synthesis, spectroscopic, computational (DFT/B3LYP), AChE inhibition and antioxidant studies of imidazole derivative

Science.gov (United States)

Ahmad, Faheem; Alam, Mohammad Jane; Alam, Mahboob; Azaz, Shaista; Parveen, Mehtab; Park, Soonheum; Ahmad, Shabbir

2018-01-01

The present study reports the synthesis and evaluation of biological properties of 3a,8a-dihydroxy-8-oxo-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazol-2(1H)-iminium chloride (3). The structure was confirmed by the FTIR, NMR, MS, CHN microanalysis and X-ray crystallographic analysis. Quantum chemical calculations have been performed at B3LYP-D3/6-311++G(d,p) level of theory to study the molecular geometry, IR, (1H and 13C) NMR, UV/Vis spectra and other molecular parameters of the asymmetric unit of crystal of imidazole compound (3). An empirical dispersion correction to hybrid functional (B3LYP-D3) has been incorporated in the present calculations due to presence of non-covalent interaction, Cl⋯H-O, in the present compound. The remarkable agreement has been observed between theoretical data and those measured experimentally. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The synthesized imidazole derivative showed promising antioxidant property and inhibitory activity against acetylcholinesterase (AChE). Molecular docking was also performed in order to explain in silico antioxidant studies and to ascertain the probable binding mode of compound with the amino acid residues of protein.

Applications in Foreign Currency Prima CV Ellindo Money Changer

OpenAIRE

Wisnu Sutrisno; Ire Puspa Wardhani, Skom, MMSI

2004-01-01

This explains the scientific writing about the design of application programs forforeign currency transactions by using Visual Basic 6.0 programming language.In scientific writing database is also used by Visual Data Manager (VisData)integrated in Visual Basic 6.0 program itself. Consists of three tables namelyCurrency,Customer and Transaction.In the end application program for foreign currency transactions will be applied to theCV. Prima Ellindo Money Changer for ease in performing activitie...

Chemical chaperones exceed the chaperone effects of RIC-3 in promoting assembly of functional α7 AChRs.

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Alexander Kuryatov

Full Text Available Functional α7 nicotinic acetylcholine receptors (AChRs do not assemble efficiently in cells transfected with α7 subunits unless the cells are also transfected with the chaperone protein RIC-3. Despite the presence of RIC-3, large amounts of these subunits remain improperly assembled. Thus, additional chaperone proteins are probably required for efficient assembly of α7 AChRs. Cholinergic ligands can act as pharmacological chaperones to promote assembly of mature AChRs and upregulate the amount of functional AChRs. In addition, we have found that the chemical chaperones 4-phenylbutyric acid (PBA and valproic acid (VPA greatly increase the amount of functional α7 AChRs produced in a cell line expressing both α7 and RIC-3. Increased α7 AChR expression allows assay of drug action using a membrane potential-sensitive fluorescent indicator. Both PBA and VPA also increase α7 expression in the SH-SY5Y neuroblastoma cell line that endogenously expresses α7 AChRs. VPA increases expression of endogenous α7 AChRs in hippocampal neurons but PBA does not. RIC-3 is insufficient for optimal assembly of α7 AChRs, but provides assay conditions for detecting additional chaperones. Chemical chaperones are a useful pragmatic approach to express high levels of human α7 AChRs for drug selection and characterization and possibly to increase α7 expression in vivo.

PACMAN: PRIMA astrometric instrument software

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Abuter, Roberto; Sahlmann, Johannes; Pozna, Eszter

2010-07-01

The dual feed astrometric instrument software of PRIMA (PACMAN) that is currently being integrated at the VLTI will use two spatially modulated fringe sensor units and a laser metrology system to carry out differential astrometry. Its software and hardware compromises a distributed system involving many real time computers and workstations operating in a synchronized manner. Its architecture has been designed to allow the construction of efficient and flexible calibration and observation procedures. In parallel, a novel scheme of integrating M-code (MATLAB/OCTAVE) with standard VLT (Very Large Telescope) control software applications had to be devised in order to support numerically intensive operations and to have the capacity of adapting to fast varying strategies and algorithms. This paper presents the instrument software, including the current operational sequences for the laboratory calibration and sky calibration. Finally, a detailed description of the algorithms with their implementation, both under M and C code, are shown together with a comparative analysis of their performance and maintainability.

Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

International Nuclear Information System (INIS)

Orlandi, Ivan; Casatta, Nadia; Vai, Marina

2012-01-01

ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality.

Morphological redescription and DNA barcoding of Linevitshia prima Makarchenko, 1987 (Diptera: Chironomidae: Diamesinae) from Amur River basin (Russian Far East), with notes on systematics of the genus.

Science.gov (United States)

Makarchenko, Eugenyi A; Semenchenko, Alexander A

2014-10-10

Additions and corrections to the diagnosis of the genus Linevitshia for male adult, pupa and larva are given, and systematic position of the genus is discussed. Illustrated redescription of adult male and first description of 4th instar larva of L. prima Makarchenko from Amur River basin are provided. Comparison of data based on a new material with those of L. yezoensis Endo showed that the latter name is a junior synonym of L. prima. The species-specificity of L. prima COI sequences is analyzed and the sequences are presented as diagnostic characters-molecular markers of L. prima.

Dowód prima facie w postępowaniu cywilnym dotyczącym szkód powstałych w związku z leczeniem

OpenAIRE

Białkowski, Michał

2014-01-01

The objective of this paper is to present main perspectives expressed by representatives of Polish legal doctrine as well as several examples of applications of prima facie evidence in legal cases submitted to Polish Supreme Court. Although not codified in Polish civil procedure prima facie evidence is applied in cases concerning claims for compensation for damages such as those occurred during medical treatment or inflicted by employees. The paper tries to answer whether prima facie evidence...

Acetylcholinesterase Inhibitors (AChEI's for the treatment of visual hallucinations in schizophrenia: A review of the literature

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Patel Sachin S

2010-09-01

Full Text Available Abstract Background Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition. Methods A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia. Results No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group. Discussion Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly. Conclusions We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.

Preparation and comparison of a-C:H coatings using reactive sputter techniques

Energy Technology Data Exchange (ETDEWEB)

Keunecke, M., E-mail: martin.keunecke@ist.fraunhofer.d [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Weigel, K.; Bewilogua, K. [Fraunhofer Institute for Surface Engineering and Thin Films (IST), Braunschweig (Germany); Cremer, R.; Fuss, H.-G. [CemeCon AG, Wuerselen (Germany)

2009-12-31

Amorphous hydrogenated carbon (a-C:H) coatings are widely used in several industrial applications. These coatings commonly will be prepared by plasma activated chemical vapor deposition (PACVD). The main method used to prepare a-C:H coating in industrial scale is based on a glow discharge in a hydrocarbon gas like acetylene or methane using a substrate electrode powered with medium frequency (m.f. - some 10 to 300 kHz). Some aims of further development are adhesion improvement, increase of hardness and high coating quality on complex geometries. A relatively new and promising technique to fulfil these requirements is the deposition of a-C:H coatings by a reactive d.c. magnetron sputter deposition from a graphite target with acetylene as reactive gas. An advancement of this technique is the deposition in a pulsed magnetron sputter process. Using these three mentioned techniques a-C:H coatings were prepared in the same deposition machine. For adhesion improvement different interlayer systems were applied. The effect of different substrate bias voltages (d.c. and d.c. pulse) was investigated. By applying the magnetron sputter technique in the d.c. pulse mode, plastic hardness values up to 40 GPa could be reached. Besides hardness other mechanical properties like resistance against abrasive wear were measured and compared. Cross sectional SEM images showed the growth structure of the coatings.

Pengkajian Rakitan Teknologi Budidaya Kentang dan Strategi Pengembangannya : Studi Kasus di Wilayah Prima Tani Lahan Kering Dataran Tinggi Kabupaten Magetan

OpenAIRE

Santoso, Pudji; Yuniarti; Purnomo, Sudarmadi; Subandi

2009-01-01

Pengkajian Rakitan Teknologi Budidaya Kentang dan Strategi Pengembangannya : Studi Kasus di Wilayah Prima Tani Lahan Kering Dataran Tinggi Kabupaten Magetan. The assessment on improving the cultivation technology of potato as demonstration plot in farmer's land was done in Prima Tani area of Magetan regency in Genilangit village, during dry season on June – September 2007. Collecting data was done using farm record keeping method on the application of improving cultivation technology of potat...

EVALUACIÓN AMBIENTAL PARA PROCESOS QUE USAN RESIDUOS DE LA INDUSTRIA DE LOS BIOCOMBUSTIBLES COMO MATERIAS PRIMAS

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Mónica Julieth Valencia Botero

Full Text Available La industria creciente de los biocombustibles genera grandes cantidades de residuos que tienen alto potencial para la obtención de productos con alto valor agregado. En el presente documento se lleva a cabo el análisis de ciclo de vida (ACV para el glicerol y el bagazo de caña de azúcar durante su producción y para su uso como materia prima en cuatro procesos diferentes. El objetivo fue determinar el impacto ambiental de los cuatro procesos, por medio de la cuantificación de gases de efecto invernadero (GEI asociados al ciclo de vida. Los resultados indican que las emisiones de GEI asociadas a los procesos que utilizan el glicerol como materia prima son mayores que las emisiones de GEI para los procesos que involucran bagazo de caña de azúcar, pero que el aprovechamiento del glicerol podría considerarse más eficiente, ya que las emisiones por unidad de masa en el uso del glicerol son 75% inferiores a las emisiones calculadas para los procedimientos utilizando bagazo de caña como materia prima.

Aplicaciones de la Función de Smarandache y las Funciones Prima y Coprima

OpenAIRE

Ruiz, Sebastián Martín

2002-01-01

Un libro para los amantes de los números: La función de Smarandache aplicada a los números perfectos, congruencias. También, las funciones prima y coprima de Smarandache en conexión con expresiones de los números primos.

Neonikotinoid İnsektisitlere Bağlı Olarak Drosophila melanogaster’in AChE Aktivitesinde Meydana Gelen Değişikliklerin Bitkisel Ekstraktlar ile Giderilmesi Üzerine Araştırmalar

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Sedat Ünver

2014-12-01

Full Text Available Bu çalışmada, Drosophila melanogaster’in ergin bireylerinde bulunan asetil kolinesteraz (AChE enzim aktivitesi üzerine İmidakloprid (İMİ ve Asetamiprid (ASE  insektisitlerinin etkileri araştırılmıştır. Ayrıca farklı bitkilere ait su ekstraktlarının (Salvia lavandulifolia, Hypericum scabrum, Capsella bursa-pastoris ve Teucrium orientale iyileştirici etkileri de in vivo olarak incelenmiştir. Bu amaçla iki deney grubu oluşturulmuştur. İlk deney grubunda ergin bireylere yalnızca farklı dozlarda insektisit (0,5; 1,0; 1,5 ve 2,0 ppm, diğer deney grubunda ise insektisit + bitki ekstraktları (1:1 v/v birlikte uygulanmıştır. Uygulamalar sonucunda insektisitler doz artışına bağlı olarak ergin bireylerde AChE aktivitesini artırmıştır (P<0,05. Ancak insektisitler bitkisel ekstraktlar ile birlikte uygulanınca enzim aktivitesi tekrar kontrol grubuna yaklaşmıştır (P<0,05.

Sustaining Competitive Advantage in Prima Sakti

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Kristin Handoyo

2016-06-01

Full Text Available Didirikan pada tahun 1993, Prima Sakti adalah sebuah perusahaan metal stamping dan plastic injection parts. Setelah lebih dari dua dekade, perusahaan ini telah berkembang menjadi sebuah perusahaan yang kompleks dalam hal ukuran, pasar dan produk. Penelitian kualitatif ini dipandu oleh sejumlah teori sebagai landasan dan menggunakan triangulasi data. Hasil dan pembahasan menunjukkan adanya perkembangan perusahaan dari sistem made-to-order menjadi sistem hybrid antara sistem made-to-order dan made-to-stock untuk memaksimalkan kapasitas dalam menerapkan cost leadership. Target pasar juga meluas dalam hal melanjutkan penetrasi pasar, pengembangan pasar dan pengembangan produk. Hasil dan pembahasan juga mengindikasi bahwa untuk mendapatkan keunggulan kompetitif, perusahaan mengintegrasi strategi cost leadership dan differentiation. Sebagai penutup, peneliti mengusulkan sebuah teori-mini yang didasarkan pada sejumlah variabel antara lain reputasi perusahaan, kualitas produk, pelayanan, learning effect, economies of scale, economies of scope dan capacity utilization yang mungkin memengaruhi keunggulan kompetitif untuk diuji secara kuantitatif.

The current agonists and positive allosteric modulators of α7 nAChR for CNS indications in clinical trials

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Taoyi Yang

2017-11-01

Full Text Available The alpha-7 nicotinic acetylcholine receptor (α7 nAChR, consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

Science.gov (United States)

Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon

2018-03-26

α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.

Anti-parallel dimer and tetramer formation of propylene carbonate

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Ayana Tagawa

2017-09-01

Full Text Available Raman scattering and infrared (IR absorption spectra of enantiopure (R-propylene carbonate ((RPC and racemic propylene carbonate (PC were recorded at room temperature, 25 °C, in benzene (Bz solution and in the pure liquid state to investigate the presence of dimers and other higher order intermolecular associations. (RPC and PC both demonstrated a strong C=O stretching vibrational band. The band exhibited changes in its shape and resonance wavenumber highly dependent on the concentrations of PCs, whereas a difference between the chirality of (RPC and PC had little influence. In an extremely dilute condition, doubly split bands were observed at 1807 and 1820 cm-1 in both Raman and IR spectra, which are assigned to the characteristic bands of isolated monomeric PCs. An additional band appeared at 1795 cm-1 in a dilute to concentrated regime, and its magnitude strengthened with increasing concentrations accompanied with slight increasing in the magnitude of 1807 cm-1 band in Raman spectra, while an increase in the magnitude of 1807 cm-1 band was clearly greater than that of 1795 cm-1 band in IR spectra. The spectrum changes at 1795 and 1807 cm-1 were attributed to characteristics of anti-parallel dimer formation of PCs caused by strong dipole-dipole interactions between C=O groups. Moreover, another additional signal was clearly observed at 1780-1790 cm-1 in a concentrated regime, and became the primary signal in the pure liquid state with slight increasing in the intensity of 1795 cm-1 band in Raman spectra. On the other hand, in IR spectra the observed increasing of 1780-1790 cm-1 band was much less than that of 1795 cm-1 band. These newly found spectrum changes in the concentrated regime are attributed to the formation of anti-parallel tetramers of PCs based on the characteristics of band selection rule found in Raman and IR spectra. Equilibrium constants for the anti-parallel dimer (KD and tetramer formation (KT of PCs in Bz solution and in

[First trimester screening for Down syndrome at Prima facie. A 6-year survey].

Science.gov (United States)

Roth, P; Bernard, J-P; Meyer, V; Beaujard, M-P; Salomon, L-J; Ville, Y

2016-02-01

To evaluate the results of screening for trisomy 21 by the combined risk of first trimester (as defined by the decree of June 23, 2009) in the Prima facie structure. Single center study involving all patients that were seen for first trimester screening at Prima facie with singleton living pregnancy, not obtained by embryo donation, between 1 January 2009 and 31 December 2014. Eighteen thousand two hundred and fifty-one patients were included, of which underwent screening for trisomy 21 by the combined risk. One thousand and forty-six (6.1%) had a calculated risk higher than 1/250. Seventy-five were affected by trisomy 21, of whom 65 in the high risk group. The sensitivity and specificity of screening are 86.7% and 94.4%. The median nuchal translucency was 0.98 MoM. Screening for trisomy 21 by calculating the combined risk of first trimester enabled to detect 86.7% of trisomy 21 with a false positive rate of 5.6%. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The PRIMA Test Facility: SPIDER and MITICA test-beds for ITER neutral beam injectors

Science.gov (United States)

Toigo, V.; Piovan, R.; Dal Bello, S.; Gaio, E.; Luchetta, A.; Pasqualotto, R.; Zaccaria, P.; Bigi, M.; Chitarin, G.; Marcuzzi, D.; Pomaro, N.; Serianni, G.; Agostinetti, P.; Agostini, M.; Antoni, V.; Aprile, D.; Baltador, C.; Barbisan, M.; Battistella, M.; Boldrin, M.; Brombin, M.; Dalla Palma, M.; De Lorenzi, A.; Delogu, R.; De Muri, M.; Fellin, F.; Ferro, A.; Fiorentin, A.; Gambetta, G.; Gnesotto, F.; Grando, L.; Jain, P.; Maistrello, A.; Manduchi, G.; Marconato, N.; Moresco, M.; Ocello, E.; Pavei, M.; Peruzzo, S.; Pilan, N.; Pimazzoni, A.; Recchia, M.; Rizzolo, A.; Rostagni, G.; Sartori, E.; Siragusa, M.; Sonato, P.; Sottocornola, A.; Spada, E.; Spagnolo, S.; Spolaore, M.; Taliercio, C.; Valente, M.; Veltri, P.; Zamengo, A.; Zaniol, B.; Zanotto, L.; Zaupa, M.; Boilson, D.; Graceffa, J.; Svensson, L.; Schunke, B.; Decamps, H.; Urbani, M.; Kushwah, M.; Chareyre, J.; Singh, M.; Bonicelli, T.; Agarici, G.; Garbuglia, A.; Masiello, A.; Paolucci, F.; Simon, M.; Bailly-Maitre, L.; Bragulat, E.; Gomez, G.; Gutierrez, D.; Mico, G.; Moreno, J.-F.; Pilard, V.; Kashiwagi, M.; Hanada, M.; Tobari, H.; Watanabe, K.; Maejima, T.; Kojima, A.; Umeda, N.; Yamanaka, H.; Chakraborty, A.; Baruah, U.; Rotti, C.; Patel, H.; Nagaraju, M. V.; Singh, N. P.; Patel, A.; Dhola, H.; Raval, B.; Fantz, U.; Heinemann, B.; Kraus, W.; Hanke, S.; Hauer, V.; Ochoa, S.; Blatchford, P.; Chuilon, B.; Xue, Y.; De Esch, H. P. L.; Hemsworth, R.; Croci, G.; Gorini, G.; Rebai, M.; Muraro, A.; Tardocchi, M.; Cavenago, M.; D'Arienzo, M.; Sandri, S.; Tonti, A.

2017-08-01

The ITER Neutral Beam Test Facility (NBTF), called PRIMA (Padova Research on ITER Megavolt Accelerator), is hosted in Padova, Italy and includes two experiments: MITICA, the full-scale prototype of the ITER heating neutral beam injector, and SPIDER, the full-size radio frequency negative-ions source. The NBTF realization and the exploitation of SPIDER and MITICA have been recognized as necessary to make the future operation of the ITER heating neutral beam injectors efficient and reliable, fundamental to the achievement of thermonuclear-relevant plasma parameters in ITER. This paper reports on design and R&D carried out to construct PRIMA, SPIDER and MITICA, and highlights the huge progress made in just a few years, from the signature of the agreement for the NBTF realization in 2011, up to now—when the buildings and relevant infrastructures have been completed, SPIDER is entering the integrated commissioning phase and the procurements of several MITICA components are at a well advanced stage.

Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

Directory of Open Access Journals (Sweden)

Vuslat Yilmaz

Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

Reciprocal activation of α5-nAChR and STAT3 in nicotine-induced human lung cancer cell proliferation.

Science.gov (United States)

Zhang, Yao; Jia, Yanfei; Li, Ping; Li, Huanjie; Xiao, Dongjie; Wang, Yunshan; Ma, Xiaoli

2017-07-20

Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors (nAChRs). Genome-wide association studies (GWAS) show that CHRNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 (pSTAT3) expression, smoking history and lower survival of non-small cell lung cancer (NSCLC) samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the JAK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChIP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial Parts of Ferulago trifida: Antimicrobial, Antioxidant, AChE Inhibitory, General Toxicity, MTT Assay and Larvicidal Activities.

Science.gov (United States)

Tavakoli, Saeed; Vatandoost, Hassan; Zeidabadinezhad, Reza; Hajiaghaee, Reza; Hadjiakhoondi, Abbas; Abai, Mohammad Reza; Yassa, Narguess

2017-09-01

We aimed to investigate different biological properties of aerial parts essential oil of Ferulago trifida Boiss and larvicidal activity of its volatile oils from all parts of plant. Essential oil was prepared by steam distillation and analyzed by Gas chromatography and GC/Mass. Antioxidant, antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal activity of F. trifida essential oil against malaria vector Anopheles stephensi was carried out according to the method described by WHO. In GC and GC/MS analysis, 58 compounds were identified in the aerial parts essential oil, of which E-verbenol (9.66%), isobutyl acetate (25.73%) and E-β-caryophyllene (8.68%) were main compounds. The oil showed (IC 50 = 111.2μg/ml) in DPPH and IC 50 = 21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil demonstrated toxicity with (LD 50 = 1.1μg/ml) in brine shrimp lethality test and with (IC 50 = 22.0, 25.0 and 42.55 μg/ml) on three cancerous cell lines (MCF-7, A-549 and HT-29) respectively. LC 50 of stem, root, aerial parts, fruits, and flowers essential oils against larvae of An. stephensi were equal with 10.46, 22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities, essential oil was effective on all specimens except Escherichia coli , Aspergillus niger and Candida albicans. The essential oil showed moderate antioxidant activity, strong antimicrobial properties and good toxic effect in brine shrimp test and MTT assay on three cancerous cell lines.

Prima facie evidence against spin-two Higgs impostors

Science.gov (United States)

Ellis, John; Sanz, Verónica; You, Tevong

2013-10-01

The new particle X recently discovered by the ATLAS and CMS Collaborations is widely expected to have spin zero, but this remains to be determined. The leading alternative is that X has spin two, presumably with graviton-like couplings. We show that measurements of the X particle to pairs of vector bosons constrain such scenarios. In particular, a graviton-like Higgs impostor in scenarios with a warped extra dimension of AdS type is prima facie excluded, principally because they predict too small a ratio between the X couplings to WW and ZZ, compared with that to photons. The data also disfavour universal couplings to pairs of photons and gluons, which would be predicted in a large class of graviton-like models.

Prima Facie Evidence against Spin-Two Higgs Impostors

CERN Document Server

Ellis, John; You, Tevong

2013-01-01

The new particle X recently discovered by the ATLAS and CMS Collaborations is widely expected to have spin zero, but this remains to be determined. The leading alternative is that X has spin two, presumably with graviton-like couplings. We show that measurements of the X particle to pairs of vector bosons constrain such scenarios. In particular, a graviton-like Higgs impostor in scenarios with a warped extra dimension of AdS type is prima facie excluded, principally because they predict too small a ratio between the X couplings to WW and ZZ, compared with that to photons. The data also disfavour universal couplings to pairs of photons and gluons, which would be predicted in a large class of graviton-like models.

Prima facie evidence against spin-two Higgs impostors

International Nuclear Information System (INIS)

Ellis, John; Sanz, Verónica; You, Tevong

2013-01-01

The new particle X recently discovered by the ATLAS and CMS Collaborations is widely expected to have spin zero, but this remains to be determined. The leading alternative is that X has spin two, presumably with graviton-like couplings. We show that measurements of the X particle to pairs of vector bosons constrain such scenarios. In particular, a graviton-like Higgs impostor in scenarios with a warped extra dimension of AdS type is prima facie excluded, principally because they predict too small a ratio between the X couplings to WW and ZZ, compared with that to photons. The data also disfavour universal couplings to pairs of photons and gluons, which would be predicted in a large class of graviton-like models

Prima facie evidence against spin-two Higgs impostors

Energy Technology Data Exchange (ETDEWEB)

Ellis, John [Theoretical Particle Physics and Cosmology Group, Physics Department, King' s College London, London WC2R 2LS (United Kingdom); TH Division, Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Sanz, Verónica, E-mail: vsanz@yorku.ca [TH Division, Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Department of Physics and Astronomy, York University, Toronto, ON, M3J 1P3 (Canada); You, Tevong [Theoretical Particle Physics and Cosmology Group, Physics Department, King' s College London, London WC2R 2LS (United Kingdom)

2013-10-07

The new particle X recently discovered by the ATLAS and CMS Collaborations is widely expected to have spin zero, but this remains to be determined. The leading alternative is that X has spin two, presumably with graviton-like couplings. We show that measurements of the X particle to pairs of vector bosons constrain such scenarios. In particular, a graviton-like Higgs impostor in scenarios with a warped extra dimension of AdS type is prima facie excluded, principally because they predict too small a ratio between the X couplings to WW and ZZ, compared with that to photons. The data also disfavour universal couplings to pairs of photons and gluons, which would be predicted in a large class of graviton-like models.

Exposure to radio-frequency electromagnetic waves alters acetylcholinesterase gene expression, exploratory and motor coordination-linked behaviour in male rats.

Science.gov (United States)

Obajuluwa, Adejoke Olukayode; Akinyemi, Ayodele Jacob; Afolabi, Olakunle Bamikole; Adekoya, Khalid; Sanya, Joseph Olurotimi; Ishola, Azeez Olakunle

2017-01-01

Humans in modern society are exposed to an ever-increasing number of electromagnetic fields (EMFs) and some studies have demonstrated that these waves can alter brain function but the mechanism still remains unclear. Hence, this study sought to investigate the effect of 2.5 Ghz band radio-frequency electromagnetic waves (RF-EMF) exposure on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA expression level as well as locomotor function and anxiety-linked behaviour in male rats. Animals were divided into four groups namely; group 1 was control (without exposure), group 2-4 were exposed to 2.5 Ghz radiofrequency waves from an installed WI-FI device for a period of 4, 6 and 8 weeks respectively. The results revealed that WiFi exposure caused a significant increase in anxiety level and affect locomotor function. Furthermore, there was a significant decrease in AChE activity with a concomitant increase in AChE mRNA expression level in WiFi exposed rats when compared with control. In conclusions, these data showed that long term exposure to WiFi may lead to adverse effects such as neurodegenerative diseases as observed by a significant alteration on AChE gene expression and some neurobehavioral parameters associated with brain damage.

Progress in the realization of the PRIMA neutral beam test facility

Science.gov (United States)

Toigo, V.; Boilson, D.; Bonicelli, T.; Piovan, R.; Hanada, M.; Chakraborty, A.; Agarici, G.; Antoni, V.; Baruah, U.; Bigi, M.; Chitarin, G.; Dal Bello, S.; Decamps, H.; Graceffa, J.; Kashiwagi, M.; Hemsworth, R.; Luchetta, A.; Marcuzzi, D.; Masiello, A.; Paolucci, F.; Pasqualotto, R.; Patel, H.; Pomaro, N.; Rotti, C.; Serianni, G.; Simon, M.; Singh, M.; Singh, N. P.; Svensson, L.; Tobari, H.; Watanabe, K.; Zaccaria, P.; Agostinetti, P.; Agostini, M.; Andreani, R.; Aprile, D.; Bandyopadhyay, M.; Barbisan, M.; Battistella, M.; Bettini, P.; Blatchford, P.; Boldrin, M.; Bonomo, F.; Bragulat, E.; Brombin, M.; Cavenago, M.; Chuilon, B.; Coniglio, A.; Croci, G.; Dalla Palma, M.; D'Arienzo, M.; Dave, R.; De Esch, H. P. L.; De Lorenzi, A.; De Muri, M.; Delogu, R.; Dhola, H.; Fantz, U.; Fellin, F.; Fellin, L.; Ferro, A.; Fiorentin, A.; Fonnesu, N.; Franzen, P.; Fröschle, M.; Gaio, E.; Gambetta, G.; Gomez, G.; Gnesotto, F.; Gorini, G.; Grando, L.; Gupta, V.; Gutierrez, D.; Hanke, S.; Hardie, C.; Heinemann, B.; Kojima, A.; Kraus, W.; Maeshima, T.; Maistrello, A.; Manduchi, G.; Marconato, N.; Mico, G.; Moreno, J. F.; Moresco, M.; Muraro, A.; Muvvala, V.; Nocentini, R.; Ocello, E.; Ochoa, S.; Parmar, D.; Patel, A.; Pavei, M.; Peruzzo, S.; Pilan, N.; Pilard, V.; Recchia, M.; Riedl, R.; Rizzolo, A.; Roopesh, G.; Rostagni, G.; Sandri, S.; Sartori, E.; Sonato, P.; Sottocornola, A.; Spagnolo, S.; Spolaore, M.; Taliercio, C.; Tardocchi, M.; Thakkar, A.; Umeda, N.; Valente, M.; Veltri, P.; Yadav, A.; Yamanaka, H.; Zamengo, A.; Zaniol, B.; Zanotto, L.; Zaupa, M.

2015-08-01

The ITER project requires additional heating by two neutral beam injectors, each accelerating to 1 MV a 40 A beam of negative deuterium ions, to deliver to the plasma a power of about 17 MW for one hour. As these requirements have never been experimentally met, it was recognized as necessary to setup a test facility, PRIMA (Padova Research on ITER Megavolt Accelerator), in Italy, including a full-size negative ion source, SPIDER, and a prototype of the whole ITER injector, MITICA, aiming to develop the heating injectors to be installed in ITER. This realization is made with the main contribution of the European Union, through the Joint Undertaking for ITER (F4E), the ITER Organization and Consorzio RFX which hosts the Test Facility. The Japanese and the Indian ITER Domestic Agencies (JADA and INDA) participate in the PRIMA enterprise; European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache and others are also cooperating. Presently, the assembly of SPIDER is on-going and the MITICA design is being completed. The paper gives a general overview of the test facility and of the status of development of the MITICA and SPIDER main components at this important stage of the overall development; then it focuses on the latest and most critical issues, regarding both physics and technology, describing the identified solutions.

HIV status: the prima facie right not to know the result.

Science.gov (United States)

Chan, Tak Kwong

2016-02-01

When a patient regains consciousness from Cryptococcus meningitis, the clinician may offer an HIV test (in case it has not already been done) (scenario 1) or offer to tell the patient his HIV status (in case the test has already been performed with a positive result while the patient was unconscious) (scenario 2). Youngs and Simmonds proposed that the patient has the prima facie right to refuse an HIV test in scenario 1 but not the prima facie right not to be told the HIV status in scenario 2. I submit that the claims to the right of refusal in both scenarios are similarly strong as they should both be grounded in privacy, self determination or dignity. But a conscientious agent should bear in mind that members of the public also have the right not to be harmed. When the circumstance allows, a proper balance of the potential benefits and harm for all the competing parties should guide the clinical decision as to whose right should finally prevail. Where a full ethical analysis is not possible, the presumption should favour respecting the patient's right of refusal in both scenarios. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

Science.gov (United States)

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

2017-11-01

Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.

The Burger Court and the Prima Facie Case in Employment Discrimination Litigation: A Critique.

Science.gov (United States)

Friedman, Joel William

1979-01-01

The unprincipled and contrived reasoning running through these opinions manifests an intentional effort by the Court to impede litigants' ability to secure their rights to equal employment opportunity by raising the requirements of the prima facie case. Available from Fred B. Rothman & Co., 10368 West Centennial Road, Littleton, CO 80123; sc…

PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53

DEFF Research Database (Denmark)

Zandi, Roza; Selivanova, Galina; Christensen, Camilla Laulund

2011-01-01

Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1(Met) (p53-dependent reactivation of massive apoptosis), also known as APR-246, is a small molecule, which restores tumor suppressor...... function to mutant p53 and induces cancer cell death in various cancer types. Since p53 is mutated in more than 90% of SCLC, we investigated the ability of PRIMA-1(Met) to induce apoptosis and inhibit tumor growth in SCLC with different p53 mutations....

Calculo y comparacion de la prima de un reaseguro de salud usando el modelo de opciones de Black-Scholes y el modelo actuarial

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Luis Eduardo Giron

2015-12-01

Full Text Available La presente investigación pretende calcular y comparar la prima de un reaseguro  usando el modelo de opciones de Black-Scholes y el modelo clásico actuarial tradicional. El período de análisis va desde enero de 2011 hasta diciembre de 2012. Los resultados obtenidos muestran que el modelo de Black-Scholes, que se utiliza normalmente para valorar opciones financieras, puede ser también usado para la estimación de primas de reaseguros de salud; y que la prima neta estimada a partir de este modelo se aproxima a las establecidas por el método actuarial, excepto cuando el deducible del reaseguro es muy alto (por encima de $200.000.000.

Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial Parts of Ferulago trifida: Antimicrobial, Antioxidant, AChE Inhibitory, General Toxicity, MTT assay and Larvicidal Activities

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Saeed Tavakoli

2017-10-01

Full Text Available Background: We aimed to investigate different biological properties of aerial parts essential oil of Ferulago trifida Boiss and larvicidal activity of its volatile oils from all parts of plant.Methods: Essential oil was prepared by steam distillation and analyzed by Gas chromatography and GC/Mass. Anti­oxidant, antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal activity of F. trifida essential oil against malaria vector Anoph­eles stephensi was carried out according to the method described by WHO.Results: In GC and GC/MS analysis, 58 compounds were identified in the aerial parts essential oil, of which E-ver­benol (9.66%, isobutyl acetate (25.73% and E-β-caryophyllene (8.68% were main compounds. The oil showed (IC50= 111.2µg/ml in DPPH and IC50= 21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil demonstrated toxicity with (LD50= 1.1µg/ml in brine shrimp lethality test and with (IC50= 22.0, 25.0 and 42.55 µg/ml on three cancerous cell lines (MCF-7, A-549 and HT-29 respectively. LC50 of stem, root, aerial parts, fruits, and flowers essential oils against larvae of An. stephensi were equal with 10.46, 22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities, essential oil was effective on all specimens except Escherichia coli, Asper­gillus niger and Candida albicans.Conclusion: The essential oil showed moderate antioxidant activity, strong antimicrobial properties and good toxic effect in brine shrimp test and MTT assay on three cancerous cell lines.

Analisis Pengaruh Keterlibatan Kerja dan Kepuasan Kerja terhadap Organizational Citizenship Behavior di PT Prima Graphia Digital

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Andrew Adi Saputra

2013-11-01

Full Text Available PT Prima Graphia Digital is a company engaged in the area of digital printing, locates at Kalibaru Timur Street IV No 5-7, Senen, Central Jakarta, Indonesia, 10460. The purpose of this research is to analyze the effect of job involvement and work satisfaction towards Organizational Citizenship Behavior in PT. Prima Graphia Digital. Research used associative method. Data used were primary and secondary data obtained through observation, interview and questionnaire distribution to 86 staffs of the company as respondents. After obtaining the data, then data were processed using Pearson correlation, simple and multiple regression. Results showed that job involvement has positive effect and is significant towards Organizational Citizenship Behavior. Similarly, work satisfaction does also have a positive effect and is significant towards Organizational Citizenship Behavior. Furthermore, job involvement and work satisfaction simultaneously have a significant effect towards Organizational Citizenship Behavior.

Pengembangan Aplikasi E-Crm pada PT Trafoindo Prima Perkasa

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Honni Honni

2008-10-01

Full Text Available Various surveys show that the key to corporate success lies not only on the product or service being offered but how far the company’s efforts to satisfy the needs of its customers. Companies have to provide products or services that match customer needs and wants, and then maintain close relations with customers. Customer loyalty will be the key to success, not only in the short term but sustainable competitive advantage. This is because customer loyalty has strategic value for the company. One way that proved effective and successful to meet and satisfy customer needs is through the CRM (Customer Relationship Management. CRM is not new in the business world. Customer Relationship has long been applied by traditional businessmen. Technology in the form of a web can be utilized as a catalyst in improving the quality of CRM. Combining Technology and CRM in a business called E-CRM. E-CRM application development web based on PT Trafoindo Prima Perkasa aims to analyze and design company and customer needs. The research method used in this writing is descriptive survey method primarily associated with the customer. The analysis tool used is the model porter five forces and industry analysis: CPM Matrix, the External Factor Evaluation Matrix (EFE, the Internal Factor Evaluation Matrix (IFE, SWOT Matrix, IE Matrix, SPACE Matrix, and Grand Strategy Matrix to identify alternative strategies can be applied. Alternative strategy is then measured with a Matrix QSP charm, coupled with the approach of Object Oriented Analysis and Design as the basis for the development of E-CRM application based on web. Conclusions obtained are E-CRM applications have produced work as expected.Keywords: development, application of E-CRM, Trafoindo Prima Perkasa

Targeting α4β2 nAChRs in CNS disorders: Perspectives on positive allosteric modulation as a therapeutic approach

DEFF Research Database (Denmark)

Grupe, Morten; Grunnet, Morten; Bastlund, Jesper F.

2015-01-01

The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional character......The nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels broadly involved in regulating neurotransmission in the central nervous system (CNS) by conducting cation currents through the membrane of neurons. Many different nAChR subtypes exist with each their functional...... characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric α4β2 nAChR, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various CNS disorders...... and temporal aspects of neurotransmission as well as higher subtype selectivity, hypothetically resulting in high clinical efficacy with minimal adverse effects. In this MiniReview, we describe the currently identified compounds, which potentiate the effects of agonists at the α4β2 nAChR. The potential...

Calcium imaging with genetically encoded sensor Case12: Facile analysis of α7/α9 nAChR mutants.

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Irina Shelukhina

Full Text Available Elucidation of the structural basis of pharmacological differences for highly homologous α7 and α9 nicotinic acetylcholine receptors (nAChRs may shed light on their involvement in different physiological functions and diseases. Combination of site-directed mutagenesis and electrophysiology is a powerful tool to pinpoint the key amino-acid residues in the receptor ligand-binding site, but for α7 and α9 nAChRs it is complicated by their poor expression and fast desensitization. Here, we probed the ligand-binding properties of α7/α9 nAChR mutants by a proposed simple and fast calcium imaging method. The method is based on transient co-expression of α7/α9 nAChR mutants in neuroblastoma cells together with Ric-3 or NACHO chaperones and Case12 fluorescent calcium ion sensor followed by analysis of their pharmacology using a fluorescence microscope or a fluorometric imaging plate reader (FLIPR with a GFP filter set. The results obtained were confirmed by electrophysiology and by calcium imaging with the conventional calcium indicator Fluo-4. The affinities for acetylcholine and epibatidine were determined for human and rat α7 nAChRs, and for their mutants with homologous residues of α9 nAChR incorporated at positions 117-119, 184, 185, 187, and 189, which are anticipated to be involved in ligand binding. The strongest decrease in the affinity was observed for mutations at positions 187 and 119. The L119D mutation of α7 nAChR, showing a larger effect for epibatidine than for acetylcholine, may implicate this position in pharmacological differences between α7 and α9 nAChRs.

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

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Muhammad Yar

2015-03-01

Full Text Available Alzheimer's disease (AD is a fast growing neurodegenerative disorder of the central nervous system and anti-oxidants can be used to help suppress the oxidative stress caused by the free radicals that are responsible for AD. A series of selected synthetic indole derivatives were biologically evaluated to identify potent new antioxidants. Most of the evaluated compounds showed significant to modest antioxidant properties (IC50 value 399.07 140.0±50 µM. Density Functional Theory (DFT studies were carried out on the compounds and their corresponding free radicals. Differences in the energy of the parent compounds and their corresponding free radicals provided a good justification for the trend found in their IC50 values. In silico, docking of compounds into the proteins acetylcholinesterase (AChE and butyrylcholinesterase (BChE, which are well known for contributing in AD disease, was also performed to predict anti-AD potential.

Precision and linearity targets for validation of an IFNγ ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides

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Lyerly Herbert K

2008-03-01

Full Text Available Abstract Background Single-cell assays of immune function are increasingly used to monitor T cell responses in immunotherapy clinical trials. Standardization and validation of such assays are therefore important to interpretation of the clinical trial data. Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNγ-based ELISPOT and cytokine flow cytometry (CFC, as well as tetramer assays. Results Precision was measured in cryopreserved PBMC with a low, medium, or high response level to a CMV pp65 peptide or peptide mixture. Intra-assay precision was assessed using 6 replicates per assay; inter-assay precision was assessed by performing 8 assays on different days; and inter-operator precision was assessed using 3 different operators working on the same day. Percent CV values ranged from 4% to 133% depending upon the assay and response level. Linearity was measured by diluting PBMC from a high responder into PBMC from a non-responder, and yielded R2 values from 0.85 to 0.99 depending upon the assay and antigen. Conclusion These data provide target values for precision and linearity of single-cell assays for those wishing to validate these assays in their own laboratories. They also allow for comparison of the precision and linearity of ELISPOT, CFC, and tetramer across a range of response levels. There was a trend toward tetramer assays showing the highest precision, followed closely by CFC, and then ELISPOT; while all three assays had similar linearity. These findings are contingent upon the use of optimized protocols for each assay.

Una community emergente tra progettazione territorio e infrastrutture La prima conferenza Autodesk degli utenti italiani

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Redazione Redazione

2005-10-01

Full Text Available La prima edizione dell’Autodesk User Conference dedicata aiSistemi Informativi Territoriali ed alla progettazione delle infrastrutture, tenutasi a Roma il 29 settembre 2005, diventerà l’appuntamento fisso sulla convergenza tra tecnologie CAD e GISche molti reclamavano da tempo.

The α7-nACh nicotinic receptor and its role in memory and selected diseases of the central nervous system

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Urszula Baranowska

2017-07-01

Full Text Available α7-nACh is one of the major nicotinic cholinergic receptor subtypes found in the brain. It is broadly expressed in the hippocampal and cortical neurons, the regions which play a key role in memory formation. Although α7-nACh receptors may serve as postsynaptic receptors mediating classical neurotransmission, they usually function as presynaptic modulators responsible for the release of other neurotransmitters, such as glutamate, γ-aminobutyric acid, dopamine, and norepinephrine. They can, therefore, affect a wide array of neurobiological functions. In recent years, research has found that a large number of agonists and positive allosteric modulators of α7-nAChR induce beneficial effects on learning and memory. Consistently, mice deficient in chrna7 (the gene encoding α7-nAChR protein, are characterized by memory deficits. In addition, decreased expression and function of α7-nAChR is associated agoniwith many neurological diseases including schizophrenia, bipolar disorder, learning disability, attention deficit hyperactivity disorder, Alzheimer disease, autism, and epilepsy. In the recent years many animal experiments and clinical trials using α7-nAChR ligands were conducted. The results of these studies strongly indicate that agonists and positive allosteric modulators of α7-nAChR are promising therapeutic agents for diseases associated with cognitive deficits.

Plant integration of MITICA and SPIDER experiments with auxiliary plants and buildings on PRIMA site

Energy Technology Data Exchange (ETDEWEB)

Fellin, Francesco, E-mail: francesco.fellin@igi.cnr.it; Boldrin, Marco; Zaccaria, Pierluigi; Agostinetti, Piero; Battistella, Manuela; Bigi, Marco; Palma, Samuele Dal Bello Mauro Dalla; Fiorentin, Aldo; Luchetta, Adriano; Maistrello, Alberto; Marcuzzi, Diego; Ocello, Edoardo; Pasqualotto, Roberto; Pavei, Mauro; Pomaro, Nicola; Rizzolo, Andrea; Toigo, Vanni; Valente, Matteo; Zanotto, Loris; Calore, Luca; and others

2015-10-15

Highlights: • Focus on plant integration work supporting the realization of SPIDER and MITICA fusion experiments hosted in PRIMA buildings complex in Padova, Italy. • Huge effort of coordination and integration among many stakeholders, taking into account several constrains coming from experiments requirements (on-going) and precise time schedule and budget on buildings construction. • The paper also deals of interfaces management, coordination and integration of many competences, problems solving to find best solution also considering other aspects like safety and maintenance. - Abstract: This paper presents a description of the PRIMA (Padova Research on ITER Megavolt Accelerator) Plant Integration work, aimed at the construction of PRIMA Buildings, which will host two nuclear fusion test facilities named SPIDER and MITICA, finalized to test and optimize the neutral beam injectors for ITER experiment. These activities are very complex: inputs coming from the experiments design are changing time to time, while the buildings construction shall fulfill precise time schedule and budget. Moreover the decision process is often very long due to the high number of stakeholders (RFX, IO, third parties, suppliers, domestic agencies from different countries). The huge effort includes: forecasting what will be necessary for the integration of many experimental plants; collecting requirements and translating into inputs; interfaces management; coordination meetings with hundreds of people with various and different competences in construction and operation of fusion facilities, thermomechanics, electrical and control, buildings design and construction (civil plants plus architectural and structural aspects), safety, maintenance and management. The paper describes these activities and also the tools created to check and to validate the building design, to manage the interfaces and the organization put in place to achieve the required targets.

Plant integration of MITICA and SPIDER experiments with auxiliary plants and buildings on PRIMA site

International Nuclear Information System (INIS)

Fellin, Francesco; Boldrin, Marco; Zaccaria, Pierluigi; Agostinetti, Piero; Battistella, Manuela; Bigi, Marco; Palma, Samuele Dal Bello Mauro Dalla; Fiorentin, Aldo; Luchetta, Adriano; Maistrello, Alberto; Marcuzzi, Diego; Ocello, Edoardo; Pasqualotto, Roberto; Pavei, Mauro; Pomaro, Nicola; Rizzolo, Andrea; Toigo, Vanni; Valente, Matteo; Zanotto, Loris; Calore, Luca

2015-01-01

Highlights: • Focus on plant integration work supporting the realization of SPIDER and MITICA fusion experiments hosted in PRIMA buildings complex in Padova, Italy. • Huge effort of coordination and integration among many stakeholders, taking into account several constrains coming from experiments requirements (on-going) and precise time schedule and budget on buildings construction. • The paper also deals of interfaces management, coordination and integration of many competences, problems solving to find best solution also considering other aspects like safety and maintenance. - Abstract: This paper presents a description of the PRIMA (Padova Research on ITER Megavolt Accelerator) Plant Integration work, aimed at the construction of PRIMA Buildings, which will host two nuclear fusion test facilities named SPIDER and MITICA, finalized to test and optimize the neutral beam injectors for ITER experiment. These activities are very complex: inputs coming from the experiments design are changing time to time, while the buildings construction shall fulfill precise time schedule and budget. Moreover the decision process is often very long due to the high number of stakeholders (RFX, IO, third parties, suppliers, domestic agencies from different countries). The huge effort includes: forecasting what will be necessary for the integration of many experimental plants; collecting requirements and translating into inputs; interfaces management; coordination meetings with hundreds of people with various and different competences in construction and operation of fusion facilities, thermomechanics, electrical and control, buildings design and construction (civil plants plus architectural and structural aspects), safety, maintenance and management. The paper describes these activities and also the tools created to check and to validate the building design, to manage the interfaces and the organization put in place to achieve the required targets.

Vitisin B, a resveratrol tetramer, inhibits migration through inhibition of PDGF signaling and enhancement of cell adhesiveness in cultured vascular smooth muscle cells

International Nuclear Information System (INIS)

Ong, Eng-Thaim; Hwang, Tsong-Long; Huang, Yu-Ling; Lin, Chwan-Fwu; Wu, Wen-Bin

2011-01-01

Vascular smooth muscle cells (VSMCs) play an important role in normal vessel formation and in the development and progression of cardiovascular diseases. Grape plants contain resveratrol monomer and oligomers and drinking of wine made from grape has been linked to 'French Paradox'. In this study we evaluated the effect of vitisin B, a resveratrol tetramer, on VSMC behaviors. Vitisin B inhibited basal and PDGF-induced VSMC migration. Strikingly, it did not inhibit VSMC proliferation but inversely enhanced cell cycle progression and proliferation. Among the tested resveratrol oligomers, vitisin B showed an excellent inhibitory activity and selectivity on PDGF signaling. The anti-migratory effect by vitisin B was due to direct inhibition on PDGF signaling but was independent of interference with PDGF binding to VSMCs. Moreover, the enhanced VSMC adhesiveness to matrix contributed to the anti-migratory effect by vitisin B. Fluorescence microscopy revealed an enhanced reorganization of actin cytoskeleton and redistribution of activated focal adhesion proteins from cytosol to the peripheral edge of the cell membrane. This was confirmed by the observation that enhanced adhesiveness was repressed by the Src inhibitor. Finally, among the effects elicited by vitisin B, only the inhibitory effect toward basal migration was partially through estrogen receptor activation. We have demonstrated here that a resveratrol tetramer exhibited dual but opposite actions on VSMCs, one is to inhibit VSMC migration and the other is to promote VSMC proliferation. The anti-migratory effect was through a potent inhibition on PDGF signaling and novel enhancement on cell adhesion. - Highlights: → Several resveratrol oligomers from grape plants are examined on VSMC behaviors. → Tetraoligomer vitisin B shows excellent inhibitory activity and selectivity. → It exerts dual but opposing actions: anti-migratory and pro-proliferative effects. → The anti-migratory effect results from anti

Use of a charge reducing agent to enable intact mass analysis of cysteine-linked antibody-drug-conjugates by native mass spectrometry

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Kamila J. Pacholarz

2016-06-01

Full Text Available Antibody-drug-conjugates (ADC are a growing class of anticancer biopharmaceuticals. Conjugation of cysteine linked ADCs, requires initial reduction of mAb inter-chain disulfide bonds, as the drugs are attached via thiol chemistry. This results in the active mAb moiety being transformed from a covalently linked tetramer to non-covalently linked complexes, which hinders precise determination of drug load with LC–MS. Here, we show how the addition of the charge reducing agent triethylammonium acetate (TEAA preserves the intact mAb structure, is well suited to the study of cysteine linked conjugates and facilitates easy drug load determination by direct infusion native MS.

Going up in Smoke? A Review of nAChRs-based Treatment Strategies for Improving Cognition in Schizophrenia

Science.gov (United States)

Boggs, Douglas L.; Carlson, Jon; Cortes-Briones, Jose; Krystal, John H.; D’Souza, D. Cyril

2015-01-01

Cognitive impairment is known to be a core deficit in schizophrenia. Existing treatments for schizophrenia have limited efficacy against cognitive impairment. The ubiquitous use of nicotine in this population is thought to reflect an attempt by patients to self-medicate certain symptoms associated with the illness. Concurrently there is evidence that nicotinic receptors that have lower affinity for nicotine are more important in cognition. Therefore, a number of medications that target nicotinic acetylcholine receptors (nAChRs) have been tested or are in development. In this article we summarize the clinical evidence of nAChRs dysfunction in schizophrenia and review clinical studies testing either nicotine or nicotinic medications for the treatment of cognitive impairment in schizophrenia. Some evidence suggests beneficial effects of nAChRs based treatments for the attentional deficits associated with schizophrenia. Standardized cognitive test batteries have failed to capture consistent improvements from drugs acting at nAChRs. However, more proximal measures of brain function, such as ERPs relevant to information processing impairments in schizophrenia, have shown some benefit. Further work is necessary to conclude that nAChRs based treatments are of clinical utility in the treatment of cognitive deficits of schizophrenia. PMID:24345265

In search of allosteric modulators of a7-nAChR by solvent density guided virtual screening.

Science.gov (United States)

Dey, Raja; Chen, Lin

2011-04-01

Nicotinic acetylcholine receptors (nAChR) are pentameric ligand gated ion channels whose activity can be modulated by endogenous neurotransmitters as well as by synthetic ligands that bind the same or distinct sites from the natural ligand. The subtype of α7 nAChR has been considered as a potenial therapeutic target for Alzheimer's disease, schizophrenia and other neurological and psychiatric disorders. Here we have developed a homology model of α7 nAChR based on two high resolution crystal structures with Brookhaven Protein Data Bank (PDB) codes 2QC1 and 2WN9 for threading on one monomer and then for building a pentamer, respectively. A number of small molecule binding sites are identified using Pocket Finder (J. An, M. Tortov, and R. Abagyan, Molecular & Cellular Proteomics, 4.6, 752-761 (2005)) of Internal Coordinate Mechanics (ICM). Remarkably, these computer-identified sites match perfectly with ordered solvent densities found in the high-resolution crystal structure of α1 nAChR, suggesting that the surface cavities in the α7 nAChR model are likely binding sites of small molecules. A high throughput virtual screening by flexible ligand docking of 5008 small molecule compounds was performed at three potential allosteric modulator (AM) binding sites of α7 nAChR using Molsoft ICM software (R. Abagyan, M. Tortov and D. Kuznetsov, J Comput Chem 15, 488-506, (1994)). Some experimentally verified allosteric modulators of α7 like CCMI comp-6, LY 7082101, 5-HI, TQS, PNU-120596, genistein, and NS-1738 ranked among top 100 compounds, while the rest of the compounds in the list could guide further search for new allosteric modulators.

Determinación de sílice libre en materias primas para la industria del cemento

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Calleja, J.

1965-12-01

Full Text Available Not availableLa existencia de sílice libre en las materias primas y, por lo tanto, en los crudos empleados en la fabricación de cemento Portland es desventajosa por la escasa reactividad de esta sílice, sobre todo si no posee una finura suficiente. La determinación de sílice cuarzosa en tales materiales es decisiva para la buena marcha de la clinkerización en fábricas cuyas materias primas adolecen de la desventaja de contenerla. Los métodos propugnados suelen ser poco reproducibles y precisos, y dan resultados bastante erráticos. En el presente trabajo, y después de haber ensayado diversos métodos citados en la bibliografía, se describe y recomienda un procedimiento, basado en el ataque del material por ácido pirofosfórico. Las variables que juegan en el proceso descrito son el tamaño de grano de la muestra, en particular el de la sílice libre, la temperatura y el tiempo de ataque. En las condiciones que se especifican se consigue una disolución prácticamente total de los silicatos, sin que apenas se· disuelvan las partículas más finas de cuarzo. Con ello se consigue una exactitud y una precisión tal como pone de manifiesto el análisis estadístico de los resultados obtenidos al determinar sílice libre en diversas materias primas y crudos para cemento.

When two is not enough: a CtIP tetramer is required for DNA repair by Homologous Recombination.

Science.gov (United States)

Forment, Josep V; Jackson, Stephen P; Pellegrini, Luca

2015-01-01

Homologous recombination (HR) is central to the repair of double-strand DNA breaks that occur in S/G2 phases of the cell cycle. HR relies on the CtIP protein (Ctp1 in fission yeast, Sae2 in budding yeast) for resection of DNA ends, a key step in generating the 3'-DNA overhangs that are required for the HR strand-exchange reaction. Although much has been learned about the biological importance of CtIP in DNA repair, our mechanistic insight into its molecular functions remains incomplete. It has been recently discovered that CtIP and Ctp1 share a conserved tetrameric architecture that is mediated by their N-terminal domains and is critical for their function in HR. The specific arrangement of protein chains in the CtIP/Ctp1 tetramer indicates that an ability to bridge DNA ends might be an important feature of CtIP/Ctp1 function, establishing an intriguing similarity with the known ability of the MRE11-RAD50-NBS1 complex to link DNA ends. Although the exact mechanism of action remains to be elucidated, the remarkable evolutionary conservation of CtIP/Ctp1 tetramerisation clearly points to its crucial role in HR.

Unconventional field induced phases in a quantum magnet formed by free radical tetramers

Science.gov (United States)

Saúl, Andrés; Gauthier, Nicolas; Askari, Reza Moosavi; Côté, Michel; Maris, Thierry; Reber, Christian; Lannes, Anthony; Luneau, Dominique; Nicklas, Michael; Law, Joseph M.; Green, Elizabeth Lauren; Wosnitza, Jochen; Bianchi, Andrea Daniele; Feiguin, Adrian

2018-02-01

We report experimental and theoretical studies on the magnetic and thermodynamic properties of NIT-2Py, a free radical based organic magnet. From magnetization and specific-heat measurements we establish the temperature versus magnetic field phase diagram which includes two Bose-Einstein condensates (BEC) and an infrequent half-magnetization plateau. Calculations based on density functional theory demonstrate that magnetically this system can be mapped to a quasi-two-dimensional structure of weakly coupled tetramers. Density matrix renormalization group calculations show the unusual characteristics of the BECs where the spins forming the low-field condensate are different than those participating in the high-field one.

Inhibitory effects of psychotropic drugs on the acetylcholine receptor-operated potassium current (IK.ACh) in guinea-pig atrial myocytes.

Science.gov (United States)

Okada, Muneyoshi; Watanabe, Shinya; Matada, Takashi; Asao, Yoko; Hamatani, Ramu; Yamawaki, Hideyuki; Hara, Yukio

2013-01-01

Influences of psychotropic drugs, six antipsychotics and three antidepressants, on acetylcholine receptor-operated potassium current (IK.ACh) were examined by a whole-cell patch clamp method in freshly isolated guinea-pig atrial myocyte. IK.ACh was induced by a superfusion of carbachol (CCh) or by an intracellular application of guanosine 5'-[thio] triphosphate (GTPγS). To elucidate mechanism for anticholinergic action, IC50 ratio, the ratio of IC50 for GTPγS-activated IK.ACh to CCh-induced IK.ACh, was calculated. Antipsychotics and antidepressants inhibited CCh-induced IK.ACh in a concentration-dependent manner. The IC50 values were as follows; chlorpromazine 0.53 μM, clozapine 0.06 μM, fluphenazine 2.69 μM, haloperidol 2.66 μM, sulpiride 42.3 μM, thioridazine 0.07 μM, amitriptyline 0.03 μM, imipramine 0.22 μM and maprotiline 1.81 μM. The drugs, except for sulpiride, inhibited GTPγS-activated IK.ACh with following IC50 values; chlorpromazine 1.71 μM, clozapine 14.9 μM, fluphenazine 3.55 μM, haloperidol 2.73 μM, thioridazine 1.90 μM, amitriptyline 7.55 μM, imipramine 7.09 μM and maprotiline 5.93 μM. The IC50 ratio for fluphenazine and haloperidol was close to unity. The IC50 ratio for chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine and maprotiline was much higher than unity. The present findings suggest that the psychotropics studied suppress IK.ACh. Chlorpromazine, clozapine, thioridazine, amitriptyline, imipramine, maprotiline and sulpiride are preferentially acting on muscarinic receptor. Fluphenazine and haloperidol may act on G protein and/or potassium channel.

Deposition of a-C:H films on a nanotrench pattern by bipolar PBII and D

International Nuclear Information System (INIS)

Hirata, Yuki; Nakahara, Yuya; Nagato, Keisuke; Choi, Junho

2016-01-01

In this study, hydrogenated amorphous carbon (a-C:H) films were deposited on a nanotrench pattern (300 nm pitch, aspect ratio: 2.0) by bipolar-type plasma based ion implantation and deposition technique (bipolar PBII and D), and the effects of bipolar pulse on the film properties were investigated. Moreover, the behaviour of ions and radicals surrounding the nanotrench was analyzed to clarify the coating mechanism and properties of the a-C:H films on the nanotrench. Further, thermal nanoimprint lithography was carried out using the nanotrench pattern coated with a-C:H films as the mold, and the mold release properties were evaluated. All nanotrench surfaces were successfully coated with the a-C:H films, but the film thickness on the top, sidewall, and bottom surfaces of the trench were not uniform. The surface roughness of the a-C:H films was found to decrease at a higher positive voltage; this happens due to the higher electron temperature around the nanotrench because of the surface migration of plasma particles arrived on the trench. The effects of the negative voltage on the behaviour of ions and radicals near the sidewall of the nanotrench are quite similar to those near the microtrench reported previously (Park et al 2014 J. Phys. D: Appl. Phys . 47 335306). However, the positive pulse voltage was also found to affect the behaviour of ions and radicals near the sidewall surface. The incident angles of ions on the sidewall surface increased with the positive pulse voltage because the energy of incoming ions on the trench decreases with increasing positive voltage. Moreover, the incident ion flux on the sidewall is affected by the positive voltage history. Further, the radical flux decreases with increasing positive voltage. It can be concluded that a higher positive voltage at a lower negative voltage condition is good to obtain better film properties and higher film thickness on the sidewall surface. Pattern transfer properties for the nanoimprint formed by

Studiare i prezzi dei libri nell'Europa della prima età moderna: questioni e fonti

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Angela Nuovo

2017-09-01

Full Text Available Il contributo presenta in modo sintetico il quadro concettuale all'interno del quale uno studio dei prezzi dei libri nella prima età moderna dovrebbe muoversi, così come i problemi metodologici da affrontare. Nonostante la natura di manufatto semi-industriale ponga il libro a stampa in una classe merceologica del tutto particolare nell'economia pre-industriale, è possibile utilizzare le categorie generali di domanda e offerta per identificare alcuni fattori atti ad impostare specifici percorsi di ricerca basati sull'analisi storico-economica. La storia del libro può essere quindi messa in relazione con alcuni temi classici della storia economica, allo scopo di inserire il problema del commercio librario e dei prezzi dei libri in un dibattito storiografico più ampio. Tra le fonti disponibili per lo studio dei prezzi dei libri nella prima età moderna, l'inventario di bottega di Bernardo Giunti (Department of Special Collections, UCLA, Collection 170/622 è una chiara testimonianza del fiorente mercato librario allora esistente a Venezia. Le quasi 12.000 registrazioni incluse nella lista dei libri in vendita riflettono gli scopi e gli obiettivi dell’azienda. La struttura di questo documento è decisamente complessa, frutto di più di venti anni di uso continuo (1600-1620 c.. Lungo questo periodo di tempo, il documento sembra essere evoluto da un semplice elenco o catalogo ad uso del personale interno a un importante strumento per la gestione della bottega e del suo magazzino. Quasi ogni titolo presenta un prezzo, e ciò rende questo inventario una delle fonti più ampie e significative per lo studio dei prezzi dei libri nella prima età moderna.This project has received funding from the European Research Council (ERC under the European Union's Horizon 2020 research and innovation programme (Grant Agreement n° 694476.

Using DR52c/Ni2+ mimotope tetramers to detect Ni2+ reactive CD4+ T cells in patients with joint replacement failure.

Science.gov (United States)

Zhang, Yan; Wang, Yang; Anderson, Kirsten; Novikov, Andrey; Liu, Zikou; Pacheco, Karin; Dai, Shaodong

2017-09-15

T cell mediated hypersensitivity to nickel (Ni 2+ ) is one of the most common causes of allergic contact dermatitis. Ni 2+ sensitization may also contribute to the failure of Ni 2+ containing joint implants, and revision to non-Ni 2+ containing hardware can be costly and debilitating. Previously, we identified Ni 2+ mimotope peptides, which are reactive to a CD4 + T cell clone, ANi2.3 (Vα1, Vβ17), isolated from a Ni 2+ hypersensitive patient with contact dermatitis. This T cell is restricted to the major histocompatibility complex class II (MHCII) molecule, Human Leukocyte Antigen (HLA)-DR52c (DRA, DRB3*0301). However, it is not known if Ni 2+ induced T cell responses in sensitized joint replacement failure patients are similar to subjects with Ni 2+ induced contact dermatitis. Here, we generated DR52c/Ni 2+ mimotope tetramers, and used them to test if the same Ni 2+ T cell activation mechanism could be generalized to Ni 2+ sensitized patients with associated joint implant failure. We confirmed the specificity of these tetramers by staining of ANi2.3T cell transfectomas. The DR52c/Ni 2+ mimotope tetramer detected Ni 2+ reactive CD4 + T cells in the peripheral blood mononuclear cells (PBMC) of patients identified as Ni 2+ sensitized by patch testing and a positive Ni 2+ LPT. When HLA-typed by a DR52 specific antibody, three out of four patients were DR52 positive. In one patient, Ni 2+ stimulation induced the expansion of Vβ17 positive CD4 + T cells from 0.8% to 13.3%. We found that the percentage of DR52 positivity and Vβ17 usage in Ni 2+ sensitized joint failure patients are similar to Ni sensitized skin allergy patients. Ni 2+ independent mimotope tetramers may be a useful tool to identify the Ni 2+ reactive CD4 + T cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Fabrication of a Highly-sensitive Acetylcholine Sensor Based on AChOx Immobilized Smart-chips

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M. M. RAHMAN

2011-03-01

Full Text Available Acetylcholine (ACh sensor based on acetylcholine oxidase (AChOx on EDC activated thioglycolic acid self-assembled monolayer (TGA-SAM using smart-chip has been developed. The simple cyclic voltammetry (CV, at 0.1 V/s technique is performed in total investigation, where 0.5M K3Fe(CN6 is utilized as a standard mediator in phosphate buffer solution (PBS, 0.1M. The ACh sensor exhibited a lower detection limit (DL, 0.1392 ± 0.005 nM, a wide linear dynamic range (LDR, 1.0 nM to 1.0 mM, good linearity (R=0.9951, and higher sensitivity (7.3543 ± 0.2 μAμM-1cm-2, and required small sample volume (70.0 μL as well as good stability and reproducibility. The smart-chip system employed a simple and efficient approach to the immobilization of enzymes onto active sensitive surface, which can enhance sensor performances to a large group of bio-molecules for wide range of biomedical applications in health care fields.

Co-overexpression of bacterial GroESL chaperonins partly overcomes non-productive folding and tetramer assembly of E. coli-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) carrying the prevalent disease-causing K304E mutation

DEFF Research Database (Denmark)

Bross, P; Andresen, B S; Winter, V

1993-01-01

, tetramer formation and yield of enzyme activity of wild-type MCAD is largely independent of GroESL co-overexpression; (ii) the larger part of the K304Q mutant is insoluble without and solubility is enhanced with GroESL co-overexpression; solubility correlates with the amount of tetramer detected...... and the enzyme activity measured as observed for the wild-type protein. (iii) Solubility of the K304E mutant is in a similar fashion GroESL responsive as the K304Q mutant, but the amount of tetramer observed and the enzyme activity measured do not correlate with the amount of soluble K304E MCAD protein detected...

Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology

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Luis F. Padilla-Morales

2016-03-01

Full Text Available The presented data provides additional information about the assessment of affinity purified nicotinic acetylcholine receptor (nAChR rich membrane solubilized with long chain (16 saturated carbons lysophospholipid with glycerol headgroup (LFG-16. The assessment of stability and functionality of solubilized membrane protein is a critical step prior to further crystallization trails. One of the key factors for this task is the appropriate choice of a detergent that can support nAChR activity and stability comparable to the crude membranes. The stability of the nAChR-LFG-16 complex incorporated into lipid cubic phase (LCP was monitored for a period of 30 days by means of fluorescence recovery after photobleaching (FRAP and the functionality was evaluated after its incorporation into Xenopus oocyte by means of the two electrode voltage clamp technique. Keywords: Detergents, Fluorescence recovery after photobleaching, Lipidic Cubic Phase, nAChR, Planar lipid bilayer, Two-electrode voltage clamp

Altered levels of acetylcholinesterase in Alzheimer plasma.

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María-Salud García-Ayllón

Full Text Available BACKGROUND: Many studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE pose a major problem. PRINCIPAL FINDINGS: Here we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were approximately 20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G(1+G(2 forms and not G(4 tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer's disease (AD patients compared to age and gender-matched controls. This increase correlates with an increase in the G(1+G(2 forms, the subset of AChE species which are increased in Alzheimer's brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer's plasma, attributed in part to AChE-T subunits common in brain and CSF. CONCLUSION: Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.

Confirming a Role for α9nAChRs and SK Potassium Channels in Type II Hair Cells of the Turtle Posterior Crista

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Xiaorong Xu Parks

2017-11-01

Full Text Available In turtle posterior cristae, cholinergic vestibular efferent neurons (VENs synapse on type II hair cells, bouton afferents innervating type II hair cells, and afferent calyces innervating type I hair cells. Electrical stimulation of VENs releases acetylcholine (ACh at these synapses to exert diverse effects on afferent background discharge including rapid inhibition of bouton afferents and excitation of calyx-bearing afferents. Efferent-mediated inhibition is most pronounced in bouton afferents innervating type II hair cells near the torus, but becomes progressively smaller and briefer when moving longitudinally through the crista toward afferents innervating the planum. Sharp-electrode recordings have inferred that efferent-mediated inhibition of bouton afferents requires the sequential activation of alpha9-containing nicotinic ACh receptors (α9*nAChRs and small-conductance, calcium-dependent potassium channels (SK in type II hair cells. Gradations in the strength of efferent-mediated inhibition across the crista likely reflect variations in α9*nAChRs and/or SK activation in type II hair cells from those different regions. However, in turtle cristae, neither inference has been confirmed with direct recordings from type II hair cells. To address these gaps, we performed whole-cell, patch-clamp recordings from type II hair cells within a split-epithelial preparation of the turtle posterior crista. Here, we can easily visualize and record hair cells while maintaining their native location within the neuroepithelium. Consistent with α9*nAChR/SK activation, ACh-sensitive currents in type II hair cells were inward at hyperpolarizing potentials but reversed near −90 mV to produce outward currents that typically peaked around −20 mV. ACh-sensitive currents were largest in torus hair cells but absent from hair cells near the planum. In current clamp recordings under zero-current conditions, ACh robustly hyperpolarized type II hair cells. ACh

Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

National Research Council Canada - National Science Library

Daoud, Sayed S

2006-01-01

The main purpose of the study is to identify novel protein-protein interactions in various locations of cells to establish the molecular mechanisms of mutant p53 reactivation with PRIMA-1 in breast cancer cells...

Biallelic mutation of UNC50, encoding a protein involved in AChR trafficking, is responsible for arthrogryposis.

Science.gov (United States)

Abiusi, Emanuela; D'Alessandro, Manuela; Dieterich, Klaus; Quevarec, Loic; Turczynski, Sandrina; Valfort, Aurore-Cecile; Mezin, Paulette; Jouk, Pierre Simon; Gut, Marta; Gut, Ivo; Bessereau, Jean Louis; Melki, Judith

2017-10-15

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Homozygosity mapping of disease loci combined with whole exome sequencing in a consanguineous family presenting with lethal AMC allowed the identification of a homozygous frameshift deletion in UNC50 gene (c.750_751del:p.Cys251Phefs*4) in the index case. To assess the effect of the mutation, an equivalent mutation in the Caenorhabditis elegans orthologous gene was created using CRISPR/Cas9. We demonstrated that unc-50(kr331) modification caused the loss of acetylcholine receptor (AChR) expression in C. elegans muscle. unc-50(kr331) animals were as resistant to the cholinergic agonist levamisole as unc-50 null mutants suggesting that AChRs were no longer expressed in this animal model. This was confirmed by using a knock-in strain in which a red fluorescent protein was inserted into the AChR locus: no signal was detected in unc-50(kr331) background, suggesting that UNC-50, a protein known to be involved in AChR trafficking, was no longer functional. These data indicate that biallelic mutation in the UNC50 gene underlies AMC through a probable loss of AChR expression at the neuromuscular junction which is essential for the cholinergic transmission during human muscle development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PERANCANGAN PENJADWALAN PREVENTIVE MAINTENANCE PADA PT. ARTHA PRIMA SUKSES MAKMUR

Directory of Open Access Journals (Sweden)

Yugowati Praharsi

2015-06-01

Full Text Available PT. Artha Prima Sukses Makmur memiliki lima mesin dalam menjalankan kegiatan produksi sol sepatu yang berlangsung 24 jam setiap hari, sehingga kegiatan perawatan dan pemeliharaan perlu dilakukan dengan baik dan dijadwalkan agar tidak mengganggu kegiatan produksi yang sedang berlangsung. Kerusakan mesin saat ini masih terhitung tinggi dan memerlukan waktu perbaikan yang cukup lama. Perancangan penjadwalan maintenancediperlukan untuk mengurangi downtime pada mesin, sehingga tidak menghambat dan mengganggu jadwal produksi. Penjadwalan yang diusulkan adalah preventive maintenance dengan metode age replacement. Berdasarkan prinsip Pareto terdapat dua mesin kritis dari lima mesin yang ada.Hasil perhitungan dari data kerusakan mesin sebelumnya diketahui, jika dilakukan preventive maintenance downtime akan berkurang sebanyak 2.85%, dan terjadi penghematan sebesar 38%.

PERANCANGAN PENJADWALAN PREVENTIVE MAINTENANCE PADA PT. ARTHA PRIMA SUKSES MAKMUR

Directory of Open Access Journals (Sweden)

Yugowati Praharsi

2015-06-01

Full Text Available PT. Artha Prima Sukses Makmur memiliki lima mesin dalam menjalankan kegiatan produksi sol sepatu yang berlangsung 24 jam setiap hari, sehingga kegiatan perawatan dan pemeliharaan perlu dilakukan dengan baik dan dijadwalkan agar tidak mengganggu kegiatan produksi yang sedang berlangsung. Kerusakan mesin saat ini masih terhitung tinggi dan memerlukan waktu perbaikan yang cukup lama. Perancangan penjadwalan  maintenancediperlukan untuk mengurangi downtime pada mesin, sehingga tidak menghambat dan mengganggu jadwal produksi. Penjadwalan yang diusulkan adalah preventive maintenance dengan metode age replacement. Berdasarkan prinsip Pareto terdapat dua mesin kritis dari lima mesin yang ada.Hasil perhitungan dari data kerusakan mesin sebelumnya diketahui, jika dilakukan preventive maintenance downtime akan berkurang sebanyak 2.85%, dan terjadi penghematan sebesar 38%.

Reactivity of a Pt(100) cluster modified by adsorption of a nickel tetramer

Energy Technology Data Exchange (ETDEWEB)

Ortiz, E V; Lopez, M B [Centro de Investigaciones Fisicoquimicas, Teoricas y Aplicadas (CIFTA), Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Catamarca, Av. Belgrano 300, (4700), Catamarca (Argentina); Castro, E A, E-mail: mblopez@fcasuser.unca.edu.a [INIFTA, CONICET, Universidad Nacional de la Plata, Diag. 113 y 64, Suc.4, C.C. 16, (1900), La Plata (Argentina)

2009-05-01

The aim of this paper is to report a study of the reactivity of Pt(100) cluster and the same system modified by a nickel tetramer towards the atomic hydrogen adsorption. This study was carried out in the framework of density functional theory which provides global and local indexes that can be used to characterize the reactivity. The analyzed reactivity descriptors were: chemical potential, chemical hardness, electrophilicity index and Fukui function. The results showed that the global reactivity descriptor predicts that the platinum cluster modified by nickel is more reactive than the pure platinum cluster and that the local Fukui function provides information about the most susceptible site to electrophilic attack in platinum cluster.

Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

DEFF Research Database (Denmark)

Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

2010-01-01

The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target...

Producción de biodiesel a partir de materias primas no convencionales

OpenAIRE

Aguilar Sánchez, Rocío

2011-01-01

Proyecto Fin de Carrera leído en la Universidad Rey Juan Carlos en el curso académico 2010/2011. Directores del Proyecto: Gabriel Morales Sánchez y Rebeca Sánchez Vázquez Actualmente, para la producción industrial de biodiesel se emplean aceites vegetales de alta calidad como materia prima, y se utilizan catalizadores básicos homogéneos, KOH o NaOH. Los productos de reacción son FAME y glicerina. Sin embargo, debido a los problemas derivados del uso de aceites vegetales comestible...

El tratamiento actuarial de los periodos de carencia y el contraseguro de primas en el seguro de dependencia.

Directory of Open Access Journals (Sweden)

Ricote Gil, Fernando.

2003-01-01

Full Text Available La dependencia es un estado en el que se encuentran las personas que por razones ligadas a la falta o la pérdida de autonomía física, psíquica o intelectual tienen necesidad de asistencia y/o atención significativa para la realización los actos corrientes de la vida diaria. Dentro de la iniciativa privada, el sector asegurador juega un importante papel para la prestación de garantías derivadas de esta cobertura. Un aspecto fundamental en el estudio de esta cobertura es la consideración de los periodos de carencia y el tratamiento del contraseguro de primas durante los mismo. Se analiza el riesgo actuarial y su tratamiento en esta cobertura y la incidencia en la valoración actuarial de las primas por prestaciones de dependencia.

Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang, E-mail: molpharm@163.com; Sun, Yang, E-mail: yangsun@nju.edu.cn

2013-03-01

In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

International Nuclear Information System (INIS)

Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang; Sun, Yang

2013-01-01

In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

JESTIANALYSIS OF CICERO'S ORATIO IN CATILINAM PRIMA FROM THE ASPECT OF PHONOSTYLISTICS AND LEXICOSTYLISTICS

Directory of Open Access Journals (Sweden)

Sanja Merzić

2013-05-01

Full Text Available This work represents an analysis of Cicero's speech Oratio in Catilinam Prima on two levels: phonostylistic and lexicostylistic with the goal to represent expressive voice function and figures of speech on phonostylistic level and to represent lexic with additional meaning, relations between words and lexico-syntactic figures on lexicostylistic level. Also, the purpose of the speech is to show what makes Cicero's speeches specific and successful.

Objective justification and Prima Facie anti-competitive unilateral conduct : an exploration of EU Law and beyond

NARCIS (Netherlands)

Vijver, Tjarda Desiderius Oscar van der

2014-01-01

The prohibition of anti-competitive unilateral conduct by firms with market power is not absolute, but allows for derogation. For the purposes of EU law, the ECJ has accepted that a so-called ‘objective justification’ plea may be invoked in the case of a prima facie abuse of dominance. Even though

Deposition and characterisation of multilayer hard coatings. Ti/TiNδ/TiCxNy/(TiC) a-C:H/(Ti) a-C:H

International Nuclear Information System (INIS)

Burinprakhon, T.

2001-02-01

Multilayer hard coatings containing Ti, TiNδ, TiC x N y , (TiC m ) a-C:H, (TiC n ) a-C:H, and (Ti) a-C:H were deposited on commercially pure titanium substrates by using an asymmetric bipolar pulsed-dc reactive magnetron sputtering of a titanium target, with Ar, Ar+N 2 , Ar+N 2 +CH 4 , and Ar+CH 4 gas mixtures. The microstructures, elemental compositions and bonding states of the interlayers and the coating surfaces were studied by using cross-sectional transmission electron microscopy (XTEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The microstructure development of the multilayer coating was strongly influenced by target poisoning. As a result of the complete poisoning of the titanium target during the deposition of TiNδ and TiC x N y interlayers, the a-C:H interlayers containing graded titanium and nitrogen contents were found to develop successively to the TiC x N y interlayer without the formation of near-stoichiometric TiC. The (TiC m ) a-C:H interlayer consisted of nano-particles of distorted fcc crystal structure embedded in the a-C:H matrix. The (TiC n ) a-C:H and (Ti) a-C:H top layers were found to be a-C:H matrix without nano-particles. In the (Ti) a-C:H top layer there was no measurable amount of Ti observed, regardless of the variation of CH 4 concentration between 37.5 and 60 % flow rate in Ar+-CH4 gas mixture. The top layer (Ti) a-C:H was found to contain approximately 10 atomic % nitrogen, due to N 2 contamination during deposition caused by low conductance of N 2 through the nominally closed valve of the mass flow controller. The change of the CH 4 concentration during deposition of the top layer (Ti) a-C:H, however, showed a strong influence on the hydrogen content. The comparison of the fluorescence background of the Raman spectra revealed that hydrogen-less (Ti) a-C:H was deposited at a CH 4 concentration of less than 50 % flow rate in Ar. The hardness

The relationship of reports of aches and joint pains to the menopausal transition: a longitudinal study.

Science.gov (United States)

Szoeke, C E; Cicuttini, F M; Guthrie, J R; Dennerstein, L

2008-02-01

OBJECTIVES Part I: To determine factors associated with reported joint symptoms across the menopausal transition. Part II: To investigate the relationship between symptom reporting and radiological arthritis in postmenopausal women. DESIGN Part I: The Melbourne Women's Mid-life Health Project, commenced in 1991, is a population-based prospective study of 438 Australian-born women, aged 45-55 years and menstruating at baseline; they were interviewed annually over 8 years. The retention rate was 88% (n = 387). Part II: After 12 years of follow-up, 257 (57%) women returned for assessment and 224 agreed to undergo X-rays of their hands and knees. METHODS Part I: Annual fasting blood collection, physical measurements, and interviews including questions about bothersome aches or stiff joints in the previous 2 weeks. A score for this symptom was calculated from the product of the severity and frequency data. These data were analyzed using random-effects time-series regression models. Part II: X-rays were scored for evidence of osteoarthritis using a validated scale, by two investigators who were blinded to questionnaire results. RESULTS Part I: 'Aches and stiff joints' were the most commonly reported symptom and reporting increased over time in the longitudinal study. Variables significantly associated with reporting bothersome aches and stiff joints were high body mass index (BMI) (p Part II: The relationship between radiological osteoarthritis and symptom reports approached statistical significance (p = 0.06). Knee osteoarthritis was significantly associated with symptom reports (p = 0.008) but not hand osteoarthritis (p = 0.2). Menopausal status, BMI, employment status and depressed mood were all associated with the experience of bothersome aches and stiff joints. Aches and stiff joints, common in postmenopausal women, are not necessarily indicative of radiological osteoarthritis.

Efficient expression of functional (α6β22β3 AChRs in Xenopus oocytes from free subunits using slightly modified α6 subunits.

Directory of Open Access Journals (Sweden)

Carson Kai-Kwong Ley

Full Text Available Human (α6β2(α4β2β3 nicotinic acetylcholine receptors (AChRs are essential for addiction to nicotine and a target for drug development for smoking cessation. Expressing this complex AChR is difficult, but has been achieved using subunit concatamers. In order to determine what limits expression of α6* AChRs and to efficiently express α6* AChRs using free subunits, we investigated expression of the simpler (α6β22β3 AChR. The concatameric form of this AChR assembles well, but is transported to the cell surface inefficiently. Various chimeras of α6 with the closely related α3 subunit increased expression efficiency with free subunits and produced pharmacologically equivalent functional AChRs. A chimera in which the large cytoplasmic domain of α6 was replaced with that of α3 increased assembly with β2 subunits and transport of AChRs to the oocyte surface. Another chimera replacing the unique methionine 211 of α6 with leucine found at this position in transmembrane domain 1 of α3 and other α subunits increased assembly of mature subunits containing β3 subunits within oocytes. Combining both α3 sequences in an α6 chimera increased expression of functional (α6β22β3 AChRs to 12-fold more than with concatamers. This is pragmatically useful, and provides insights on features of α6 subunit structure that limit its expression in transfected cells.

Three-dimensional plasmonic chiral tetramers assembled by DNA origami.

Science.gov (United States)

Shen, Xibo; Asenjo-Garcia, Ana; Liu, Qing; Jiang, Qiao; García de Abajo, F Javier; Liu, Na; Ding, Baoquan

2013-05-08

Molecular chemistry offers a unique toolkit to draw inspiration for the design of artificial metamolecules. For a long time, optical circular dichroism has been exclusively the terrain of natural chiral molecules, which exhibit optical activity mainly in the UV spectral range, thus greatly hindering their significance for a broad range of applications. Here we demonstrate that circular dichroism can be generated with artificial plasmonic chiral nanostructures composed of the minimum number of spherical gold nanoparticles required for three-dimensional (3D) chirality. We utilize a rigid addressable DNA origami template to precisely organize four nominally identical gold nanoparticles into a three-dimensional asymmetric tetramer. Because of the chiral structural symmetry and the strong plasmonic resonant coupling between the gold nanoparticles, the 3D plasmonic assemblies undergo different interactions with left and right circularly polarized light, leading to pronounced circular dichroism. Our experimental results agree well with theoretical predictions. The simplicity of our structure geometry and, most importantly, the concept of resorting on biology to produce artificial photonic functionalities open a new pathway to designing smart artificial plasmonic nanostructures for large-scale production of optically active metamaterials.

On quanta, mind, and matter: Hans Primas in Context. H. Atmanspacher, A. Amann, U. Müller-Herold (Eds), Kluwer, Boston, 1999, pp. 398 + viii, US192.00 £133.56 (hardback), ISBN 0-7923-5696-9

Science.gov (United States)

Halvorson, Hans

This book consists of a collection of 18 articles by students, colleagues, and friends of the theoretical chemist/philosopher of science, Hans Primas. Although the articles are written in honor of Primas, the editors state that the collection is not a Festschrift, but that it simply 'takes up some of the discussions that Primas has initiated or inspired' (p. 2). Due to the breadth of Primas' intellectual interests, the result is a highly eclectic collection of articles, whose topics range through (i) the historical development of experimental NMR spectroscopy, (ii) Jungian psychology, (iii) a defense of determinism in the rationalistic tradition of Leibniz, to (iv) a mathematical exposition of 'operator trigonometry.' However, since our space-and my expertise-is limited, the following comments will be restricted to those articles that deal with the mathematical and conceptual foundations of physics, a subject to which Primas has made a large contribution.

The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

Energy Technology Data Exchange (ETDEWEB)

Schaal, Courtney [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States); Padmanabhan, Jaya [Department of Molecular Medicine and USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, FL 33612 (United States); Chellappan, Srikumar, E-mail: Srikumar.Chellappan@moffitt.org [Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612 (United States)

2015-07-31

Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer.

The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

International Nuclear Information System (INIS)

Schaal, Courtney; Padmanabhan, Jaya; Chellappan, Srikumar

2015-01-01

Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer

Modification of the histone tetramer at the H3-H3 interface impacts tetrasome conformations and dynamics

Science.gov (United States)

Ordu, Orkide; Kremser, Leopold; Lusser, Alexandra; Dekker, Nynke H.

2018-03-01

Nucleosomes consisting of a short piece of deoxyribonucleic acid (DNA) wrapped around an octamer of histone proteins form the fundamental unit of chromatin in eukaryotes. Their role in DNA compaction comes with regulatory functions that impact essential genomic processes such as replication, transcription, and repair. The assembly of nucleosomes obeys a precise pathway in which tetramers of histones H3 and H4 bind to the DNA first to form tetrasomes, and two dimers of histones H2A and H2B are subsequently incorporated to complete the complex. As viable intermediates, we previously showed that tetrasomes can spontaneously flip between a left-handed and right-handed conformation of DNA-wrapping. To pinpoint the underlying mechanism, here we investigated the role of the H3-H3 interface for tetramer flexibility in the flipping process at the single-molecule level. Using freely orbiting magnetic tweezers, we studied the assembly and structural dynamics of individual tetrasomes modified at the cysteines close to this interaction interface by iodoacetamide (IA) in real time. While such modification did not affect the structural properties of the tetrasomes, it caused a 3-fold change in their flipping kinetics. The results indicate that the IA-modification enhances the conformational plasticity of tetrasomes. Our findings suggest that subnucleosomal dynamics may be employed by chromatin as an intrinsic and adjustable mechanism to regulate DNA supercoiling.

Throat ache ans swelling of the neck: first symptoms of Lemierre's syndrome

NARCIS (Netherlands)

de Lange, J.; Ybema, A; Baas, E. M.

2014-01-01

Lemierre's syndrome, a thrombophlebitis of the internal jugular vein, is a rare disorder, usually caused by the microorganism Fusobacterium necrophorum. Throat ache and swelling of the neck are often the first symptoms. Without adequate treatment, Lemierre's syndrome may result in thrombosis of the

Identificación de dos formas polimórficas cristalinas de clopidogrel bisulfato en materia prima farmacéutica

Directory of Open Access Journals (Sweden)

German Leonardo Madrigal Redondo

Full Text Available Introducción: el clopidogrel bisulfato existe en numerosas formas cristalinas, que varían en su estabilidad fisicoquímica, por lo que algunas de estas formas, patentadas o no, son útiles en la fabricación de medicamentos. Objetivo: identificar las formas cristalinas existentes en dos muestras de clopidogrel bisulfato materia prima comercializadas para la fabricación de medicamentos y el estado de pureza de ambas muestras. Métodos: las muestras de materia prima se obtuvieron de una industria nacional. Se examinaron mediante técnicas analíticas avanzadas como difracción de rayos X, calorimetría diferencial de barrido, termogravimetría y espectroscopia infrarroja. Se compararon los valores encontrados con los del estado del arte reconocidos en la literatura revisada para el clopidogrel bisulfato materias primas y tomados como referencia. Resultados: se obtuvieron los difractogramas, termogramas y espectros de absorción correspondientes a las muestras analizadas. Se utilizó el software TA Universal Analysis para obtener el porcentaje de descomposición, punto de fusión y picos identificadores en las muestras. Conclusiones: la muestra 1 contiene la forma cristalina I del bisulfato de clopidogrel, que no es pura ya que existe una banda característica de la presencia de contaminación con la forma cristalina II. La muestra 2 corresponde a la forma cristalina II del producto en forma pura.

Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

Energy Technology Data Exchange (ETDEWEB)

McPherson, D.W.; Luo, H.; Knapp, F.F. Jr.

1994-06-01

Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

Does Your Patient's Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review.

Science.gov (United States)

Kanniyan, Kalaivanan; Pathak, Aditya C; Dhammi, Ish Kumar; Jain, Anil Kumar

2014-01-01

Alkaptonuria is a very rare inborn error of amino acid metabolism due to deficient homogentisic acid (HGA) oxidase enzyme leading to accumulation of HGA in plasma, cartilage, other tissues of human body and its excretion in urine. It has both systemic and peripheral signs and symptoms. Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. Alkaptonuria itself is very rare occurrence with no specific treatment option available to reverse the effect as yet. A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. Later on laboratory and the radiological investigation patient was diagnosed to have alkaptonuria without ochronosis. No other systemic manifestation was present. Patient was treated conservatively and responded well. Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. One must be aware of this inborn error of metabolism. Early diagnosis though being "diagnosis of exclusion" for low back-ache, high index of suspicion is advantageous as symptomatic treatment of the alkaptonuria can be initiated and evaluation of other systemic organs can be done in early stages itself.

[Children's and adolescent's use of medicine for aches and psychological problems: secular trends from 1988 to 2006.

DEFF Research Database (Denmark)

Holstein, Bjørn; Andersen, Anette; Due, Pernille

2009-01-01

INTRODUCTION: Medicine use for aches and psychological problems is common among adolescents. Medicines are toxic and may have harmful side effects. It is therefore important to study change over time and patterns of medicine use. The objective of this paper is to describe self-reported medicine use...... for headaches, stomach-aches, difficulties in falling asleep, and nervousness among 11-, 13-, and 15-year-old boys and girls from 1968 to 2006. MATERIAL AND METHODS: The data material is 6 comparable and representative cross-sectional studies of 11-, 13-, and 15-year-olds from 1988, 1991, 1994, 1998, 2002......: There was a significant increase in 11-, 13-, and 15-year-old student's use of medicine for aches and psychological problems from 1988 to 2006. In the same period, there was a decrease in the prevalence of students who reported pains monthly. Udgivelsesdato: 2009-Jan-5...

Aging of oxygen and hydrogen plasma discharge treated a-C:H and ta-C coatings

Energy Technology Data Exchange (ETDEWEB)

Bachmann, Svenja [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Schulze, Marcus [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Morasch, Jan [Institute of Materials Science, Technische Universität Darmstadt, Surface Science Division, Jovanka-Bonschits-Straße 2, 64287 Darmstadt (Germany); Hesse, Sabine [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); Hussein, Laith [Eduard-Zintl-Institut, Department of Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Str. 12, 64287, Darmstadt (Germany); Krell, Lisa; Schnagl, Johann [BMW Group, Hufelandstraße 4, 80788 Munich (Germany); Stark, Robert W. [Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 16, 64287 Darmstadt (Germany); Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str. 10, 64287 Darmstadt (Germany); and others

2016-05-15

Highlights: • The water CA of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C changes from hydrophillic to hydrophobic on aging. • XPS study indicates that the decrease in surface energy of plasma treated a-C:H and ta-C could be due to adsorption of organic component from air. • The COFLFM of O{sub 2} and H{sub 2} plasma treated a-C:H and ta-C decreased upon aging. • The COF of glycerol lubricated ta-C showed no sign of change upon aging. - Abstract: Surface modification with gas plasma is an efficient and easy way to improve the surface energy and the tribological behavior of diamond-like carbon (DLC) coatings, e.g., in biomedical implants or as protective coatings. However, the long-term performance of the plasma treated DLC coatings is not fully clear. We thus studied the long-term stability of two kinds of DLC coatings, namely (a) hydrogenated amorphous carbon (a-C:H) and (b) tetrahedral amorphous carbon (ta-C) treated at different radio frequency (RF) power and time of oxygen (O{sub 2}) and hydrogen (H{sub 2}) plasma. Their surface properties, e.g. surface wettability, structure and tribological behavior, were studied at regular intervals for a period of two months using contact angle goniometer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), lateral force microscopy (LFM) and ball on disc apparatus. The surface energy of both the coatings decreased upon aging. The higher the RF power and time of treatment, the higher was the hydrophobicity upon aging. XPS analysis showed that the increase in hydrophobicity could be due to adsorption of unavoidable volatile organic components in the atmosphere. The H{sub 2} plasma treated ta-C was capable of rearranging its structural bonds upon aging. The nano-friction measurements by LFM showed that the coefficient of friction of plasma treated a-C:H and ta-C decreased upon aging. The results indicate that the surface properties of plasma treated a‐C:H and ta‐C are not stable on long-term and are

Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

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Bopanna I Kalappa

2010-11-01

Full Text Available The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596.An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71% of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1-5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV the entire pyramidal neuron and occasionally

The Student-Athlete and the National Collegiate Athletic Association: The Need for a Prima Facie Tort Doctrine

Science.gov (United States)

Duckworth, Roy D., III

1975-01-01

In examining whether courts have jurisdiction to hear student-athlete grievances against the National Collegiate Athletic Association (NCAA) the author rejects the position that the NCAA's activities are under cover of state law, and instead proposes that the student-athlete's remedy lies in an action against the NCAA for a prima facie tort. (JT)

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

Science.gov (United States)

Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

2016-05-02

The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.

Attenuated nicotine‐like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily

Science.gov (United States)

Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy

2016-01-01

Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659

nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: current trends and perspectives

Science.gov (United States)

Parikh, Vinay; Kutlu, Munir Gunes; Gould, Thomas J.

2016-01-01

Introduction The prevalence of tobacco use in the population with schizophrenia is enormously high. Moreover, nicotine dependence is found to be associated with symptom severity and poor outcome in patients with schizophrenia. The neurobiological mechanisms that explain schizophrenia-nicotine dependence comorbidity are not known. This study systematically reviews the evidence highlighting the contribution of nicotinic acetylcholine receptors (nAChRs) to nicotine abuse in schizophrenia. Methods Electronic data bases (Medline, Google Scholar, and Web of Science) were searched using the selected key words that match the aims set forth for this review. A total of 275 articles were used for the qualitative synthesis of this review. Results Substantial evidence from preclinical and clinical studies indicated that dysregulation of α7 and β2-subunit containing nAChRs account for the cognitive and affective symptoms of schizophrenia and nicotine use may represent a strategy to remediate these symptoms. Additionally, recent meta-analyses proposed that early tobacco use may itself increase the risk of developing schizophrenia. Genetic studies demonstrating that nAChR dysfunction that may act as a shared vulnerability factor for comorbid tobacco dependence and schizophrenia were found to support this view. The development of nAChR modulators was considered an effective therapeutic strategy to ameliorate psychiatric symptoms and to promote smoking cessation in schizophrenia patients. Conclusions The relationship between schizophrenia and smoking is complex. While the debate for the self-medication versus addiction vulnerability hypothesis continues, it is widely accepted that a dysfunction in the central nAChRs represent a common substrate for various symptoms of schizophrenia and comorbid nicotine dependence. PMID:26803692

Effects of acetylcholine (ACh) and norepinephrine (NE) on phosphatidylinositol 4,5-bisphosphate (PIP2) turnover in rabbit cornea

International Nuclear Information System (INIS)

Akhtar, R.A.; Abdel-Latif, A.A.

1986-01-01

Muscarinic cholinergic and α 1 -adrenergic agonists provoke hydrolysis of PIP 2 into diacylglycerol (DG) and inositol trisphosphate (IP 3 ) in a wide variety of tissue. Recently, IP 3 has been shown to mobilize Ca 2+ from ER in several permeabilized tissue preparations. Although rabbit cornea is enriched in ACh and NE, the physiological function of these neurotransmitters is unclear. The present studies were initiated to determine the effects of cholinergic and adrenergic agonists on PIP 2 turnover in the cornea. Addition of ACh or NE (50 μM each) to the 32 P-labeled corneas for 10 min decreased the radioactivity in PIP 2 by 33 and 36%, and increased the radioactivity in phosphatidic acid by 72 and 52%, respectively. When the corneas were labeled with myo-[ 3 H]inositol, ACh and NE increased the accumulation of IP 3 by 92 and 48%, respectively. The effects of ACh and NE on phospholipid labeling and IP 3 accumulation were specifically inhibited by atropine (10 μM) and prazosin (10 μM), respectively. The data suggest the presence of muscarinic cholinergic and α 1 -adrenergic receptors in the rabbit cornea. Furthermore, activation of these receptors leads to cleavage of PIP 2 into DG and IP 3 which may function as second messengers in this tissue

Aurantoside K, a New Antifungal Tetramic Acid Glycoside from a Fijian Marine Sponge of the Genus Melophlus

Directory of Open Access Journals (Sweden)

Rohitesh Kumar

2012-01-01

Full Text Available A new tetramic acid glycoside, aurantoside K, was isolated from a marine sponge belonging to the genus Melophlus. The structure of the compound was elucidated on the basis of spectroscopic analysis (1H NMR, 1H–1H COSY, HSQC, and HMBC, as well as high-resolution ESILCMS. Aurantoside K did not show any significant activity in antimalarial, antibacterial, or HCT-116 cytotoxicity assays, but exhibited a wide spectrum of antifungal activity against wild type Candida albicans, amphotericin-resistant C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia and Sordaria sp.

Genotoxicity Assessment of Chlorotrifluoroethylene Tetramer Acid using a Battery of In Vitro and In Vivo/In Vitro Assays

Science.gov (United States)

1990-12-01

hypolipidemic ixgent, clofibrate (Lalwani et al., 1983). However, numerous industrial chemicals such as phthalate eater plasticizers and phenoxy acid ...AD-A240 492 AA..MRL-TR-90-069 ~l~iiIIi1111fl GENOTOXICITY ASSESSMENT OF CHLOROTRIFLUOROETHYLENE TETRAMER ACID USING A BATTERY OF IN VITRO AND IN VIVO... Acid Using a Battery of In Vitro and In Vivo,/n Vitro Assays PE 62202F 6. AUTHOR(S) PR 6302 TA 630201 C. S. Godin, B. C. Myhr, T. E. Lawlor, R. R. Young

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

Science.gov (United States)

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

2017-04-01

Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV

Projeto de Redução do Desperdício de Matéria-Prima: Estudo de Caso na Indústria de Embalagens de Papel no Brasil

Directory of Open Access Journals (Sweden)

Gleison Hidalgo Hidalgo Martins

2014-02-01

Full Text Available Pode-se dizer que em se tratando de produção industrial os desperdícios que podem ocorrer ao longo dos processos são diversos, vão de matéria-prima à recursos financeiros. No entanto pode-se classificar o desperdício de matéria-prima como sendo o mais urgente deste setor e também o mais passivo de ser estudado, uma vez que impacta diretamente no fluxo fabril e na quantidade do produto acabado. O conteúdo desta pesquisa apresenta argumentos através de embasamento teórico e prático que apontam para a importância de trabalhos sobre as possíveis causas do problema do desperdício de matéria-prima nas linhas industriais de embalagem de papel assim como as formas de combater e reagir ao problema.DOI:10.5585/gep.v4i3.186

Use of "one-pot, mix-and-read" peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

DEFF Research Database (Denmark)

Svitek, Nicholas; Hansen, Andreas Martin; Steinaa, Lucilla

2014-01-01

Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8(+) cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and re...

Does Your Patient’s Urine Turns Dark? Alkaptonuria and Low Back Ache: A Literature Review

Science.gov (United States)

Kanniyan, Kalaivanan; Pathak, Aditya C; Dhammi, Ish Kumar; Jain, Anil Kumar

2014-01-01

Introduction: Alkaptonuria is a very rare inborn error of amino acid metabolism due to deficient homogentisic acid (HGA) oxidase enzyme leading to accumulation of HGA in plasma, cartilage, other tissues of human body and its excretion in urine. It has both systemic and peripheral signs and symptoms. Though low back is a common symptom of alkaptonuria but, in the absence of ochronosis it is rare. Alkaptonuria itself is very rare occurrence with no specific treatment option available to reverse the effect as yet. Case Report: A 38-year-old male, embroidery worker presented with chronic low back ache with history of staining of clothes in infancy. Later on laboratory and the radiological investigation patient was diagnosed to have alkaptonuria without ochronosis. No other systemic manifestation was present. Patient was treated conservatively and responded well. Conclusion: Though alkaptonuria is a very rare disease, and the occurrence of low back-ache in absence of ochronosis is much rarer. One must be aware of this inborn error of metabolism. Early diagnosis though being “diagnosis of exclusion” for low back-ache, high index of suspicion is advantageous as symptomatic treatment of the alkaptonuria can be initiated and evaluation of other systemic organs can be done in early stages itself. PMID:27298997

Exploração de subprodutos de maçã como matérias-primas alternativas em formulações para Columba livia

OpenAIRE

Ferreira, João Manuel Silva Loureiro Alves

2015-01-01

O crescimento da população humana deverá continuar até 2050. Por este motivo, a competição por matérias-primas entre a nossa alimentação e a alimentação animal será inevitável, tornando importante o recurso a matérias-primas alternativas, provenientes dos excedentes da indústria alimentar, como o bagaço de maçã e o resíduo da filtração do sumo concentrado denominado por retentato de maçã. Dentro das gamas de produtos fabricados pela indústria da alimentação animal, temos as rações para pom...

Sasaran Strategis Perusahaan Perkebunan Kelapa Sawit Teladan Prima Group

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Sali Subakti

2017-09-01

Full Text Available Teladan Prima Group (TPG as one of the palm oil plantations company have a strategic objectives in perspective of financial, customer, internal business processes, and learning and growth with the implementation of the Balanced Scorecard (BSC. The efforts to improve of high productivity of all resources that owned, are effectiveness managed with cost efficiency is the ultimate goal of company performance measurement. The problems occurred, management is confronted on the issues of the achievement of company performance targets that are not optimal and the strategic objectives of the company have not been cascaded down in a balanced way. The purpose of this research is to analyze of the strategic objectives and the implementation of BSC by using the technique of analysis of fourteen strategic objectives of the company in the four BSC perspectives with the integration of analytic network process (ANP. Results from the processing of primary data obtained through in-depth interviews and pairwise comparison of 7 respondents on the company executive level shows the results: financial perspective has the biggest weighting 42.21%, internal business process perspective 27.45%, customer perspective 16.29% growth and learning perspective 14.04% with consistency ratio (CR 2.14% which means the respondent opinion is acceptable and consistent.Keywords: strategic objectives, balanced scorecard, ANP, oil palmAbstrak: Teladan Prima Group (TPG sebagai salah satu perusahaan perkebunan kelapa sawit memiliki sasaran strategi dalam perspektif kinerja keuangan, pelanggan, proses bisnis internal dan pembelajaran dan pertumbuhan dengan penerapan Balanced Scorecard (BSC. Upaya peningkatan produktivitas sumberdaya yang dimiliki, dengan efektivitas pengelolaan dan efisiensi biaya merupakan tujuan akhir dari pengukuran kinerja perusahaan. Permasalahan yang terjadi, manajemen dihadapkan pada isu pencapaian target kinerja perusahaan yang belum optimum dan sasaran strategis

LA VALIDEZ PRIMA FACIE Y EL PRINCIPIO DE DERROTABILIDAD DE LAS NORMAS JURÍDICAS

OpenAIRE

GARCÍA-YZAGUIRRE, JOSÉ VÍCTOR

2012-01-01

El presente artículo pretende explorar las implicancias teóricas del concepto prima facie y como este se relaciona con el principio de derrotabilidad, el cual es aplicable para justificar el incumplimiento de un deber jurídico a causa del acatamiento de otro en un contexto en el que ambos son incompatibles entre sí. Partiremos desde su sustento conceptual analizando cuál es el rol y la importancia del contexto en el razonamiento jurídico hasta arribar a pautas concretas de cómo opera en la pr...

Perancangan Sistem Informasi Penjualan dan Persediaan pada PT Selatan Jaya Prima Perkasa

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Stephanie Surja

2013-12-01

Full Text Available This study aims to analyze the organization needs in sales and stock company process that related with the current business process at PT Selatan Jaya Prima Perkasa. The result will be used for developing an integrated system that can be the solution for the company needs in running their sales and to control theirinventory stock status as the main business of the company. The analyzed result in the company needs will be documented using unified modeling language. This information system is expected to simplify ease the company’s activitis in sales process and inventory stock control. This system will also minimize the data lost and human error usually caused by manual process of transactional data storage.

Inactivation of JAK2/STAT3 Signaling Axis and Downregulation of M1 mAChR Cause Cognitive Impairment in klotho Mutant Mice, a Genetic Model of Aging

Science.gov (United States)

Park, Seok-Joo; Shin, Eun-Joo; Min, Sun Seek; An, Jihua; Li, Zhengyi; Hee Chung, Yoon; Hoon Jeong, Ji; Bach, Jae-Hyung; Nah, Seung-Yeol; Kim, Won-Ki; Jang, Choon-Gon; Kim, Yong-Sun; Nabeshima, Yo-ichi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2013-01-01

We previously reported cognitive dysfunction in klotho mutant mice. In the present study, we further examined novel mechanisms involved in cognitive impairment in these mice. Significantly decreased janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3) phosphorylation were observed in the hippocampus of klotho mutant mice. A selective decrease in protein expression and binding density of the M1 muscarinic cholinergic receptor (M1 mAChR) was observed in these mice. Cholinergic parameters (ie, acetylcholine (ACh), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE)) and NMDAR-dependent long-term potentiation (LTP) were significantly impaired in klotho mutant mice. McN-A-343 (McN), an M1 mAChR agonist, significantly attenuated these impairments. AG490 (AG), a JAK2 inhibitor, counteracted the attenuating effects of McN, although AG did not significantly alter the McN-induced effect on AChE. Furthermore, AG significantly inhibited the attenuating effects of McN on decreased NMDAR-dependent LTP, protein kinase C βII, p-ERK, p-CREB, BDNF, and p-JAK2/p-STAT3-expression in klotho mutant mice. In addition, k252a, a BDNF receptor tyrosine kinase B (TrkB) inhibitor, significantly counteracted McN effects on decreased ChAT, ACh, and M1 mAChR and p-JAK2/p-STAT3 expression. McN-induced effects on cognitive impairment in klotho mutant mice were consistently counteracted by either AG or k252a. Our results suggest that inactivation of the JAK2/STAT3 signaling axis and M1 mAChR downregulation play a critical role in cognitive impairment observed in klotho mutant mice. PMID:23389690

Figuraciones de la escritura de un a opera prima en la obra de César Aira

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Graciela Villanueva

2012-10-01

Full Text Available Una de las formas que adopta la reflexión sobre los comienzos en la obra de César Aira es la figuración de la escritura de una opera prima. Los escritores noveles aparecen ya en la ficción airiana de los años 90 (en El volante, por ejemplo, pero su frecuencia aumenta en las novelas de la década siguiente (Varamo, El mago, Parménides, La vida nueva. Por muy distintos que sean los protagonistas de todas estas novelas, los planteos que surgen al narrar cómo cada uno de ellos se convierte en escritor guardan una estrecha relación con la poética del propio César Aira. La figuración de la escritura de una opera prima prolonga y completa una reflexión ya iniciada anteriormente, por ejemplo en el diálogo que las primeras novelas de Aira entablan con los textos fundadores de la literatura argentina, en el diálogo con el Génesis bíblico propuesto por El congreso de literatura y en las páginas que El vestido rosa consagra a la cuestión del comienzo de la ficción, páginas que Diario de la hepatitis y Fragmento de un diario en los Alpes desarrollan y enriquecen en las décadas siguientes.La figuration de l’écriture d’une opera prima est une des formes adoptées par la réflexion sur le commencement dans la fiction de de César Aira. Les écrivains débutants apparaissent déjà dans les romans des années 90 (dans Le prospectus, par exemple, mais leur fréquence augmente dans les romans des années 2000 (Varamo, Le magicien, Parménide, La vie nouvelle. Les héros de tous ces romans ont beau être très différents, les idées qui naissent du récit de la manière dont ils ont commencé à écrire sont étroitement liées à la poétique de César Aira. La figuration de l’écriture d’une première œuvre prolonge et complète une réflexion que Aira avait entamée à travers le dialogue que ses premiers romans établissent avec les textes fondateurs de la littérature argentine, à travers le dialogue entre le Livre biblique de

Uso de rejeitos de granitos como matérias-primas cerâmicas

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Menezes R. R.

2002-01-01

Full Text Available A indústria do beneficiamento de granito gera uma enorme quantidade de rejeitos, que poluem e degradam o meio ambiente. Assim este trabalho tem por objetivo caracterizar e avaliar as possibilidades de utilização dos rejeitos da serragem de granitos gerados pelas indústrias de beneficiamento da Região Nordeste, como matéria-prima cerâmica alternativa na produção de blocos e revestimentos cerâmicos. Foram coletadas amostras de resíduos da serragem de granito em empresas da Paraíba, Ceará e Pernambuco, em seguida foi realizada sua caracterização através da determinação da distribuição granulométrica, massa específica real e área específica (BET e de análise química, ATD, ATG, DRX, MEV. Após caracterização foram conduzidos ensaios tecnológicos com composições cerâmicas a fim de avaliar a possibilidade de adição dos resíduos em massas cerâmicas para confecção de blocos e revestimentos cerâmicos. Com base nos resultados verificou-se que os resíduos apresentam características físicas e mineralógicas semelhantes as das matérias-primas cerâmicas convencionais e que corpos cerâmicos formulados com resíduos apresentam características dentro das especificações da normalização brasileira tanto para blocos como para revestimentos cerâmicos.

Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

Energy Technology Data Exchange (ETDEWEB)

Hirata, Yuki; Choi, Junho, E-mail: choi@mech.t.u-tokyo.ac.jp [Department of Mechanical Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)

2015-08-28

Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a

Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

Science.gov (United States)

Hirata, Yuki; Choi, Junho

2015-08-01

Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from -1.0 to -15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation

Effect of a nicotine vaccine on nicotine binding to the beta2-nAChRs in vivo in human tobacco smokers

Science.gov (United States)

Esterlis, Irina; Hannestad, Jonas O.; Perkins, Evgenia; Bois, Frederic; D’Souza, D. Cyril; Tyndale, Rachel F.; Seibyl, John P.; Hatsukami, Dorothy M.; Cosgrove, Kelly P.; O’Malley, Stephanie S.

2013-01-01

Objective Nicotine acts in the brain to promote smoking in part by binding to the beta2-containing nicotinic acetylcholine receptors (β2*-nAChRs) and acting in the mesolimbic reward pathway. The effects of nicotine from smoking one tobacco cigarette are significant (80% of β2*-nAChRs occupied for >6h). This likely contributes to the maintenance of smoking dependence and low cessation outcomes. Development of nicotine vaccines provides potential for alternative treatments. We used [123I]5IA-85380 SPECT to evaluate the effect of 3′-AmNic-rEPA on the amount of nicotine that binds to the β2*-nAChRs in the cortical and subcortical regions in smokers. Method Eleven smokers (36years (SD=13); 19cig/day (SD=11) for 10years (SD=7) who were dependent on nicotine (Fagerström Test of Nicotine Dependence score =5.5 (SD=3); plasma nicotine 9.1 ng/mL (SD=5)) participated in 2 SPECT scan days: before and after immunization with 4–400μg doses of 3′-AmNic-rEPA. On SPECT scan days, 3 30-min baseline emission scans were obtained, followed by administration of IV nicotine (1.5mg/70kg) and up to 9 30-min emission scans. Results β2*-nAChR availability was quantified as VT/fP and nicotine binding was derived using the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding (F=5.19, df=1,10, p=0.05). Significant positive correlations were observed between nicotine bound to β2*-nAChRs and nicotine injected before but not after vaccination (p=0.05 vs. p=0.98). There was a significant reduction in the daily number of cigarettes and desire for a cigarette (p=.01 and p=.04, respectively). Conclusions This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to β2*-nAChRs and disrupt the relationship between nicotine administered vs. nicotine available to occupy β2*-nAChRs. PMID:23429725

RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

Science.gov (United States)

Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

2015-02-01

Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening

DEFF Research Database (Denmark)

Hombrink, Pleun; Hadrup, Sine R; Bakker, Arne

2011-01-01

the technical feasibility of high-throughput analysis of antigen-specific T-cell responses in small patient samples. However, the high-sensitivity of this approach requires the use of potential epitope sets that are not solely based on MHC binding, to prevent the frequent detection of T-cell responses that lack......T-cell recognition of minor histocompatibility antigens (MiHA) plays an important role in the graft-versus-tumor (GVT) effect of allogeneic stem cell transplantation (allo-SCT). However, the number of MiHA identified to date remains limited, making clinical application of MiHA reactive T......MHC-tetramer-based enrichment and multi-color flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were generated. The isolation of a T-cell line specifically recognizing target cells expressing the MAP4K1(IMA) antigen demonstrates that identification of MiHA through this approach is in principle...

Not all hypochondroplasia families are linked to chromosome 4p16.3

Energy Technology Data Exchange (ETDEWEB)

Rousseau, F.; Munnich, A.; Merrer, M.Le. [INSERM, Paris (France)] [and others

1994-09-01

Achondroplasia (ACH, MIM 100800) and hypochondroplasia (HCH, MIM 146000) are short limb dwarfism with enlarged head sharing some specific radiological features. Inter- and intrafamilial clinical variability and histolopathological aspects of the growth cartilage suggested that ACH and HCH are allelic disorders. Recently, the gene for achondroplasia was mapped to chromosome 4p and no recombinants were found in 9 families with hypochondroplasia between D4S111 and the telomere (Zmax=1.70, {theta}=0). By using an additional polymorphic DNA marker which detects VNTR-like polymorphism at the D4S227 locus and a new microsatellite at locus D4S? (AFM163yc1), we observed recombinant events with markers of the chromosome 4p16.3 in 3/10 hypochondroplasia families, indicating that not all hypochondroplasia families are linked to chromosome 4p. A fibroblast growth factor receptor (FGFR3) expressed in chondrocytes during endochondral ossification which is located in the 2.5 Mb candidate region for achondroplasia was regarded as a good candidate gene. No major rearrangement of the FGFR3 gene was detected by Southern blot analysis using an FGFR3 cDNA probe. Further investigations will be required to conclude as to the possible involvement of this gene in ACH.

Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone.

Science.gov (United States)

Ismaya, Wangsa T; Rozeboom, Henriëtte J; Weijn, Amrah; Mes, Jurriaan J; Fusetti, Fabrizia; Wichers, Harry J; Dijkstra, Bauke W

2011-06-21

Tyrosinase catalyzes the conversion of phenolic compounds into their quinone derivatives, which are precursors for the formation of melanin, a ubiquitous pigment in living organisms. Because of its importance for browning reactions in the food industry, the tyrosinase from the mushroom Agaricus bisporus has been investigated in depth. In previous studies the tyrosinase enzyme complex was shown to be a H(2)L(2) tetramer, but no clues were obtained of the identities of the subunits, their mode of association, and the 3D structure of the complex. Here we unravel this tetramer at the molecular level. Its 2.3 Å resolution crystal structure is the first structure of the full fungal tyrosinase complex. The complex comprises two H subunits of ∼392 residues and two L subunits of ∼150 residues. The H subunit originates from the ppo3 gene and has a fold similar to other tyrosinases, but it is ∼100 residues larger. The L subunit appeared to be the product of orf239342 and has a lectin-like fold. The H subunit contains a binuclear copper-binding site in the deoxy-state, in which three histidine residues coordinate each copper ion. The side chains of these histidines have their orientation fixed by hydrogen bonds or, in the case of His85, by a thioether bridge with the side chain of Cys83. The specific tyrosinase inhibitor tropolone forms a pre-Michaelis complex with the enzyme. It binds near the binuclear copper site without directly coordinating the copper ions. The function of the ORF239342 subunits is not known. Carbohydrate binding sites identified in other lectins are not conserved in ORF239342, and the subunits are over 25 Å away from the active site, making a role in activity unlikely. The structures explain how calcium ions stabilize the tetrameric state of the enzyme.

Lac repressor: Crystallization of intact tetramer and its complexes with inducer and operator DNA

International Nuclear Information System (INIS)

Pace, H.C.; Lu, P.; Lewis, M.

1990-01-01

The intact lac repressor tetramer, which regulates expression of the lac operon in Escherichia coli, has been crystallized in the native form, with an inducer, and in a ternary complex with operator DNA and an anti-inducer. The crystals without DNA diffract to better than 3.5 angstrom. They belong to the monoclinic space group C2 and have cell dimensions a = 164.7 angstrom, b = 75.6 angstrom, and c = 161.2 angstrom, with α = γ = 90 degree and β = 125.5 degree. Cocrystals have been obtained with a number of different lac operator-related DNA fragments. The complex with a blunt-ended 16-base-pair strand yielded tetragonal bipyramids that diffract to 6.5 angstrom. These protein-DNA cocrystals crack upon exposure to the gratuitous inducer isopropyl β-D-thiogalactoside, suggesting a conformational change in the repressor-operator complex

Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

Energy Technology Data Exchange (ETDEWEB)

Machaalani, R., E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Ghazavi, E. [Bosch Institute, The University of Sydney, NSW 2006 (Australia); School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Hinton, T. [School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Waters, K.A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Hennessy, A. [School of Medicine, University of Western Sydney, NSW 2751 (Australia); Heart Research Institute, 7 Eliza St Newtown, NSW 2042 (Australia)

2014-05-01

Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

International Nuclear Information System (INIS)

Machaalani, R.; Ghazavi, E.; Hinton, T.; Waters, K.A.; Hennessy, A.

2014-01-01

Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta

Kinetics of Hydrocarbon formation in a-C:H film deposition plasmas

International Nuclear Information System (INIS)

De la Cal, E.; Tabares, F.L.

1993-01-01

The formation of C 2 and C 3 hydrocarbons during the PACVD of a-C-H films from admixtures of methane with H 2 and He has been investigated by mass spectrometry under several deposition condition. The time evolution of the observed species indicates that the formation mechanism of ethylene and acetylene are sensitive to the conditions of the wall during the growing of the film. Acetylene are sensitive to the conditions of the wall during the growing of the carburized metal. (Author)

Nueva materia prima borácica como componente de esmaltes cerámicos. Estudio de su solubilidad en suspensiones acuosas concentradas

Directory of Open Access Journals (Sweden)

Galindo, M.

2009-02-01

Full Text Available This paper presents an alternative to the use of conventional ceramic frits as raw materials that contribute boron to glaze compositions: a new semi-processed borate (patent pending (WO 2007/148101. The solubility of this new raw material is analysed and compared with that exhibited by conventional ceramic frits and other, natural and processed borates. This comparative analysis has been performed by determining the boron percentage present in the liquid phase of several glaze compositions prepared with each of these raw materials, modifying the type of deflocculant used and the solid/liquid contact time. The results of this study demonstrate the low solubility of the new semi-processed borate and its suitability for use in ceramic glaze formulation.

En el presente trabajo se presenta una alternativa a la utilización de fritas cerámicas convencionales como materias primas que aportan boro a las composiciones de esmalte: un nuevo borato sintético (patente pendiente WO2007/148101. Se ha estudiado y comparado la solubilidad de esta nueva materia prima con la que exhiben las fritas cerámicas convencionales y otros boratos, tanto naturales como sintéticos. Para ello, se ha determinado el porcentaje de boro presente en la fase líquida de varios esmaltes preparados con cada una de dichas materias primas, modificando el tipo de desfloculante utilizado y el tiempo de contacto sólido/líquido. El resultado de este trabajo ha puesto de manifiesto la baja solubilidad que presenta el nuevo borato sintético y su aptitud para ser usado en la formulación de esmaltes cerámicos.

Extracellular polysaccharidases synthesized by the epiphytic lichen Evernia prunastri (L.) Ach.

Science.gov (United States)

Yagüe, E; Orus, M I; Estevez, M P

1984-03-01

Evernia prunastri Ach., an epiphytic lichen growing on Quercus rotundifolia Lam., produces a β-1,4-glucanase (EC 3.2.1.4) and a polygalacturonase (EC 3.2.1.15). The activity of these polysaccharidases increases as a response to incubation of the lichen with carboxymethylcellulose or sodium polygalacturonate, respectively. This increase in activity is thought to be the result of enzyme induction because it is inhibited by both cycloheximide and 8-azaguanine. Both polysaccharide-degrading enzymes are partially secreted into the incubation media.

Aging of oxygen and hydrogen plasma discharge treated a-C:H and ta-C coatings

Science.gov (United States)

Bachmann, Svenja; Schulze, Marcus; Morasch, Jan; Hesse, Sabine; Hussein, Laith; Krell, Lisa; Schnagl, Johann; Stark, Robert W.; Narayan, Suman

2016-05-01

Surface modification with gas plasma is an efficient and easy way to improve the surface energy and the tribological behavior of diamond-like carbon (DLC) coatings, e.g., in biomedical implants or as protective coatings. However, the long-term performance of the plasma treated DLC coatings is not fully clear. We thus studied the long-term stability of two kinds of DLC coatings, namely (a) hydrogenated amorphous carbon (a-C:H) and (b) tetrahedral amorphous carbon (ta-C) treated at different radio frequency (RF) power and time of oxygen (O2) and hydrogen (H2) plasma. Their surface properties, e.g. surface wettability, structure and tribological behavior, were studied at regular intervals for a period of two months using contact angle goniometer, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), lateral force microscopy (LFM) and ball on disc apparatus. The surface energy of both the coatings decreased upon aging. The higher the RF power and time of treatment, the higher was the hydrophobicity upon aging. XPS analysis showed that the increase in hydrophobicity could be due to adsorption of unavoidable volatile organic components in the atmosphere. The H2 plasma treated ta-C was capable of rearranging its structural bonds upon aging. The nano-friction measurements by LFM showed that the coefficient of friction of plasma treated a-C:H and ta-C decreased upon aging. The results indicate that the surface properties of plasma treated a-C:H and ta-C are not stable on long-term and are influenced by the environmental conditions.

A folding pathway for betapep-4 peptide 33mer: from unfolded monomers and beta-sheet sandwich dimers to well-structured tetramers.

OpenAIRE

Mayo, K. H.; Ilyina, E.

1998-01-01

It was recently reported that a de novo designed peptide 33mer, betapep-4, can form well-structured beta-sheet sandwich tetramers (Ilyina E, Roongta V, Mayo KH, 1997b, Biochemistry 36:5245-5250). For insight into the pathway of betapep-4 folding, the present study investigates the concentration dependence of betapep-4 self-association by using 1H-NMR pulsed-field gradient (PFG)-NMR diffusion measurements, and circular dichroism. Downfield chemically shifted alphaH resonances, found to arise o...

Linking sub-individual and supra-individual effects in Daphnia magna exposed to sub-lethal concentration of chlorpyrifos.

Science.gov (United States)

Ferrario, Claudia; Parolini, Marco; De Felice, Beatrice; Villa, Sara; Finizio, Antonio

2018-04-01

The main objective of the present study was to investigate possible links between sub-individual and supra-individual levels (i.e. population level) biomarkers in D. magna exposed to sublethal concentrations of the insecticide chlorpyrifos (CPF). To achieve the aim, 8-day old individuals were exposed for 96 h to two environmentally relevant concentrations of CPF (50 and 250 ng/L). Sub-individual level effects were investigated by measuring the activity of antioxidant (SOD, CAT, and GPx) and detoxifying (GST) enzymes, as well as by measuring the acetylcholinesterase (AChE) inhibition. In addition, the effects at supra-individual level were assessed by using a video-tracking system and analyzing changes in swimming capabilities (i.e. percentage of activity time, distance moved, and velocity). Our data have shown that daphnids exposed to both CPF concentrations were in a condition of stress which was highlighted by changes in both sub- and supra-individual biomarkers. Moreover, our results highlighted that the lowest tested CPF concentration did not modulate the antioxidant and detoxifying enzymes, whereas, an inhibition of AChE and a decrease of some parameters related to swimming behaviour (distance moved and velocity) were noted. On the contrary, significant changes in all the sub-individual biomarkers were measured at the highest tested concentration. In addition, organisms recovered the movement capability (distance moved) and also activate a mechanism of avoidance (increased swimming velocity). On the other hand, a reduction in the percent of active time was measured and this was attributed to the energy spent by organisms to activate antioxidant and detoxifying enzymes and the mechanism of avoidance. Based on these results, our study suggests the existence of a link between sub- and supra-individual levels, as the activation or non-activation in the antioxidant and detoxifying enzymes activities can led to different modifications of the swimming behaviour

L'universo prima del Big Bang cosmologia e teoria delle stringhe

CERN Document Server

Gasperini, Maurizio

2002-01-01

Termini come "universo in espansione", "big bang", "singolarità iniziale" sono ormai entrati a far parte del linguaggio comune. L'idea che l'universo che oggi osserviamo abbia avuto origine da una grossa esplosione (big bang) è ormai ampiamente diffusa e accettata nella moderna cultura popolare, a tutti i libelli. Ma cosa c'era prima del big bang? E ha senso porsi questo interrogativo in un contesto scientifico? I recenti progressi della fisica teoria, e in particolare della cosiddetta teoria delle stringhe, suggeriscono una risposta a questa domanda, fornendo degli strumenti matematici capaci, in linea di principio, di ricostruire la storia dell'universo spingendosi anche oltre l'istante del big bang. Ne emerge un possibile scenario cosmologico nel quale l'universo, anzichè essere "appena nato" al momento del big bang, era piuttosto nel punto di mezzo della sua evoluzione, di durata probabilmente infinita. In questo libro si cerca di illustrare tale scenario usando un linguaggio non troppo tecnico, rivolt...

Tuning of the microstructure, mechanical and tribological properties of a-C:H films by bias voltage of high frequency unipolar pulse

International Nuclear Information System (INIS)

Wang, Jia; Cao, Zhongyue; Pan, Fuping; Wang, Fuguo; Liang, Aimin; Zhang, Junyan

2015-01-01

Highlights: • a-C:H films deposited by high frequency unipolar pulse PECVD. • The film structures can be adjusted by bias voltage. • More graphitic structures form at high bias voltage. • The mechanical and tribological properties are improved by these structures. - Abstract: Amorphous hydrogenated carbon (a-C:H) films were prepared by high frequency unipolar pulse plasma-enhanced chemical vapor deposition in CH 4 , Ar, and H 2 atmosphere with the bias voltage in the range of −800 –−1600 V. The microstructures and mechanical properties of a-C:H films were investigated via high resolution transmission electron microscope (HRTEM), Raman spectroscopy, and Nanoindenter. The results reveal that the curved and straight graphitic microstructures appear in amorphous carbon matrix, and their contents increase obviously with the bias voltage. At the same time, the corresponding hardness decreases and elastic recovery increases, however even in such a case films still possess excellent mechanical properties. According to the tribological property characterization, we believe that the bias voltage also influences their tribological performances significantly, the higher the bias voltage finally gets, the lower the friction coefficient and wear rate occur. These results indicate that the microstructures of a-C:H films can be tuned efficiently by bias voltage and the films with good mechanical and tribological properties can be obtained at a higher range.

Tuning of the microstructure, mechanical and tribological properties of a-C:H films by bias voltage of high frequency unipolar pulse

Energy Technology Data Exchange (ETDEWEB)

Wang, Jia; Cao, Zhongyue; Pan, Fuping [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Fuguo, E-mail: fgwang@licp.cas.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Liang, Aimin [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Zhang, Junyan, E-mail: zhangjunyan@licp.cas.cn [State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000 (China)

2015-11-30

Highlights: • a-C:H films deposited by high frequency unipolar pulse PECVD. • The film structures can be adjusted by bias voltage. • More graphitic structures form at high bias voltage. • The mechanical and tribological properties are improved by these structures. - Abstract: Amorphous hydrogenated carbon (a-C:H) films were prepared by high frequency unipolar pulse plasma-enhanced chemical vapor deposition in CH{sub 4}, Ar, and H{sub 2} atmosphere with the bias voltage in the range of −800 –−1600 V. The microstructures and mechanical properties of a-C:H films were investigated via high resolution transmission electron microscope (HRTEM), Raman spectroscopy, and Nanoindenter. The results reveal that the curved and straight graphitic microstructures appear in amorphous carbon matrix, and their contents increase obviously with the bias voltage. At the same time, the corresponding hardness decreases and elastic recovery increases, however even in such a case films still possess excellent mechanical properties. According to the tribological property characterization, we believe that the bias voltage also influences their tribological performances significantly, the higher the bias voltage finally gets, the lower the friction coefficient and wear rate occur. These results indicate that the microstructures of a-C:H films can be tuned efficiently by bias voltage and the films with good mechanical and tribological properties can be obtained at a higher range.

Structural Insights into the Association of Hif1 with Histones H2A-H2B Dimer and H3-H4 Tetramer.

Science.gov (United States)

Zhang, Mengying; Liu, Hejun; Gao, Yongxiang; Zhu, Zhongliang; Chen, Zijun; Zheng, Peiyi; Xue, Lu; Li, Jixi; Teng, Maikun; Niu, Liwen

2016-10-04

Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production.

Science.gov (United States)

Dong, Miao-Wu; Li, Ming; Chen, Jie; Fu, Tong-Tong; Lin, Ke-Zhi; Ye, Guang-Hua; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao; Yu, Lin-Sheng; Fan, Yan-Yan

2016-04-01

Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages.

Pirenzepine block of ACh-induced mucus secretion in tracheal submucosal gland cells

International Nuclear Information System (INIS)

Farley, J.M.; Dwyer, T.M.

1991-01-01

Muscarinic stimulation of mucus secretion, as measured by the release of [ 3 H]glycoprotein, was studied in explants from the tracheal epithelium of weanling swine. The mucus glycoprotein secretion was transient, ceasing within the first 10 min of a continuous exposure to 100 μM ACh. Increasing the solutions' osmotic pressure did not alter basal mucus glycoprotein secretion. Mucus glycoprotein secretion was inhibited by 2-10 μM PZP, indicting that the M 3 muscarinic receptors mediate cholinergic stimulation of mucus production

La validez prima facie y el principio de derrotabilidad de Las normas jurídicas

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José Víctor García-Yzaguirre

2012-01-01

Full Text Available El presente artículo pretende explorar las implicancias teóricas del concepto prima facie y como este se relaciona con el principio de derrotabilidad, el cual es aplicable para justificar el incumplimiento de un deber jurídico a causa del acatamiento de otro en un contexto en el que ambos son incom- patibles entre sí. Partiremos desde su sustento conceptual analizando cuál es el rol y la importancia del contexto en el razonamiento jurídico hasta arribar a pautas concretas de cómo opera en la práctica judicial ofreciendo algunos ejemplos hipotéticos y jurisprudenciales.

Study of fuel element characteristic of SM and SMP (SM-PRIMA) fuel assemblies

International Nuclear Information System (INIS)

Klinov, A.V.; Kuprienko, V.A.; Lebedev, V.A.; Makhin, V.M.; Tuchnin, L.M.; Tsykanov, V.A.

1999-01-01

The paper discusses the techniques and results of reactor tests and post-reactor investigations of the SM reactor fuel elements and fuel elements developed in the process of designing the specialized PRIMA test reactor with the SM reactor fuel elements used as a prototype and which are referred to as the SMP fuel elements. The behavior of fuel elements under normal operating conditions and under deviation from normal operating conditions was studied to verify the calculation techniques, to check the calculation results during preparation of the SM reactor safety substantiation report and to estimate the possibility of using such fuel elements in other projects. During tests of fuel rods under deviation from normal operating conditions their advantages were shown over fuel elements, the components of which were produced using the Al-based alloys. (author)

Crystallization and preliminary x-ray crystallography data of the dimer of tetramer s (abcd)2 of extracellular hemoglobin from Glossoscolex paulistus in cyano met form

International Nuclear Information System (INIS)

Ferreira, Frederico M.; Oliveira, Paulo S.L. de; Oliva, Glaucius

1996-01-01

Full text. The extracellular hemoglobin from Glossoscolex paulistus has a molecular weight near to 3.1 x 10 6 Da and a structure organized in a double-layered hexagonal oligomer. The tertiary complex of dimer of tetramers (abcd) 2 was obtained by chromography in Sephadex G-200, in pH 9.0, as a result of alkaline dissociation. Aiming to obtain a better understanding of the oligomeric structure and specially for the inter subunit interactions the extracellular hemoglobins, we have obtained crystals of dimer of tetramers (abcd) 2 of hemoglobin from Glossoscolex and we are studying the in behavior in different conditions of precipitants and pH's. Our goal is to solve the crystal structure in order to characterize, at atomic level, the subunits contacts, heme environment and differences in residues involved in oxygenation in order to understand in this hemoglobin. The crystallization experiments the protein concentration in the cyanomet form was about 10 mg/ml and the experiments were carried out at 18 0 C. The optimal crystallization condition achieved from factorial assays was 10% (w/v). Polyethylene glycol (PEG) 8,000 and 8%(v/v) ethylene glycol in 100 mM HEPES pH 7.5. The optimization of this condition was carried out with the variation of PEG concentrations from 6% up to 10% (by 1% step) and pH between 7.0 and 8.0. A quite critical p-H-dependence has been observed on crystal nucleation, decreasing from pH 7.0, in which the number of microcrystals in higher, up to pH 8.0, in which crystals did not appear even at higher PEG 8,000 (10% w/v). As several structures of hemoglobin from different sources (vertebrate and invertebrates) are available, we hope to solve their structure of hemoglobin from Glossoscolex paulistus by Molecular Replacement, even though the tetramer organization may be different in the earthworm as compared related to other known tetrameric hemoglobin structures. (author)

Role of ERK signaling pathway in up-regulation of γ-AChR during development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats%ERK信号通路在烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时γ-AChR上调中的作用

Institute of Scientific and Technical Information of China (English)

靳天; 王宏; 吴进; 李士通

2016-01-01

Objective To evaluate the role of ERK signaling pathway in up-regulation of fetal gamma-acetylcholine receptor (μ-AChR) during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.Methods Thirty adult male SPF Sprague-Dawley rats,weighing 230-250 g,aged 9-10 weeks,were randomly divided into 3 groups (n=10 each) using a random number table:control group (C group),burn group (B group) and ERK1/2 inhibitor U0126 group (U group).The surface area of bilateral hindlimbs was shaved,and the tibialis anterior muscle of the right hiudlimb was exposed to 95 ℃ copper for 12 s in anesthetized rats.At 1.5 h after burn,15 mg/kg U0126 was injected intraperitoneally in group U,and the equal volume of dimethyl sulfoxide was given in C and B groups.The tibialis anterior muscle was obtained on 7th day after establishment of the model for determination of the expression of μ-AChR and adult epsilon-AChR (ε-AChR) mRNA in skeletal muscle cells using real-time polymerase chain reaction.The concentration-effect curve of rocuronium was drawn using muscular tension experiment,and the half inhibitory concentration (IC50) and 95％ confidence interval were calculated.Resuits Compared with group C,the expression of μ-AChR mRNA in skeletal muscle cells was significantly up-regulated,and the IC50 was significantly increased in group B (P＜0.05).Compared with group B,the expression of γ-AChR mRNA in skeletal muscle cells was significantly down-regulated,and the IC50 was significantly decreased in group U (P＜0.05).There was no significant difference in the expression of ε-AChR in skeletal muscle cells between the three groups (P＞0.05).Conclusion Up-regulation of μ,-AChR is dependent on activation of ERK signaling pathway during the development of resistance to non-depolarizing muscular relaxants in skeletal muscles of burned rats.%目的 评价细胞外信号调节激酶(ERK)信号通路在烧伤大鼠骨骼肌对非去极化肌松药抵抗形成时胎儿型乙酰胆碱受体(γ-ACh

Kinetics of Hydrocarbon formation in a-C:H Film deposition plasmas

International Nuclear Information System (INIS)

Cal, E. de la; Tabares, F. L.

1993-01-01

The formation of C2 and Cp hydrocarbons during the PACVD of a-C:H films from admixtures of methane with H2 and He has been investigated by mass spectrometry under several deposition condition. The time evolution of the observed species indicates that the formation mechanisms of ethylene and acetylene are sensitive to the conditions of the wall during the growing of the film. Acetylene are sensitive to the conditions of the wall during the growing of the film. Acetylene formation was found to be directly related to the formation of the film on top of the carburized metal. (Author) 12 refs

Analysis of the effect on growth kinetics of gamma prima phase in Inconel 713C alloys

International Nuclear Information System (INIS)

Thorp, S.I.; Versaci, R.A.; Ges, A.; Palacio, H.A.

1993-01-01

This work shows the analysis of the effect on growth kinetics of gamma prima phase in Inconel 713C alloy of two thermic treatments. In this study, SEM are used and the results are analyzed by means of the theory developed by Lifshitz, Slyozov and Wagner (LSW theory). The findings have revealed that with such theory it is not possible to determine if the process of growth is controlled either through diffusion or through diffusion in the interface as to the time employed in the experiment (2600 hours); the time required is approximately 10000 hours. (Author)

Anti-allergic role of cholinergic neuronal pathway via α7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model.

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Takeshi Yamamoto

Full Text Available The prevalence of food allergy (FA has increased in developed countries over the past few decades. However, no effective drug therapies are currently available. Therefore, we investigated cholinergic anti-inflammatory pathway as a regulatory system to ameliorate disrupted mucosal immune homeostasis in the gut based on the pathophysiological elucidation of mucosal mast cells (MMCs in a murine FA model. BALB/c mice sensitized with ovalbumin received repeated oral ovalbumin for the development of FA. FA mice developed severe allergic diarrhea and exhibited enhanced type 2 helper T (Th2 cell immune responses in both systemic immunity and mucosal immunity, along with MMCs hyperplasia in the colon. MMCs were localized primarily in the strategic position of the mucosal epithelium. Furthermore, the allergic symptoms did not develop in p85α disrupted phosphoinositide-3 kinase-deficient mice that lacked mast cells in the gut. Vagal stimulation by 2-deoxy-D-glucose and drug treatment with nicotinic ACh receptor (nAChR agonists (nicotine and α7 nAChR agonist GTS-21 alleviated the allergic symptoms in the FA mice. Nicotine treatment suppressed MMCs hyperplasia, enhanced MPO and upregulated mRNA expression of Th1 and Th2 cytokines in the FA mice colon. MMCs, which are negatively regulated by α7 nAChRs, were often located in close proximity to cholinergic CGRP-immunoreactive nerve fibers in the FA mice colon. The present results reveal that the cholinergic neuroimmune interaction via α7 nAChRs on MMCs is largely involved in maintaining intestinal immune homeostasis and can be a target for a new therapy against mucosal immune diseases with homeostatic disturbances such as FA.

Application of a coherent risk measure in the price calculation of an income insurance (annuities = Aplicación de una medida de riesgo coherente para el cálculo de la prima de riesgo en un seguro de rentas

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Montserrat Hernández Solís

2013-12-01

Full Text Available Una práctica común que realizan las entidades aseguradoras es la de modificar las tasas de mortalidad instantánea al aplicar el principio de prima neta con el fin de hacer frente a las desviaciones desfavorables de la siniestralidad. Este documento proporciona una respuesta matemática a esta cuestión mediante la aplicación de la función de distorsión de potencia de Wang. Tanto la prima neta y la función de distorsión de Wang son medidas de riesgo coherentes, siendo este último aplicado por primera vez en el campo delos seguros de vida.Utilizando las leyes de Gompertz y Makeham primero calculamos la prima a nivel general y en una segunda parte, se aplica el principio de cálculo de la prima basado en función de distorsión de potencia de Wang para calcular el recargo sobre la prima de riesgo ajustada. El precio de prima única de riesgo se ha aplicado a una forma de cobertura de seguro de supervivencia, el seguro de rentas.La principal conclusión que puede extraerse es que mediante el uso de la función de distorsión, la nueva tasa instantánea de mortalidad es directamente proporcional a un múltiplo, que es justamente el exponente de esta función y hace que el riesgo de longevidad sea mayor. Esta es la razón por la prima de riesgo ajustada es superior a la prima neta.Modification of instantaneous mortality rates when applying the net premium principle in order to cope with unfavorable deviations in claims, is common practice carried out by insurance companies. This paper provides a mathematical answer to this matter by applying Wang’s power distortion function. Both net premium and Wang’s distortion function are coherent risk measures, the latter being first applied to the field of life insurance.Using the Gompertz and Makeham laws we first calculate the premium at a general level and in a second part, the principle of premium calculation based on Wang´s power distortion function is applied to calculate the adjusted risk

Developmental exposure to chlorpyrifos alters reactivity to environmental and social cues in adolescent mice

International Nuclear Information System (INIS)

Ricceri, Laura; Markina, Nadja; Valanzano, Angela; Fortuna, Stefano; Cometa, Maria Francesca; Meneguz, Annarita; Calamandrei, Gemma

2003-01-01

Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G 4 (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF

Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

Science.gov (United States)

McCoy, Portia; Norton, Thomas T; McMahon, Lori L

2008-07-01

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

Immunocytochemical localization of choline acetyltransferase and muscarinic ACh receptors in the antenna during development of the sphinx moth Manduca sexta.

Science.gov (United States)

Clark, Julie; Meisner, Shannon; Torkkeli, Päivi H

2005-04-01

Immunocytochemistry with monoclonal antibodies was used to investigate the locations of muscarinic acetylcholine receptors (mAChR) and choline acetyltransferase (ChAT) in sections of the developing antennae of the moth Manduca sexta. The results were correlated with a previous morphological investigation in the developing antennae which allowed us to locate different cell types at various stages of development. Our findings indicated that the muscarinic cholinergic system was not restricted to the sensory neurons but was also present in glial and epidermal cells. By day 4-5 of adult development, immunoreactivity against both antibodies was present in the axons of the antennal nerve, and more intense labeling was present in sections from older pupae. At days 4-9, the cell bodies of the sensory neurons in the basal part of the epidermis were also intensely immunolabeled by the anti-mAChR antibody. In mature flagella, large numbers of cells, some with processes into hairs, were strongly labeled by both antibodies. Antennal glial cells were intensely immunolabeled with both antibodies by days 4-5, but in later stages, it was not possible to discriminate between glial and neural staining. At days 4-9, we observed a distinctly labeled layer of epidermal cells close to the developing cuticle. The expression of both ChAT and mAChRs by neurons in moth antennae may allow the regulation of excitability by endogenous ACh. Cholinergic communication between neurons and glia may be part of the system that guides axon elongation during development. The cholinergic system in the apical part of the developing epidermis could be involved in cuticle formation.

Tort recovery of acid rain damages in the United States--observations on plaintiff's prima facie case

Energy Technology Data Exchange (ETDEWEB)

Honabach, D.R.

1982-01-01

Common law tort doctrine has long supplied a judicially administered vehicle for dealing with harms suffered by one party as a result of the activities of another. As such, it might be used to address the problem of acid rain. Before tort law may be used, however, a would-be plaintiff must make out a prima facie case. While traditional applications of tort doctrine might effectively prevent plaintiff from doing so, recent court decisions suggest that plaintiff might nevertheless be successful in obtaining at least partial recovery.

Interfacial reactions between indium tin oxide and triphenylamine tetramer layers induced by photoirradiation

International Nuclear Information System (INIS)

Satoh, Toshikazu; Fujikawa, Hisayoshi; Yamamoto, Ichiro; Murasaki, Takanori; Kato, Yoshifumi

2008-01-01

The effects of photoirradiation on the interfacial chemical reactions between indium tin oxide (ITO) films and layers of triphenylamine tetramer (TPTE) were investigated by using in situ x-ray photoelectron spectroscopy (XPS). Thin TPTE layers deposited onto sputter-deposited ITO films were irradiated with violet light-emitting diodes (peak wavelength: 380 nm). Shifts in the peak positions of spectral components that originated in the organic layer toward the higher binding-energy side were observed in the XPS profiles during the early stages of irradiation. No further peak shifts were observed after additional irradiation. An increase in the ratio of the organic component in the O 1s spectra was also observed during the photoirradiation. The ratio of the organic component increased in proportion to the cube root of the irradiation time. These results suggest that photoirradiation induces an increase in the height of the carrier injection barrier at the interface between TPTE and ITO in the early stages of the irradiation, possibly due to the rapid diffusion controlled formation and growth of an oxidized TPTE layer, which is considered to act as a high resistance layer

[Sulfatide-loaded CD1d tetramer to detect typeII NKT cells in mice].

Science.gov (United States)

Zhang, Gu-qin; Nie, Han-xiang; Yang, Jiong; Yu, Hong-ying

2012-07-01

To create a method of detecting typeII natural killer T (NKT) cells of mice. Biotinylated mouse CD1d monomers were mixed with sulfatide at a molar ratio of 1:3 (protein:lipid) and incubated at room temperature overnight, and then 80 μg of streptavidin-PE was added into 200 μg of the CD1d-sulfatide mixture and incubated at room temperature for 4 h to get sulfatide/CD1d tetramer. Flow cytometry was used to detect the percentage of typeII NKT cells in mononuclear cells (MNCs) of lung and spleen of normal mice, as well as the percentage of typeII NKT cells in spleen MNCs of mice after stimulated with sulfatide. In normal mice, the percentage of typeII NKT cells accounted for (0.875±0.096)% and (1.175±0.263)% in MNCs of spleen and lung; the percentage in spleen MNCs after activated with sulfatide was (2.75±0.603)%, which significantly increased as compared with that in normal mice (PNKT cells in mice.

Structure of a designed, right-handed coiled-coil tetramer containing all biological amino acids.

Science.gov (United States)

Sales, Mark; Plecs, Joseph J; Holton, James M; Alber, Tom

2007-10-01

The previous design of an unprecedented family of two-, three-, and four-helical, right-handed coiled coils utilized nonbiological amino acids to efficiently pack spaces in the oligomer cores. Here we show that a stable, right-handed parallel tetrameric coiled coil, called RH4B, can be designed entirely using biological amino acids. The X-ray crystal structure of RH4B was determined to 1.1 Angstrom resolution using a designed metal binding site to coordinate a single Yb(2+) ion per 33-amino acid polypeptide chain. The resulting experimental phases were particularly accurate, and the experimental electron density map provided an especially clear, unbiased view of the molecule. The RH4B structure closely matched the design, with equivalent core rotamers and an overall root-mean-square deviation for the N-terminal repeat of the tetramer of 0.24 Angstrom. The clarity and resolution of the electron density map, however, revealed alternate rotamers and structural differences between the three sequence repeats in the molecule. These results suggest that the RH4B structure populates an unanticipated variety of structures.

Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens.

Science.gov (United States)

Magarinos, Natalia J; Bryant, Katherine J; Fosang, Amanda J; Adachi, Roberto; Stevens, Richard L; McNeil, H Patrick

2013-08-01

Mouse mast cell protease (mMCP)-6-null C57BL/6 mice lost less aggrecan proteoglycan from the extracellular matrix of their articular cartilage during inflammatory arthritis than wild-type (WT) C57BL/6 mice, suggesting that this mast cell (MC)-specific mouse tryptase plays prominent roles in articular cartilage catabolism. We used ex vivo mouse femoral head explants to determine how mMCP-6 and its human ortholog hTryptase-β mediate aggrecanolysis. Exposure of the explants to recombinant hTryptase-β, recombinant mMCP-6, or lysates harvested from WT mouse peritoneal MCs (PMCs) significantly increased the levels of enzymatically active matrix metalloproteinases (MMP) in cartilage and significantly induced aggrecan loss into the conditioned media, relative to replicate explants exposed to medium alone or lysates collected from mMCP-6-null PMCs. Treatment of cartilage explants with tetramer-forming tryptases generated aggrecan fragments that contained C-terminal DIPEN and N-terminal FFGVG neoepitopes, consistent with MMP-dependent aggrecanolysis. In support of these data, hTryptase-β was unable to induce aggrecan release from the femoral head explants obtained from Chloe mice that resist MMP cleavage at the DIPEN↓FFGVG site in the interglobular domain of aggrecan. In addition, the abilities of mMCP-6-containing lysates from WT PMCs to induce aggrecanolysis were prevented by inhibitors of MMP-3 and MMP-13. Finally, recombinant hTryptase-β was able to activate latent pro-MMP-3 and pro-MMP-13 in vitro. The accumulated data suggest that human and mouse tetramer-forming tryptases are MMP convertases that mediate cartilage damage and the proteolytic loss of aggrecan proteoglycans in arthritis, in part, by activating the zymogen forms of MMP-3 and MMP-13, which are constitutively present in articular cartilage.

Sensibilidade à secagem da matéria-prima cerâmica da Formação Corumbataí na região do Polo Cerâmico de Santa Gertrudes, SP

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A. A. Azzi

2015-06-01

Full Text Available As argilas provenientes da Formação Corumbataí são atualmente a principal fonte de matéria-prima para as indústrias do Polo Cerâmico de Santa Gertrudes. 73% das indústrias desse polo que utilizam o processo de secagem via seca são hoje alvo de crescente pressão dos órgãos de controle ambiental devido à emissão de partículas (poeira associado ao processo de secagem da matéria-prima. Neste trabalho, foram realizados quatro diferentes testes de secagem em três tipos de matéria-prima (D, I e M da Formação Corumbataí, com umidades naturais iniciais de 8%, 18% e 19%, respectivamente, para poder avaliar a sensibilidade à secagem. Dentre os testes analisados neste trabalho estão o processo natural de secagem ao sol, secagem ao vento, secagem ao sol combinado a uma corrente de vento, e secagem ao sol com matéria-prima previamente umedecida em água corrente. Os testes foram ainda correlacionados à análise termogravimétrica. A análise por difração de raios X, juntamente com as análises química e petrográfica mostrou que as amostras D, I e M contêm predominantemente filossilicatos 2:1 como illitas (25-30% e esmectitas (15-25%, e em menor quantidade caulinita (0-15% e clorita (0-5%. Os resultados dos experimentos de secagem associados à mineralogia mostram que entre 100 °C e 200 °C nos gráficos de termogravimetria pode indicar de modo rápido a sensibilidade à secagem que o material apresenta, uma vez que a maior perda de umidade obtida nesta faixa indica a maior quantidade de minerais do grupo das esmectitas, que por sua vez conferem ao material menor sensibilidade à secagem. Além disso, os procedimentos de secagem natural sugerem que secar separadamente a matéria-prima pode resultar em maior eficiência do processo de secagem.

Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays

Science.gov (United States)

Iorio, Raffaele; Fryer, James P.; Hinson, Shannon R.; Fallier-Becker, Petra; Wolburg, Hartwig; Pittock, Sean J.; Lennon, Vanda A.

2012-01-01

The principal central nervous system (CNS) water channel, aquaporin-4 (AQP4), is confined to astrocytic and ependymal membranes and is the target of a pathogenic autoantibody, neuromyelitis optica (NMO)-IgG. This disease-specific autoantibody unifies a spectrum of relapsing CNS autoimmune inflammatory disorders of which NMO exemplifies the classic phenotype. Multiple sclerosis and other immune-mediated demyelinating disorders of the CNS lack a distinctive biomarker. Two AQP4 isoforms, M1 and M23, exist as homotetrameric and heterotetrameric intramembranous particles (IMPs). Orthogonal arrays of predominantly M23 particles (OAPs) are an ultrastructural characteristic of astrocytic membranes. We used high-titered serum from 32 AQP4-IgG-seropositive patients and 85 controls to investigate the nature and molecular location of AQP4 epitopes that bind NMO-IgG, and the influence of supramolecular structure. NMO-IgG bound to denatured AQP4 monomers (68% of cases), to native tetramers and high order arrays (90% of cases), and to AQP4 in live cell membranes (100% of cases). Disease-specific epitopes reside in extracellular loop C more than in loops A or E. IgG binding to intracellular epitopes lacks disease specificity. These observations predict greater disease specificity and sensitivity for tissue-based and cell-based serological assays employing “native” AQP4 than assays employing denatured AQP4 and fragments. NMO-IgG binds most avidly to plasma membrane surface AQP4 epitopes formed by loop interactions within tetramers and by intermolecular interactions within high order structures. The relative abundance and localization of AQP4 high order arrays in distinct CNS regions may explain the variability in clinical phenotype of NMO spectrum disorders. PMID:22906356

Chemopreventive Effects of the p53-Modulating Agents CP-31398 and Prima-1 in Tobacco Carcinogen-Induced Lung Tumorigenesis in A/J Mice

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Chinthalapally V. Rao

2013-09-01

Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Expression of the p53 tumor suppressor protein is frequently altered in tobacco-associated lung cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP-31398 and Prima-1, on 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week-old mice were treated with a single dose of NNK (10 µmol/mouse by intraperitoneal injection and, 3 weeks later, were randomized to mice fed a control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or 300 ppm Prima-1 for either 17 weeks (10 mice/group or 34 weeks (15 mice/group to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001 lung adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%, respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly suppressed (P < .0001 lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks. Importantly, these results suggest that both p53 modulators cause a delay in the progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung tumors from mice exposed to p53-modulating agents showed a significantly reduced tumor cell proliferation and increased accumulation of wild-type p53 in the nucleus. An increase in p21- and apoptotic-positive cells was also observed in lung tumors of mice exposed to p53-modulating agents. These results support a chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung adenocarcinoma formation.

Aplicación de una medida de riesgo coherente para el cálculo de la prima de riesgo en un seguro de rentas = Application of a coherent risk measure in the price calculation of an income insurance (annuities

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Montserrat Hernández Solís

2014-07-01

Full Text Available Resumen Una práctica común que realizan las entidades aseguradoras es la de modificar las tasas de mortalidad instantánea al aplicar el principio de prima neta con el fin de hacer frente a las desviaciones desfavorables de la siniestralidad. Este documento proporciona una respuesta matemática a esta cuestión mediante la aplicación de la función de distorsión de potencia de Wang. Tanto la prima neta y la función de distorsión de Wang son medidas de riesgo coherentes, siendo este último aplicado por primera vez en el campo delos seguros de vida. Utilizando las leyes de Gompertz y Makeham primero calculamos la prima a nivel general y en una segunda parte, se aplica el principio de cálculo de la prima basado en función de distorsión de potencia de Wang para calcular el recargo sobre la prima de riesgo ajustada. El precio de prima única de riesgo se ha aplicado a una forma de cobertura de seguro de supervivencia, el seguro de rentas. La principal conclusión que puede extraerse es que mediante el uso de la función de distorsión, la nueva tasa instantánea de mortalidad es directamente proporcional a un múltiplo, que es justamente el exponente de esta función y hace que el riesgo de longevidad sea mayor. Esta es la razón por la prima de riesgo ajustada es superior a la prima neta. Abstract Modification of instantaneous mortality rates when applying the net premium principle in order to cope with unfavorable deviations in claims, is common practice carried out by insurance companies. This paper provides a mathematical answer to this matter by applying Wang’s power distortion function. Both net premium and Wang’s distortion function are coherent risk measures, the latter being first applied to the field of life insurance. Using the Gompertz and Makeham laws we first calculate the premium at a general level and in a second part, the principle of premium calculation based on Wang´s power distortion function is applied to calculate

EFEKTIVITAS METODE ROLE PLAYING PADA MENDESKRIPSIKAN PELAYANAN PRIMA UNTUK MENINGKATKAN HASIL BELAJAR

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Indah Tri Lestari

2013-02-01

Full Text Available Tujuan dari penelitian ini adalah untuk mengetahui efektivitas metode pembelajaran role playing pada pokok bahasan mendeskripsikan pelayanan prima untuk meningkatkan hasil belajar siswa kelas X Administrasi Perkantoran SMK Hidayah Semarang. Subjek penelitian ini adalah siswa kelas X AP SMK Hidayah Semarang Tahun Ajaran 2011/2012. Prosedur penelitian ini merupakan siklus kegiatan pembelajaran yang terdiri dari dua siklus, dimana setiap siklus meliputi perencanaan, pelaksanaan tindakan, pengamatan dan refleksi. Instrumen pengumpulan data dalam penelitian ini adalah tes evaluasi yang berupa tes objektif pada tiap akhir siklus dan lembar observasi untuk aktivitas siswa dan kinerja guru. Hasil belajar kognitif siswa pada siklus I sebesar 74,5 dengan ketuntasan klasikal 66,7%. Rata-rata hasil belajar siklus II sebesar 82,5 dengan ketuntasan klasikal 96,7%. Adapun sikap siswa terhadap pembelajaran pada siklus I sebesar 55% dan pada siklus II mencapai peningkatan sebesar 87,5%. Sedangkan kinerja guru pada siklus I mencapai 58,3% dan pada siklus II meningkat menjadi 93,1%. Penerapan metode pembelajaran role playing pada pokok bahasan mendeskripsikan pelayanan prima efektif untuk meningkatkan hasil belajar siswa kelas X Administrasi Perkantoran SMK Hidayah Semarang. Abstract ___________________________________________________________________ The purpose from this research was to determine effectiveness of role playing in describing excellent service to improve students� result class X AP Hidayah Vocational School of Semarang year 2011/2012. The subject of this research is the class X AP of Hidayah Vocational School of Semarang year 2011/2012. The procedure of this research is a cycle of learning activities that consists of two cycles, in which each cycle includes planning, implementation of the action, observation and reflection. Instrument of data collection is the evaluation tests in the form of objective tests at each end of the cycle and observation

The nervus terminalis in the chick: a FMRFamide-immunoreactive and AChE-positive nerve.

Science.gov (United States)

Wirsig-Wiechmann, C R

1990-07-16

The chick terminal nerve (TN) was examined by immunocytochemical and histochemical methods. Molluscan cardioexcitatory peptide-immunoreactive (FMRFamide-ir) and acetylcholinesterase (AChE)-positive TN perikarya and fibers were distributed along olfactory and trigeminal nerves. FMRFamide-ir TN fibers terminated in the olfactory lamina propria and epithelium and in ganglia along the rostroventral nasal septum. This initial description of several populations of avian TN neurons should provide the foundation for future developmental studies of this system.

Utilización de una nueva materia prima borácica para la formulación de esmaltes

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Gómez-Tena, M. P.

2010-10-01

contenido en B₂O₃ entre un 10-11 % en peso. Es en gran parte amorfo, siendo el cuarzo la fase cristalina presente de forma mayoritaria. Características tales, como presentar una baja solubilidad y formar fácilmente fase vítrea, hace que sea posible utilizar el nuevo borato, como materia prima en composiciones de esmalte. Su aptitud para la formulación de esmaltes, ha sido el resultado de varios años de investigación en colaboración con el Instituto de Tecnología Cerámica. En este trabajo se ha estudiado la viabilidad de fabricar esmaltes cerámicos haciendo uso de una nueva materia prima borácica sintética, la cual permite aportar boro a la composición de los esmaltes sin necesidad de hacerlo en forma fritada. Se ha podido obtener vidriados con similares características técnicas y estéticas que los obtenidos a partir de esmaltes de uso industrial que contienen fritas típicas en su composición, por lo que resulta posible formular esmaltes mediante el empleo de la nueva materia prima de boro sintética. De los resultados se deriva, que la utilización de esta nueva materia prima (E-4972 es especialmente adecuada para la obtención de vidriados de bajo brillo a elevada temperatura.

Pengaruh Jenis Nasabah dan Frekuensi Pencairan Pembiayaan terhadap Profit Margin di Bank Pembiayaan Rakyat Syariah (BPRS Sarana Prima Mandiri Pamekasan

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Sundari Aniga

2016-06-01

Full Text Available Bank is a financial institution whose main activities to collect funds and distribute funds to the community. Factors that very influence in the bank's success in obtaining profit is by increasing the disbursement frequency of financing and client’s types as one of the factors that influence the amount of profit margin obtained bank. Based on that, then there are two problems who became a study principal in this research as follows: first: Is there any influence of customer type and financing liquefaction frequency towards Profit Margin in BPRS Sarana Prima Mandiri Pamekasan; second, which is the most influential variable on the Profit Margin in BPRS Sarana Prima Mandiri Pamekasan. This Research uses a quantitative approach with research type is multiple linear regression. The amount of data used in this research as many as 20 data taken from published reports of Quarterly Bank Indonesia and published reports BPRS Sarana Prima Mandiri in January 2011 until December 2015. The research results of T Test of the respective T count X1 amounted to 3.184 and variable X2 amounted to 2.475 and T table amounted to 2.101, (X1 = 3.184> 2.101 and X2 = 2.475> 2.101, it can be concluded the results of the partial test (T test shows that all variables X (Customer type and financing liquefaction frequency effect on variable Y (Profit Margin partially significantly ≤ 0.05 X1 (Customer type greater influence than X2 (financing liquefaction frequency T count X1 greater  exceeds X2. Equation Y = ( -16.387 0.399X1 + 0186 + X2 + e, based on multiple regression analysis, the regression coefficient obtained shows, customer type (b1 = 0.399 become the largest independent variables that influence Profit Margin (Y. While base testing the determinant coefficient using the program SPSS acquired adjusted R2 amounted to 0.732 or 73.2% means variable of Customer Type Financing and financing liquefaction frequency affect toward the profit margin amounted to 73.2% while the

Intent v. Impact: The Standard of Proof Necessary to Establish a Prima Facie Case of Race Discrimination under 42 U.S.C. Section 1981.

Science.gov (United States)

Heiser, Walter

1979-01-01

Considers action's impact and intent as proof; analyzes language, purpose, and legislative history of civil rights statutes; and concludes that the Supreme Court will likely require proof of intent to sustain a prima facie case of discrimination. Available from San Diego Law Review Association, University of San Diego School of Law, San Diego,…

Density functional and ab initio study of the tautomeric forms of 3-acetyl tetronic and 3-acetyl tetramic acids

International Nuclear Information System (INIS)

Skylaris, Chris-Kriton; Igglessi-Markopoulou, Olga; Detsi, Anastasia; Markopoulos, John

2003-01-01

We propose all the accessible paths of interconversion between the tautomers of 3-acetyl tetronic and 3-acetyl tetramic acids by performing calculations with the density functional B3LYP method and the ab initio MP2 method. Our findings clarify at the atomic level the mechanisms of the equilibria between these tautomers, a topic so far only partially understood on the basis of studies by nuclear magnetic resonance (NMR) spectroscopy. We show that thermal effects via relative Gibbs free energies ΔG must be taken into account in order to reach good quantitative agreement with the available experimental information on the ratios of the most stable tautomers. The calculated 1 H and 13 C chemical shifts are in agreement with the experimental values from NMR spectroscopy

Evidence for new resonances in the K-barN system: A prima facie case for the even-wave harmonic-oscillator model

International Nuclear Information System (INIS)

Kamath, S.G.

1978-01-01

Arguments are presented to show that the new resonance parameters obtained by Alston-Garnjost et al. in a recent analysis of the K-barN system from 365 to 1320 MeV/c provide a prima facie case for the even-wave harmonic-oscillator theory of baryonic states in the framework of SU(6)/sub W/ x O(3). A new quantum classification of the Λ states belonging to the (70,1 - ) is also proposed

Classification and regression tree (CART) analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria

Science.gov (United States)

Dyer, Betsey D.; Kahn, Michael J.; LeBlanc, Mark D.

2008-01-01

Classification and regression tree (CART) analysis was applied to genome-wide tetranucleotide frequencies (genomic signatures) of 195 archaea and bacteria. Although genomic signatures have typically been used to classify evolutionary divergence, in this study, convergent evolution was the focus. Temperature optima for most of the organisms examined could be distinguished by CART analyses of tetranucleotide frequencies. This suggests that pervasive (nonlinear) qualities of genomes may reflect certain environmental conditions (such as temperature) in which those genomes evolved. The predominant use of GAGA and AGGA as the discriminating tetramers in CART models suggests that purine-loading and codon biases of thermophiles may explain some of the results. PMID:19054742

热应激复合敌敌畏中毒对小鼠全血乙酰胆碱脂酶和组织抗氧化能力的影响%Effects of heat stress with organophosphorus pesticide intoxication on blood AChE activity and tissue anti-oxidation ability in mice

Institute of Scientific and Technical Information of China (English)

蔡颖; 谢首佳; 赵远鹏; 董兆君; 邹仲敏

2012-01-01

Objective To explore the combined effect of heat stress with organophosphorus O , O-dimethyl-O-2, 2-di-chlorovinylphosphate (DDVP) intoxication on blood acetyl choli nest erase (AChE) activity and tissue lipid peroxidation. Methods Fifty-four mice were randomly divided into control group , heat stress group and heat stress combined with DDVP poisoning group (the combined group). Mice were put into experiment chamber with (60 ±5)% relative humidity. The chamber temperature was 24℃ for control group , and 38 or 40℃; for heat stress group. One hour later, mice in combined group were intraperitoneally given 9 or 15 mg/kg DDVP. Saline of an equal volume was applied to control and heat stress groups. After 30 minutes, the mice were sacrificed and samples of the blood , heart, brain, and liver were collected. Blood AChE activity, tissue SOD activity, MDA content and · OH inhibiting ability in tissue homogenates of the brain , heart and liver were determined respectively. Results Mice became agitated and restless with increased activity when exposed to 38 or 40℃ ambient temperature. Water intake and body mass were decreased . Compared with temperature-matched controls, the heat exposure combined with DDVP poisoning at 38 or 40℃ caused significant decline of blood AChE activity , tissue SOD activity and · OH inhibiting ability, and increase of tissue MDA content in the brain , heart and liver ( P < 0. 05 ). Heat stress and organophosphorus pesticide intoxication showed synergistic interaction between the above parameters . Conclusion Under present experimental conditions , both ambient temperature and organophosphorus poisoning can significant -ly suppress the blood AChE activity while causing enhanced tissue lipid peroxidation . These data suggest that oxidative stress plays a role in the aggregative effect of organophosphorus intoxication under high ambient temperature .%目的 研究热应激复合有机磷敌敌畏(O,O-dimethyl-O-2,2-dichlorovinylphosphate

Avaliação da aplicação do processo de hidroesterificação na produção de biodiesel a partir de matérias-primas de baixa qualidade

OpenAIRE

Santos, Letícia Karen dos [UNESP

2016-01-01

A produção de biodiesel a partir de Óleos e Gorduras Residuais (OGR), óleos brutos e outras matérias-primas com acidez elevada e alto teor de umidade, tem se tornado um desafio para a cadeia produtiva de biodiesel. Neste cenário surge como alternativa a hidroesterificação, processo que envolve duas etapas consecutivas: a hidrólise térmica seguida de esterificação o que permite o uso de qualquer matéria-prima graxa. Neste estudo foi avaliada a produção de biodiesel por hidroesterificação de ól...

Evaluación de distintas materias primas para la producción de almácigo de tomate

OpenAIRE

Fernando Richmond

2010-01-01

Se evaluaron mezclas de materias primas naturales en diferentes proporciones y en el siguiente orden: fibra de coco (Cocos nucifera), aserrín de melina (Gmelina arborea) y abono orgánico Coope Victoria, para utilizarlos como sustrato en la etapa de almácigo de tomate híbrido FBM-17. Se hicieron mezclas entre sí de fibra de coco y aserrín de melina en diferentes proporciones (30%, 40% y 50% de cada material), para un total de 9 tratamientos; el abono orgánico se agregó para completar el 100%. ...

Gres porcelánico esmaltado producido por vía seca: materias primas fundentes

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Boschi, A. O.

2012-04-01

densificación y, por consiguiente, determinan la temperatura de cocción y la deformación piroplástica. Los agentes fundentes que se usan habitualmente en las composiciones de gres porcelánico son: feldespatos, filitas (usadas en Brasil y nefelinas. Estas materias primas no son solubles al agua, lo que las hace particularmente adecuadas para las composiciones de gres porcelánico tradicional producido por vía húmeda. Sin embargo, existe un gran grupo de materias primas solubles que también tienen un gran potencial como fundentes y que podrían utilizarse en los procesos de vía seca. En este contexto, el objetivo de este trabajo ha sido determinar el potencial fundente de las materias primas solubles al agua, o parcialmente solubles al agua, en una composición de gres porcelánico. La efectividad de varios boratos, es decir, la colemanita, la ulexita, la hidroboracita, así como el carbonato sódico, fueron ensayados en un estudio de tipo comparativo. Los resultados de este estudio indican que la incorporación de pequeñas cantidades de estos fundentes es suficiente para reducir la temperatura de cocción de forma importante, sin causar una alta deformación piroplástica de los soportes. Los mejores resultados se obtuvieron con las composiciones que contenían hidroboracita. Este resultado es especialmente relevante para la creación de composiciones alternativas de piezas de gres porcelánico producidas por vía seca. El proceso de vía seca es, en la actualidad, un tema de especial interés, debido a las cuestiones medioambientales y económicas.

The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

DEFF Research Database (Denmark)

Munro, G; Hansen, Rikke Rie; Erichsen, Hk

2012-01-01

BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.

Science.gov (United States)

Chao, Chih-Kai; Balasubramanian, Narayanaganesh; Gerdes, John M; Thompson, Charles M

2018-06-16

In this study, the mechanisms of HuAChE and HuBChE inhibition by Me-P(O) (OPNP) (OR) [PNP = p-nitrophenyl; R = CH 2 CH 3 , CH 2 CH 2 F, OCH(CH 3 ) 2 , OCH(CH 3 ) (CH 2 F)] representing surrogates and fluoro-surrogates of VX and sarin were studied by in vitro kinetics and mass spectrometry. The in vitro measures showed that the VX- and fluoro-VX surrogates were relatively strong inhibitors of HuAChE and HuBChE (k i  ∼ 10 5 -10 6  M -1 min -1 ) and underwent spontaneous and 2-PAM-mediated reactivation within 30 min. The sarin surrogates were weaker inhibitors of HuAChE and HuBChE (k i  ∼ 10 4 -10 5  M -1 min -1 ), and in general did not undergo spontaneous reactivation, although HuAChE adducts were partially reactivatable at 18 h using 2-PAM. The mechanism of HuAChE and HuBChE inhibition by the surrogates was determined by Q-TOF and MALDI-TOF mass spectral analyses. The surrogate-adducted proteins were trypsin digested and the active site-containing peptide bearing the OP-modified serine identified by Q-TOF as triply- and quadruply-charged ions representing the respective increase in mass of the attached OP moiety. Correspondingly, monoisotopic ions of the tryptic peptides representing the mass increase of the OP-adducted peptide was identified by MALDI-TOF. The mass spectrometry analyses validated the identity of the OP moiety attached to HuAChE or HuBChE as MeP(O) (OR)-O-serine peptides (loss of the PNP leaving group) via mechanisms consistent with those found with chemical warfare agents. MALDI-TOF MS analyses of the VX-modified peptides versus time showed a steady reduction in adduct versus parent peptide (reactivation), whereas the sarin-surrogate-modified peptides remained largely intact over the course of the experiment (24 h). Overall, the presence of a fluorine atom on the surrogate modestly altered the rate constants of inhibition and reactivation, however, the mechanism of inhibition (ejection of PNP group) did not change

Effect of mating materials on wear properties of amorphous hydrogenated carbon (a-C:H coating and tetrahedral amorphous carbon (ta-C coating in base oil boundary lubrication condition

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Xiang Li

2017-12-01

Full Text Available In this study, wear behavior of amorphous hydrogenated carbon (a-C:H coating and tetrahedral amorphous carbon (ta-C coating when sliding against various mating materials in base oil boundary lubrication condition is comparatively investigated to find out the optimal combinations of DLC/mating material and corresponding wear mechanism of both DLC coating. Tribological tests were performed in a cylinder-on-disc tribometer, Field Emission Scanning Electron Microscopy, Raman spectroscopy is used for characterization of ta-C and a-C:H worn surface. The results show that the specific wear rate of ta-C coating increases along with the hardness and roughness of mating material increases, while the specific wear rate of a-C:H coating increases together with an increment in the ID/IG ratio. It is concluded that for ta-C coating, local stress concentration-induced microfracture is the main wear mechanism in relative high wear scenario, along with minor graphitization-induced wear which prevails in low wear scenario. On the other hand, a-C:H coating showed that simultaneous generation and removal of the graphitized layer on the contact surface is the predominant wear mechanism.

The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function.

Science.gov (United States)

Araud, Tanguy; Graw, Sharon; Berger, Ralph; Lee, Michael; Neveu, Estele; Bertrand, Daniel; Leonard, Sherry

2011-10-15

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. Schizophrenic patients have low levels of α7*nAChR, as measured by binding of the ligand [(125)I]-α-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of α7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with α7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer

International Nuclear Information System (INIS)

Kalmár, Alexandra; Péterfia, Bálint; Hollósi, Péter; Galamb, Orsolya; Spisák, Sándor; Wichmann, Barnabás; Bodor, András; Tóth, Kinga; Patai, Árpád V.; Valcz, Gábor; Nagy, Zsófia Brigitta; Kubák, Vivien; Tulassay, Zsolt; Kovalszky, Ilona; Molnár, Béla

2015-01-01

Colorectal cancer (CRC) development is accompanied by changes in expression for several genes; but the details of the underlying regulatory procesess remain unknown. Our aims were to assess the role of epigenetic processes in tumour formation and to identify characteristic DNA methylation and miRNA alterations in the colorectal adenoma-carcinoma sequence. Whole genome expression profiling was performed on colonic biopsy samples (49 healthy normal, 49 colorectal adenoma (AD), 49 CRC); on laser capture microdissected (LCM) epithelial and stromal cells from 6 CRC-normal adjacent tissue (NAT) samples pairs, and on demethylated human CRC cell lines using HGU133 Plus 2.0 microarrays (Affymetrix). Methylation status of genes with gradually altering expression along the AD-CRC sequence was further analysed on 10–10 macrodissected and 5–5 LCM samples from healthy colon, from adenoma and from CRC biopsy samples using bisulfite-sequencing PCR (BS-PCR) followed by pyrosequencing. In silico miRNA prediction for the selected genes was performed with miRWALK algorithm, miRNA expression was analysed on 3 CRC-NAT sample pairs and 3 adenoma tissue samples using the Human Panel I + II (Exiqon). SFRP1 immunohistochemistry experiments were performed. A set of transcripts (18 genes including MAL, SFRP1, SULT1A1, PRIMA1, PTGDR) showed decreasing expression (p < 0.01) in the biopsy samples along the adenoma-carcinoma sequence. Three of those (COL1A2, SFRP2, SOCS3) showed hypermethylation and THBS2 showed hypomethylation both in AD and in CRC samples compared to NAT, while BCL2, PRIMA1 and PTGDR showed hypermethylation only in the CRC group. miR-21 was found to be significantly (p < 0.01) upregulated in adenoma and tumour samples compared to the healthy colonic tissue controls and could explain the altered expression of genes for which DNA methylation changes do not appear to play role (e.g. BCL2, MAL, PTGS2). Demethylation treatment could upregulate gene expression of genes that were

Asignación de primas en el seguro del automóvil utilizando el Análisis en ComponentesPrincipales Funcionales = Premium allocation in the car insurance by using Functional Principal Component Analysis.

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Herranz Peinado, C. Patricia

2007-01-01

Full Text Available El estudio de las primas de riesgo en el seguro del automóvil es de suma importancia, debido a la gran competitividad existente en el mercado asegurador. En este artículo se pretende proponer un sistema de bonificación-penalización de las primas de riesgo utilizando el Análisis Funcional en Componentes Principales. En concreto, se realiza un estudio empírico con los datos reales de una compañía aseguradora con cobertura nacional. Aplicando el sistema propuesto de bonificación-penalización a los perfiles de comportamiento de los asegurados, se obtienen las primas de riesgo para cada uno de los perfiles considerados y tramos de edad. = The study of the premium risk in the car insurance is really important because the insurance market is very competitive. In this article we show a bonus-malus method of risk premiums. To do this, we use the Functional Principal Component Analysis. More precisely, we explain an empirical study with the real data of an insurance company. By applying the bonus-malus method that we have given, we are able to obtain the premium risk for different profiles and age ranges.

Le Visage de la Victoire di Henry De Groux: la riscoperta di un’opera antimilitarista del tempo della Prima guerra mondiale

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Carol Morganti

2014-03-01

Full Text Available Il presente intervento è dedicato a un’importante raccolta di incisioni, oggi riscoperta: Le Visage de la Victoire, eseguita dall’artista belga Henry De Groux. Costituita da oltre 40 incisioni (acqueforti e vernici molli, è stata realizzata nel corso della Prima Guerra Mondiale al fine di denunciare l’inutile massacro in corso. Si tratta di opere di ispirazione visionaria, che rivelano significati universali, mettendo il maestro belga in rapporto di affinità con artisti quali Goya e Otto Dix.

EVALUACIÓN DE MATERIAS PRIMAS EN UNA PLANTA DE BENEFICIO DE ARENA DE SILICE PARA AUMENTAR LA EFICIENCIA ENERGÉTICA DEL PROCESO DE MOLIENDA

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BEATRIZ ÁLVAREZ-RODRÍGUEZ

2013-01-01

Full Text Available El presente trabajo tiene por objetivo primordial optimizar el consumo energético y reducir la contaminación ambiental asociada, por la liberación de CO2, en una planta de micronización de sílice. La metodología empleada consiste en aplicar la teoría de Bond para la selección de materias primas a tratar en la mencionada planta, la cual dependiendo de las necesidades actuales opera con dos tamaños de molienda d100, 50 y 75μm. Los ensayos experimentales se llevaron a cabo sobre muestras tomadas en la planta, teniendo en cuenta que las tres materias primas son de distinta procedencia y de similares características químicas y mineralógicas. Del análisis de los resultados obtenidos se concluye que el consumo energético de la planta puede reducirse hasta algo más de un 30% en ambos tamaños y evitando las emisiones de CO2 en 293,83 kg y 128,86 kg por hora de funcionamiento respectivamente.

Hydrogen behaviour study in plasma facing a-C:H and a-SiC:H hydrogenated amorphous materials for fusion reactors

International Nuclear Information System (INIS)

Barbier, Gauzelin

1997-01-01

Plasma facing components of controlled fusion test devices (tokamaks) are submitted to several constraints (irradiation, high temperatures). The erosion (physical sputtering and chemical erosion) and the hydrogen recycling (retention and desorption) of these materials influence many plasma parameters and thus affect drastically the tokamak running. Firstly, we will describe the different plasma-material interactions. It will be pointed out, how erosion and hydrogen recycling are strongly related to both chemical and physical properties of the material. In order to reduce this interactions, we have selected two amorphous hydrogenated materials (a-C:H and a-SiC:H), which are known for their good thermal and chemical qualities. Some samples have been then implanted with lithium ions at different fluences. Our materials have been then irradiated with deuterium ions at low energy. From our results, it is shown that both the lithium implantation and the use of an a-SiC:H substrate can be benefit in enhancing the hydrogen retention. These results were completed with thermal desorption studies of these materials. It was evidenced that the hydrogen fixation was more efficient in a -SiC:H than in a-C:H substrate. Results in good agreement with those described above have been obtained by exposing a-C:H and a-SiC:H samples to the scrape off layer of the tokamak of Varennes (TdeV, Canada). A modeling of hydrogen diffusion under irradiation has been also proposed. (author)

The Adversarial Principle in Prima Facie Judgments of the Legal Thesis Firmed in the Trial of Repetitive Cases

Directory of Open Access Journals (Sweden)

Juliana Provedel Cardoso

2016-10-01

Full Text Available The present articles objective is to analyse the highly effective adversarial principle from the Constitutional Democratic State of Law and the cooperative process structure. In this sense, an analysis of the repetitive cases model is made with special relevance to the Civil Procedure Codice 2015, put in evidence the preliminary injunction, the repetitive appeals and the resolution incident repetitive demands. With the establishment of the premises, an analysis of the adversarial principle is made on prima facie judgments of the legal thesis firmed in the trial of repetitive cases, in view of the motivation of the court decision (speech of the case and law (speech of the precedents.

Mejoramiento de la gestión de compras e inventario de materia prima en la empresa Cepeda Cía. Ltda.

OpenAIRE

Villacís Mayorga, Grace Silvana

2015-01-01

En los resultados obtenidos en el proyecto "Diagnóstico de la Gestión de Compras y Control de Inventarios en la Empresa Cepeda Cía. Ltda.", se determinaron problemas de excesos y desabastecimientos de materia prima, procedimientos no actualizados del sistema de gestión; falta de un control formal o técnico en la gestión de los procesos de compra y control de inventarios evidenciándose que se requiere de planificación y orden. Para el mejoramiento del Proceso de Compras e Inventarios de Materi...

New-generation radiotracers for nAChR and NET

Energy Technology Data Exchange (ETDEWEB)

Ding Yushin [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)]. E-mail: ding@bnl.gov; Fowler, Joanna [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

2005-10-01

Advances in radiotracer chemistry and instrumentation have merged to make positron emission tomography (PET) a powerful tool in the biomedical sciences. Positron emission tomography has found increased application in the study of drugs affecting the brain and whole body, including the measurement of drug pharmacokinetics (using a positron-emitter-labeled drug) and drug pharmacodynamics (using a labeled tracer). Thus, radiotracers are major scientific tools enabling investigations of molecular phenomena, which are at the heart of understanding human disease and developing effective treatments; however, there is evidently a bottleneck in translating basic research to clinical practice. In the meantime, the poor ability to predict the in vivo behavior of chemical compounds based on their log P's and affinities emphasizes the need for more knowledge in this area. In this article, we focus on the development and translation of radiotracers for PET studies of the nicotinic acetylcholine receptor (nAChR) and the norepinephrine transporter (NET), two molecular systems that urgently need such an important tool to better understand their functional significance in the living human brain.

Semisynthetic hemoglobin A: Reconstitution of functional tetramer from semisynthetic α-globin

International Nuclear Information System (INIS)

Sahni, G.; Cho, Y.J.; Iyer, K.S.; Khan, S.A.; Seetharam, R.; Acharya, A.S.

1989-01-01

The optimal conditions for the semisynthesis of α-globin through Staphylococcus aureus V8 protease condensation of a synthetic fragment (α 1-30 ) with the complementary apo fragment (α 31-141 ) in the presence of structure-inducing organic cosolvents and the reconstitution of the functional tetramer from semisynthetic α-globin have been investigated. The protease-catalyzed ligation of the complementary apo fragments α 1-30 and α 31-141 proceeds with very high selectivity at pH 6.0 and 4 degree C in the presence of 1-propanol as the organic cosolvent. A 30% 1-propanol solution was optimal for the semisynthetic reaction, and the synthetic reaction attained an equilibrium (approximately 50%) in 72 h. The synthetic reaction proceeds smoothly over a wide pH range (pH 5-8). Besides, the semisynthetic system is flexible, and it also proceeded well if trifluoroethanol or 2-propanol was used instead of 1-propanol. However, glycerol, a versatile organic cosolvent used in all other proteosynthetic reactions reported in the literature, was not very efficient as an organic cosolvent in the present synthetic reaction. The semisynthetic α-globin prepared with 1-propanol as the organic cosolvent has been reconstituted into HbA. The semisynthetic HbA was then purified by CM-cellulose chromatography. The semisynthetic HbA is indistinguishable from native HbA, in terms of its structural and functional properties. The semisynthetic approach provides the flexibility in protein engineering studies for the incorporation of spectroscopic labels ( 13 C- and/or 15 N-labeled amino acids), noncoded amino acids, or unnatural bond functionalities, which at present is not possible with genetic approaches

Acetylcholine receptor (AChR) clustering is regulated both by glycogen synthase kinase 3β (GSK3β)-dependent phosphorylation and the level of CLIP-associated protein 2 (CLASP2) mediating the capture of microtubule plus-ends.

Science.gov (United States)

Basu, Sreya; Sladecek, Stefan; Pemble, Hayley; Wittmann, Torsten; Slotman, Johan A; van Cappellen, Wiggert; Brenner, Hans-Rudolf; Galjart, Niels

2014-10-31

The postsynaptic apparatus of the neuromuscular junction (NMJ) traps and anchors acetylcholine receptors (AChRs) at high density at the synapse. We have previously shown that microtubule (MT) capture by CLASP2, a MT plus-end-tracking protein (+TIP), increases the size and receptor density of AChR clusters at the NMJ through the delivery of AChRs and that this is regulated by a pathway involving neuronal agrin and several postsynaptic kinases, including GSK3. Phosphorylation by GSK3 has been shown to cause CLASP2 dissociation from MT ends, and nine potential phosphorylation sites for GSK3 have been mapped on CLASP2. How CLASP2 phosphorylation regulates MT capture at the NMJ and how this controls the size of AChR clusters are not yet understood. To examine this, we used myotubes cultured on agrin patches that induce AChR clustering in a two-dimensional manner. We show that expression of a CLASP2 mutant, in which the nine GSK3 target serines are mutated to alanine (CLASP2-9XS/9XA) and are resistant to GSK3β-dependent phosphorylation, promotes MT capture at clusters and increases AChR cluster size, compared with myotubes that express similar levels of wild type CLASP2 or that are noninfected. Conversely, myotubes expressing a phosphomimetic form of CLASP2 (CLASP2-8XS/D) show enrichment of immobile mutant CLASP2 in clusters, but MT capture and AChR cluster size are reduced. Taken together, our data suggest that both GSK3β-dependent phosphorylation and the level of CLASP2 play a role in the maintenance of AChR cluster size through the regulated capture and release of MT plus-ends. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

XPS study of the ultrathin a-C:H films deposited onto ion beam nitrided AISI 316 steel

International Nuclear Information System (INIS)

Meskinis, S.; Andrulevicius, M.; Kopustinskas, V.; Tamulevicius, S.

2005-01-01

Effects of the steel surface treatment by nitrogen ion beam and subsequent deposition of the diamond-like carbon (hydrogenated amorphous carbon (a-C:H) and nitrogen doped hydrogenated amorphous carbon (a-CN x :H)) films were investigated by means of the X-ray photoelectron spectroscopy (XPS). Experimental results show that nitrogen ion beam treatment of the AISI 316 steel surface even at room temperature results in the formation of the Cr and Fe nitrides. Replacement of the respective metal oxides by the nitrides takes place. Formation of the C-N bonds was observed for both ultrathin a-C:H and ultrathin a-CN x :H layers deposited onto the nitrided steel. Some Fe and/or Cr nitrides still were presented at the interface after the film deposition, too. Increased adhesion between the steel substrate and hydrogenated amorphous carbon layer after the ion beam nitridation was explained by three main factors. The first two is steel surface deoxidisation/passivation by nitrogen as a result of the ion beam treatment. The third one is carbon nitride formation at the nitrided steel-hydrogenated amorphous carbon (or a-CN x :H) film interface

Teater : Tänavused balletipreemiad. "Prima la Donna". Kontsertetendus "Sina ja mina". Rahvakultuur : Laste murdelaulu ja -luulepäevad tänavu Hageris / Vesta Uuetoa

Index Scriptorium Estoniae

Uuetoa, Vesta

2002-01-01

Rahvusooperis laulab "Boheemis" külaline Soomest - Ari Grönthal. Kadrioru lossis antakse üle traditsioonilised balletiauhinnad. 20.-26. V toimub rahvusooperis Estonia ooperi ja balletifestival "Prima la Donna", mille teemaks on saatuslikud, tähelepanuväärsed ja jõulised naised. Kurt Weilli ja Lotte Lenya elu draamas ja muusikas on lavastanud Mart Kampus. 18. ja 19. mail saavad Hageris kokku murdelaulu ja -luulega tegelevad lapsed

Tribological properties of amorphous hydrogenated (a-C:H) and hydrogen-free tetrahedral (ta-C) diamond-like carbon coatings under jatropha biodegradable lubricating oil at different temperatures

International Nuclear Information System (INIS)

Mobarak, H.M.; Masjuki, H.H.; Mohamad, E. Niza; Kalam, M.A.; Rashedul, H.K.; Rashed, M.M.; Habibullah, M.

2014-01-01

Highlights: • We tested a-C:H and ta-C DLC coatings as a function of temperature. • Jatropha oil contains large amounts of polar components that enhanced the lubricity of coatings. • CoF decreases with increasing temperature for both contacts. • Wear rate increases with increasing temperature in a-C:H and decreases in ta-C DLC. • At high temperature, ta-C coatings confer more protection than a-C:H coatings. - Abstract: The application of diamond-like carbon (DLC) coatings on automotive components is emerging as a favorable strategy to address the recent challenges in the industry. DLC coatings can effectively lower the coefficient of friction (CoF) and wear rate of engine components, thereby improving their fuel efficiency and durability. The lubrication of ferrous materials can be enhanced by a large amount of unsaturated and polar components of oils. Therefore, the interaction between nonferrous coatings (e.g., DLC) and vegetable oil should be investigated. A ball-on-plate tribotester was used to run the experiments. Stainless steel plates coated with amorphous hydrogenated (a-C:H) DLC and hydrogen-free tetrahedral (ta-C) DLC that slide against 440C stainless steel ball were used to create a ball-on-plate tribotester. The wear track was investigated through scanning electron microscopy. Energy dispersive and X-ray photoelectron spectroscopies were used to analyze the tribofilm inside the wear track. Raman analysis was performed to investigate the structural changes in the coatings. At high temperatures, the CoF in both coatings decreased. The wear rate, however, increased in the a-C:H but decreased in the ta-C DLC-coated plates. The CoF and the wear rate (coated layer and counter surface) were primarily influenced by the graphitization of the coating. Tribochemical films, such as polyphosphate glass, were formed in ta-C and acted as protective layers. Therefore, the wear rate of the ta-C DLC was lower than that of the-C:H DLC

Tribological properties of amorphous hydrogenated (a-C:H) and hydrogen-free tetrahedral (ta-C) diamond-like carbon coatings under jatropha biodegradable lubricating oil at different temperatures

Energy Technology Data Exchange (ETDEWEB)

Mobarak, H.M., E-mail: mobarak.ho31@yahoo.com; Masjuki, H.H.; Mohamad, E. Niza, E-mail: edzrol@um.edu.my; Kalam, M.A.; Rashedul, H.K.; Rashed, M.M.; Habibullah, M.

2014-10-30

Highlights: • We tested a-C:H and ta-C DLC coatings as a function of temperature. • Jatropha oil contains large amounts of polar components that enhanced the lubricity of coatings. • CoF decreases with increasing temperature for both contacts. • Wear rate increases with increasing temperature in a-C:H and decreases in ta-C DLC. • At high temperature, ta-C coatings confer more protection than a-C:H coatings. - Abstract: The application of diamond-like carbon (DLC) coatings on automotive components is emerging as a favorable strategy to address the recent challenges in the industry. DLC coatings can effectively lower the coefficient of friction (CoF) and wear rate of engine components, thereby improving their fuel efficiency and durability. The lubrication of ferrous materials can be enhanced by a large amount of unsaturated and polar components of oils. Therefore, the interaction between nonferrous coatings (e.g., DLC) and vegetable oil should be investigated. A ball-on-plate tribotester was used to run the experiments. Stainless steel plates coated with amorphous hydrogenated (a-C:H) DLC and hydrogen-free tetrahedral (ta-C) DLC that slide against 440C stainless steel ball were used to create a ball-on-plate tribotester. The wear track was investigated through scanning electron microscopy. Energy dispersive and X-ray photoelectron spectroscopies were used to analyze the tribofilm inside the wear track. Raman analysis was performed to investigate the structural changes in the coatings. At high temperatures, the CoF in both coatings decreased. The wear rate, however, increased in the a-C:H but decreased in the ta-C DLC-coated plates. The CoF and the wear rate (coated layer and counter surface) were primarily influenced by the graphitization of the coating. Tribochemical films, such as polyphosphate glass, were formed in ta-C and acted as protective layers. Therefore, the wear rate of the ta-C DLC was lower than that of the-C:H DLC.

Analysis of glycation induced protein cross-linking inhibitory effects of some antidiabetic plants and spices.

Science.gov (United States)

Perera, Handunge Kumudu Irani; Handuwalage, Charith Sandaruwan

2015-06-09

Protein cross-linking which occurs towards the latter part of protein glycation is implicated in the development of chronic diabetic complications. Glycation induced protein cross-linking inhibitory effects of nine antidiabetic plants and three spices were evaluated in this study using a novel, simple, electrophoresis based method. Methanol extracts of thirteen plants including nine antidiabetic plants and three spices were used. Lysozyme and fructose were incubated at 37 °C in the presence or absence of different concentrations of plant extracts up to 31 days. Standard glycation inhibitor aminoguanidine and other appropriate controls were included. A recently established sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE) method was used to detect the products of protein cross-linking in the incubation mixtures. High molecular weight protein products representing the dimer, trimer and tetramer of lysozyme were detected in the presence of fructose. Among the nine antidiabetic plants, seven showed glycation induced protein cross-linking inhibitory effects namely Ficus racemosa (FR) stem bark, Gymnema sylvestre (GS) leaves, Musa paradisiaca (MP) yam, Phyllanthus debilis (PD) whole plant, Phyllanthus emblica (PE) fruit, Pterocarpus marsupium (PM) latex and Tinospora cordifolia (TC) leaves. Inhibition observed with Coccinia grandis (CG) leaves and Strychnos potatorum (SP) seeds were much low. Leaves of Gymnema lactiferum (GL), the plant without known antidiabetic effects showed the lowest inhibition. All three spices namely Coriandrum sativum (CS) seeds, Cinnamomum zeylanicum (CZ) bark and Syzygium aromaticum (SA) flower buds showed cross-link inhibitory effects with higher effects in CS and SA. PD, PE, PM, CS and SA showed almost complete inhibition on the formation of cross-linking with 25 μg/ml extracts. Methanol extracts of PD, PE, PM, CS and SA have shown promising inhibitory effects on glycation induced protein cross-linking.

Avaliação da qualidade de matérias-primas de ruibarbo utilizadas em formulações farmacêuticas

Directory of Open Access Journals (Sweden)

O.V. Sousa

Full Text Available As plantas denominadas de ruibarbo sintetizam antraquinonas e taninos, que são responsáveis pelos efeitos laxante e adstringente, respectivamente. Análises da qualidade de cinco matérias-primas de ruibarbo foram realizadas a fim de detectar adulterações. As reações para antraquinonas e taninos foram positivas. Os constituintes rapônticos foram observados na amostra de Rheum palmatum (2. As medidas de cinzas totais para Rheum palmatum (2 e Ferraria cathartica estão acima do esperado. Conforme resultados, as amostras de Rheum palmatum (2 e Ferraria cathartica devem estar adulteradas.

The Dsu Article 3.8 Presumption that an Infringement Constitutes a Prima Facie Case of Nullification or Impairment: When Does it Operate and Why?

OpenAIRE

Arwel Davies

2010-01-01

This article considers the origin, meaning and current relevance of the Dispute Settlement Understanding (DSU) Article 3.8 presumption that a government measure which infringes World Trade Organization (WTO) obligations constitutes a prima facie case of nullification or impairment. It is argued that the prevailing interpretation of this provision is inconsistent with its plain language and may have contributed to the tendency of respondent states to invoke the presumption in order to undermin...

Nonlinear drift-diffusion model of gating in K and nACh ion channels

Energy Technology Data Exchange (ETDEWEB)

Vaccaro, S.R. [Department of Physics, University of Adelaide, Adelaide, South Australia 5005 (Australia)], E-mail: svaccaro@physics.adelaide.edu.au

2007-09-03

The configuration of a sensor regulates the transition between the closed and open states of both voltage and ligand gated channels. The closed state dwell-time distribution f{sub c}(t) derived from a Fokker-Planck equation with a nonlinear diffusion coefficient is in good agreement with experimental data and can account for the power law approximation to f{sub c}(t) for a delayed rectifier K channel and a nicotinic acetylcholine (nACh) ion channel. The solution of a master equation which approximates the Fokker-Planck equation provides a better description of the small time behaviour of the dwell-time distribution and can account for the empirical rate-amplitude correlation for these ion channels.

Detection of GAD65 Autoreactive T-Cells by HLA Class I Tetramers in Type 1 Diabetic Patients

Directory of Open Access Journals (Sweden)

Laura Giuliani

2009-01-01

Full Text Available Type 1 diabetes (T1D is an autoimmune disease, in which pancreatic β cells are destroyed in genetically predisposed individuals. While the direct contribution of autoantibodies to the disease pathogenesis is controversial, it is generally recognised that the mechanism of β cell destruction is mediated by autoreactive T cells that had escaped the thymic selection. We aimed to design a method to detect circulating CD8+ T cells autoreactive against an epitope of the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65 ex vivo in T1D patients by using HLA class I tetramers. Low frequencies of GAD65 peptide-specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood lymphocytes (PBMC of normal controls after GAD65 peptide-specific stimulation. Conversely, their frequencies were significantly higher than in controls in PBMC of T1D patients after GAD65 peptide stimulation. These preliminary data are encouraging in order to develop a reliable assay to be employed in large-scale screening studies.

31 CFR 363.143 - What happens if an ACH payment used to purchase a certificate of indebtedness is later reversed?

Science.gov (United States)

2010-07-01

... processed security transactions, including securities that were purchased as gifts and securities that have... to purchase a certificate of indebtedness is later reversed? 363.143 Section 363.143 Money and... Indebtedness § 363.143 What happens if an ACH payment used to purchase a certificate of indebtedness is later...

3D Printing of Aniline Tetramer-Grafted-Polyethylenimine and Pluronic F127 Composites for Electroactive Scaffolds.

Science.gov (United States)

Dong, Shi-Lei; Han, Lu; Du, Cai-Xia; Wang, Xiao-Yu; Li, Lu-Hai; Wei, Yen

2017-02-01

Electroactive hydrogel scaffolds are fabricated by the 3D-printing technique using composites of 30% Pluronic F127 and aniline tetramer-grafted-polyethylenimine (AT-PEI) copolymers with various contents from 2.5% to 10%. The synthesized AT-PEI copolymers can self-assemble into nanoparticles with the diameter of ≈50 nm and display excellent electroactivity due to AT conjugation. The copolymers are then homogeneously distributed into 30% Pluronic F127 solution by virtue of the thermosensitivity of F127, denoted as F/AT-PEI composites. Macroscopic photographs of latticed scaffolds elucidate their excellent printability of F/AT-PEI hydrogels for the 3D-printing technique. The conductivities of the printed F/AT-PEI scaffolds are all higher than 2.0 × 10 -3 S cm -1 , which are significantly improved compared with that of F127 scaffold with only 0.94 × 10 -3 S cm -1 . Thus, the F/AT-PEI scaffolds can be considered as candidates for application in electrical stimulation of tissue regeneration such as repair of muscle and cardiac nerve tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Linking biomedical engineering ethics case study approach and policy.

Science.gov (United States)

Dibrell, William; Dobie, Elizabeth Ann

2007-01-01

In this paper we link bioengineering case study methods to the development of policy. The case study approach to ethics is an excellent way to show the complex nature of practical/moral reasoning. This approach can, however, lead to a kind of overwhelming complexity. The individual nature of each case makes it difficult to identify the most important information and difficult to see what moral considerations are most relevant. In order to make the overwhelming complexity less debilitating, we present a framework for moral decision making derived from suggestions made by W.D. Ross and Virginia Held. Ross articulates the multiple sources of morality and Held deepens the discussion by reminding us of the foundational importance of care and sympathy to our moral natures. We show how to use the notion of prima facie duty and discuss moral conflict. In doing this, we show how the framework, applied to cases, can be of assistance in helping us develop policies and codes of ethics with sufficient plasticity to be useful in the complex world of the bioengineer.

Voltage sensitivity of M2 muscarinic receptors underlies the delayed rectifier-like activation of ACh-gated K(+) current by choline in feline atrial myocytes.

Science.gov (United States)

Navarro-Polanco, Ricardo A; Aréchiga-Figueroa, Iván A; Salazar-Fajardo, Pedro D; Benavides-Haro, Dora E; Rodríguez-Elías, Julio C; Sachse, Frank B; Tristani-Firouzi, Martin; Sánchez-Chapula, José A; Moreno-Galindo, Eloy G

2013-09-01

Choline (Ch) is a precursor and metabolite of the neurotransmitter acetylcholine (ACh). In canine and guinea pig atrial myocytes, Ch was shown to activate an outward K(+) current in a delayed rectifier fashion. This current has been suggested to modulate cardiac electrical activity and to play a role in atrial fibrillation pathophysiology. However, the exact nature and identity of this current has not been convincingly established. We recently described the unique ligand- and voltage-dependent properties of muscarinic activation of ACh-activated K(+) current (IKACh) and showed that, in contrast to ACh, pilocarpine induces a current with delayed rectifier-like properties with membrane depolarization. Here, we tested the hypothesis that Ch activates IKACh in feline atrial myocytes in a voltage-dependent manner similar to pilocarpine. Single-channel recordings, biophysical profiles, specific pharmacological inhibition and computational data indicate that the current activated by Ch is IKACh. Moreover, we show that membrane depolarization increases the potency and efficacy of IKACh activation by Ch and thus gives the appearance of a delayed rectifier activating K(+) current at depolarized potentials. Our findings support the emerging concept that IKACh modulation is both voltage- and ligand-specific and reinforce the importance of these properties in understanding cardiac physiology.

Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system.

Science.gov (United States)

Rovira, X; Vivó, M; Serra, J; Roche, D; Strange, P G; Giraldo, J

2009-01-01

Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

Modification of the philanthotoxin-343 polyamine moiety results in different structure-activity profiles at muscle nicotinic ACh, NMDA and AMPA receptors

DEFF Research Database (Denmark)

Mellor, I R; Brier, T J; Pluteanu, F

2003-01-01

Voltage-dependent, non-competitive inhibition by philanthotoxin-343 (PhTX-343) analogues, with reduced charge or length, of nicotinic acetylcholine receptors (nAChR) of TE671 cells and ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4...

Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

International Nuclear Information System (INIS)

DuRant, Sarah E.; Hopkins, William A.; Talent, Larry G.

2007-01-01

We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 μg/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards

Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide

Energy Technology Data Exchange (ETDEWEB)

DuRant, Sarah E. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States); University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States); Hopkins, William A. [Wildlife Ecotoxicology and Physiological Ecology Program, Department of Fisheries and Wildlife Sciences, Virginia Polytechnic Institute and State University, 444 Latham Hall, Blacksburg, VA 24061 (United States) and University of Georgia, Savannah River Ecology Laboratory, PO Drawer E, Aiken, SC 29802 (United States)]. E-mail: hopkinsw@vt.edu; Talent, Larry G. [Department of Zoology, Oklahoma State University, Stillwater, OK 74078 (United States)

2007-09-15

We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 {mu}g/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. - Exposure to an acetylcholinesterase-inhibiting pesticide alters locomotor performance in western fence lizards.

In vitro activity of ACH-702, a new isothiazoloquinolone, against Nocardia brasiliensis compared with econazole and the carbapenems imipenem and meropenem alone or in combination with clavulanic acid.

Science.gov (United States)

Vera-Cabrera, Lucio; Campos-Rivera, Mayra Paola; Escalante-Fuentes, Wendy G; Pucci, Michael J; Ocampo-Candiani, Jorge; Welsh, Oliverio

2010-05-01

The in vitro activities of ACH-702 and other antimicrobials against 30 Nocardia brasiliensis isolates were tested. The MIC(50) (MIC for 50% of the strains tested) and MIC(90) values of ACH-702 were 0.125 and 0.5 microg/ml. The same values for econazole were 2 and 4 microg/ml. The MIC(50) and MIC(90) values of imipenem and meropenem were 64 and >64 microg/ml and 2 and 8 microg/ml, respectively; the addition of clavulanic acid to the carbapenems had no effect.

Principles and equations for measuring and interpreting protein stability: From monomer to tetramer.

Science.gov (United States)

Bedouelle, Hugues

2016-02-01

The ability to measure the thermodynamic stability of proteins with precision is important for both academic and applied research. Such measurements rely on mathematical models of the protein denaturation profile, i.e. the relation between a global protein signal, corresponding to the folding states in equilibrium, and the variable value of a denaturing agent, either heat or a chemical molecule, e.g. urea or guanidinium hydrochloride. In turn, such models rely on a handful of physical laws: the laws of mass action and conservation, the law that relates the protein signal and concentration, and the one that relates stability and denaturant value. So far, equations have been derived mainly for the denaturation profiles of homomeric proteins. Here, we review the underlying basic physical laws and show in detail how to derive model equations for the unfolding equilibria of homomeric or heteromeric proteins up to trimers and potentially tetramers, with or without folding intermediates, and give full demonstrations. We show that such equations cannot be derived for pentamers or higher oligomers except in special degenerate cases. We expand the method to signals that do not correspond to extensive protein properties. We review and expand methods for uncovering hidden intermediates of unfolding. Finally, we review methods for comparing and interpreting the thermodynamic parameters that derive from stability measurements for cognate wild-type and mutant proteins. This work should provide a robust theoretical basis for measuring the stability of complex proteins. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Influence of nitrogen on the tribological properties of a-C:H layers on the polycarbonate substrates

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Rafal M. Nowak

2008-12-01

Full Text Available Polycarbonate (PC possesses many commercial applications. However, PC is still limited to non-abrasive and chemical-free environments due to its low hardness, low scratching resistance and high susceptibility to chemical attacks. To overcome this limitation, PC can be coated by hydrogenated amorphous carbon layers. The a-C:H layers have very attractive properties such as high hardness, infrared transparency, chemical inertness, low friction coefficients, and biocompatibility. Addition of nitrogen in the structure allows lowering internal stress and improve tribological properties of a-C:H layers. In this work, a-C:N:H layers were deposited from mixture CH4/N2 gases by RF PECVD method. Effects of the nitrogen incorporation on structure and tribological properties of deposited layers were investigated. The structure of layers were characterized by Fourier Transform Infrared spectroscopy (FTIR and X-ray photoelectron spectroscopy (XPS. The friction coefficient, wear resistance of a-C:H:N layers were estimated by tribometer in ball-on-disc configuration. The IR spectra of the obtained layers have demonstrated a presence of nitrogen bonded both to carbon and to hydrogen. A formation of the following bonds has been confirmed: -C≡N, -NH2, -C−NH2, >C=NH. They are all typical for a-C:N:H layers. The tribological tests have shown that the layers reduce the friction coefficient of the polycarbonate (up to 50 % and considerably improve wear resistance.

The resveratrol tetramer (--hopeaphenol inhibits type III secretion in the gram-negative pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa.

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Caroline E Zetterström

Full Text Available Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (--hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (--hopeaphenol in three different gram-negative bacteria. (--Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (--hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

Estimasi Nilai Pasar Wajar Ekuitas PT Prima Layanan Nasional Enjiniring Dalam Persiapan Initial Public Offering (IPO

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Ahmad Rizani

2015-11-01

Full Text Available PT Prima Layanan Nasional Enjiniring (PT PLN Enjiniring plans to conduct an initial public offering in 2012 that is intended for business development. Purpose of this research was to estimate the fair market value of equity of PT PLN Enjiniring in the framework of an initial public offering. Fair market value of equity of PT PLN Enjiniring is acquired by using discounted cash flow-free cash flow to equity method. Information used for this research come from two secondary data from financial reports and other information contained in the annual report 2008-2010 PT PLN Enjiniring years audited by public accountants, comperative financial reports, and company’s stock data comparison. The estimated fair market value of equity of PT PLN Enjiniring per December 31st 2011 by using the method of discounted cash flow-free cash flow to equity is obtained indication the fair market value of equity amounting to Rp2.583.155.716.515.

GaAs laser therapy reestablishes the morphology of the NMJ and nAChRs after injury due to bupivacaine.

Science.gov (United States)

Pissulin, Cristiane Neves Alessi; de Souza Castro, Paula Aiello Tomé; Codina, Flávio; Pinto, Carina Guidi; Vechetti-Junior, Ivan Jose; Matheus, Selma Maria Michelin

2017-02-01

Local anesthetics are used to relieve pre- and postoperative pain, acting on both sodium channels and nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ). Bupivacaine acts as a non-competitive antagonist and has limitations, such as myotoxicity, neurotoxicity, and inflammation. Low-level laser therapy (LLLT) has anti-inflammatory, regenerative, and analgesic effects. The aim of the present study was to evaluate the effects of a gallium arsenide laser (GaAs) on the morphology of the NMJ and nAChRs after application of bupivacaine in the sternomastoid muscle. Thirty-two adult male Wistar rats received injections of bupivacaine 0.5% (Bupi: right antimere) and 0.9% sodium chloride (Cl: left antimere). Next, the animals were divided into a Control group (C) and a Laser group (LLLT). The laser group received LLLT (GaAs 904nm, 50mW, 4,8J) in both antimeres for five consecutive days. After seven days, the animals were euthanized and the surface portion of the sternomastoid muscle was removed, frozen, and subjected to morphological and morphometric analyses of the NMJs (nonspecific esterase reaction), confocal laser scanning, and an ultrastructural analysis. The nAChRs were quantified by Western blotting. In the chloride group, the morphology and morphometry of the NMJs remained stable. The maximum diameters of the NMJs were lower in the Bupi (15.048±1.985) and LLLT/Bupi subgroups (15.456±1.983) compared to the Cl (18.502±2.058) and LLLT/Cl subgroups (19.356±2.522) (pbupivacaine, with recovery in the junctional folds and active zone. There was an increase in the perimeter of the LLLT/Bupi subgroup (150.33) compared to the Bupi subgroup (74.69) (pbupivacaine, providing important data supporting the use of LLLT in therapeutic protocols for injuries triggered by local anesthetics. Copyright © 2016 Elsevier B.V. All rights reserved.

Análise do posicionamento da empresa Baldo S/A na obtenção da matéria-prima erva-mate

OpenAIRE

Gurski, Clóvis Roberto

2003-01-01

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Sócio-Econômico. Programa de Pós-Graduação em Economia. Esse trabalho teve como objetivo identificar e analisar a forma de obtenção de matéria-prima erva-mate pela empresa BALDO S/A, filial 16, sediada no município de São Mateus do Sul, no estado do Paraná, a partir dos conceitos da Teoria dos Custos de Transação. Para tanto, esta pesquisa, de natureza exploratória, utilizou como instrumento para coleta de dados, um qu...

Essential oil from lemon peels inhibit key enzymes linked to neurodegenerative conditions and pro-oxidant induced lipid peroxidation.

Science.gov (United States)

Oboh, Ganiyu; Olasehinde, Tosin A; Ademosun, Ayokunle O

2014-01-01

This study sought to investigate the effects of essential oil from lemon (Citrus limoni) peels on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in vitro. The essential oil was extracted by hydrodistillation, dried with anhydrous Na2SO4 and characterized using gas chromatography. Antioxidant properties of the oil and inhibition of pro-oxidant-induced lipid peroxidation in rats brain homogenate were also assessed. The essential oil inhibited AChE and BChE activities in a concentration-dependent manner. GC analysis revealed the presence of sabinene, limonene, α-pinene, β-pinene, neral, geranial, 1,8-cineole, linalool, borneol, α-terpineol, terpinen-4-ol, linalyl acetate and β-caryophyllene. Furthermore, the essential oil exhibited antioxidant activities as typified by ferric reducing property, Fe(2+)-chelation and radicals [DPPH, ABTS, OH, NO] scavenging abilities. The inhibition of AChE and BChE activities, inhibition of pro-oxidant induced lipid peroxidation and antioxidant activities could be possible mechanisms for the use of the essential oil in the management and prevention of oxidative stress-induced neurodegeneration.

PROCESO ENZIMATICO PARA LA PRODUCCION DE METIL ESTERES DE ACIDOS GRASOS UTILIZANDO ACEITES RESIDUALES DE FRITURA EN MEZCLA CON ACEITE DE RAPS COMO MATERIA PRIMA

OpenAIRE

AZOCAR ULLOA; LAURA HAYDEE; AZOCAR ULLOA; LAURA HAYDEE

2010-01-01

Los procesos catalizados por lipasas han sido ampliamente investigados como alternativa para la producción de metil ésteres de ácidos grasos (fatty acid methyl ester, FAME) o biodiesel. El interés en este proceso radica en que a diferencia de los procesos convencionales catalizados con sales alcalinas, los procesos catalizados con lipasas permiten el uso de materias primas alternativas y de menor costo, tales como el aceite residual de fritura (waste frying oil, WFO). Pese a los l...

A melting pot it's not. ACHE study finds healthcare management still dominated by whites, men despite efforts to promote greater diversity.

Science.gov (United States)

Burda, David

2003-08-11

A study by the American College of Healthcare Executives reveals that efforts to promote racial and gender diversity among the industry's top ranks haven't been as successful as hoped. ACHE President and Chief Executive Officer Thomas Dolan, left, said the results should prompt healthcare executives to analyze what's happening within their own four walls.

阿仑膦酸钠对绝经后骨质疏松性骨痛的疗效分析%Effect analysis of alendronate on postmenopausal osteoporosis with bone ache

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

@@ Background: Osteoporosis is a metabolic bone disease characterized by low bone component and regeneration of the microstructure of bone tissues, osteoporosis occurs in postmenopausal women for decreased estrogen level. Those women with osteoporosis often suffer from bone ache, such as pain at low back, back, knees and heels. In severe cases, there may be crookback or non- violent fracture. Objective: To discuss treatment effect of the Alendronate on 56 postmenopausal women with bone ache caused by osteoporosis. Unit: 210 Hospital of PLA.

miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.

Science.gov (United States)

Shang, Fei-Fei; Xia, Qing-Jie; Liu, Wei; Xia, Lei; Qian, Bao-Jiang; You, Ling; He, Mu; Yang, Jin-Liang; Wang, Ting-Hua

2016-03-11

Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

CONDIÇÕES DE ARMAZENAGEM E QUALIDADE DA MATÉRIA PRIMA: ESTUDO DE CASO EM UMA DERIVADORA DE ALIMENTOS A BASE DE MILHO

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Samara Pereira Dias

2017-12-01

Full Text Available O processo de armazenagem, de alguma forma, tem influência direta na produção e no status do produto final derivado. Foi possível constatar neste estudo de caso, que o sistema de armazenagem da empresa está deficitário, necessitando de melhorias, principalmente quando da entrada da matéria prima para produção. Tais problemas, como impurezas, grãos quebrados e ardidos, são gerados no próprio armazém, por falta de prudência e coordenação. Constatações que contrariam o objetivo do armazenamento que é a conservação das particularidades dos grãos e que podem desmerecer os atributos do produto fim, em termos de sabor, características físico químicas e condições visuais. Entre as possíveis causas dos distúrbios, estão a falta de manutenção das máquinas, as ineficientes aeração e aferição da termometria. Como sugestão, além das melhorias sobre os problemas citados, a implantação de gestão e estratégia de estoques, de programas e controle de qualidade, desenvolvimento dos agentes produtores, planejamento e métodos de solução de problemas. O declínio da qualidade da matéria prima, o milho, pode resultar em efeito cadeia, prejudicando o produto final, logo, lesando os resultados financeiros da organização.

Structural and Functional Characterization of a Single-chain Peptide-MHC Molecule that Modulates both Naive and Activated CD8plus T Cells

Energy Technology Data Exchange (ETDEWEB)

D Samanta; G Mukherjee; U Ramagopal; R Chaparro; S Nathenson; T DiLorenzo; S Almo

2011-12-31

Peptide-MHC (pMHC) multimers, in addition to being tools for tracking and quantifying antigen-specific T cells, can mediate downstream signaling after T-cell receptor engagement. In the absence of costimulation, this can lead to anergy or apoptosis of cognate T cells, a property that could be exploited in the setting of autoimmune disease. Most studies with class I pMHC multimers used noncovalently linked peptides, which can allow unwanted CD8{sup +} T-cell activation as a result of peptide transfer to cellular MHC molecules. To circumvent this problem, and given the role of self-reactive CD8{sup +} T cells in the development of type 1 diabetes, we designed a single-chain pMHC complex (scK{sup d}.IGRP) by using the class I MHC molecule H-2K{sup d} and a covalently linked peptide derived from islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP{sub 206-214}), a well established autoantigen in NOD mice. X-ray diffraction studies revealed that the peptide is presented in the groove of the MHC molecule in canonical fashion, and it was also demonstrated that scK{sup d}.IGRP tetramers bound specifically to cognate CD8{sup +} T cells. Tetramer binding induced death of naive T cells and in vitro- and in vivo-differentiated cytotoxic T lymphocytes, and tetramer-treated cytotoxic T lymphocytes showed a diminished IFN-{gamma} response to antigen stimulation. Tetramer accessibility to disease-relevant T cells in vivo was also demonstrated. Our study suggests the potential of single-chain pMHC tetramers as possible therapeutic agents in autoimmune disease. Their ability to affect the fate of naive and activated CD8{sup +} T cells makes them a potential intervention strategy in early and late stages of disease.

Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways.

Science.gov (United States)

Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó-Ollé, Anna; Cilleros-Mañé, Víctor; Just-Borràs, Laia

2018-01-01

In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR) in the mammalian neuromuscular junction (NMJ). Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally). These observations underlie the relevance of AR in the NMJ function.

Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

Directory of Open Access Journals (Sweden)

Josep Tomàs

2018-04-01

Full Text Available In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR in the mammalian neuromuscular junction (NMJ. Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally. These observations underlie the relevance of AR in the NMJ function.

Thin films of hydrogenated amorphous carbon (a-C:H) obtained through chemical vapor deposition assisted by plasma; Peliculas delgadas de carbono amorfo hidrogenado (a-C:H) obtenidas mediante deposito quimico de vapores asistido por plasma

Energy Technology Data Exchange (ETDEWEB)

Mejia H, J.A.; Camps C, E.E.; Escobar A, L.; Romero H, S.; Chirino O, S. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Muhl S, S. [IIM-UNAM, 04510 Mexico D.F. (Mexico)

2004-07-01

Films of hydrogenated amorphous carbon (a-C:H) were deposited using one source of microwave plasma with magnetic field (type ECR), using mixtures of H{sub 2}/CH{sub 4} in relationship of 80/20 and 95/05 as precursory gases, with work pressures of 4X10{sup -4} to 6x10{sup -4} Torr and an incident power of the discharge of microwaves with a constant value of 400 W. It was analyzed the influence among the properties of the films, as the deposit rate, the composition and the bonding types, and the deposit conditions, such as the flow rates of the precursory gases and the polarization voltage of the sample holders. (Author)

Caracterización bromatológica de especies y subproductos vegetales en el trópico húmedo de Colombia

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Dissa Enith Mosquera Perea

2013-12-01

Full Text Available Se determinó el potencial nutritivo para especies pecuarias de recursos locales existentes en el municipio de Quibdó, departamento del Chocó (Colombia, teniendo en cuenta la composición bromatológica y digestibilidad in vitro de la materia seca (DIVMS en hojas de árbol del pan (Arthocarpus altilis Z., pacó (Gustavia superba Kunth. y achín (Colocasia esculenta Linn, cáscaras del fruto de chontaduro (Bractris gasipaess Kunth. y de plátano (Musa paradisiaca L.. El análisis bromatológico incluyó materia seca (MS, proteína bruta (PB, ceniza (Cen, fibra detergente ácida (FDA, fibra detergente neutra (FDN, lignina detergente ácida (LDA y energía bruta (EB. Las hojas de achín y de árbol del pan presentaron los contenidos más altos de PB (27.78 y 19.38% y de EB (3911 y 3981 cal/g, respectivamente. Los valores de DIVMS más altos se presentaron en cáscaras de chontaduro (78.9% y hojas de achín (68.6%. En general, los recursos en estudio presentan valor nutritivo similar al de forrajes cultivados, por tanto, son una alternativa posible para la sustitución parcial de materias primas costosas en dietas para animales de granja.

Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142

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Rekosh David

2008-05-01

Full Text Available Abstract AIDS-associated, CCR5-tropic (R5 HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors 1. In contrast to other reports 123, this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.

Resíduo industrial como matéria-prima alternativa para a produção de filtros cerâmicos refratários

OpenAIRE

Carvalho,A. C.; Raupp-Pereira,F.; Rodrigues Neto,J. B.; Oliveira,A. P. Novaes de

2015-01-01

ResumoO desenvolvimento de atividades de valorização de resíduos sólidos pode viabilizar a produção de produtos industriais com elevado potencial de reaproveitamento como fonte alternativa mineral. Atualmente, os resíduos sólidos industriais tornaram-se uma importante linha de pesquisa na área de Engenharia. Apesar disso, poucos estudos têm sido realizados com interação efetiva de parâmetros ambientais, econômicos e sociais que demonstram aplicações destas matérias-primas pela indústria de tr...

Tradução Oral à Prima Vista na formação do intérprete: considerações pedagógicas

OpenAIRE

Gloria Regina Loreto Sampaio

2017-01-01

A Tradução Oral à Prima Vista (TrPV) é um elemento de relevância para a formação do intérprete e um componente essencial para o desempenho do futuro profissional em muitos ambientes de atuação. Consequentemente, a prática da TrPV se faz presente em cursos de formação bem estruturados. Neste escrito, após uma breve referência à natureza, complexidade e desafios impostos pela TrPV, e tendo como base uma vivência docente extensa da autora, será apresentada uma possível abordagem pedagógica, volt...

Biocompatible Silver-containing a-C:H and a-C coatings: AComparative Study

Energy Technology Data Exchange (ETDEWEB)

Endrino, Jose Luis; Allen, Matthew; Escobar Galindo, Ramon; Zhang, Hanshen; Anders, Andre; Albella, Jose Maria

2007-04-01

Hydrogenated diamond-like-carbon (a-C:H) and hydrogen-free amorphous carbon (a-C) coatings are known to be biocompatible and have good chemical inertness. For this reason, both of these materials are strong candidates to be used as a matrix that embeds metallic elements with antimicrobial effect. In this comparative study, we have incorporated silver into diamond-like carbon (DLC) coatings by plasma based ion implantation and deposition (PBII&D) using methane (CH4) plasma and simultaneously depositing Ag from a pulsed cathodic arc source. In addition, we have grown amorphous carbon - silver composite coatings using a dual-cathode pulsed filtered cathodic-arc (FCA) source. The silver atomic content of the deposited samples was analyzed using glow discharge optical spectroscopy (GDOES). In both cases, the arc pulse frequency of the silver cathode was adjusted in order to obtain samples with approximately 5 at.% of Ag. Surface hardness of the deposited films was analyzed using the nanoindentation technique. Cell viability for both a-C:H/Ag and a-C:/Ag samples deposited on 24-well tissue culture plates has been evaluated.

Development of an in vitro potency assay for human skeletal muscle derived cells.

Science.gov (United States)

Thurner, Marco; Asim, Faheem; Garczarczyk-Asim, Dorota; Janke, Katrin; Deutsch, Martin; Margreiter, Eva; Troppmair, Jakob; Marksteiner, Rainer

2018-01-01

Potency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals. CD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence. CD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected. AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal

Biophysical characterization of inwardly rectifying potassium currents (I(K1) I(K,ACh), I(K,Ca)) using sinus rhythm or atrial fibrillation action potential waveforms

DEFF Research Database (Denmark)

Tang, Chuyi; Skibsbye, Lasse; Yuan, Lei

2015-01-01

Although several physiological, pathophysiological and regulatory properties of classical inward rectifier K+ current I(K1), G-protein coupled inwardly-rectifying K+ current I(K,ACh) and the small-conductance Ca2+ activated K+ current I(K,Ca) have been identified, quantitative biophysical details...

Utilización de cenizas volantes y mineralizadores como materia prima en la fabricación de cemento

Directory of Open Access Journals (Sweden)

Palomo Sánchez, Ángel

1983-03-01

Full Text Available In this research the process of formation of a low energy clinker is studied, when fly-ashes (rich in sulphates and lime and fluorspar are used as raw materials (fly-ashes replaces to the tradicional raw mix partially. The availability of those fly-ashes is shown since clinker at 1.340 °C is obtained. The mineralogical composition, mineralizer capacity and temperature of formation of the new liquid phase is studied.

En el presente trabajo se estudia el proceso de formación de un clínker de bajo consumo energético, empleando como materia prima cenizas volantes sulfocálcicas (en sustitución parcial del crudo tradicional y fluorita. Se demuestra la validez de dichas cenizas volantes, obteniendo clínker a 1.340 °C. Se estudia la composición mineralógica, capacidad de mineralización y temperatura de formación de la nueva fase líquida.

Clasificación en tiempo real de materias primas mediante un sensor espectroscópico de imagen y técnicas lineales de procesado de datos

OpenAIRE

García Allende, Pilar Beatriz; Conde Portilla, Olga María; Mirapeix Serrano, Jesús María; Cubillas de Cos, Ana María; López Higuera, José Miguel

2007-01-01

RESUMEN: En este artículo se presenta un nuevo método de procesado de imágenes hiperespectrales capturadas mediante un sensor espectroscópico de imagen. Basado en un algoritmo de clasificación lineal, permite mejorar las restricciones de tiempo real que planteaba un sistema de clasificación de materia prima diseñado previamente. El procesado de datos consta de dos bloques: compresión de características e interpretación de las mismas. La compresión se realiza empleando Análisis de Componentes ...

DIAGNÓSTICO DOS FORNECEDORES DE MATÉRIA-PRIMA DA CONQUISTA MONTANHISMO: A IMPORTÂNCIA DA GESTÃO DA QUALIDADE PARA O DESENVOLVIMENTO DA ORGANIZAÇÃO [doi: 10.5329/RECADM.20050402003

Directory of Open Access Journals (Sweden)

Sandro Antonio Malinowski

2005-11-01

Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 Resumo Este trabalho pretende propor um procedimento operacional objetivo para avaliar e qualificar os fornecedores de matéria-prima e insumos da Conquista Equipamentos para Montanhismo, segundo os critérios de avaliação da Norma ISO 9001:2000 item 7.4.1 – que trata do processo de aquisição. Os fornecedores de matéria-prima e insumos são avaliados segundo os seguintes critérios: entrega de pedidos, atendimento, qualidade dos produtos ou serviços apresentados e pelo interesse na resolução de problemas decorrentes do fornecimento. Nesse sentido, realizamos entre outubro e dezembro de 2003 uma pesquisa com cento e sete empresas que fornecem matéria-prima para a Conquista Montanhismo. Com a pesquisa pretendemos obter indicadores de desempenho que permitam à Conquista Montanhismo conhecer melhor seus fornecedores e conseqüentemente melhorar a qualidade de seus produtos.   Palavras-chave: organização, qualidade, fornecedores, clientes.   Abstract This work intends to consider an objective operational procedure to evaluate and to characterize the raw material suppliers and insumos of the Conquest Equipment, according to criteria of evaluation of Norm ISO 9001:2000 item 7.4.1 - that it deals with the acquisition process. The raw material suppliers and insumos are evaluated according to following criteria: delivery of order, attendance, presented product quality or services and interest in the resolution of decurrent problems of the supply. In this direction, we carry through between October and December of 2003 a research with one hundred and seven companies who supply raw material the Montanhismo Conquest. With the research we intend to get performance pointers that allow the Montanhismo Conquest to know its suppliers better and consequently to improve the quality of its products.   Key Words: organization, quality, suppliers, customers.

Changes in parasympathetic system in medulla oblongata in male pigs in the course of tachycardia-induced cardiomyopathy.

Science.gov (United States)

Tomaszek, Alicja; Kiczak, Liliana; Bania, Jacek; Krupa, Paweł; Pasławska, Urszula; Zacharski, Maciej; Janiszewski, Adrian; Stefaniak, Tadeusz; Zyśko, Dorota; Ardehali, Hossein; Jankowska, Ewa A; Ponikowski, Piotr

2013-10-01

Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. α7 nicotinic acetylcholine receptor (α7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy. The mRNA levels of AChE, ChAT, α7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of α7nAChR using Western blotting. The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and α7nAChR mRNA in MO, an increase in AChE activity (all pmedulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF. Copyright © 2013 Elsevier B.V. All rights reserved.

Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif

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Leonardo Pisani

2016-03-01

Full Text Available The need for developing real disease-modifying drugs against neurodegenerative syndromes, particularly Alzheimer’s disease (AD, shifted research towards reliable drug discovery strategies to unveil clinical candidates with higher therapeutic efficacy than single-targeting drugs. By following the multi-target approach, we designed and synthesized a novel class of dual acetylcholinesterase (AChE-monoamine oxidase B (MAO-B inhibitors through the decoration of the 2H-chromen-2-one skeleton. Compounds bearing a propargylamine moiety at position 3 displayed the highest in vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 µM and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM. Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM under oxidative stress conditions promoted by two mitochondrial toxins (oligomycin-A and rotenone. In a Madin-Darby canine kidney (MDCKII-MDR1 cell-based transport study, Compound 3h was able to permeate the BBB-mimicking monolayer and did not result in a glycoprotein-p (P-gp substrate, showing an efflux ratio = 0.96, close to that of diazepam.

IMPACTO DEL MATERIAL RECICLADO EN LOS INVENTARIOS DE MATERIAS PRIMAS DE UNA EMPRESA MANUFACTURERA

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Guillermo Antonio Salinas López

Full Text Available En el presente trabajo, se diseña un modelo de dinámica de sistemas, que junto con algunos indicadores de gestión, se usan para dimensionar el impacto del uso del material reciclado en una industria. Lo anterior, con el fin de proveer mejores elementos en la toma de decisiones sobre la gestión de las existencias de materias primas. Para esto se hace una revisión de los principales elementos que inciden en el esquema productivo de una empresa caso de estudio, con la cual se obtiene, una caracterización de la industria y posterior configuración de la estructura y las relaciones del sistema, para modelar y simular utilizando el software Vensim DSS. A partir de dichas simulaciones, se revisa el comportamiento del sistema, así como las variaciones que presenta, ante diferentes escenarios y cambios en sus parámetros más relevantes. Al final, se obtiene un modelo que ilustra el comportamiento de los niveles de inventario de distintos tipos de materiales, así como los valores de algunos indicadores logísticos y energéticos, que revelan el importante trabajo por realizar, en materia de reciclaje en la región del Valle del Cauca y Colombia en general.

Neurotrophin-4 couples to locally modulated ACh release at the end of neuromuscular synapse maturation.

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Garcia, N; Santafe, M M; Tomas, M; Lanuza, M A; Besalduch, N; Tomas, J

2010-01-01

We use immunocytochemistry to show that neurotrophin-4 (NT-4) and its receptor proteins (p75(NTR) and tropomyosin-related tyrosine kinase B) are present in neonatal neuromuscular junctions (NMJ) colocalized with several synaptic markers. NT-4 incubation (1h, in the range 2-12 nM) does not change the size of the endplate potential between P6 and P45. However, extended exposure (3h) to a relatively low dose of NT-4 (2 nM) potentiates ACh release (approx. 70%) in adult but not in neonatal muscles. The present results suggest that the developmental mechanism of axonal competition and neonatal elimination of redundant synapses cannot be modulated by added NT-4. However, this neurotrophin was able to modulate synaptic transmission locally in the adult NMJ.

The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: the influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents.

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Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L; Gündisch, Daniela

2013-12-01

3,7-Diazabicyclo[3.3.1]nonane is a naturally occurring scaffold interacting with nicotinic acetylcholine receptors (nAChRs). When one nitrogen of the 3,7-diazabicyclo[3.3.1]nonane scaffold was implemented in a carboxamide motif displaying a hydrogen bond acceptor (HBA) functionality, compounds with higher affinities and subtype selectivity for α4β2(∗) were obtained. The nature of the HBA system (carboxamide, sulfonamide, urea) had a strong impact on nAChR interaction. High affinity ligands for α4β2(∗) possessed small alkyl chains, small un-substituted hetero-aryl groups or para-substituted phenyl ring systems along with a carboxamide group. Electrophysiological responses of selected 3,7-diazabicyclo[3.3.1]nonane derivatives to Xenopus oocytes expressing various nAChR subtypes showed diverse activation profiles. Compounds with strongest agonistic profiles were obtained with small alkyl groups whereas a shift to partial agonism/antagonism was observed for aryl substituents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

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Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

2014-11-01

Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. Copyright © 2014 Elsevier B.V. All rights reserved.

Process control by optical emission spectroscopy during growth of a-C:H from a CH₄ plasma by plasma-enhanced chemical vapour deposition

DEFF Research Database (Denmark)

Barholm-Hansen, C; Bentzon, MD; Vigild, Martin Etchells

1994-01-01

During the growth of a-C:H thin films for tribological applications, the characteristic optical emission from a CH4 plasma was used to estimate growth conditions such as the degree of dissociation of the feed gas, the deposition rate and the presence of impurities. Films were fabricated with vari...

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

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Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Morphology, optical and electrical properties of Cu-Ni nanoparticles in a-C:H prepared by co-deposition of RF-sputtering and RF-PECVD

Energy Technology Data Exchange (ETDEWEB)

Ghodselahi, T., E-mail: ghodselahi@ipm.ir [School of Physics, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of); Vesaghi, M.A. [School of Physics, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of); Department of Physics, Sharif University of Technology, P.O. Box 11365-9161, Tehran (Iran, Islamic Republic of); Gelali, A.; Zahrabi, H.; Solaymani, S. [Young Researchers Club, Islamic Azad University, Kermanshah Branch, Kermanshah (Iran, Islamic Republic of)

2011-11-01

We report optical and electrical properties of Cu-Ni nanoparticles in hydrogenated amorphous carbon (Cu-Ni NPs - a-C:H) with different surface morphology. Ni NPs with layer thicknesses of 5, 10 and 15 nm over Cu NPs - a-C:H were prepared by co-deposition of RF-sputtering and RF-Plasma Enhanced Chemical Vapor Deposition (RF-PECVD) from acetylene gas and Cu and Ni targets. A nonmetal-metal transition was observed as the thickness of Ni over layer increases. The surface morphology of the sample was described by a two dimensional (2D) Gaussian self-affine fractal, except the sample with 10 nm thickness of Ni over layer, which is in the nonmetal-metal transition region. X-ray diffraction profile indicates that Cu NPs and Ni NPs with fcc crystalline structure are formed in these films. Localized Surface Plasmon Resonance (LSPR) peak of Cu NPs is observed around 600 nm in visible spectra, which is widen and shifted to lower wavelengths as the thickness of Ni over layer increases. The variation of LSPR peak width correlates with conductivity variation of these bilayers. We assign both effects to surface electron delocalization of Cu NPs.

Design, synthesis, biological evaluation and docking study of 5-oxo-4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors.

Science.gov (United States)

Khoobi, Mehdi; Alipour, Masoumeh; Sakhteman, Amirhossein; Nadri, Hamid; Moradi, Alireza; Ghandi, Mehdi; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas

2013-10-01

A series of fused coumarins namely 5-oxo-4,5-dihydropyrano[3,2-c]chromenes linked to N-benzylpyridinium scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The 1-(4-fluorobenzyl)pyridinium derivative 6g showed the most potent anti-AChE activity (IC50 value=0.038 μM) and the highest AChE/BuChE selectivity (SI>48). The docking study permitted us to rationalize the observed structure-affinity relationships and to detect possible binding modes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Thin films of hydrogenated amorphous carbon (a-C:H) obtained through chemical vapor deposition assisted by plasma

International Nuclear Information System (INIS)

Mejia H, J.A.; Camps C, E.E.; Escobar A, L.; Romero H, S.; Chirino O, S.; Muhl S, S.

2004-01-01

Films of hydrogenated amorphous carbon (a-C:H) were deposited using one source of microwave plasma with magnetic field (type ECR), using mixtures of H 2 /CH 4 in relationship of 80/20 and 95/05 as precursory gases, with work pressures of 4X10 -4 to 6x10 -4 Torr and an incident power of the discharge of microwaves with a constant value of 400 W. It was analyzed the influence among the properties of the films, as the deposit rate, the composition and the bonding types, and the deposit conditions, such as the flow rates of the precursory gases and the polarization voltage of the sample holders. (Author)

Examen de auditoría integral al componente primas por cobrar de Seguros Sucre S.A. correspondiente al periodo del 01 enero 2012 al 31 diciembre del 2012

OpenAIRE

Merrill Ochoa, Yanina Alexandra

2014-01-01

La elaboración del presente trabajo comprende el desarrollo del examen de auditoría integral al componente primas por cobrar de Seguros Sucre S.A. correspondiente al periodo del 01 enero 2012 al 31 diciembre 2012. El examen se basa en la normativa aplicable al sector asegurador y documentación interna como manuales de políticas y procedimientos del proceso evaluado. Se podrán encontrar capítulos que generan una retrospectiva general del negocio de los seguros y cuál es la importancia del co...

Differential Expression of P450 Genes and nAChR Subunits Associated With Imidacloprid Resistance in Laodelphax striatellus (Hemiptera: Delphacidae).

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Zhang, Yueliang; Liu, Baosheng; Zhang, Zhichun; Wang, Lihua; Guo, Huifang; Li, Zhong; He, Peng; Liu, Zewen; Fang, Jichao

2018-05-28

Imidacloprid is a key insecticide used for controlling sucking insect pests, including the small brown planthopper (Laodelphax striatellus, Fallén) (Hemiptera: Delphacidae), an important agricultural pest of rice. A strain of L. striatellus (YN-ILR) developed 21-fold resistance when selected with imidacloprid on a susceptible YN strain. An in vitro study on piperonyl butoxide synergism indicated that enhanced detoxification mediated by cytochrome P450s contributed to imidacloprid resistance to some extent, and multiple P450 genes showed altered expression in the imidacloprid-resistant YN-ILR strain compared with the susceptible YN strain (CYP425B1-CYP6BD10 had 1.51- to 11.45-fold higher expression, CYP4CE2-CYP4DD1V2 had 0.12- to 0.57-fold lower expression). While there were no mutations in target nicotinic acetylcholine receptor (nAChR) genes, subunits of Lsα1, Lsβ1, and Lsβ3 in the YN-ILR strain showed 3.86-, 4.39-, and 2.59-fold higher expression and Lsa8 displayed 0.38-fold lower expression than the YN strain. Moreover, 21-fold moderate imidacloprid resistance in individuals of L. striatellus did not produce a fitness cost. The findings suggest that L. striatellus has the capacity to develop resistance to imidacloprid through P450 detoxification and potential target nAChR expression changes, and moderate imidacloprid resistance was not associated with a fitness cost.

Wnt3a induces the expression of acetylcholinesterase during osteoblast differentiation via the Runx2 transcription factor.

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Xu, Miranda L; Bi, Cathy W C; Liu, Etta Y L; Dong, Tina T X; Tsim, Karl W K

2017-07-28

Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, non-neuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation. Because several lines of evidence indicate that AChE activity in osteoblast could be triggered by Wnt/β-catenin signaling, we added recombinant human Wnt3a to cultured osteoblasts and found that this addition induced expression of the ACHE gene and protein product. This Wnt3a-induced AChE expression was blocked by the Wnt-signaling inhibitor Dickkopf protein-1 (DKK-1). We hypothesized that the Runt-related transcription factor 2 (Runx2), a downstream transcription factor in Wnt/β-catenin signaling, is involved in AChE regulation in osteoblasts, confirmed by the identification of a Runx2-binding site in the ACHE gene promoter, further corroborated by ChIP. Of note, Runx2 overexpression in osteoblasts induced AChE expression and activity of the ACHE promoter tagged with the luciferase gene. Moreover, deletion of the Runx2-binding site in the ACHE promoter reduced its activity during osteoblastic differentiation, and addition of 5-azacytidine and trichostatin A to differentiating osteoblasts affected AChE expression, suggesting epigenetic regulation of the ACHE gene. We conclude that AChE plays a role in osteoblastic differentiation and is regulated by both Wnt3a and Runx2. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Sucralose induces biochemical responses in Daphnia magna.

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Ann-Kristin Eriksson Wiklund

Full Text Available The intense artificial sweetener sucralose has no bioconcentration properties, and no adverse acute toxic effects have been observed in standard ecotoxicity tests, suggesting negligible environmental risk. However, significant feeding and behavioural alterations have been reported in non-standard tests using aquatic crustaceans, indicating possible sublethal effects. We hypothesized that these effects are related to alterations in acetylcholinesterase (AChE and oxidative status in the exposed animals and investigated changes in AChE and oxidative biomarkers (oxygen radical absorbing capacity, ORAC, and lipid peroxidation, TBARS in the crustacean Daphnia magna exposed to sucralose (0.0001-5 mg L(-1. The sucralose concentration was a significant positive predictor for ORAC, TBARS and AChE in the daphnids. Moreover, the AChE response was linked to both oxidative biomarkers, with positive and negative relationships for TBARS and ORAC, respectively. These joint responses support our hypothesis and suggest that exposure to sucralose may induce neurological and oxidative mechanisms with potentially important consequences for animal behaviour and physiology.

Autoantibodies to neuronal antigens in children with focal epilepsy and no prima facie signs of encephalitis.

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Borusiak, Peter; Bettendorf, Ulrich; Wiegand, Gert; Bast, Thomas; Kluger, Gerhard; Philippi, Heike; Münstermann, Dieter; Bien, Christian G

2016-07-01

There is increasing awareness of neuronal autoantibodies and their impact on the pathogenesis of epilepsy. We investigated children with focal epilepsy in order to provide an estimate of autoantibody frequency within a pediatric population without prima facie evidence of encephalitis using a broad panel of autoantibodies. This was done to assess the specificity of antibodies and to see whether antibodies might be of modifying influence on the course of focal epilepsies. We searched for autoantibodies in 124 patients with focal epilepsy (1-18 years; mean 10; 6 years). Sera were tested using a broad panel of surface and intracellular antigens. We found autoantibodies in 5/124 patients (4%): high-positive GAD65 antibodies (n = 1), low-positive GAD65 antibodies (N = 1), VGKC complex antibodies not reactive with LGI1 or CASPR2 (n = 3). We did not find any distinctive features distinguishing antibody positive patients from those without antibodies. The antibodies found in this cohort are probably neither disease-specific nor pathogenic. This has been suggested before for these antigenic targets. Moreover, they do not seem to modify disease severity in the antibody-positive epilepsy patients. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Bioorthogonal Chemistry for the Isolation and Study of Newly Synthesized Histones and Their Modifications.

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Arnaudo, Anna M; Link, A James; Garcia, Benjamin A

2016-03-18

The nucleosome is an octamer containing DNA wrapped around one histone H3-H4 tetramer and two histone H2A-H2B dimers. Within the nucleosome, histones are decorated with post-translational modifications. Previous studies indicate that the H3-H4 tetramer is conserved during DNA replication, suggesting that old tetramers serve as a template for the modification of newly synthesized tetramers. Here, we present a method that merges bioorthogonal chemistry with mass spectrometry for the study of modifications on newly synthesized histones in mammalian cells. HeLa S3 cells are dually labeled with the methionine analog azidohomoalanine and heavy (13)C6,(15)N4 isotope labeled arginine. Heavy amino acid labeling marks newly synthesized histones while azidohomoalanine incorporation allows for their isolation using bioorthogonal ligation. Labeled mononucleosomes were covalently linked via a copper catalyzed reaction to a FLAG-GGR-alkyne peptide, immunoprecipitated, and subjected to mass spectrometry for quantitative modification analysis. Mononucleosomes containing new histones were successfully isolated using this approach. Additionally, the development of this method highlights the potential deleterious effects of azidohomoalanine labeling on protein PTMs and cell cycle progression, which should be considered for future studies utilizing bioorthogonal labeling strategies in mammalian cells.

La Génesis de los Universales en Prasastapada y la Génesis de Los Principia Prima y los Universales en Aristóteles

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Fernando Tola

2015-03-01

Full Text Available En este artículo los autores ofrecen un nuevo caso en soporte de su tesis concerniente a las frecuentes coincidencias temáticas en las Filosofías de la India y de Occidente, que ellos han desarrolladoen especial en sus libros On the Myth of the Opposition between Indian Thought and Western Philosophy, Hildesheim: Olms Verlag, 2004, reseñado por Ernst Steinkellner en Wiener Zeitschrift fürdie Kunde Südasiens Band XLVIII 2004, 224-225, y Yoga. Un Camino Místico Universal, Barcelona: Editorial Kairós, 2006. Dicha tesis apunta a lo que podríamos llamar una suerte de globalidad intrínseca del pensar filosófico, más allá de la cultura de que se trate. Prasastapada (circa segunda mitad del siglo VII d.C., en Prasastapadabhasya (llamado también Padarthadharmasngraha, Libro V: Samanyapadarthanirupana, da dos descripciones de la génesis de los universales. Describe primeramente de una manera abstracta y concisa el proceso de surgimiento de todo samanya, «universal», y después explica de una manera más concreta el surgimiento del universal inferior y del superior (satta, «la existencia», a través de la reiteración de la percepción de objetos que presentan similares atributos y de la intervención del recuerdo de percepciones similares pasadas. Aristóteles (siglo IV a.C., en Analytica Posteriora, Libro II, Capítulo XIX, y Temistio (circa 317-circa387, en su comentario, explican a su vez el modo en que son aprehendidos los principios universales o premisas de la demostración (principia prima. Los autores de este artículo muestran cómo la descripción de Aristóteles y Temistio de la génesis de los principia prima y los universales concuerda de manera sorprendente con la de Prasastapada concerniente a los universales.

O Monte das Ferraduras (Fentáns, Cotobade: novos achádegos de arte rupestre. Descripción e interpretación

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Quintas González, Fernando

2008-12-01

Full Text Available In these lines we present the description and interpretation of a new rock engraving found in O Monte das Ferraduras (Fentáns, Galiza. This finding, was the result of an intensive exploration in the area, the most outstanding of this panel is one possible representation of a “rossa camuna” design unknown in the northwest of the Iberian Peninsula.
We think therefore, this is singular finding deserve an analisys about parallels found in Western Europe, it will help us to understand the chronological contexts of this panel.

Nestas liñas, preséntase a descrición e interpretación dun novo petróglifo atopado en O Monte das Ferraduras, (Fentáns, Cotobade. Este achádego foi froito dunha prospección intensiva na zona, o máis chamativo deste panel é unha posible representación dunha “rosa camuna”, deseño éste descoñecido no noroeste la Península Ibérica.
Cremos, polo tanto, que ante a singularidade do achádego, deberíamos dar a coñecer cales son as características desta rocha, así como presentar os paralelismos atopados con Europa Occidental que, nos axudarán a comprender os contextos cronológicos nos que se ubica dita rocha.

Adsorption of alcohols and fatty acids onto hydrogenated (a-C:H) DLC coatings

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Simič, R.; Kalin, M.; Kovač, J.; Jakša, G.

2016-02-01

Information about the interactions between lubricants and DLC coatings is scarce, despite there having been many studies over the years. In this investigation we used ToF-SIMS, XPS and contact-angle analyses to examine the adsorption ability and mechanisms with respect to two oiliness additives, i.e., hexadecanol and hexadecanoic acid, on an a-C:H coating. In addition, we analyzed the resistance of the adsorbed films to external influences like solvent cleaning. The results show that both molecules adsorb onto surface oxides and hydroxides present on the initial DLC surface and shield these structures with their hydrocarbon tails. This makes the surfaces less polar, which is manifested in a smaller polar component of the surface energy. We also showed that ultrasonic cleaning in heptane has no significant effect on the quantity of adsorbed molecules or on their chemical state. This not only shows the relatively strong adsorption of these molecules, but also provides useful information for future experimental work. Of the two examined molecules, the acid showed a greater adsorption ability than the alcohol, which explains some of the previously reported better tribological properties in the case of the acid with respect to the alcohol.

Ramalina farinacea (L. Ach. ve Usnea intermedia (A.Massal. Jatta Likenlerinin Antimikrobiyal Aktiviteleri Üzerine Araştırmalar

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Neslihan ŞİRİN

2015-04-01

Full Text Available Bu çalışmada Bursa-Uludağ Milli Park civarından toplanan Ramalina farinacea (L. Ach. ve Usnea intermedia (A. Massal. Jatta likenlerinin Bacillus cereus ATCC 7064, Bacillus licheniformis ATCC 14580, Citrobacter freundii ATCC 8090, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25992, Klebsiella oxytoca ATCC 8724, Listeria innocua ATCC 33090, Proteus vulgaris ATCC 8427, Pseudomonas aeruginosa ATCC 27853, Salmonella enteridis ATCC 13076, Salmonella typhimurium CCM 5445, Shigella flexneri ATCC 12022, Staphylococcus aureus ATCC 6538P, Staphylococcus epidermidis ATCC 3699, Streptococcus pyogenes ATCC 19615, Yersinia pestis ATCC 19428, Candida albicans ATCC 90028, Candida glabrata ATCC 90030, Candida lipolytica ATCC 8660, Candida parapsilosis ATCC 22019, Candida tropicalis ATCC 4563, Cryptococcus neoformans ATCC 32045, Debaryomyces hansenii DSM 70238,  Saccharomyces cerevisiae ATCC 9796 türlerine karşı antimikrobiyal aktiviteleri araştırılmıştır.Bulgulara göre; Ramalina farinacea (L. Ach. likeninin en yüksek antimikrobiyal aktivitesi Salmonella enteritidis ATCC 13076 ve Candida albicans ATCC 90028 türlerine karşı bulunurken, Usnea intermedia (A. Massal Jatta likeninin en yüksek antimikrobiyal aktivitesi Streptococcus pyogenes ATCC 19615 ve Candida albicans ATCC 90028 türlerinde ölçülmüştür. Liken türlerinin diğer tüm mikroorganizmalara karşı farklı seviyelerde antimikrobiyal aktivite gösterdikleri saptanmıştır.Anahtar Kelimeler: Antimikrobiyal Aktivite, Ramalina farinacea, Usnea intermedia

Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients

Science.gov (United States)

Nordberg, Agneta; Darreh-Shori, Taher; Peskind, Elaine; Soininen, Hilkka; Mousavi, Malahat; Eagle, Gina; Lane, Roger

2014-01-01

Background The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings AD patients aged 50–85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman’s colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2%increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID:19199870

Determination of spirocyclic tetronic/tetramic acid derivatives and neonicotinoid insecticides in fruits and vegetables by liquid chromatography and mass spectrometry after dispersive liquid-liquid microextraction.

Science.gov (United States)

Pastor-Belda, Marta; Garrido, Isabel; Campillo, Natalia; Viñas, Pilar; Hellín, Pilar; Flores, Pilar; Fenoll, José

2016-07-01

Dispersive liquid-liquid microextraction was used to preconcentrate three spirocyclic tetronic/tetramic acid derivatives (spirotetramat, spiromesifen and spirodiclofen) and five neonicotinoid (thiamethoxam, chlotianidin, imidacloprid, acetamiprid and thiacloprid) insecticides previously extracted from fruit and vegetable matrices with acetonitrile. The organic enriched phase was evaporated, reconstituted in 25μL acetonitrile and analyzed by reversed-phase liquid chromatography with tandem mass spectrometry using a triple quadrupole in selected reaction monitoring mode. Enrichment factors in the 15-100 range were obtained. A matrix effect was observed, the detection limits varying between 0.025 and 0.5ngg(-1), depending on the compound and the sample matrix. The developed method was applied to the analysis of 25 samples corresponding to five different fruit and vegetable matrices. Only thiamethoxam was detected in a lemon sample at a concentration close to the quantification limit, and spiromesifen and spirotetramat at concentrations between 11.6 and 54.5ngg(-1). Copyright © 2016 Elsevier Ltd. All rights reserved.

A liberdade de expressão como direito fundamental preferencial prima facie (análise crítica e proposta de revisão ao padrão jurisprudencial brasileiro)

OpenAIRE

Cláudio Márcio de Carvalho Chequer

2010-01-01

Em um Estado Democrático de Direito, o direito fundamental à liberdade de expressão deve ser tratado de forma heterogênea, sendo capaz de gozar de um status de direito fundamental preferencial prima facie nas hipóteses em que estiver relacionado a um tema de interesse público, tendo em vista a ocorrência de duas premisssas existentes nesses casos: a do direito que a sociedade tem de saber a respeito dos assuntos de interesse público e a do dever que a imprensa tem de informar a respeito desse...

De la escena ritual a la teatral en una obra de teatro indígena prehispánico: Rabinal Achí o Danza del Tun From Ritual to Theatre Stage in a Pre-Hispanic Indigenous Drama: Rabinal Achí or Danza del Tun

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Patricia Henríquez Puentes

2008-12-01

Full Text Available El Rabinal Achí o Danza del Tun es arte escénico fundacional del teatro latinoamericano y clave para el proceso de desarrollo del teatro occidental del siglo XX, en tanto cifra ese momento en el que rito y teatro se contenían mutuamente, es decir, en que el espectáculo se hacía a los ojos de Dios y de los hombres. La propuesta escénica entonces, difuminaba los límites entre el espacio destinado al espectador y al actor; la flor y el canto, es decir, la expresión artística, se ampliaba en el tiempo y el espacio invadiendo todas las esferas de lo social; la comunidad vivenciaba la experiencia de revinculación con la divinidad, restableciendo el cíclico equilibrio cósmico; el espectáculo operaba como catalizador de una experiencia espiritual y el actor, como su facilitador.The Rabinal Achí or Dance of the Tun is a founding theatrical play of Latin-American theatre and key for the development process of western theatre during the 20th century; it encodes the moment in which rite and theatre were mutually contained, i.e., in that the spectacle was done for the eyes of God and man. The stage design at the time, blurred the limits between the space destined for the spectator and for the actor; flower and song, i.e., the artistic expression, it was extended in time and space invading all the social spheres; the community underwent the experience of reconnecting with divinity, re-establishing the cyclical cosmic balance; the spectacle operated as a catalyst of a spiritual experience and the actor, as its facilitator.

alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H

2009-01-01

in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

Physiological response of the lichen Phaeophyscia hispidula (Ach.) Essl., to the urban environment of Pauri and Srinagar (Garhwal), Himalayas, India.

Science.gov (United States)

Shukla, Vertika; Upreti, Dalip K

2007-12-01

The present study was designed with an aim to observe the effect of increasing urbanization and traffic activity on the physiology of a foliose lichen, Phaeophyscia hispidula (Ach.) Essl., collected from 13 different localities, growing in their natural habitat, in Pauri and Srinagar, two cities in the Himalayas. Six parameters i.e., Chl. a, Chl. b, total pigment, chlorophyll degradation, carotenoid and total protein content, proved the most useful to assess air pollution, were measured. Chlorophyll content and protein content are an efficient parameter to measure the air quality of a region. The study indicates that P. hispidula is pollution tolerant (adaptation) and able to withstand local emissions from vehicle exhausts.

APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium.

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Li, Jing; Li, Cheng; Wang, Guoliang; Liu, Zhen; Chen, Pei; Yang, Qichen; Dong, Nuo; Wu, Huping; Liu, Zuguo; Li, Wei

2016-02-01

Squamous metaplasia is a common pathologic condition in ocular surface diseases for which there is no therapeutic medication in clinic. In this study, we investigated the effect of a small molecule, APR-246/PRIMA-1(Met), on squamous metaplasia in human conjunctival epithelium. Human conjunctival explants were cultured for up to 12 days under airlifting conditions. Epithelial cell differentiation and proliferation were assessed by Cytokeratin 10 (K10), K14, K19, Pax6, MUC5AC, and p63 immunostaining patterns. β-catenin and TCF-4 immunofluorescent staining and real-time PCR characterized Wnt signaling pathway involvement. Pterygium clinical samples were cultured under airlifting conditions with or without APR-246 for 4 days. p63, K10, β-catenin, and TCF-4 expression in pterygial epithelium was determined by immunofluorescent staining and real-time PCR. Airlift conjunctival explants resulted in increased stratification and intrastromal epithelial invagination. Such pathology was accompanied by increases in K10, K14, and p63 expression, whereas K19 and Pax6 levels declined when compared to those in freshly isolated tissue. On the other hand, APR-246 reversed all of these declines in K10, K14, and p63 expression. Furthermore, K19 and Pax6 increased along with rises in goblet cell density. These effects of APR-246 were accompanied by near restoration of normal conjunctival epithelial histology. APR-246 also reversed squamous metaplasia in pterygial epithelium that had developed after 4 days in ex vivo culture. Reductions in squamous metaplasia induced by APR-246 suggest it may provide a novel therapeutic approach in different squamous metaplasia-associated ocular surface diseases.

A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

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Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

2009-06-01

Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

Energy Technology Data Exchange (ETDEWEB)

Liu, Guodong; Wang, Jun; Barry, Richard C.; Petersen, Catherine E.; Timchalk, Charles; Gassman, Paul L.; Lin, Yuehe

2008-11-01

A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.

Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and α-glucosidase inhibitory activity of Cynometra cauliflora L. leaves.

Science.gov (United States)

Ado, Muhammad Abubakar; Abas, Faridah; Ismail, Intan Safinar; Ghazali, Hasanah M; Shaari, Khozirah

2015-02-01

The aim of the current study was (i) to evaluate the bioactive potential of the leaf methanolic extract of Cynometra cauliflora L., along with its respective hexane, dichloromethane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and aqueous fractions, in inhibiting the enzymes α-glucosidase, acetylcholinesterase (AChE) and tyrosinase as well as evaluating their antioxidant activities. (ii) In addition, in view of the limited published information regarding the metabolite profile of C. cauliflora, we further characterized the profiles of the EtOAc and n-BuOH fractions using liquid chromatography-diode array detection-electrospray ionization-tandem mass spectrometry. The leaf methanolic extract of C. cauliflora exhibited potent inhibition of all three enzymes and high antioxidant activity. The bioactivity was found to be concentrated in the EtOAc and n-BuOH fractions. A total of 18 compounds were identified in these bioactive fractions, comprising a procyanidin trimer, procyanidin tetramer, procyanidin hexamer, taxifolin pentoside, catechin, vitexin, isovitexin, kaempferol hexoside, quercetin pentoside, quercetin hexoside, apigenin-6-C-glucoside-8-C-glucoside, kaempferol-coumaroyl hexoside and isorhamnetin hexoside. The results indicated that C. cauliflora, the leaves in particular, is a rich source of bioactive compounds and could be beneficial for further development of high-value phytomedicinal preparations and functional food products. © 2014 Society of Chemical Industry.

Características generales, propiedades, yacimientos y aplicaciones de pirofilita. II. Yacimientos, aplicaciones y utilización como materia prima cerámica

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Sánchez Soto, P. J.

1998-10-01

Full Text Available In this work, the main world deposits of pyrophyllite are indicated according to the literature, showing the available production data. It is emphasized the research focusing on mining and characterization of raw materials containing pyrophyllite, which shows a marked applied interest. It is described and reviewed the most relevant applications of pyrophyllite and pyrophyllite raw materials, in especial refractories and ceramics, fillers, building materials, catalysts and as a high-pressure medium for synthesis of materials. Finally, it is also described and reviewed its use as raw material for the preparation of advanced materials, such as sialon, emphasizing the possibilities of application of pyrophyllite raw materials in our country as a result of distinct investigations of relevant interest performed by several Research Institutes and University Departments. It is deduced that pyrophyllite and pyrophyllite raw materials are increasing in relative importance in many applied fields, as compared with other layer silicates, such as talc and kaolinite.

En este trabajo se indican los principales yacimientos mundiales de pirofilita según la bibliografía, los datos de producción disponibles, además de revisar las investigaciones más destacadas sobre prospección y caracterización de materias primas que contienen pirofilita y que presentan un marcado interés aplicado. Se realiza una amplia revisión de las principales aplicaciones a las que se destinan dichas materias primas, en especial para la preparación de materiales cerámicos y refractarios, su uso como carga, en la construcción, obtención de catalizadores y síntesis de materiales a alta presión debido a sus propiedades. Por último, se describen y revisan sus aplicaciones en la preparación de nuevos materiales y materiales avanzados, como son los sialones, destacando su potencial de utilización en nuestro país como resultado de diversas investigaciones de inter

La prima de riesgo recargada en un seguro de rentas: tarificación mediante el uso de una medida de riesgo coherente || The Risk Recharged Premium for a Survival Life Insurance: Recharged Premium through the Use of a Coherent Risk Measure

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Hernández Solís, Montserrat

2013-01-01

Full Text Available En este estudio se obtiene un principio de cálculo de primas, para el ramo de vida, basado en una medida de riesgo coherente, la esperanza distorsionada transformada proporcional del tanto instantáneo (Wang, 1995, que justifique la recomendación de Solvencia II de reducir, para un seguro de rentas, el efecto del tanto instantáneo de mortalidad y conseguir de este modo una prima recargada implícitamente para hacer frente a las desviaciones desfavorables de la siniestralidad real. La modalidad de seguro seleccionada parael estudio ha sido el de rentas, seguro con cobertura de supervivencia, calculándose la prima única de riesgo para las cuatro leyes de supervivencia más aceptadas, como son la primera y segunda de Dormoy, la ley de Gomperzt y la ley de Makeham. La selección de estas leyes ha sido por ser las que mejor se ajustan al modelo mediante el empleo de las tablas de mortalidad elaboradas por Pérez (2000. En los seguros de vida con cobertura de supervivencia, una experiencia de siniestralidad negativa para la compañía significa que los asegurados son más longevos de lo esperado. Así, cuando se calculan las primas, es una práctica común añadir un margen de seguridad implícito, en forma de porcentaje, a las probabilidades de fallecimiento qx, o bien emplear una tabla de mortalidad cuyas probabilidades de fallecimiento sean inferiores a las del grupo humano considerado. Esto se puede interpretar como un decremento del tanto instantáneo con un múltiplo. En este artículo se demuestra que el empleo de la función de distorsión, hasta ahora empleada en el ramo de no vida y siendo la novedad su aplicación al ramo de vida asegurador, produce este mismo efecto, pero mediante el cálculo de una prima recargada de manera implícita. || The goal of this study is to get a premium calculation principle, for the life insurance business, based on a coherent risk measure (Wang, 1995 in the form of power, called Proportional Hazards (PH

Materias primas no tradicionales en la industria cerámica

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Caligaris, R.

2000-10-01

cerámicos con el fin de mejorar sus propiedades finales. Todos los compactos, obtenidos por prensado uniaxial de estos polvos, recibieron tratamientos térmicos adecuados a sus composiciones, para luego ser caracterizados por diversas técnicas entre las que se pueden mencionar: dilatometría, difracción de rayos X, porosidad, microdureza, microscopías óptica y electrónica de barrido y análisis por dispersión de energías. Del análisis de los resultados obtenidos en estos estudios, se concluyó que los materiales ensayados constituyen una potencial fuente de materia prima para la industria cerámica.

The role of alpha-7 nicotinic receptors in food intake behaviors

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Kristina L. McFadden

2014-06-01

Full Text Available Nicotine alters appetite and energy expenditure, leading to changes in body weight. While the exact mechanisms underlying these effects are not fully established, both central and peripheral involvement of the alpha-7 nicotinic acetylcholine receptor (α7nAChR has been suggested. Centrally, the α7nAChR modulates activity of hypothalamic neurons involved in food intake regulation, including proopiomelanocortin (POMC and neuropeptide Y (NPY. α7nAChRs also modulate glutamatergic and dopaminergic systems controlling reward processes that affect food intake. Additionally, α7nAChRs are important peripheral mediators of chronic inflammation, a key contributor to health problems in obesity. This review focuses on nicotinic cholinergic effects on eating behaviors, specifically those involving the α7nAChR, with the hypothesis that α7nAChR agonism leads to appetite suppression. Recent studies are highlighted that identify links between α7nAChR expression and obesity, insulin resistance, and diabetes and describe early findings showing an α7nAChR agonist to be associated with reduced weight gain in a mouse model of diabetes. Given these effects, the α7nAChR may be a useful therapeutic target for strategies to treat and manage obesity.

Tradução Oral à Prima Vista na formação do intérprete: considerações pedagógicas

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Gloria Regina Loreto Sampaio

2017-12-01

Full Text Available A Tradução Oral à Prima Vista (TrPV é um elemento de relevância para a formação do intérprete e um componente essencial para o desempenho do futuro profissional em muitos ambientes de atuação. Consequentemente, a prática da TrPV se faz presente em cursos de formação bem estruturados. Neste escrito, após uma breve referência à natureza, complexidade e desafios impostos pela TrPV, e tendo como base uma vivência docente extensa da autora, será apresentada uma possível abordagem pedagógica, voltada à aquisição da competência em TrPV e a um desempenho de qualidade nessa modalidade híbrida, situada no espaço fronteiriço tradução escrita e tradução oral.

Determinação das emissões de dióxido de carbono das matérias primas do concreto produzido na região norte do Rio Grande do Sul

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Jair Frederico Santoro

Full Text Available Resumo O concreto é um dos materiais mais usados na construção civil no Brasil, e seu uso difundido advém da grande facilidade de execução e adaptação às mais diversas formas. Reduzir o consumo dos materiais envolvidos na produção do concreto é uma das maneiras de buscar uma maior sustentabilidade da construção civil. Estas reduções de consumo de materiais, se avaliadas levando-se em conta também os impactos que a produção e o transporte dos mesmos geram no meio ambiente, podem vir a aprimorar ou redirecionar as conclusões ou decisões a serem tomadas em relação à busca de uma maior sustentabilidade ambiental. Dentro deste enfoque foram levantadas e avaliadas as emissões de dióxido de carbono (CO2, impactos ambientais gerados quando da extração/produção e transporte até o local de utilização das matérias primas do concreto. Juntamente foram levantadas e avaliadas as emissões na produção e transporte do concreto até a obra. Dentre as conclusões do estudo constatou-se que menores resistências características do concreto produzirão menores emissões de CO2, e que a influência do transporte nas emissões é significativa devido às longas distâncias percorridas pela maior parte das matérias primas.

Effects of L-arginine and Nω-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats

Institute of Scientific and Technical Information of China (English)

Xiao-Ming Wei; Wei Yang; Li-Xia Liu; Wen-Xiu Qi

2013-01-01

Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity,learning and memory.In the present study,we assessed the effects of L-arginine and Nω-nitro-L-arginine methylester (L-NAME,a nitric oxide synthase inhibitor) on learning and memory.Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor),L-NAME,or 0.9％ NaCI (control),once daily for seven consecutive days.Twelve hours after the last injection,they underwent an electric shock-paired Y maze test.Twenty-four hours later,the rats' memory of the safe illuminated arm was tested.After that,the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit,and immunohistochemistry and Western blots,respectively.We found that,compared to controls,L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion,and made fewer errors during the memory-testing session.In contrast,L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion,and made more errors during the memory-testing session.In parallel,NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.Similarly,α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats,compared to controls.These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus,as well as with learning and memory performance in the Y-maze.

Physiological response of the lichen Phaeophyscia hispidula (Ach.) Essl., to the urban environment of Pauri and Srinagar (Garhwal), Himalayas, India

International Nuclear Information System (INIS)

Shukla, Vertika; Upreti, Dalip K.

2007-01-01

The present study was designed with an aim to observe the effect of increasing urbanization and traffic activity on the physiology of a foliose lichen, Phaeophyscia hispidula (Ach.) Essl., collected from 13 different localities, growing in their natural habitat, in Pauri and Srinagar, two cities in the Himalayas. Six parameters i.e., Chl. a, Chl. b, total pigment, chlorophyll degradation, carotenoid and total protein content, proved the most useful to assess air pollution, were measured. Chlorophyll content and protein content are an efficient parameter to measure the air quality of a region. The study indicates that P. hispidula is pollution tolerant (adaptation) and able to withstand local emissions from vehicle exhausts. - Lichen response due to ambient environmental changes

KANDUNGAN KARBON DI HUTAN RAWA GAMBUT KAWASAN KONSERVASI PT NATIONAL SAGO PRIMA, KEPULAUAN MERANTI, RIAU

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Yusi Rosalina

2013-07-01

Full Text Available This study was conducted to collect information regarding carbon storage, particularly the carbon stored in the aboveground biomass as well as in the peat soil. The study site was in a conservation area of the PT National Sago Prima belonging to the PT Sampoerna Agro Tbk. Group. The work was undertaken in January-February 2012. The total aboveground biomass and carbon storage in the research site indicates  that the conservation area is a secondary peat swamp forest, with the biomass of 149.18 ton/ha and carbon stock of 70.12 ton C/ha. The aboveground biomass and carbon consisted of biomass and carbon of tree (83.97 ton/ha containing 39.47 ton C/ha, respectively, saplings (20.69 ton/ha containing 9.72 ton C/ha and seedlings and undergrowth plants (0.03 ton/ha containing 0.01 ton C/ha, wood  necromass (24.06 ton/ha containing 11.31 ton C/ha, and litter (20.44 ton/ha containing 9.61 ton C/ha. An allometric equation was developed for Pandanus atrocarpus Griff. providing an estimated total biomass and carbon of 5.16 ton/ha containing 2.42 ton C/ha. The underground C with the mean peat depth of 5.5 m, mean bulk density of  0.18 g/cm3, and the mean organic C of 46.6 % was 464.895,94 ton C/ha. In the entire conservation forest area of 541 ha the total aboveground biomassa and carbon storage was estimated to be  80,708.64 ton and 37,934.00 ton C, while the total underground carbon was 238,96 million MT C.

Influence of acid rain components on radiocesium-137 desorption from Cetraria islandica (L. Ach. lichen

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Miljanić Šćepan S.

2012-01-01

Full Text Available Desorption of 137Cs from Cetraria islandica (L. Ach. lichen was performed by five consecutive desorptions with five identical solution volumes. Solutions of H2SO4, HNO3 and their mixtures, with pH 4.61, 5.15 and 5.75 were used for desorption. The desorbed amount of 137Cs (average value, all solutions used from lichen, for a given pH value was 49.2% for pH 4.61; 47.0% for pH 5.15 and 47.6% for pH 5.75. The obtained values of the desorbed amount of 137Cs from lichen are in accordance with the data obtained in earlier work, when 46.2 % 137Cs was desorbed from lichen for pH 3.75, and 47.2% was desorbed for pH 2.87. A higher percentage of 59.8%, obtained for pH 2.00 indicates increased activity of H+ ions. The amount of desorbed 137Cs from lichen using solutions corresponding to acid rain cannot be lower than the stated values as they contain other substances besides the acid solutions used in this work.

Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development.

Science.gov (United States)

Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó, Anna; Cilleros, Víctor

2017-01-01

During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ) are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR), adenosine autoreceptors (AR) and trophic factor receptors (TFR, for neurotrophins and trophic cytokines) during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development

Directory of Open Access Journals (Sweden)

Josep Tomàs

2017-05-01

Full Text Available During the histogenesis of the nervous system a lush production of neurons, which establish an excessive number of synapses, is followed by a drop in both neurons and synaptic contacts as maturation proceeds. Hebbian competition between axons with different activities leads to the loss of roughly half of the neurons initially produced so connectivity is refined and specificity gained. The skeletal muscle fibers in the newborn neuromuscular junction (NMJ are polyinnervated but by the end of the competition, 2 weeks later, the NMJ are innervated by only one axon. This peripheral synapse has long been used as a convenient model for synapse development. In the last few years, we have studied transmitter release and the local involvement of the presynaptic muscarinic acetylcholine autoreceptors (mAChR, adenosine autoreceptors (AR and trophic factor receptors (TFR, for neurotrophins and trophic cytokines during the development of NMJ and in the adult. This review article brings together previously published data and proposes a molecular background for developmental axonal competition and loss. At the end of the first week postnatal, these receptors modulate transmitter release in the various nerve terminals on polyinnervated NMJ and contribute to axonal competition and synapse elimination.

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

Directory of Open Access Journals (Sweden)

Hafsa Amat-Ur-Rasool

Full Text Available Alzheimer's disease (AD, a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh. The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE, an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals and self-drawn ligands were compared with Food and Drug Administration (FDA approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

Science.gov (United States)

Amat-Ur-Rasool, Hafsa; Ahmed, Mehboob

2015-01-01

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain.

Science.gov (United States)

Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Bogacz, Anna; Gryszczynska, Agnieszka; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Piasecka, Anna; Napieczynska, Hanna; Szulc, Michał; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Cichocka, Joanna; Bobkiewicz-Kozlowska, Teresa; Czerny, Boguslaw; Mrozikiewicz, Przemyslaw M

2013-12-01

Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain. © 2013. Published by Elsevier B.V. All rights reserved.

Un modelo econométrico de medición de las relaciones de sustitución entre materias primas compradas para la producción de piensos compuestos y su asignación

OpenAIRE

Peeters, Ludo; Surry, Yves

1993-01-01

El objeto de este artículo es presentar un modelo econométrico para estimar las relaciones de sustitución entre las materias primas compradas para la producción de piensos compuestos y su asignación entre los diferentes tipos de piensos para diferentes tipos de ganado utilizando una función dual de costes. Dicho modelo se aplica a las industrias belga y neerlandesa de piensos compuestos. El modelo empírico utiliza una función de costes Simétrica Generalizada de McFadden de outputs múltiples q...

Caracterização de matérias-primas cerâmicas do Vale do Rio Caí Characterization of ceramic raw materials from the Caí River Valley, RS, Brazil

Directory of Open Access Journals (Sweden)

J. E. Zorzi

2012-12-01

Full Text Available Este trabalho tem como objetivo a caracterização química e mineralógica de matérias-primas argilosas utilizadas pelas indústrias cerâmicas do Vale do Rio Caí, RS. Essa região, situada entre Porto Alegre e a Serra Gaúcha, é o maior centro produtor cerâmico para construção civil do estado do Rio Grande do Sul. Apesar da importância da indústria cerâmica para a economia local e do Estado, a grande maioria das argilas disponíveis para consumo nunca foi caracterizada satisfatoriamente e não existem dados técnicos e científicos que possam orientar tanto a correta exploração das jazidas quanto o desenvolvimento de produtos cerâmicos de maior valor agregado. Neste trabalho foram feitas análises por fluorescência e difração de raios X das principais argilas utilizadas pela indústria cerâmica da região. De acordo com o método de análise hierárquica de agrupamentos e tendo como base a composição química das amostras, foram identificados três grupos de matérias-primas: argilas residuais (ou primárias e dois grupos de argilas transportadas (ou secundárias. A diferenciação das matérias-primas em grupos se manifesta também na composição de fases das amostras, tal como determinada por difração de raios X e análise racional.This work aims to characterize the chemistry and mineralogy of clay raw materials used in the heavy clay industry of the Caí River Valley, in southern Brazil. This region lies between Porto Alegre and Serra Gaúcha and is regarded as the major production center of brick and tiles in the Rio Grande do Sul. Despite the importance of this activity for both the local and state economy, the vast majority of clay raw materials have never been satisfactorily characterized, so there is not adequate data to guide its correct exploitation or to allow the development of ceramic products of higher quality. In this work X-ray fluorescence and diffraction were applied to analyze the clays largely used by

Estado da arte da aplicação do processo de hidroesterificação na produção de biodiesel a partir de matérias-primas de baixa qualidade

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Letícia Karen dos Santos

2015-12-01

Full Text Available O maior problema encontrado na produção de biodiesel pelos processos convencionais de transesterificação está na aquisição de matérias-primas, que devem ser de acidez e teor de umidade reduzidos, característica atendida pelos óleos vegetais refinados, o qual gera um custo elevado e inviabiliza o uso de diversas oleaginosas. O processo de hidroesterificação é a mais moderna alternativa na produção de biodiesel, pois permite o uso de qualquer matéria-prima graxa com teores elevados de acidez (ácidos graxos e umidade (água; esse processo envolve uma etapa de hidrólise seguida de esterificação. A hidrólise consiste em uma reação química entre a gordura (ou óleo com a água, gerando glicerina e ácidos graxos. Após a hidrólise, os ácidos graxos gerados são esterificados com metanol/etanol, obtendo-se o metil/etiléster com elevada pureza (biodiesel. Esse artigo traz um estudo da aplicação do processo de hidroesterificação para a produção de biodiesel utilizando óleos brutos, óleo de microalga, óleos residuais e gordura animal. Atuando em uma nova estratégia na cadeia produtiva do biodiesel, visando à solução de obstáculos técnicos, e consequentemente, contribuindo para o aumento do biodiesel na matriz energética e o desenvolvimento econômico e social deste mercado.

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro.

Science.gov (United States)

Oboh, Ganiyu; Odubanjo, Veronica O; Bello, Fatai; Ademosun, Ayokunle O; Oyeleye, Sunday I; Nwanna, Emem E; Ademiluyi, Adedayo O

2016-03-01

Avocado pear (Persea americana Mill.) leaves and seeds are used in traditional medicine for the treatment/management of Alzheimer disease (AD); however, information on the mechanism of actions is limited. This study sought to investigate the effect of P. americana leaf and seed aqueous extracts on some enzymes linked with AD (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] activities) and their antioxidant potentials in vitro. The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of Fe2+- and sodium nitroprusside-induced thiobarbiturate reactive species [TBARS] production in rat brain homogenates, radicals [1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and nitric oxide] scavenging and iron [Fe] chelation abilities) were investigated. Phenolic content and phytochemical screening were carried out. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). The extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID. The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Influence of the Melissa officinalis Leaf Extract on Long-Term Memory in Scopolamine Animal Model with Assessment of Mechanism of Action

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Marcin Ozarowski

2016-01-01

Full Text Available Melissa officinalis (MO, English: lemon balm, Lamiaceae, one of the oldest and still most popular aromatic medicinal plants, is used in phytomedicine for the prevention and treatment of nervous disturbances. The aim of our study was to assess the effect of subchronic (28-fold administration of a 50% ethanol extract of MO leaves (200 mg/kg, p.o. compared with rosmarinic acid (RA, 10 mg/kg, p.o. and huperzine A (HU, 0.5 mg/kg, p.o. on behavioral and cognitive responses in scopolamine-induced rats. The results were linked with acetylcholinesterase (AChE, butyrylcholinesterase (BuChE, and beta-secretase (BACE-1 mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex of rats. In our study, MO and HU, but not RA, showed an improvement in long-term memory. The results were in line with mRNA levels, since MO produced a decrease of AChE mRNA level by 52% in the cortex and caused a strong significant inhibition of BACE1 mRNA transcription (64% in the frontal cortex; 50% in the hippocampus. However, the extract produced only an insignificant inhibition of AChE activity in the frontal cortex. The mechanisms of MO action are probably more complicated, since its role as a modulator of beta-secretase activity should be taken into consideration.

Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein

DEFF Research Database (Denmark)

Andersson, Anne-Marie Carola; Håkansson, Kjell Ove; Jensen, Benjamin Anderschou Holbech

2012-01-01

by diverse influenza A viruses, a vaccine (M2e-NSP4) was constructed linking M2e (in its consensus sequence) to the rotavirus fragment NSP4(98-135); due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2...

Acetylcholinesterase complexed with bivalent ligands related to huperzine a: experimental evidence for species-dependent protein-ligand complementarity.

Science.gov (United States)

Wong, Dawn M; Greenblatt, Harry M; Dvir, Hay; Carlier, Paul R; Han, Yi-Fan; Pang, Yuan-Ping; Silman, Israel; Sussman, Joel L

2003-01-15

Acetylcholinesterase (AChE) inhibitors improve the cognitive abilities of Alzheimer patients. (-)-Huperzine A [(-)-HupA], an alkaloid isolated from the club moss, Huperzia serrata, is one such inhibitor, but the search for more potent and selective drugs continues. Recently, alkylene-linked dimers of 5-amino-5,6,7,8-tetrahydroquinolinone (hupyridone, 1a), a fragment of HupA, were shown to serve as more potent inhibitors of AChE than (-)-HupA and monomeric 1a. We soaked two such dimers, (S,S)-(-)-bis(10)-hupyridone [(S,S)-(-)-2a] and (S,S)-(-)-bis(12)-hupyridone [(S,S)-(-)-2b] containing, respectively, 10 and 12 methylenes in the spacer, into trigonal TcAChE crystals, and solved the X-ray structures of the resulting complexes using the difference Fourier technique, both to 2.15 A resolution. The structures revealed one HupA-like 1a unit bound to the "anionic" subsite of the active-site, near the bottom of the active-site gorge, adjacent to Trp84, as seen for the TcAChE/(-)-HupA complex, and the second 1a unit near Trp279 in the "peripheral" anionic site at the top of the gorge, both bivalent molecules thus spanning the active-site gorge. The results confirm that the increased affinity of the dimeric HupA analogues for AChE is conferred by binding to the two "anionic" sites of the enzyme. Inhibition data show that (-)-2a binds to TcAChE approximately 6-7- and > 170-fold more tightly than (-)-2b and (-)-HupA, respectively. In contrast, previous data for rat AChE show that (-)-2b binds approximately 3- and approximately 2-fold more tightly than (-)-2a and (-)-HupA, respectively. Structural comparison of TcAChE with rat AChE, as represented by the closely related mouse AChE structure (1maa.pdb), reveals a narrower gorge for rat AChE, a perpendicular alignment of the Tyr337 ring to the gorge axis, and its conformational rigidity, as a result of hydrogen bonding between its hydroxyl group and that of Tyr341, relative to TcAChE Phe330. These structural differences in the

Requirement of Nicotinic Acetylcholine Receptor Subunit β2 in the Maintenance of Spiral Ganglion Neurons during Aging

Science.gov (United States)

Bao, Jianxin; Lei, Debin; Du, Yafei; Ohlemiller, Kevin K.; Beaudet, Arthur L.; Role, Lorna W.

2008-01-01

Age-related hearing loss (presbycusis) is a major health concern for the elderly. Loss of spiral ganglion neurons (SGNs), the primary sensory relay of the auditory system, is associated consistently with presbycusis. The causative molecular events responsible for age-related loss of SGNs are unknown. Recent reports directly link age-related neuronal loss in cerebral cortex with the loss of high-affinity nicotine acetylcholine receptors (nAChRs). In cochlea, cholinergic synapses are made by olivocochlear efferent fibers on the outer hair cells that express α9 nAChR subunits and on the peripheral projections of SGNs that express α2, α4 –7, and β2–3 nAChR subunits. A significantly decreased expression of the β2 nAChR subunit in SGNs was found specifically in mice susceptible to presbycusis. Furthermore, mice lacking the β2 nAChR subunit (β2−/−), but not mice lacking the α5 nAChR subunit (α5−/−), have dramatic hearing loss and significant reduction in the number of SGNs. Our findings clearly established a requirement for β2 nAChR subunit in the maintenance of SGNs during aging. PMID:15788760

Concetualização de um modelo de indexação da volatilidade do preço das matérias-primas ao preço do produto final na grande distribuição

OpenAIRE

Costa, Laura Maria Oliveira

2017-01-01

As relações estabelecidas na cadeia de abastecimento do leite são, em Portugal e muitos outros países, caracterizadas pela disparidade de poder e dimensão entre os intervenientes da cadeia, resultando num ambiente instável e de elevada precariedade no setor. Em particular, os produtores, no primeiro nível da cadeia, são altamente dependentes do preço das matérias-primas agroalimentares, o seu principal custo de produção, que tem registado um elevado grau de volatilidade. Atualmente, os con...

Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

Science.gov (United States)

Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

2017-09-01

Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

Long-term results of aortic valve replacement with Edwards Prima Plus stentless bioprosthesis: eleven years' follow up.

Science.gov (United States)

Auriemma, Stefano; D'Onofrio, Augusto; Brunelli, Massimo; Magagna, Paolo; Paccanaro, Mariemma; Rulfo, Fanny; Fabbri, Alessandro

2006-09-01

The Edwards Lifesciences Prima Plus stentless valve (ELSV) is a bioprosthesis manufactured from a porcine aortic root. The study aim was to evaluate late clinical outcomes after aortic valve replacement (AVR) with ELSV implanted as a miniroot in patients with aortic valve disease. Between 1993 and 2004, 318 patients (232 males, 86 females; mean age 69 +/- 9 years; range: 37-83 years) underwent AVR with the ELSV. Preoperatively, 102 patients (32%), 162 (51%) and 54 (17%) were in NYHA classes I/II, III and IV, respectively. Aortic stenosis, aortic regurgitation and combined lesions were present in 124 patients (39%), 114 (36%) and 41 (13%), respectively. Twenty patients (6%) were referred for an acute aortic dissection, 20 (6%) for an aortic root aneurysm, and 139 (44%) had an associated aneurysmal dilatation of the ascending aorta. The ascending aorta was replaced in 159 patients (50%); aortic arch replacement was required in 10 (3%). Coronary artery bypass graft was performed in 86 patients (27%). The follow up was based on clinical data. Operative mortality was 5% (n = 17). There were 49 late deaths (5.2%/pt-yr). Valve-related mortality occurred in 10 patients (1%/pt-yr). Actuarial survival at five and 10 years was 78% and 33%, respectively. Actuarial freedom from valve reoperation and structural valve deterioration at 10 years were 100% and 64%. Actuarial freedom from embolic events and endocarditis at 10 years were 84% and 81%, respectively. The ELSV, when implanted as a miniroot, provided good early and long-term results in terms of survival and freedom from major complications.

Determinación espectrofotométrica de un producto activo zeolítico en materia prima y tabletas vaginales

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Mercedes Machuá Veitía

1999-12-01

Full Text Available El empleo de productos activos zeolíticos como fármacos de acción específica requiere el desarrollo de técnicas analíticas para el control de la calidad de las formas terminadas. Se desarrolló y validó un método espectrofotométrico de análisis para una zeolita activada con cinc (PAZ-ZZ a partir de la reacción con zincón. Se evaluó la linealidad, precisión, exactitud y especificidad del método propuesto. La técnica se aplicó posteriormente al análisis de materia prima PAZ-ZZ y tabletas vaginales que contienen este principio activo; los resultados se compararon con los obtenidos para espectroscopia de absorción atómica.The use of active zeolitic products as drugs of specific action requires the development of analytical techniques to control the quality of the finished product. A spectrophotometric method of analysis was validated for a zinc?activated zeolite (PAZ-ZZ, starting from the reaction with zincum. The lineality, precision, exactitude and specificity of the proposed method were evaluated. This technique was later applied to the analysis of PAZ-ZZ raw material and vaginal tablets containing this active principle. The results were compared with those obtained for atomic absortion spectroscopy.

Social Groups, Explanation and Ontological Holism | Sheehy ...

African Journals Online (AJOL)

The paper begins from the claim that ontological holism is given prima facie plausibility by the apparently ineliminable role of groups in some descriptions and explanations of the social domain. If the individualist accepts the link between indispensabilty and realism, then individualism must show that groups cannot play the ...

Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn

Science.gov (United States)

Aittaleb, Mohamed; Chen, Po-Ju; Akaaboune, Mohammed

2015-01-01

ABSTRACT Rapsyn, a scaffold protein, is required for the clustering of acetylcholine receptors (AChRs) at contacts between motor neurons and differentiating muscle cells. Rapsyn is also expressed in cells that do not express AChRs. However, its function in these cells remains unknown. Here, we show that rapsyn plays an AChR-independent role in organizing the distribution and mobility of lysosomes. In cells devoid of AChRs, rapsyn selectively induces the clustering of lysosomes at high density in the juxtanuclear region without affecting the distribution of other intracellular organelles. However, when the same cells overexpress AChRs, rapsyn is recruited away from lysosomes to colocalize with AChR clusters on the cell surface. In rapsyn-deficient (Rapsn−/−) myoblasts or cells overexpressing rapsyn mutants, lysosomes are scattered within the cell and highly dynamic. The increased mobility of lysosomes in Rapsn−/− cells is associated with a significant increase in lysosomal exocytosis, as evidenced by increased release of lysosomal enzymes and plasma membrane damage when cells were challenged with the bacterial pore-forming toxin streptolysin-O. These findings uncover a new link between rapsyn, lysosome positioning, exocytosis and plasma membrane integrity. PMID:26330529

Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy.

Science.gov (United States)

Niebroj-Dobosz, I; Hausmanowa-Petrusewicz, I

1989-09-01

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.

[A comparative analysis of the informative value of anti-AChR-antibody radioimmunoassay and laser correlation spectroscopy in myasthenia gravis].

Science.gov (United States)

Alchinova, I B; Yakovenko, E N; Sidnev, D V; Dedaev, S Yu; Sanadze, A G; Karganov, M Yu

An aim of the study was to compare informative value of traditional approach (anti-AChR antibody radioimmunoassay) and evaluation of metabolic shifts by laser correlation spectroscopy in myasthenia gravis. The search for the relationship between the disease severity in 77 patients, 12-80 years and the distribution pattern of subfraction serum components revealed three informative zones: 6-15, 27-67, and 127-223 nm. In patients without disturbances of vital functions, the contribution of the first zone particles into light scatter increases and that of the third zone particles decreases. Considerable differences attaining the level of statistical significance in zones 6 and 20 nm were revealed in the spectra of serum from patients with myasthenia gravis of the same severity with and without thymoma. This opens prospects for dynamic monitoring of the efficiency of therapy.

Chemical Composition and Cholinesterase Inhibitory Activity of Different Parts of Daucus aristidis Coss. Essential Oils from Two Locations in Algeria

OpenAIRE

Mebarka Lamamra; Hocine Laouer; Smain Amira; Ilkay Erdogan Orhan; Fatma Sezer Senol; Betul Demirci; Salah Akkal

2017-01-01

The chemical composition of the essential oils obtained by hydrodistillation from the different parts of Daucus aristidis Coss. (syn. Ammiopsis aristidis Batt.) (Apiaceae) from two locations (Ghoufi and Bousaada) in East of Algeria, was investigated for the first time by GC and GC-MS and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, the enzymes linked to Alzheimer’s disease, by a spectrophotometric method of Ellman using ELISA m...

The link between Foreign Language Classroom Anxiety, Second Language Tolerance of Ambiguity and Self-rated English proficiency among Chinese learners

Directory of Open Access Journals (Sweden)

Jean-Marc Dewaele

2013-10-01

Full Text Available Previous research has suggested that high levels of Foreign Language Classroom Anxiety (FLCA have a negative effect on foreign language learning (Horwitz, 2001; Lu & Liu, 2011 while moderate levels of Second Language Tolerance of Ambiguity (SLTA are believed to boost foreign language learning (Ely, 1995. There is prima facie evidence that both dimensions are inversely related as Foreign Language Learning contexts are full of ambiguities which may contribute to anxiety. However, the relationship between FLCA and SLTA has been under-researched. The present study is an attempt to fill this gap by investigating the link between SLTA and FLCA in English of 73 secondary school students in Hong Kong. They filled out an online questionnaire consisting of the Foreign Language Classroom Anxiety Scale (Horwitz, Horwitz, & Cope, 1986 and the Second Language Tolerance of Ambiguity Scale (Ely, 1995. Statistical analyses revealed that FLCA, SLTA and Self-rated English proficiency predict half of the variance in each other; in other words, students who were more tolerant of second language ambiguity were less anxious in their EFL classes and they also felt more proficient.

The Link between Foreign Language Classroom Anxiety, Second Language Tolerance of Ambiguity and Self-Rated English Proficiency among Chinese Learners

Science.gov (United States)

Dewaele, Jean-Marc; Ip, Tsui Shan

2013-01-01

Previous research has suggested that high levels of Foreign Language Classroom Anxiety (FLCA) have a negative effect on foreign language learning (Horwitz, 2001; Lu & Liu, 2011) while moderate levels of Second Language Tolerance of Ambiguity (SLTA) are believed to boost foreign language learning (Ely, 1995). There is prima facie evidence that…

In silico development of new acetylcholinesterase inhibitors.

Science.gov (United States)

Pascoini, A L; Federico, L B; Arêas, A L F; Verde, B A; Freitas, P G; Camps, I

2018-04-19

In this work, we made use of fragment-based drug design (FBDD) and de novo design to obtain more powerful acetylcholinesterase (AChE) inhibitors. AChE is associated with Alzheimer's disease (AD). It was found that the cholinergic pathways in the cerebral cortex are compromised in AD and the accompanying cholinergic deficiency contributes to the cognitive deterioration of AD patients. In the FBDD approach, fragments are docked into the active site of the protein. As fragments are molecular groups with a low number of atoms, it is possible to study their interaction with localized amino acids. Once the interactions are measured, the fragments are organized by affinity and then linked together to form new molecules with a high degree of interaction with the active site. In the other approach, we used the de novo design technique starting from reference drugs used in the AD treatment. These drugs were broken into fragments (seeds). In the growing strategy, fragments were added to each seed, growing new molecules. In the linking strategy, two or more separated seeds were linked with different fragments. Both strategies combined produced a library of more than 2 million compounds. This library was filtered using absorption, distribution, metabolism, and excretion properties. The resulting library with around six thousand compounds was filtered again. In this case, structures with Tanimoto coefficients >.85 were discarded. The final library with 1500 compounds was submitted to docking studies. As a result, 10 compounds with better interaction energy than the reference drugs were obtained.

Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

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Nils Klüver

Full Text Available Acetylcholinesterase (AChE inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM, in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB and 2,4-dinitrophenol (DNP. A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.

Crystal structure of N-(quinolin-6-ylhydroxylamine

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Anuruddha Rajapakse

2014-11-01

Full Text Available The title compound, C9H8N2O, crystallized with four independent molecules in the asymmetric unit. The four molecules are linked via one O—H...N and two N—H...N hydrogen bonds, forming a tetramer-like unit. In the crystal, molecules are further linked by O—H...N and N—H...O hydrogen bonds forming layers parallel to (001. These layers are linked via C—H...O hydrogen bonds and a number of weak C—H...π interactions, forming a three-dimensional structure. The crystal was refined as a non-merohedral twin with a minor twin component of 0.319.

Myasthenia Gravis With Thymoma, Manifesting as AChR-Ab-Positive, Distinct Bulbar Palsy Accompanied by Dysgeusia: A Case Series and Review of Literature

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Kai Zhu

2018-04-01

Full Text Available In this review, we summarized three cases of myasthenia gravis (MG with taste disorder and describe their clinical features in detail. Three MG patients presented with significant bulbar palsy symptoms, high AChR-Ab titers, and negative MuSK-Ab, were diagnosed with thymoma. Furthermore, we observed that dysgeusia could manifest earlier than the occurrence of typical MG symptoms, even predict a MG relapse or a myasthenic crisis in the course of MG. We believe that dysgeusia is a non-motor symptom of MG, which especially exists in MG patients with thymoma and serious bulbar palsy. Therefore, being alert to this symptom may facilitate the early diagnosis of MG and judge the progress of the disease.

Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications

Energy Technology Data Exchange (ETDEWEB)

Noridomi, Kaori; Watanabe, Go; Hansen, Melissa N.; Han, Gye Won; Chen, Lin (USC)

2017-04-25

The nicotinic acetylcholine receptor (nAChR) is a major target of autoantibodies in myasthenia gravis (MG), an autoimmune disease that causes neuromuscular transmission dysfunction. Despite decades of research, the molecular mechanisms underlying MG have not been fully elucidated. Here, we present the crystal structure of the nAChR α1 subunit bound by the Fab fragment of mAb35, a reference monoclonal antibody that causes experimental MG and competes with ~65% of antibodies from MG patients. Our structures reveal for the first time the detailed molecular interactions between MG antibodies and a core region on nAChR α1. These structures suggest a major nAChR-binding mechanism shared by a large number of MG antibodies and the possibility to treat MG by blocking this binding mechanism. Structure-based modeling also provides insights into antibody-mediated nAChR cross-linking known to cause receptor degradation. Our studies establish a structural basis for further mechanistic studies and therapeutic development of MG.

Neurofibromatosis Type 1 Associated with Hashimoto’s Thyroiditis: Coincidence or Possible Link

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Junaid Nabi

2013-01-01

Full Text Available Introduction. Hashimoto's thyroiditis is a common form of chronic autoimmune thyroid disease (AITD and often coexists with other autoimmune diseases, but Hashimoto’s thyroiditis associated with an autosomal dominant neurofibromatosis type 1 is exceedingly rare. Case Presentation. A 30-year-old Bengali woman presented to the OPD with complaints of aching pain and tingling sensation in her hands and feet. Physical examination revealed dysmorphic facies, nodular swelling in the neck, cafe-au-lait spots, and neurofibromas covering the entire surface of her body. Her thyroid hormones were within normal limits. Thyroid ultrasound revealed a cystic area in the left lobe of the gland, and ultrasound-guided fine needle aspiration cytology revealed lymphocytic infiltration of the gland, suggesting Hashimoto’s thyroiditis. High levels of autoimmune antibodies such as antithyroglobulin and antimicrosomal antibodies confirmed the diagnosis. Conclusion. When encountered with a patient of Neurofibromatosis type 1, a physician should be careful about the possibility of a concomitant autoimmune disease. Clinical presentation of neurofibromatosis and Noonan syndrome often overlaps and recent studies have implicated a mutation in NF1 gene in the etiology of NFNS. More extensive reports and further investigations of such patients having combination of neurofibromatosis type 1 and autoimmune thyroiditis will certainly provide better understanding of this link in the near future.

Liquid chromatography/mass spectrometry investigation of the impact of thermal processing and storage on peach procyanidins.

Science.gov (United States)

Hong, Yun-Jeong; Barrett, Diane M; Mitchell, Alyson E

2004-04-21

Normal-phase liquid chromatography/mass spectrometry (LC/MS) was used to determine the levels and fate of procyanidins in frozen and canned Ross clingstone peaches as well as in the syrup used in the canning over a 3 month period. Procyanidin oligomers, monomers through undecamers, were identified in Ross clingstone peaches. Optimized methods allowed for the quantitation of oligomers through octamers. The profile of procyanidins in peaches is similar to profiles found in grapes, chocolate, and beverages linked to health benefits such as tea and wine. The monomer content in frozen peeled peaches was found to be 19.59 mg/kg. Dimers (39.59 mg/kg) and trimers (38.81 mg/kg) constituted the largest percent composition of oligomers in the peaches. Tetramers through octamers were present in levels of 17.81, 12.43, 10.62, 3.94 and 1.75 mg/kg, respectively. Thermal processing resulted in an 11% reduction in monomers, a 9% reduction in dimers, a 12% reduction in trimers, a 6% reduction in tetramers, and a 5% reduction in pentamers. Hexamers and heptamers demonstrated an approximate 30% loss, and octamers were no longer detected. Analysis of the syrup after thermal processing indicates that there is a migration of procyanidin monomers through hexamers into the syrup that can account for the losses observed during the canning process. Storage of canned peaches for 3 months demonstrated a time-related loss in higher oligomers and that by 3 months oligomers larger than tetramers are not observed. At 3 months postcanning, levels of monomers had decreased by 10%, dimers by 16%, trimers by 45%, and tetramers by 80%. A similar trend was observed in the canning syrup.

Structure of a rabbit muscle fructose-1, 6-bisphosphate aldolase A dimer variant

Energy Technology Data Exchange (ETDEWEB)

Sherawat, Manashi [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States); Tolan, Dean R., E-mail: tolan@bu.edu [Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215 (United States); Allen, Karen N., E-mail: tolan@bu.edu [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States)

2008-05-01

The X-ray crystallographic structure of a dimer variant of fructose-1, 6-bisphosphate aldolase demonstrates a stable oligomer that mirrors half of the native tetramer. The presence of product demonstrates that this is an active form. Fructose-1, 6-bisphosphate aldolase (aldolase) is an essential enzyme in glycolysis and gluconeogenesis. In addition to this primary function, aldolase is also known to bind to a variety of other proteins, a property that may allow it to perform ‘moonlighting’ roles in the cell. Although monomeric and dimeric aldolases possess full catalytic activity, the enzyme occurs as an unusually stable tetramer, suggesting a possible link between the oligomeric state and these noncatalytic cellular roles. Here, the first high-resolution X-ray crystal structure of rabbit muscle D128V aldolase, a dimeric form of aldolase mimicking the clinically important D128G mutation in humans associated with hemolytic anemia, is presented. The structure of the dimer was determined to 1.7 Å resolution with the product DHAP bound in the active site. The turnover of substrate to produce the product ligand demonstrates the retention of catalytic activity by the dimeric aldolase. The D128V mutation causes aldolase to lose intermolecular contacts with the neighboring subunit at one of the two interfaces of the tetramer. The tertiary structure of the dimer does not significantly differ from the structure of half of the tetramer. Analytical ultracentrifugation confirms the occurrence of the enzyme as a dimer in solution. The highly stable structure of aldolase with an independent active site is consistent with a model in which aldolase has evolved as a multimeric scaffold to perform other noncatalytic functions.

Tribological properties of amorphous hydrogenated (a-C:H) and hydrogen-free tetrahedral (ta-C) diamond-like carbon coatings under jatropha biodegradable lubricating oil at different temperatures

Science.gov (United States)

Mobarak, H. M.; Masjuki, H. H.; Mohamad, E. Niza; Kalam, M. A.; Rashedul, H. K.; Rashed, M. M.; Habibullah, M.

2014-10-01

The application of diamond-like carbon (DLC) coatings on automotive components is emerging as a favorable strategy to address the recent challenges in the industry. DLC coatings can effectively lower the coefficient of friction (CoF) and wear rate of engine components, thereby improving their fuel efficiency and durability. The lubrication of ferrous materials can be enhanced by a large amount of unsaturated and polar components of oils. Therefore, the interaction between nonferrous coatings (e.g., DLC) and vegetable oil should be investigated. A ball-on-plate tribotester was used to run the experiments. Stainless steel plates coated with amorphous hydrogenated (a-C:H) DLC and hydrogen-free tetrahedral (ta-C) DLC that slide against 440C stainless steel ball were used to create a ball-on-plate tribotester. The wear track was investigated through scanning electron microscopy. Energy dispersive and X-ray photoelectron spectroscopies were used to analyze the tribofilm inside the wear track. Raman analysis was performed to investigate the structural changes in the coatings. At high temperatures, the CoF in both coatings decreased. The wear rate, however, increased in the a-C:H but decreased in the ta-C DLC-coated plates. The CoF and the wear rate (coated layer and counter surface) were primarily influenced by the graphitization of the coating. Tribochemical films, such as polyphosphate glass, were formed in ta-C and acted as protective layers. Therefore, the wear rate of the ta-C DLC was lower than that of the-C:H DLC.

Structural characterization of PTX3 disulfide bond network and its multimeric status in cumulus matrix organization.

Science.gov (United States)

Inforzato, Antonio; Rivieccio, Vincenzo; Morreale, Antonio P; Bastone, Antonio; Salustri, Antonietta; Scarchilli, Laura; Verdoliva, Antonio; Vincenti, Silvia; Gallo, Grazia; Chiapparino, Caterina; Pacello, Lucrezia; Nucera, Eleonora; Serlupi-Crescenzi, Ottaviano; Day, Anthony J; Bottazzi, Barbara; Mantovani, Alberto; De Santis, Rita; Salvatori, Giovanni

2008-04-11

PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys(317) and Cys(318) are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3(-/-) mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3(-/-) mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

Diseño e implementación de un sistema de control y monitoreo de manejo de lotes para los procesos de: almacenaje, transporte y despacho de materias primas en los predios de una planta de elaboración de cerveza

OpenAIRE

Ortiz Campos, Mario Augusto; Martin Moreno, Cesar Antonio

2009-01-01

El sistema de manejo de granos constituye la primera fase en el proceso de elaboración de cerveza y desempeña un papel muy importante en la dosificación de materias primas. El siguiente articulo presenta la implementación de un sistema de control capaz de manejar los procesos de recepción, transporte, almacenaje y despacho de dos tipos de productos: arroz y malta (cebada malteada), este último utilizado en diferentes variedades. Se considera el control de lotes y dosificación de materi...

Metal extraction from Cetraria islandica (L. Ach. lichen using low pH solutions

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ANA A. CUCULOVIC

2008-04-01

Full Text Available Extraction of metals (K, Al, Ca, Mg, Fe, Cu, Ba, Zn, Mn and Sr from dry Cetraria islandica (L. Ach. lichen was performed using solutions similar to acid rain (solution A – H2SO4–HNO3–(NH42SO4 and solution B – H2SO4–HNO3–(NH42SO4–NH4NO3. The pH values of these solutions were 2.00, 2.58, 2.87, 3.28, and 3.75. Five consecutive extractions were performed with each solution. In all solutions, the extracted metal content, except Cu and Ca, was the highest in the first extract. The highest percentage of the metals desorbed in the first extraction was obtained using solutions with low pH values, 2.00, 2.58, and 2.87. The lowest percentage in the first extraction was obtained using solutions with pH 3.28 and 3.75, indicating influence of the H+ ion on the extraction. According to the results obtained, the investigated metals form two groups. The first group includes K, Al, Ca, Mg, and Fe. They were extracted in each of the five extractions at each of the pH values. The second group includes Ba, Zn, Mn, Cu, and Sr, which were not all extracted at each pH value. The first group yielded three types of extraction curves when the logarithms of extracted metal amounts were plotted as a function of the number of successive extractions. These effects indicate that three different positions (centres of metal ion accumulation exist in the lichen (due to sorption, complex formation, or other processes present in the tissues.

Análisis de flexibilidad y tasa de servicio de los proveedores de materias primas y artículos de acondicionamiento del departamento de logística de una fábrica L'Oréal

OpenAIRE

Oumakhlouf, Yasmina

2009-01-01

El Grupo L’Oreal es el Líder mundial de la industria cosmética. Está presente en más de 150 países y la cifra de su negocio consolidada en 2008 es de 14.300 millones de euros. En todo el mundo tiene más de 49.150 empleados. El grupo L’Oreal posee 44 fábricas, 39 de Productos Terminados (PT), y 5 de Materias Primas (MP), así como 18 centrales de distribución, nacionales e internacionales. Esas fábricas se ubican en las tres grandes zonas de actividad del grupo: Europa, Asia, y América del N...

Co-overexpression of bacterial GroESL chaperonins partly overcomes non-productive folding and tetramer assembly of E. coli-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) carrying the prevalent disease-causing K304E mutation

DEFF Research Database (Denmark)

Bross, P; Andresen, B S; Winter, V

1993-01-01

underlying MCAD deficiency caused by the prevalent K304E mutation. Depending on which of the three amino acids--lysine (wild-type), glutamic acid (K304E) or glutamine (K304Q) are present at position 304 of the mature polypeptide, three different patterns were observed in our assay system: (i) solubility...... in Western blotting. In a first attempt to estimate the specific activity, we show that tetrameric K304E and K304Q mutant MCAD display a specific activity in the range of the wild-type enzyme. Taken together, our results strongly suggest, that the K304E mutation primarily impairs the rate of folding...... with negative charge at position 304 (glutamic acid) but not with a neutral charge (glutamine) negatively affects conversion to active tetramers. A possible explanation for this latter effect--charge repulsion upon subunit docking--is discussed....

Cholinergic stimulation prevents the development of autoimmune diabetes: Evidence for the modulation of Th17 effector cells via an IFNgamma-dependent mechanism

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Junu George

2016-10-01

Full Text Available Type I diabetes (T1D results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple-low-dose streptozotocin (MLD-STZ model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI. We demonstrate that pretreatment with paraoxon prevented hyperglycemia in STZ-treated C57BL/6 mice. This correlated with a reduction in T cell infiltration into pancreatic islets and preservation of the structure and functionality of β-cells. Gene expression analysis of pancreatic tissue revealed that increased peripheral cholinergic activity prevented STZ-mediated loss of insulin production, this being associated with a reduction in IL-1β, IL-6, and IL-17 proinflammatory cytokines. Intracellular cytokine analysis in splenic T cells demonstrated that inhibition of AChE led to a shift in STZ-induced immune response from a predominantly disease-causing IL-17-expressing Th17 cells to IFNγ-positive Th1 cells. Consistent with this conclusion, inhibition of AChE failed to prevent STZ-induced hyperglycemia in IFNγ-deficient mice. Our results provide mechanistic evidence for the prevention of murine T1D by inhibition of AChE and suggest a promising strategy for modulating disease severity.

Composición quimicomineralógica de las materias primas y ahorro de energía en la industria del cemento

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Soria Santamaría, Francisco

1982-06-01

Full Text Available In the field of energy saving, mainly thermic, in the cement industry, not only should we consider the possibilities in the technological process or the finished product, but also the influence of the chemical-mineral composition of the raw materials. The distinct parameters which fall into the reactivity of the crudes are analyzed, such as the size of the grain (fineness, chemical and mineral composition of the principal components. There follows an exposition of the importance of the minority components as smelting and mineralizers, finally emphasizing the interest and practical behaviour of some of them.

En el campo del ahorro de energía, principalmente térmica, en la industria cementera, no sólo deben contemplarse las posibilidades en cuanto al proceso tecnológico o el producto acabado, sino también la influencia de la composición quimicomineralógica de las materias primas. Se analizan los distintos parámetros que inciden en la reactividad de los crudos, tales como tamaño de grano (finura, composición química y mineralogía de los componentes principales. A continuación se hace una exposición de la importancia de los componentes minoritarios como fundentes y mineralizadores, destacando finalmente el interés y comportamiento práctico de alguno de ellos.

Increasing cocoa productivity and farmer capacity in surrounding area of PT Kaltim Prima Coal and PT Berau Coal

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J.B.Baon

2014-01-01

Full Text Available Based on agro-climate factors, most of surrounding area of coal mining sites in Indonesia is suitable for cocoa cultivation. However, most of cocoa farmers in the environs of coal mining sites have little access both to new technology of cocoa cultivation and to market of their cocoa products. Therefore, productivity of cocoa farms and the income of cocoa farmers are low, which may disturb social responsibility of the coal mining companies present in their surroundings. These are the consequences of poor interaction between the government, private sector and research sector. The aim of this study is to transfer and to implement good agricultural practices of cocoa in surrounding area of mining sites of Kaltim Prima Coal (KPC and Berau Coal (BC, East Kalimantan, in order to increase farmer capacity and cocoa productivity. Indonesian Coffee and Cocoa Research Institute as the developing agent of cocoa technology has established collaboration with corporate social responsibility program of KPC (already 7 years and BC (already 2 years to improve productivity and farmer capacity of cocoa farms surroundings the two cocoa mining companies. This paper discusses the aspects of natural, economic and human resources; baseline study; technology transfers; marketing partnership; cocoa productivity; farmer income after technology implementing; study of cocoa growth on post-coal-mining. It is concluded that improvement of the cocoa productivity and farmer capacity surroundings the two mining sites associated with high adoption of technology by farmers, better access to availability of knowledge for good agricultural practices, extension officers, demonstration plots, cocoa price, and length of market chains, partnership, and competition with oil palm plantations.

Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET.

Science.gov (United States)

Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; van Bokhoven, Hans; Wiman, Klas G; Zhou, Huiqing; Aberdam, Daniel; Petit, Isabelle

2013-02-05

Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18(+) cells but failed to further differentiate into K14(+) cells (epidermis/limbus) or K3/K12(+) cells (corneal epithelium). APR-246 (PRIMA-1(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves the way for future therapy of EEC.

Desorption of metals from Cetraria islandica (L. Ach. Lichen using solutions simulating acid rain

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Čučulović Ana A.

2014-01-01

Full Text Available Desorption of metals K, Al, Ca, Mg, Fe, Ba, Zn, Mn, Cu and Sr from Cetraria islandica (L. with solutions whose composition was similar to that of acid rain, was investigated. Desorption of metals from the lichen was performed by five successive desorption processes. Solution mixtures containing H2SO4, HNO3 and H2SO4-HNO3 were used for desorption. Each solution had three different pH values: 4.61, 5.15 and 5.75, so that the desorptions were performed with nine different solutions successively five times, always using the same solution volume. The investigated metals can be divided into two groups. One group was comprised of K, Ca and Mg, which were desorbed in each of the five desorption processes at all pH values used. The second group included Al, Fe, Zn, Ba, Mn and Sr; these were not desorbed in each individual desorption and not at all pH values, whereas Cu was not desorbed at all under any circumstances. Using the logarithmic dependence of the metal content as a function of the desorption number, it was found that potassium builds two types of links and is connected with weaker links in lichen. Potassium is completely desorbed, 80% in the first desorption, and then gradually in the following desorptions. Other metals are linked with one weaker link (desorption 1-38% and with one very strong link (desorption below the metal detection limit. [Projekat Ministarstva nauke Republike Srbije, br. III43009 i br. ON 172019

Anti-M(3) muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)) from the submandibular glands.

Science.gov (United States)

Reina, Silvia; Sterin-Borda, Leonor; Passafaro, Daniela; Borda, Enri

2011-05-01

We demonstrated that serum immunoglobulin G (IgG) from patients with primary Sjögren's syndrome (pSS), interacting with the second extracellular loop of human glandular M(3) muscarinic acetylcholine receptors (M(3) mAChR), trigger the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)). Enzyme-linked immunosorbent assays (ELISAs) were performed in the presence of M(3) mAChR synthetic peptide as antigen to detect in serum the autoantibodies. Further, MMP-3 and PGE(2) production were determined in the presence of anti-M(3) mAChR autoantibodies. An association was observed between serum and anti-M(3) mAChR autoantibodies and serum levels of MMP-3 and PGE(2) in pSS patients. Thus, we established that serum anti-M(3) mAChR autoantibodies, MMP-3 and PGE(2) may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M(3) mAChR peptide IgG from pSS patients, whilst stimulating salivary-gland M(3) mAChR, causes an increase in the level of MMP-3 and PGE(2) as a result of the activation of phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2) (but not COX-1). These results provide a novel insight into the role that cholinoceptor antibodies play in the development of glandular inflammation. This is the first report showing that an antibody interacting with glandular mAChR can induce the production of pro-inflammatory mediators (MMP-3/PGE(2)). Copyright © 2010 Elsevier Ltd. All rights reserved.

Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

Science.gov (United States)

Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

2014-05-01

Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

ACh-evoked membrane hyperpolarization in smooth muscle cells of rat vas deferens in vitro: Involvement of K+ channels and NO%一氧化氮和K+通道参与乙酰胆碱引起的大鼠离体输精管平滑肌细胞超极化

Institute of Scientific and Technical Information of China (English)

范平; 李丽; 刘政江; 司军强; 张志琴; 赵磊; 马克涛

2007-01-01

To explore the underlying mechanism of acetylcholine (Ach)-evoked membrane hyperpolarizing response in isolated rat vas deferens smooth muscle cells (SMCs), intracellular microelectrode recording technique and intracellular microelectrophoresis fluorescent staining technique were used to study Ach-evoked membrane hyperpolarizing response in SMCs freshly isolated from Wistar rat vas deferens. By using microelectrodes containing fluorescent dye 0.1% propidium iodide (PI), 37 and 17 cells were identified as SMCs in outer longitudinal and inner circular muscular layers, respectively. The resting membrane potentials of SMCs were (–53.56±3.88) mV and (–51.62±4.27) mV, respectively. The membrane input resistances were (2 245.60±372.50) MΩ and (2 101.50±513.50) MΩ , respectively. Ach evoked membrane hyperpolarizing response in a concentration-dependent manner with an of 36 μmol/L. This action of Ach was abolished by both a non-sepcific muscarinic (M) receptor antagonist atropine (1 μmol/L) and a selective M 3 receptor antagonist diphenylacetoxy-N-methylpiperidine-methiodide (DAMP, 100 nmol/L). Ach-evoked membrane hyperpolarization was also abolished by a nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 300 μmol/L) and suppressed by an ATP-sensitive potassium (K ATP ) channel blocker glipizide (5 μmol/L) and an inward rectifier potassium (K ir ) channel inhibitor bariumion (50 μmol/L). A combination of glipizide and bariumion abolished Ach-evoked membrane hyperpolarizing response. The results suggest that Ach-evoked membrane hyperpolarization in rat vas deferens SMCs is mediated by M 3 receptor followed with activation of K ATP channels, K ir channels, and NO release.%本文旨在探讨大鼠新鲜离体输精管平滑肌细胞中乙酰胆碱(acetylcholine,Ach)引起超极化反应的机制,采用细胞内微电极记录技术和细胞内荧光标记技术研究Ach对大鼠输精管不同走行方向平滑肌细�

Heritability and Fitness Correlates of Personality in the Ache, a Natural-Fertility Population in Paraguay

Science.gov (United States)

Bailey, Drew H.; Walker, Robert S.; Blomquist, Gregory E.; Hill, Kim R.; Hurtado, A. Magdalena; Geary, David C.

2013-01-01

The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality. PMID:23527163

Caracterización litológica y mineralógica de los materiales permo-triásicos de Castellón utilizados como materia prima cerámica: la arcilla de Moró

Directory of Open Access Journals (Sweden)

Martín-Martín, J. D.

2006-08-01

Full Text Available The aim of this work is to establish the mineralogical (XRD composition of the Permo-Triassic claystone known as Moró clay. Particular emphasis is placed on the compositional variations along the litostratigraphic section. Bulk rock XRD analysis shows a homogeneous composition dominated by quartz, phyllosilicates and hematite. Minor components 5% include potassium feldspar, dolomite and calcite. The clay minerals assemblage is formed by illite ± kaolin ± chlorite ± mixed-layer illite-smectite ± mixed-layer chlorite-smectite and reveals a sedimentary distribution pattern. The study of the lithological section allows the identification and valuation of changes in the mineralogical characteristics of the raw material. Results provide evidence for the importance of mineralogical analysis in the control of raw materials and hence their use in industrial processes.

Las lutitas de edad Pérmica que se utilizan como materia prima en la industria azulejera de Castellón se conocen en el sector cerámico como arcilla de Moró. En el presente trabajo se describen las características litológicas y composicionales de estas lutitas con el objetivo de establecer las variaciones en composición a lo largo de la serie estratigráfica tipo. Los resultados muestran una composición mineralógica de la roca total muy uniforme, formada esencialmente por cuarzo, filosilicatos y hematites. Ocasionalmente y en proporciones por debajo del 5% aparece también feldespato potásito, dolomita y calcita. La asociación de minerales de la arcilla está formada por illita ± caolinita ± clorita ± interestratificado illita-esmectita ± interestratificado clorita-esmectita y muestra un patrón de distribución sedimentario. Los resultados obtenidos ponen de manifiesto la importancia del análisis mineralógico en la caracterización de las materias primas y, por tanto, en el control de sus propiedades cerámicas y de los procesos productivos relacionados.

Molecular determinants of tetramerization in the KcsA cytoplasmic domain.

Science.gov (United States)

Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H

2014-10-01

The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. © 2014 The Protein Society.

Fourier transform coupled tryptophan scanning mutagenesis identifies a bending point on the lipid-exposed δM3 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor

Science.gov (United States)

Caballero-Rivera, Daniel; Cruz-Nieves, Omar A; Oyola-Cintrón, Jessica; Torres-Núñez, David A; Otero-Cruz, José D

2011-01-01

The nicotinic acetylcholine receptor (nAChR) is a member of a family of ligand-gated ion channels that mediate diverse physiological functions, including fast synaptic transmission along the peripheral and central nervous systems. Several studies have made significant advances toward determining the structure and dynamics of the lipid-exposed domains of the nAChR. However, a high-resolution atomic structure of the nAChR still remains elusive. In this study, we extended the Fourier transform coupled tryptophan scanning mutagenesis (FT-TrpScanM) approach to gain insight into the secondary structure of the δM3 transmembrane domain of the Torpedo californica nAChR, to monitor conformational changes experienced by this domain during channel gating, and to identify which lipid-exposed positions are linked to the regulation of ion channel kinetics. The perturbations produced by periodic tryptophan substitutions along the δM3 transmembrane domain were characterized by two-electrode voltage clamp and 125I-labeled α-bungarotoxin binding assays. The periodicity profiles and Fourier transform spectra of this domain revealed similar helical structures for the closed- and open-channel states. However, changes in the oscillation patterns observed between positions Val-299 and Val-304 during transition between the closed- and open-channel states can be explained by the structural effects caused by the presence of a bending point introduced by a Thr-Gly motif at positions 300–301. The changes in periodicity and localization of residues between the closed-and open-channel states could indicate a structural transition between helix types in this segment of the domain. Overall, the data further demonstrate a functional link between the lipid-exposed transmembrane domain and the nAChR gating machinery. PMID:21785268

The PAS domains of the major sporulation kinase in Bacillus subtilis play a role in tetramer formation that is essential for the autokinase activity.

Science.gov (United States)

Kiehler, Brittany; Haggett, Lindsey; Fujita, Masaya

2017-08-01

Sporulation in Bacillus subtilis is induced upon starvation. In a widely accepted model, an N-terminal "sensor" domain of the major sporulation kinase KinA recognizes a hypothetical starvation signal(s) and autophosphorylates a histidine residue to activate the master regulator Spo0A via a multicomponent phosphorelay. However, to date no confirmed signal has been found. Here, we demonstrated that PAS-A, the most N-terminal of the three PAS domains (PAS-ABC), is dispensable for the activity, contrary to a previous report. Our data indicated that the autokinase activity is dependent on the formation of a functional tetramer, which is mediated by, at least, PAS-B and PAS-C. Additionally, we ruled out the previously proposed notion that NAD + /NADH ratio controls KinA activity through the PAS-A domain by demonstrating that the cofactors show no effects on the kinase activity in vitro. In support of these data, we found that the cofactors exist in approximately 1000-fold excess of KinA in the cell and the cofactors' ratio does not change significantly during growth and sporulation, suggesting that changes in the cofactor ratio might not play a role in controlling KinA activity. These data may refute the widely-held belief that the activity of KinA is regulated in response to an unknown starvation signal(s). © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Residuos cerámicos para su posible uso como materia prima en la fabricación de clínker de cemento Portland: caracterización y activación alcalina

Directory of Open Access Journals (Sweden)

Martínez-Ramírez, S.

2006-03-01

Kioto. El empleo de diferentes residuos y subproductos industriales como materiales alternativos en la fabricación de cemento se ha revelado como un medio muy efectivo para alcanzar, en gran parte, esa sostenibilidad. Estos materiales alternativos pueden ser incorporados en el proceso de fabricación de cemento, por la sustitución parcial de los combustibles convencionales y/o de las materias primas del crudo y por la incorporación de adiciones activas al cemento y/o clínker.En el presente trabajo se exponen los resultados preliminares obtenidos al estudiar la composición y activación alcalina de seis residuos cerámicos cocidos con vistas a su viabilidad de sustituir, parcialmente, algunas materias primas, utilizadas en la preparación de un crudo de cemento.Los resultados obtenidos han mostrado que los seis residuos tienen una composición química y mineralógica adecuada para su posible empleo como materia prima alternativa de un crudo de cemento Portland. No son ni tóxicos ni radioactivos. Como era de esperar estos residuos tienen capacidad puzolánica. A la edad de estudio (8 días la activación alcalina de los residuos es baja. El contenido en fase amorfa y la naturaleza del activador no parecen ser factores que influyan en dicho proceso de activación. El estudio de caracterización realizado sobre las pastas activadas ha demostrado que las fases feldespáticas son las más susceptibles de disolución y reacción con las disoluciones alcalinas.

UTILIZAÇÃO DE RESÍDUOS DE MINÉRIO DE FERRO COMO MATÉRIA PRIMA PARA FABRICAÇÃO DE ARGAMASSA

Directory of Open Access Journals (Sweden)

Maria Auxiliadora Mendes Aguiar

2016-04-01

Full Text Available A quantidade cada vez maior de resíduos gerados na fase de exploração e extração de minério de ferro constitui um problema ambiental às mineradoras, devido as grandes áreas requeridas para disposição dos mesmos, bem como a constante necessidade de gerenciamento desses locais. Neste estudo foi verificada a viabilidade técnica de utilização do resíduo gerado na exploração de um minério itabirítico como matéria prima para confecção de argamassa. Foram confeccionadas diferentes formulações de argamassas através da variação da proporção cimento/resíduo e da proporção água/cimento. Para cada amostra foram determinados o tempo de pega, viscosidade e densidade, no caso da amostra fresca, e densidade e resistência à compressão para a amostra solidificada. Concluiu-se que a argamassa confeccionada com maior quantidade de resíduo (traço 1:2,5 e menor relação água/cimento (0,95 foi aquela que apresentou menor tempo de pega e maior resistência à compressão. Este resultado foi bastante satisfatório, pois o aumento de resíduo incorporado favoreceu a resistência à compressão final do produto.

Desorption of 137Cs from Cetraria islandica (L. Ach. using solutions of acids and their salts mixtures

Directory of Open Access Journals (Sweden)

ANA A. ČUČULOVIĆ

2009-06-01

Full Text Available The desorption of 137Cs from Cetraria islandica (L. Ach. lichen was investigated using the solutions: A H2SO4–HNO3–K2SO4, B H2SO4–HNO3–Na2SO4 and C H2SO4–HNO3– (NH42SO4–(NH4NO3 at pH 2.00, 2.58, 2.87, 3.28 and 3.75, similar to acid rain. After five consecutive desorptions using solutions A, B and C, from 44.0 % (solution B, pH 3.75 to 68.8 % (solution C, pH 3.28 of 137Cs had been desorbed from the lichen. In all cases, the most successful 137Cs desorption was the first one. In the presence of K+ (solution A the total amount of desorbed 137Cs did not depend on the pH of the solution and this was confirmed by the analogous reactions of Cs+ and K+, due to their similar ionic radii. The dependencies of the non-desorbed content of 137Cs on the number of desorptions gave curves indicating that at least two types of sorption occur. One of them can be dominant if suitable desorbants are used. The results indicate lichens as secondary sources of environment pollution with 137Cs.

Surface morphology and grain analysis of successively industrially grown amorphous hydrogenated carbon films (a-C:H) on silicon

Science.gov (United States)

Catena, Alberto; McJunkin, Thomas; Agnello, Simonpietro; Gelardi, Franco M.; Wehner, Stefan; Fischer, Christian B.

2015-08-01

Silicon (1 0 0) has been gradually covered by amorphous hydrogenated carbon (a-C:H) films via an industrial process. Two types of these diamond-like carbon (DLC) coatings, one more flexible (f-DLC) and one more robust (r-DLC), have been investigated. Both types have been grown by a radio frequency plasma-enhanced chemical vapor deposition (RF-PECVD) technique with acetylene plasma. Surface morphologies have been studied in detail by atomic force microscopy (AFM) and Raman spectroscopy has been used to investigate the DLC structure. Both types appeared to have very similar morphology and sp2 carbon arrangement. The average height and area for single grains have been analyzed for all depositions. A random distribution of grain heights was found for both types. The individual grain structures between the f- and r-type revealed differences: the shape for the f-DLC grains is steeper than for the r-DLC grains. By correlating the average grain heights to the average grain areas for all depositions a limited region is identified, suggesting a certain regularity during the DLC deposition mechanisms that confines both values. A growth of the sp2 carbon entities for high r-DLC depositions is revealed and connected to a structural rearrangement of carbon atom hybridizations and hydrogen content in the DLC structure.

Oxygenation properties and isoform diversity of snake hemoglobins

DEFF Research Database (Denmark)

Storz, Jay F.; Natarajan, Chandrasekhar; Moriyama, Hideaki

2015-01-01

Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer- dimer dissociation. However, standardized comparative data are lacking fo...... isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform....

Role of protein glycosylation on the expression of muscarinic receptors of N4TG1 neuroblastoma cells

International Nuclear Information System (INIS)

Ahmad, A.; Chiang, P.K.

1986-01-01

Muscarinic acetylcholine receptors (mAChR) are glycoproteins. Experiments were conducted to determine whether active glycosylation of proteins in N4TG1 neuroblastoma cells could affect the expression of muscarinic receptors on the cell surface. The binding of radioactive N-methylscopolamine, a membrane impermeable ligand, to intact cells was used as a measure of mAChR. In the presence of the inhibitors of glycosylation, such as tunicamycin, monensin and amphomycin, N-linked glycosylation of proteins in the N4TG1 cells was inhibited, as measured by the incorporation of radioactive glucosamine or mannose in proteins. At the concentrations of tunicamycin and monensin used, the glycosylation of proteins after 3 hours were drastically reduced, but the number of mAChR in the cells was not altered. The apparent lack of effect within a short incubation period could be attributed to the presence of preformed oligosaccharide dolichol readily available for N-glycosylation. However, after 24 hours, tunicamycin (0.05 μg/ml) caused a decrease in the number of mAChR by 17% without having any effect on protein synthesis. Therefore, de novo glycosylation of proteins may be required for the expression of mAChR receptors in the N4TG1 neuroblastoma cell surface

Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

Energy Technology Data Exchange (ETDEWEB)

Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

1994-09-01

Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

Kinetic and Thermodynamic Analysis of Acetyl-CoA Activation of Staphylococcus aureus Pyruvate Carboxylase.

Science.gov (United States)

Westerhold, Lauren E; Bridges, Lance C; Shaikh, Saame Raza; Zeczycki, Tonya N

2017-07-11

Allosteric regulation of pyruvate carboxylase (PC) activity is pivotal to maintaining metabolic homeostasis. In contrast, dysregulated PC activity contributes to the pathogenesis of numerous diseases, rendering PC a possible target for allosteric therapeutic development. Recent research efforts have focused on demarcating the role of acetyl-CoA, one of the most potent activators of PC, in coordinating catalytic events within the multifunctional enzyme. Herein, we report a kinetic and thermodynamic analysis of acetyl-CoA activation of the Staphylococcus aureus PC (SaPC)-catalyzed carboxylation of pyruvate to identify novel means by which acetyl-CoA synchronizes catalytic events within the PC tetramer. Kinetic and linked-function analysis, or thermodynamic linkage analysis, indicates that the substrates of the biotin carboxylase and carboxyl transferase domain are energetically coupled in the presence of acetyl-CoA. In contrast, both kinetic and energetic coupling between the two domains is lost in the absence of acetyl-CoA, suggesting a functional role for acetyl-CoA in facilitating the long-range transmission of substrate-induced conformational changes within the PC tetramer. Interestingly, thermodynamic activation parameters for the SaPC-catalyzed carboxylation of pyruvate are largely independent of acetyl-CoA. Our results also reveal the possibility that global conformational changes give rise to observed species-specific thermodynamic activation parameters. Taken together, our kinetic and thermodynamic results provide a possible allosteric mechanism by which acetyl-CoA coordinates catalysis within the PC tetramer.

Too Many Links in the Horizon; What is Next? Linked Views and Linked History

NARCIS (Netherlands)

E. Liarou (Erietta); S. Idreos (Stratos)

2011-01-01

textabstractThe trend for more online linked data becomes stronger. Foreseeing a future where ``everything" will be online and linked, we ask the critical question; what is next? We envision that managing, querying and storing large amounts of links and data is far from yet another query

Examining impacts of current-use pesticides in Southern Ontario using in situ exposures of the amphipod Hyalella azteca.

Science.gov (United States)

Bartlett, Adrienne J; Struger, John; Grapentine, Lee C; Palace, Vince P

2016-05-01

In situ exposures with Hyalella azteca were used to assess impacts of current-use pesticides in Southern Ontario, Canada. Exposures were conducted over 2 growing seasons within areas of high pesticide use: 1 site on Prudhomme Creek and 3 sites on Twenty Mile Creek. Three sites on Spencer Creek, an area of low pesticide use, were added in the second season. Surface water samples were collected every 2 wk to 3 wk and analyzed for a suite of pesticides. Hyalella were exposed in situ for 1 wk every 4 wk to 6 wk, and survival and acetylcholinesterase (AChE) activity were measured. Pesticides in surface waters reflected seasonal use patterns: lower concentrations in spring and fall and higher concentrations during summer months. Organophosphate insecticides (chlorpyrifos, azinphos methyl, diazinon) and acid herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], mecoprop) were routinely detected in Prudhomme Creek, whereas neutral herbicides (atrazine, metolachlor) dominated the pesticide signature of Twenty Mile Creek. Spencer Creek contained fewer pesticides, which were measured at lower concentrations. In situ effects also followed seasonal patterns: higher survival and AChE activity in spring and fall, and lower survival and AChE activity during summer months. The highest toxicity was observed at Prudhomme Creek and was primarily associated with organophosphates. The present study demonstrated that current-use pesticides in Southern Ontario were linked to in situ effects and identified sites of concern requiring further investigation. © 2015 Crown in the Right of Canada.

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy.

Science.gov (United States)

Bieganowska, K; Höllsberg, P; Buckle, G J; Lim, D G; Greten, T F; Schneck, J; Altman, J D; Jacobson, S; Ledis, S L; Hanchard, B; Chin, J; Morgan, O; Roth, P A; Hafler, D A

1999-02-01

Human T cell lymphotropic virus-I (HTLV-I)-associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetramers loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR Vbeta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.

Performance Refactoring of Instrumentation, Measurement, and Analysis Technologies for Petascale Computing: the PRIMA Project

Energy Technology Data Exchange (ETDEWEB)

Malony, Allen D. [Department of Computer and Information Science, University of Oregon; Wolf, Felix G. [Juelich Supercomputing Centre, Forschungszentrum Juelich

2014-01-31

The growing number of cores provided by today’s high-end computing systems present substantial challenges to application developers in their pursuit of parallel efficiency. To find the most effective optimization strategy, application developers need insight into the runtime behavior of their code. The University of Oregon (UO) and the Juelich Supercomputing Centre of Forschungszentrum Juelich (FZJ) develop the performance analysis tools TAU and Scalasca, respectively, which allow high-performance computing (HPC) users to collect and analyze relevant performance data – even at very large scales. TAU and Scalasca are considered among the most advanced parallel performance systems available, and are used extensively across HPC centers in the U.S., Germany, and around the world. The TAU and Scalasca groups share a heritage of parallel performance tool research and partnership throughout the past fifteen years. Indeed, the close interactions of the two groups resulted in a cross-fertilization of tool ideas and technologies that pushed TAU and Scalasca to what they are today. It also produced two performance systems with an increasing degree of functional overlap. While each tool has its specific analysis focus, the tools were implementing measurement infrastructures that were substantially similar. Because each tool provides complementary performance analysis, sharing of measurement results is valuable to provide the user with more facets to understand performance behavior. However, each measurement system was producing performance data in different formats, requiring data interoperability tools to be created. A common measurement and instrumentation system was needed to more closely integrate TAU and Scalasca and to avoid the duplication of development and maintenance effort. The PRIMA (Performance Refactoring of Instrumentation, Measurement, and Analysis) project was proposed over three years ago as a joint international effort between UO and FZJ to accomplish

Linked data management

CERN Document Server

Hose, Katja; Schenkel, Ralf

2014-01-01

Linked Data Management presents techniques for querying and managing Linked Data that is available on today’s Web. The book shows how the abundance of Linked Data can serve as fertile ground for research and commercial applications. The text focuses on aspects of managing large-scale collections of Linked Data. It offers a detailed introduction to Linked Data and related standards, including the main principles distinguishing Linked Data from standard database technology. Chapters also describe how to generate links between datasets and explain the overall architecture of data integration systems based on Linked Data. A large part of the text is devoted to query processing in different setups. After presenting methods to publish relational data as Linked Data and efficient centralized processing, the book explores lookup-based, distributed, and parallel solutions. It then addresses advanced topics, such as reasoning, and discusses work related to read-write Linked Data for system interoperation. Desp...

S-LINK, a data link interface specification for the LHC era

International Nuclear Information System (INIS)

Bij, H.C. van der; McLaren, R.A.; Boyle, O.

1996-01-01

In the Technical Proposals for ATLAS, CMS and ALICE there is a requirement for several thousand data links. Although there is an obvious need for standardization, this seems difficult to achieve as the links run at different speeds, over different distances and have various constraints of power consumption, size and radiation hardness. An additional complication is that today we cannot decide which will be the most cost effective technology for the implementation of the final links. Furthermore, we must allow designers of boards at each end of the link, for example readout electronics and input buffers, to work in parallel with the development of the links. The S-LINK is a new concept which should provide the benefits of standardization without the limitations. The S-LINK specification defines, at both ends of the link, a simple FIFO-like user interface which remains independent of the technology used to implement the physical link. The physical link provides transfer of event data and control words, error detection, optional flow control and test facilities. This paper describes the S-LINK specification and gives examples of the use of the S-LINK, the physical links being designed, and the test equipment that is being developed

LinkED: A Novel Methodology for Publishing Linked Enterprise Data

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Shreyas Suresh Rao

2017-01-01

Full Text Available Semantic Web technologies have redefined and strengthened the Enterprise-Web interoperability over the last decade. Linked Open Data (LOD refers to a set of best practices that empower enterprises to publish and interlink their data using existing ontologies on the World Wide Web. Current research in LOD focuses on expert search, the creation of unified information space and augmentation of core data from an enterprise context. However, existing approaches for publication of enterprise data as LOD are domain-specific, ad-hoc and suffer from lack of uniform representation across domains. The paper proposes a novel methodology called LinkED that contributes towards LOD literature in two ways: (a streamlines the publishing process through five stages of cleaning, triplification, interlinking, storage and visualization; (b addresses the latest challenges in LOD publication, namely: inadequate links, inconsistencies in the quality of the dataset and replicability of the LOD publication process. Further, the methodology is demonstrated via the publication of digital repository data as LOD in a university setting, which is evaluated based on two semantic standards: Five-Star model and data quality metrics. Overall, the paper provides a generic LOD publication process that is applicable across various domains such as healthcare, e-governance, banking, and tourism, to name a few.

Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against HCMV proteins IE1 and IE2.

Science.gov (United States)

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Osterby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette

2014-01-01

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.

Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against HCMV proteins IE1 and IE2.

Directory of Open Access Journals (Sweden)

Peter Braendstrup

Full Text Available Human cytomegalovirus (HCMV is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2. Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.

Sex-linked dominant

Science.gov (United States)

Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

Tetra-kis(2,2'-bipyrid-ine)di-μ(3)-hydroxido-bis(μ-2-oxidobenzoato)tetra-copper(II) dinitrate tetra-hydrate.

Science.gov (United States)

Feng, Miao; Gu, Chao; Mi, Huai-Feng; Hu, Tong-Liang

2011-05-01

The tetra-nuclear title complex, [Cu(4)(C(7)H(4)O(3))(2)(OH)(2)(C(10)H(8)N(2))(4)](NO(3))(2)·4H(2)O, has a crystallographically imposed centre of symmetry. The Cu(II) atoms display a distorted square-pyramidal coordination geometry and are linked by two μ(2)-phenolate O atoms from the salicylate ligands and two μ(3)-hydroxo groups, forming a Cu(4)O(4) core that adopts a 'stepped-cubane' geometry. In the crystal, the cations are linked by O-H⋯O hydrogen bonds to the nitrate anions, which are in turn connected via O-H⋯O inter-actions to centrosymmentric water tetra-mers.

Radioligand imaging of α4β2* nicotinic acetylcholine receptors in Alzheimer’s disease and Parkinson’s disease

International Nuclear Information System (INIS)

Meyer, P. M.; Tiepolt, S.; Barthel, H.; Hesse, S.; Sabri, O.

2014-01-01

The α4β2 * nicotinic acetylcholine receptors (α4β2 * -nAChR) are highly abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as memory, learning and attention as well as mood and motor function. Post mortem studies suggest that abnormalities of α4β2 * -nAChRs are closely linked to histopathological hallmarks of Alzheimer’s disease (AD), such as amyloid aggregates/oligomers and tangle pathology and of Parkinson’s disease (PD) such as Lewy body pathology and the nigrostriatal dopaminergic deficit. In this review we summarize and discuss nicotinic receptor imaging findings of 2-[18F]FA-85380 PET, [ 11 C]nicotine PET and 5-[ 123 I]IA-85380 SPECT studies investigating α4β2 * -nAChR binding in vivo and their relationship to mental dysfunction in the brain of patients with AD and patients out of the spectrum of Lewy body disorders such as PD and Lewy body dementia (DLB). Furthermore, recent developments of novel α4β2*-nAChR-specific PET radioligands, such as (-)[ 18 F]Flubatine or [ 18 F]AZAN are summarized. We conclude that α4β2*-nAChR-specific PET might become a biomarker for early diagnostics and drug developments in patients with AD, DLB and PD, even at early or prodromal stages.

IPP (INNOVACIÓN EN PRODUCTOS Y PROCESOS PARA EL SECTOR DE LAS MATERIAS PRIMAS MINERALES Y ENERGÉTICAS

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CORREA ESPINAL ALEXANDER

2010-05-01

Full Text Available Este articulo proscrita los resultados del proyecto ce Investigación IPP (Innovación ce Procesos y Productos que plantea un análisis profundo y sistémico de las cadenas productivas, basado en el estudio de la productividad y los procesos. Este proyecto se trabajo en 4 fases: Inteligencia, Experimentación. Innovación y Apropiación tecnológica. Estas etapas están dirigidas al mejoramiento continuo ce los procesos, de los productos ce la organización y de las interacciones entre los actores de la cadena productiva de las materias primas minerales y energéticas. En la fase de inteligencia, se estudiaron las características, las ecesidades. el mercado y el entorno de la cadena productiva que son el resultado del aprovechamiento de los recursos naturales y del ambiente En la segunda fase, se caracterizó la formulación, diseño c implantación ce prototipos de procesos y productos que emulen el comportamiento del proceso en un sistema real y sean amigables con el medio ambiente. Teniendo en cuenta las dos primeras fases, la tercera se caracterizó por la formulación y el diseño ce nuevos procesos y productos que mejoren la eficiencia y la productividad. En la última fase del proyecto, se planteó el servicio de apropiación tecnológica que busca transferir innovación y conocimiento de punta a la cadena. Finalmente el resultado ce IPP es la propuesta de un centro de innovación y tecnología en la Universidad Nacional de Colombia, que garantizará la apropiación y adecuación de las soluciones a las cadenas productivas, siendo una innovación para el sector de la minería, los materiales y la energía, y teniendo como principios, productos y procesos amigables con el ambiente.

Evaluación de distintas materias primas para la producción de almácigo de tomate

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Fernando Richmond

2010-01-01

Full Text Available Se evaluaron mezclas de materias primas naturales en diferentes proporciones y en el siguiente orden: fibra de coco (Cocos nucifera, aserrín de melina (Gmelina arborea y abono orgánico Coope Victoria, para utilizarlos como sustrato en la etapa de almácigo de tomate híbrido FBM-17. Se hicieron mezclas entre sí de fibra de coco y aserrín de melina en diferentes proporciones (30%, 40% y 50% de cada material, para un total de 9 tratamientos; el abono orgánico se agregó para completar el 100%. Se evaluó la variable porcentaje de germinación 7 días después de la siembra (dds y porcentaje de plantas trasplantables a 27 dds en cada parcela útil. Además, en 10 plántulas escogidas al azar dentro de cada parcela útil (a 27 dds se evaluó: altura de plántula, grosor del tallo, peso seco de raíz y parte aérea, relación raíz/parte aérea y calidad de adobe. Del total de tratamientos, los mayores valores para las variables evaluadas se obtuvieron en los 3 tratamientos donde la proporción de aserrín de melina fue 30%, junto con el tratamiento de 40% de fibra de coco + 40% de aserrín de melina + 20% de abono orgánico Coope Victoria; entre ellos el sustrato con tendencia a dar mejores resultados en todas las variables fue la mezcla 30-30-40. Los valores inferiores para las variables evaluadas se obtuvieron en el tratamiento donde no se incluyó en la mezcla abono orgánico (50-50-0, excepto para las variables porcentaje de germinación y relación raíz/parte aérea. La inclusión de abono orgánico en la mezcla del sustrato favoreció la obtención de valores satisfactorios.

Growth, characterisation and electronic applications of amorphous hydrogenated carbon

International Nuclear Information System (INIS)

Paul, S.

2000-11-01

My thesis proposes solutions to a number of riddles associated with the material, hydrogenated amorphous carbon, (a-C:H). This material has lately generated interest in the electronic engineering community, owing to some remarkable properties. The characterisation of amorphous carbon films, grown by radio frequency plasma enhanced chemical vapour deposition has been reported. The coexistence of multiple phases in the same a-C:H film manifests itself in the inconsistent electrical behaviour of different parts of the film, thus rendering it difficult to predict the nature of films. For the first time, in this thesis, a reliable prediction of Schottky contact formation on a-C:H films is reported. A novel and simple development on a Scanning Electron Microscope, configured to study the electrical properties of the grown a-C:H films, has been reported. Since device performance is crucially linked to the density of states in the film, a study of the same was undertaken in my doctoral research. I present a mathematical formalism to estimate the density of states in a-C:H. The most commonly used metal, (aluminium), for contact formation on a-C:H films, has been concluded to be the least suitable. On the basis of the study presented in this thesis, copper and chromium are judged to be the best alternatives. The resilience of a-C:H/Si heterostructures under high voltages (upto 900 V) has been reported in this thesis for the first time. The performance of a-C:H grown at room temperature on GaAs, has been studied and concluded to be satisfactory on the basis of good adherence and low leakage currents. Such a structure was motivated by the applicability in Metal Insulator Semiconductor Field Effect Transistors (MISFET). (author)

Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

Science.gov (United States)

Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

2018-02-05

Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

Muscle aches

Science.gov (United States)

... exercising and cool down afterward. Drink lots of fluids before, during, and after exercise. If you work in the same position most of the day (such as sitting at a computer), stretch at least every hour.

Procedimiento para la gestión de los impactos ambientales negativos asociados a la recuperación de materias primas en Cienfuegos, Cuba.

Directory of Open Access Journals (Sweden)

David Javier Castro Rodríguez

2016-04-01

Full Text Available El reciclaje constituye una actividad priorizada en Cuba. El objetivo fue implementar un procedimiento para la gestión de los impactos ambientales negativos asociados a los procesos operativos de la Empresa de Recuperación de Materias Primas de Cienfuegos. El procedimiento se construyó utilizando la propuesta del Instituto Andaluz de Tecnología para la gestión por procesos y los ocho pasos en la solución de problemas. Se combinaron herramientas de gestión bajo el principio de convergencia metodológica. Los impactos ambientales fueron evaluados mediante el software GAIA versión 1.0, utilizando los criterios propuestos por la Guía Metodológica de Evaluación de Impacto Ambiental de Conesa. Se identificaron 97 impactos ambientales negativos, entre severos y moderados integraron el 80.41 % de ellos. El factor ambiental más impactado fue el físico-químico con el 50.52 %. El subproceso no metálico resultó el más impactante, con el 50 % de los impactos severos negativos totales y el 34 % de los moderados. Se identificaron las principales causas asociadas y se diseñó un plan de intervención de 35 medidas con base en los principios de Producción Más Limpia. Los resultados contribuyen a lograr la gestión de los impactos ambientales negativos de la entidad y a la sostenibilidad del reciclaje.

Performance Refactoring of Instrumentation, Measurement, and Analysis Technologies for Petascale Computing. The PRIMA Project

Energy Technology Data Exchange (ETDEWEB)

Malony, Allen D. [Univ. of Oregon, Eugene, OR (United States). Dept. of Computer and Information Science; Wolf, Felix G. [Wilhelm-Johnen-Strasse, Julich (Germany). Forschungszentrum Julich GmbH

2014-01-31

The growing number of cores provided by today’s high-­end computing systems present substantial challenges to application developers in their pursuit of parallel efficiency. To find the most effective optimization strategy, application developers need insight into the runtime behavior of their code. The University of Oregon (UO) and the Juelich Supercomputing Centre of Forschungszentrum Juelich (FZJ) develop the performance analysis tools TAU and Scalasca, respectively, which allow high-­performance computing (HPC) users to collect and analyze relevant performance data – even at very large scales. TAU and Scalasca are considered among the most advanced parallel performance systems available, and are used extensively across HPC centers in the U.S., Germany, and around the world. The TAU and Scalasca groups share a heritage of parallel performance tool research and partnership throughout the past fifteen years. Indeed, the close interactions of the two groups resulted in a cross-­fertilization of tool ideas and technologies that pushed TAU and Scalasca to what they are today. It also produced two performance systems with an increasing degree of functional overlap. While each tool has its specific analysis focus, the tools were implementing measurement infrastructures that were substantially similar. Because each tool provides complementary performance analysis, sharing of measurement results is valuable to provide the user with more facets to understand performance behavior. However, each measurement system was producing performance data in different formats, requiring data interoperability tools to be created. A common measurement and instrumentation system was needed to more closely integrate TAU and Scalasca and to avoid the duplication of development and maintenance effort. The PRIMA (Performance Refactoring of Instrumentation, Measurement, and Analysis) project was proposed over three years ago as a joint international effort between UO and FZJ to

Methodological framework to identify possible adverse drug reactions using population-based administrative data [v1; ref status: indexed, http://f1000r.es/3ys

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Brian Sauer

2014-10-01

Full Text Available Purpose: We present a framework for detecting possible adverse drug reactions (ADRs using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs: known reactions (gastrointestinal, psychological disturbances, potential reactions (respiratory disturbance, novel reactions (hepatic, hematological disturbances, and death. Methods: Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression. Results: Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2, but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6 in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3. Conclusions: We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential

PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings.

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Monica Puligheddu

Full Text Available Nicotinic acetylcholine receptors (nAChRs are involved in seizure mechanisms. Hence, nocturnal frontal lobe epilepsy was the first idiopathic epilepsy linked with specific mutations in α4 or β2 nAChR subunit genes. These mutations confer gain of function to nAChRs by increasing sensitivity toward acetylcholine. Consistently, nicotine elicits seizures through nAChRs and mimics the excessive nAChR activation observed in animal models of the disease. Treatments aimed at reducing nicotinic inputs are sought as therapies for epilepsies where these receptors contribute to neuronal excitation and synchronization. Previous studies demonstrated that peroxisome proliferator-activated receptors-α (PPARα, nuclear receptor transcription factors, suppress nicotine-induced behavioral and electrophysiological effects by modulating nAChRs containing β2 subunits. On these bases, we tested whether PPARα agonists were protective against nicotine-induced seizures. To this aim we utilized behavioral and electroencephalographic (EEG experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p. or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2% for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.. Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key

Future Looks Bright for Interferometry

Science.gov (United States)

2008-09-01

First Light for the PRIMA instrument The PRIMA instrument [1] of the ESO Very Large Telescope Interferometer (VLTI) recently saw "first light" at its new home atop Cerro Paranal in Chile. When fully operational, PRIMA will boost the capabilities of the VLTI to see sources much fainter than any previous interferometers, and enable astrometric precision unmatched by any other existing astronomical facility. PRIMA will be a unique tool for the detection of exoplanets. First Light of the PRIMA Instrument ESO PR Photo 29a/08 Preparing for PRIMA "PRIMA is specifically designed to see if one star 'wobbles' to and fro because it is has unseen planetary companions", says instrument scientist Gerard van Belle. "This allows us to not only detect exoplanets, but to measure their mass." PRIMA's expected astrometric precision of tens of micro-arcseconds is unmatched by any other existing astronomical facility, whether on the ground or in orbit [2]. In addition to taking astrometric measurements PRIMA will be the key to the imaging of faint sources with the VLTI using the science instruments AMBER and MIDI. Interferometry combines the light received by two or more telescopes, concentrating on tiny differences between the signals to measure angles with exquisite precision. Using this technique PRIMA can pick out details as sharply as a single telescope with a diameter equivalent to the largest distance between the telescopes. For the VLTI, the distance between the two telescope elements is about 200 metres. The PRIMA instrument is unique amongst the VLTI instruments, in that it is effectively two interferometers in one. PRIMA will take data from two sources on the sky simultaneously: the brighter source can be used for tracking, allowing the interferometer to "stare" at the fainter source for longer than is now possible with conventional interferometers. Although there have been earlier pathfinder experiments to test this technique, PRIMA represents the first facility

Deploying Linked Open Vocabulary (LOV to Enhance Library Linked Data

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Oh, Sam Gyun

2015-06-01

Full Text Available Since the advent of Linked Data (LD as a method for building webs of data, there have been many attempts to apply and implement LD in various settings. Efforts have been made to convert bibliographic data in libraries into Linked Data, thereby generating Library Linked Data (LLD. However, when memory institutions have tried to link their data with external sources based on principles suggested by Tim Berners-Lee, identifying appropriate vocabularies for use in describing their bibliographic data has proved challenging. The objective of this paper is to discuss the potential role of Linked Open Vocabularies (LOV in providing better access to various open datasets and facilitating effective linking. The paper will also examine the ways in which memory institutions can utilize LOV to enhance the quality of LLD and LLD-based ontology design.

Selectivity of silica species in ocean observed from seasonal and local changes

Science.gov (United States)

Tanaka, Miho; Takahashi, Kazuya; Nemoto, Masao; Horimoto, Naho

2013-03-01

Silicic acids, derived from SiO2 (silica), have several chemical forms in solution. Silica is a nutrient for diatoms, which are phytoplankton in oceans. Silica species can be used as a tracer to examine the behavior of silica in nature. The speciation for silica by FAB-MS (fast atom bombardment mass spectrometry) has been carried out for seawater samples from Tokyo Bay and Sagami Bay to investigate the seasonal and locational changes of the depth profiles of silica species. The species, [Si(OH)2O2Na+]-, [Si2(OH)5O2]- ([dimer]-), [Si2(OH)4O3Na+]-, [Si(OH)7O5-] ([cyclic tetramer]-), [Si4(OH)6O6Na+]-, [Si(OH)9O]- ([linear tetramer]-) and [Si4(OH)8O5Na+]- were mainly identified by FAB-MS. The seasonal and locational changes and the reproducibility of depth profiles of silica species were determined from October 2001 to July 2002. The depth profile of the ratio of linear tetramer to cyclic tetramer reflects the activity of diatoms, implying that the linear tetramer is the preferred "food" for diatoms. In particular, the depth profile for the ratio of linear tetramer to cyclic tetramer exhibits a critical changes that depend on the season. Furthermore, the depth profiles for the samples from Sagami Bay (open ocean) indicate that seawater is easily exchanged by ocean currents (the Japan Current). Thus, silica speciation by FAB-MS can give us a new tracer indicating the characteristics of the seawater budget, which change with depth, season and ocean locality.

N-substituted-piperidines as Novel Anti-alzheimer Agents: Synthesis, antioxidant activity, and molecular docking study

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Khairia M. Youssef

2018-06-01

Full Text Available Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining carbamoylpiperidine analogs containing nipecotic acid scaffold were described. Then, a series of hybrids have been developed by introducing Free radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds showed effective AchE inhibitions, high selectivity over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of analogs containing nipecotic acid scaffold to serve in the design of N-benzyl-piperidine linked multipotent molecules for the treatment of Alzheimer Disease. Keywords: Synthesis, N-substituted-piperidines, Antioxidant activity, ATP chemiluminescence, Molecular modeling study

Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

Science.gov (United States)

Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

2012-12-15

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

More tricks with tetramers

DEFF Research Database (Denmark)

Dolton, Garry; Tungatt, Katie; Lloyd, Angharad

2015-01-01

Analysis of antigen-specific T-cell populations by flow cytometry with peptide-MHC (pMHC) multimers is now commonplace. These reagents allow the tracking and phenotyping of T cells during infection, autoimmunity and cancer, and can be particularly revealing when used for monitoring therapeutic in...

Operative Links

DEFF Research Database (Denmark)

Wistoft, Karen; Højlund, Holger

2012-01-01

educational goals, learning content, or value clarification. Health pedagogy is often a matter of retrospective rationalization rather than the starting point of planning. Health and risk behaviour approaches override health educational approaches. Conclusions: Operational links between health education......, health professionalism, and management strategies pose the foremost challenge. Operational links indicates cooperative levels that facilitate a creative and innovative effort across traditional professional boundaries. It is proposed that such links are supported by network structures, shared semantics...

Influence of Applied Bias Voltage on the Composition, Structure, and Properties of Ti:Si-Codoped a-C:H Films Prepared by Magnetron Sputtering

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Jinlong Jiang

2014-01-01

Full Text Available The titanium- and silicon-codoped a-C:H films were prepared at different applied bias voltage by magnetron sputtering TiSi target in argon and methane mixture atmosphere. The influence of the applied bias voltage on the composition, surface morphology, structure, and mechanical properties of the films was investigated by XPS, AFM, Raman, FTIR spectroscopy, and nanoindenter. The tribological properties of the films were characterized on an UMT-2MT tribometer. The results demonstrated that the film became smoother and denser with increasing the applied bias voltage up to −200 V, whereas surface roughness increased due to the enhancement of ion bombardment as the applied bias voltage further increased. The sp3 carbon fraction in the films monotonously decreased with increasing the applied bias voltage. The film exhibited moderate hardness and the superior tribological properties at the applied bias voltage of −100 V. The tribological behaviors are correlated to the H/E or H3/E2 ratio of the films.

Muscle-type nicotinic receptor blockade by diethylamine, the hydrophilic moiety of lidocaine

Directory of Open Access Journals (Sweden)

Armando eAlberola-Die

2016-02-01

Full Text Available Lidocaine bears in its structure both an aromatic ring and a terminal amine, which can be protonated at physiological pH, linked by an amide group. Since lidocaine causes multiple inhibitory actions on nicotinic acetylcholine receptors (nAChRs, this work was aimed to determine the inhibitory effects of diethylamine (DEA, a small molecule resembling the hydrophilic moiety of lidocaine, on Torpedo marmorata nAChRs microtransplanted to Xenopus oocytes. Similarly to lidocaine, DEA reversibly blocked acetylcholine-elicited currents (IACh in a dose-dependent manner (IC50 close to 70 μM, but unlike lidocaine, DEA did not affect IACh desensitization. IACh inhibition by DEA was more pronounced at negative potentials, suggesting an open-channel blockade of nAChRs, although roughly 30% inhibition persisted at positive potentials, indicating additional binding sites outside the pore. DEA block of nAChRs in the resting state (closed channel was confirmed by the enhanced IACh inhibition when pre-applying DEA before its co-application with ACh, as compared with solely DEA and ACh co-application. Virtual docking assays provide a plausible explanation to the experimental observations in terms of the involvement of different sets of drug binding sites. So, at the nAChR transmembrane (TM domain, DEA and lidocaine shared binding sites within the channel pore, giving support to their open-channel blockade; besides, lidocaine, but not DEA, interacted with residues at cavities among the M1, M2, M3 and M4 segments of each subunit and also at intersubunit crevices. At the extracellular (EC domain, DEA and lidocaine binding sites were broadly distributed, which aids to explain the closed channel blockade observed. Interestingly, some DEA clusters were located at the α-γ interphase of the EC domain, in a cavity near the orthosteric binding site pocket; by contrast, lidocaine contacted with all α-subunit loops conforming the ACh binding site, both in α-γ and �

Link-N: The missing link towards intervertebral disc repair is species-specific.

Directory of Open Access Journals (Sweden)

Frances C Bach

Full Text Available Degeneration of the intervertebral disc (IVD is a frequent cause for back pain in humans and dogs. Link-N stabilizes proteoglycan aggregates in cartilaginous tissues and exerts growth factor-like effects. The human variant of Link-N facilitates IVD regeneration in several species in vitro by inducing Smad1 signaling, but it is not clear whether this is species specific. Dogs with IVD disease could possibly benefit from Link-N treatment, but Link-N has not been tested on canine IVD cells. If Link-N appears to be effective in canines, this would facilitate translation of Link-N into the clinic using the dog as an in vivo large animal model for human IVD degeneration.This study's objective was to determine the effect of the human and canine variant of Link-N and short (s Link-N on canine chondrocyte-like cells (CLCs and compare this to those on already studied species, i.e. human and bovine CLCs. Extracellular matrix (ECM production was determined by measuring glycosaminoglycan (GAG content and histological evaluation. Additionally, the micro-aggregates' DNA content was measured. Phosphorylated (p Smad1 and -2 levels were determined using ELISA.Human (sLink-N induced GAG deposition in human and bovine CLCs, as expected. In contrast, canine (sLink-N did not affect ECM production in human CLCs, while it mainly induced collagen type I and II deposition in bovine CLCs. In canine CLCs, both canine and human (sLink-N induced negligible GAG deposition. Surprisingly, human and canine (sLink-N did not induce Smad signaling in human and bovine CLCs. Human and canine (sLink-N only mildly increased pSmad1 and Smad2 levels in canine CLCs.Human and canine (sLink-N exerted species-specific effects on CLCs from early degenerated IVDs. Both variants, however, lacked the potency as canine IVD regeneration agent. While these studies demonstrate the challenges of translational studies in large animal models, (sLink-N still holds a regenerative potential for humans.

MATERIAS PRIMAS, CONTEXTO Y PROCEDENCIA DE CUENTAS DE COLLAR EN LOS SITIOS ALAMITO (DEPTO. ANDALGALÁ, CATAMARCA (Raw Materials, Context, and Provenance of Necklace Beads at Alamito Sites (Andalgalá Department, Catamarca

Directory of Open Access Journals (Sweden)

María Soledad Gianfrancisco

2017-12-01

Full Text Available En este trabajo se presentan los resultados de análisis físicos y químicos efectuados sobre un conjunto de bienes ornamentales procedentes de los sitios Alamito. La identificación de materia prima alóctona empleada para su manufactura y la ausencia de elementos sustanciales que den cuenta de una producción local de los mismos nos permiten plantear la hipótesis de que fueron adquiridos mediante mecanismos de intercambio, como otros de los tantos productos que circularon en el flujo interregional de bienes en el contexto macrorregional del área surandina. ENGLISH: This paper presents the results of physical and chemical analyses carried out on a set of ornamental goods from Alamito sites. The identification of allochthonous material used for their manufacture and the absence of substantial elements that would indicate local production allow us to put forward the hypothesis that these ornamental goods were acquired through trade, like many other products that circulated through the interregional flow of goods in the macro-regional context of the southern Andes.

Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induce cyclooxygenase-2 activity in human gastric cancer cells: Involvement of nicotinic acetylcholine receptor (nAChR) and β-adrenergic receptor signaling pathways

International Nuclear Information System (INIS)

Shin, Vivian Yvonne; Jin, H.C.; Ng, Enders K.O.; Yu Jun; Leung, W.K.; Cho, C.H.; Sung, J.J.Y.

2008-01-01

Induction of cyclooxygenase-2 (COX-2) associates with cigarette smoke exposure in many malignancies. Nicotine and its derivative, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are the two important components in cigarette smoke that contributes to cancer development. However, the molecular mechanism(s) by which nicotine or NNK promotes gastric carcinogenesis remains largely unknown. We found that nicotine and NNK significantly enhanced cell proliferation in AGS cells that expressed both alpha7 nicotinic acetylcholine receptor (α7 nAChR) and β-adrenergic receptors. Treatment of cells with α-bungarotoxin (α-BTX, α7nAChR antagonist) or propranolol (β-adrenergic receptor antagonist) blocked NNK-induced COX-2/PGE 2 and cell proliferation, while nicotine-mediated cell growth and COX-2/PGE 2 induction can only be suppressed by propranolol, but not α-BTX. Moreover, in contrast to the dependence of growth promoting effect of nicotine on Erk activation, inhibitor of p38 mitogen-activated protein kinase (MAPK) repressed NNK-induced COX-2 upregulation and resulted in suppression of cell growth. In addition, nicotine and NNK mediated COX-2 induction via different receptors to modulate several G1/S transition regulatory proteins and promote gastric cancer cell growth. Selective COX-2 inhibitor (SC-236) caused G1 arrest and abrogated nicotine/NNK-induced cell proliferation. Aberrant expression of cyclin D1 and other G1 regulatory proteins are reversed by blockade of COX-2. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth through MAPK/COX-2 activation, which may perhaps provide a chemoprevention strategy for cigarette smoke-related gastric carcinogenesis

Light-induced cross-linking and post-cross-linking modification of polyglycidol.

Science.gov (United States)

Marquardt, F; Bruns, M; Keul, H; Yagci, Y; Möller, M

2018-02-08

The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.

Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

Science.gov (United States)

Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

2018-02-01

The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

Use of link to mammography screening information and link sharing strategies

DEFF Research Database (Denmark)

Mukai, Thomas; Bro, Flemming; Olesen, Frede

2011-01-01

-43%) reported use of the link. The difference between the two strategies was 15% (95% CI: 8-22%) (Pused the link prior to the screening event, and 37% (95% CI: 30-43%) used the link afterwards. The difference was 9% (95% CI: 0-17%) (P=0.035). Among the GPs in group 1, 40% (95% CI......Introduction: The Internet is increasingly being used for disseminating knowledge in health care. Often this is done through a ‘Uniform Resource Locator’ (URL), better known as a link. There are three ways of sharing a link: verbally, in print or electronically. Furthermore, timing and exposure...... in Central Denmark Region, we constructed a website containing screening programme information for GPs. We inserted the link to this website in different media and divided the GPs into three groups: Group 1 received a letter prior to the screening event and an electronic test result after the screening...

Wallops Low Elevation Link Analysis for the Constellation Launch/Ascent Links

Science.gov (United States)

Cheung, Keith; Ho, C.; Kantak, A.; Lee, C.; Tye, R.; Richards, E.; Sham, C.; Schlesinger, A.; Barritt, B.

2011-01-01

To execute the President's Vision for Space Exploration, the Constellation Program (CxP) was formed to build the next generation spacecraft Orion and launch vehicles Ares, to transport human and cargo to International Space Station (ISS), moon, and Mars. This paper focuses on the detailed link analysis for Orion/Ares s launch and ascent links with Wallops 11.3m antenna (1) Orion's Dissimilar Voice link: 10.24 Kbps, 2-way (2) Ares Developmental Flight Instrument link, 20 Mbps, downlink. Three launch trajectories are considered: TD7-E, F (Feb), and G (Aug). In certain launch scenarios, the critical events of main engine cutoff (MECO) and Separation occur during the low elevation regime of WFF s downrange -- less than 5 degree elevation angle. The goal of the study is to access if there is enough link margins for WFF to track the DV and DFI links.

PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study

Energy Technology Data Exchange (ETDEWEB)

Tychyj-Pinel, Christelle [Service de Medecine Nucleaire, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Benite (France); Ricard, Fabien [Service de Medecine Nucleaire, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Benite (France); Universite de Lyon, Faculte de Medecine, UCB Lyon 1, Lyon (France); Fulham, Michael [Royal Prince Alfred Hospital, Department of PET and Nuclear Medicine, Sydney (Australia); University of Sydney, Sydney Medical School, Sydney (Australia); Fournier, Marion [Centre Hospitalier Lyon Sud, The Lymphoma Academic Research Organisation (LYSARC), Pierre-Benite (France); Meignan, Michel [CHU Henri Mondor, Medicine Nucleaire, Creteil (France); Lamy, Thierry [Service d' Hematologie, CHU, Rennes (France); Vera, Pierre [Centre Henri Becquerel, Service de Medecine Nucleaire, Rouen (France); Rouen University, QuantIF (Litis EA4108), Rouen (France); Salles, Gilles [Universite de Lyon, Faculte de Medecine, UCB Lyon 1, Lyon (France); Service d' Hematologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Benite (France); Trotman, Judith [University of Sydney, Sydney Medical School, Sydney (Australia); Concord Hospital, Department of Haematology, Concord, NSW (Australia)

2014-03-15

We aimed to compare the standardized central review of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42-51, 2011; Trotman et al., J Clin Oncol 29:3194-3200, 2011) to scan review at local centres. PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579-586, 2007; Juweid et al., J Clin Oncol 25:571-578, 2007; Shankar et al., J Nucl Med 47:1059-1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257-1260, 2009; Meignan et al., Leuk Lymphoma 51:2171-2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824-1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes. Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUV{sub max}) of 11.7 (range 4.6-35.6). There was no significant association between baseline SUV{sub max} and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p = 0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8-4.6] or 5PS with a cut-off ≥3 (p = 0.12; HR 2.0; 95 % CI 0.8-4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0 % (95 % CI 3.7-55.8 %) versus 61.4 % (95 % CI 45.4-74.1 %) in PET-negative patients (p = 0.01; HR 3.1; 95 % CI 1.2-7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75 %. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1 % (95 % CI 10.2-55.0 %) vs 64.6 % (95 % CI 47.0-77.6 %) for PET

Keele Aches and Pains Study protocol: validity, acceptability, and feasibility of the Keele STarT MSK tool for subgrouping musculoskeletal patients in primary care

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Campbell P

2016-10-01

Full Text Available Paul Campbell,1 Jonathan C Hill,1 Joanne Protheroe,1 Ebenezer K Afolabi,1 Martyn Lewis,1 Ruth Beardmore,1 Elaine M Hay,1 Christian D Mallen,1 Bernadette Bartlam,1 Benjamin Saunders,1 Danielle A van der Windt,1 Sue Jowett,2 Nadine E Foster,1 Kate M Dunn1 1Arthritis Research UK Primary Care Centre, Research Institute of Primary Care and Health Sciences, Keele University, Keele, 2Health Economics Unit, University of Birmingham, Birmingham, UK Abstract: Musculoskeletal conditions represent a considerable burden worldwide, and are predominantly managed in primary care. Evidence suggests that many musculoskeletal conditions share similar prognostic factors. Systematically assessing patient’s prognosis and matching treatments based on prognostic subgroups (stratified care has been shown to be both clinically effective and cost-effective. This study (Keele Aches and Pains Study aims to refine and examine the validity of a brief questionnaire (Keele STarT MSK tool designed to enable risk stratification of primary care patients with the five most common musculoskeletal pain presentations. We also describe the subgroups of patients, and explore the acceptability and feasibility of using the tool and how the tool is best implemented in clinical practice. The study design is mixed methods: a prospective, quantitative observational cohort study with a linked qualitative focus group and interview study. Patients who have consulted their GP or health care practitioner about a relevant musculoskeletal condition will be recruited from general practice. Participating patients will complete a baseline questionnaire (shortly after consultation, plus questionnaires 2 and 6 months later. A subsample of patients, along with participating GPs and health care practitioners, will be invited to take part in qualitative focus groups and interviews. The Keele STarT MSK tool will be refined based on face, discriminant, construct, and predictive validity at baseline and 2

Scattering of neutrons by catalase: a study of molecules, subunits, and tubules

International Nuclear Information System (INIS)

Randall, J.; Starling, D.; Baldwin, J.P.; Ibel, K.

1976-01-01

The paper deals with small-angle scattering of neutrons by catalase tetramers, dimers, and monomers and with neutron diffraction by helical assemblies of tetramers in the form of tubules. A preliminary study of catalase is described

Unravelling the shape and structural assembly of the photosynthetic GAPDH-CP12-PRK complex from Arabidopsis thaliana by small-angle X-ray scattering analysis.

Science.gov (United States)

Del Giudice, Alessandra; Pavel, Nicolae Viorel; Galantini, Luciano; Falini, Giuseppe; Trost, Paolo; Fermani, Simona; Sparla, Francesca

2015-12-01

Oxygenic photosynthetic organisms produce sugars through the Calvin-Benson cycle, a metabolism that is tightly linked to the light reactions of photosynthesis and is regulated by different mechanisms, including the formation of protein complexes. Two enzymes of the cycle, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK), form a supramolecular complex with the regulatory protein CP12 with the formula (GAPDH-CP122-PRK)2, in which both enzyme activities are transiently inhibited during the night. Small-angle X-ray scattering analysis performed on both the GAPDH-CP12-PRK complex and its components, GAPDH-CP12 and PRK, from Arabidopsis thaliana showed that (i) PRK has an elongated, bent and screwed shape, (ii) the oxidized N-terminal region of CP12 that is not embedded in the GAPDH-CP12 complex prefers a compact conformation and (iii) the interaction of PRK with the N-terminal region of CP12 favours the approach of two GAPDH tetramers. The interaction between the GAPDH tetramers may contribute to the overall stabilization of the GAPDH-CP12-PRK complex, the structure of which is presented here for the first time.

Linking open vocabularies

CERN Document Server

Greifender, Elke; Seadle, Michael

2013-01-01

Linked Data (LD), Linked Open Data (LOD) and generating a web of data, present the new knowledge sharing frontier. In a philosophical context, LD is an evolving environment that reflects humankinds' desire to understand the world by drawing on the latest technologies and capabilities of the time. LD, while seemingly a new phenomenon did not emerge overnight; rather it represents the natural progression by which knowledge structures are developed, used, and shared. Linked Open Vocabularies is a significant trajectory of LD. Linked Open Vocabularies targets vocabularies that have traditionally b

Oxygenation properties and isoform diversity of snake hemoglobins.

Science.gov (United States)

Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

2015-11-01

Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. Copyright © 2015 the American Physiological Society.

A New Structural Form in the SAM/Metal-Dependent O;#8209;Methyltransferase Family: MycE from the Mycinamicin Biosynthetic Pathway

Energy Technology Data Exchange (ETDEWEB)

Akey, David L.; Li, Shengying; Konwerski, Jamie R.; Confer, Laura A.; Bernard, Steffen M.; Anzai, Yojiro; Kato, Fumio; Sherman, David H.; Smith, Janet L. (Michigan); (Toho)

2012-08-01

O-linked methylation of sugar substituents is a common modification in the biosynthesis of many natural products and is catalyzed by multiple families of S-adenosyl-l-methionine (SAM or AdoMet)-dependent methyltransferases (MTs). Mycinamicins, potent antibiotics from Micromonospora griseorubida, can be methylated at two positions on a 6-deoxyallose substituent. The first methylation is catalyzed by MycE, a SAM- and metal-dependent MT. Crystal structures were determined for MycE bound to the product S-adenosyl-l-homocysteine (AdoHcy) and magnesium, both with and without the natural substrate mycinamicin VI. This represents the first structure of a natural product sugar MT in complex with its natural substrate. MycE is a tetramer of a two-domain polypeptide, comprising a C-terminal catalytic MT domain and an N-terminal auxiliary domain, which is important for quaternary assembly and for substrate binding. The symmetric MycE tetramer has a novel MT organization in which each of the four active sites is formed at the junction of three monomers within the tetramer. The active-site structure supports a mechanism in which a conserved histidine acts as a general base, and the metal ion helps to position the methyl acceptor and to stabilize a hydroxylate intermediate. A conserved tyrosine is suggested to support activity through interactions with the transferred methyl group from the SAM methyl donor. The structure of the free enzyme reveals a dramatic order-disorder transition in the active site relative to the S-adenosyl-L-homocysteine complexes, suggesting a mechanism for product/substrate exchange through concerted movement of five loops and the polypeptide C-terminus.

Materias primas para pavimentos y revestimientos cerámicos en la región de Murcia

Directory of Open Access Journals (Sweden)

Fernández, C.

2001-10-01

Full Text Available The clay industry of the Murcia Region has never had a relevant industrial importance, with only around ten brick operations in the last few years. Today only only two brid factories are operative having certain size. The extraordinary industrial development currently experienced by the Region has leaded to the development of new initiatives which need institutional backing. In this framework and under the sponsoring of the Council of Technologies, Industry and Commerce of the Autonomic Community, the Spanish Geological Survey (ITGE has carried out a general survey for raw materials for the ceramic industry in the region, mainly aimed to find clays for ceramic gres and glazed tiles, whose results are discussed in this paper. Murcia has a very complicated geology, being carbonated marine sediments the most important lithologies. Due to it, it is difficult to find no-carbonated shales or clays to produce gres tiles. We have found six zones containing different clay types, that reach a few hundreds million tons of resources. With that clays we have produce in the laboratory gres tiles and glazed tiles of commercial quality.

La industria cerámica de la Región de Murcia no ha tenido gran importancia industrial, limitándose a una decena de fábricas de ladrillos. Hoy en día sólo operan en la región 2 fábricas de ladrillos de cierta entidad. El extraordinario desarrollo industrial que experimenta actualmente la Región suscita nuevas iniciativas empresariales, que precisan del apoyo institucional. En este marco y bajo el auspicio y con la financiación parcial de la Consejería Tecnologías, Industria y Comercio de la Comunidad Autónoma, el Instituto Tecnológico Geominero de España ha realizado en los tres últimos años una investigación general de materias primas para la industria cerámica en la región, especialmente dirigida a localizar arcillas para pavimentos y revestimientos cerámicos, cuyos resultados se exponen en este

Effect of Link Flexibility on tip position of a single link robotic arm

Science.gov (United States)

Madhusudan Raju, E.; Siva Rama Krishna, L.; Mouli, Y. Sharath Chandra; Nageswara Rao, V.

2015-12-01

The flexible robots are widely used in space applications due to their quick response, lower energy consumption, lower overall mass and operation at high speed compared to conventional industrial rigid link robots. These robots are inherently flexible, so that the kinematics of flexible robots can't be solved with rigid body assumptions. The flexibility in links and joints affects end-point positioning accuracy of the robot. It is important to model the link kinematics with precision which in turn simplifies modelling of dynamics of flexible robots. The main objective of this paper is to evaluate the effect of link flexibility on a tip position of a single link robotic arm for a given motion. The joint is assumed to be rigid and only link flexibility is considered. The kinematics of flexible link problem is evaluated by Assumed Modes Method (AMM) using MAT LAB Programming. To evaluate the effect of link flexibility (with and without payload) of robotic arm, the normalized tip deviation is found for flexible link with respect to a rigid link. Finally, the limiting inertia for payload mass is found if the allowable tip deviation is 5%.

49 CFR 1037.1 - Weights and weighing.

Science.gov (United States)

2010-10-01

... on supervised scales, establishes prima facie that the loss occurred in transit and that the railroad... in combination with a supervised weight establishes prima facie that the loss occurred in transit and... the above exception, a prima facie case of railroad liability for loss in transit has not been...

76 FR 52561 - Timely Mailing Treated as Timely Filing

Science.gov (United States)

2011-08-23

... to the only ways to establish prima facie evidence of delivery of documents that have a filing... (PDS) designated under criteria established by the IRS, will constitute prima facie evidence of... taxpayers to be able to establish the postmark date and prima facie evidence of delivery when using...

Linked Ocean Data

Science.gov (United States)

Leadbetter, Adam; Arko, Robert; Chandler, Cynthia; Shepherd, Adam

2014-05-01

"Linked Data" is a term used in Computer Science to encapsulate a methodology for publishing data and metadata in a structured format so that links may be created and exploited between objects. Berners-Lee (2006) outlines the following four design principles of a Linked Data system: Use Uniform Resource Identifiers (URIs) as names for things. Use HyperText Transfer Protocol (HTTP) URIs so that people can look up those names. When someone looks up a URI, provide useful information, using the standards (Resource Description Framework [RDF] and the RDF query language [SPARQL]). Include links to other URIs so that they can discover more things. In 2010, Berners-Lee revisited his original design plan for Linked Data to encourage data owners along a path to "good Linked Data". This revision involved the creation of a five star rating system for Linked Data outlined below. One star: Available on the web (in any format). Two stars: Available as machine-readable structured data (e.g. An Excel spreadsheet instead of an image scan of a table). Three stars: As two stars plus the use of a non-proprietary format (e.g. Comma Separated Values instead of Excel). Four stars: As three stars plus the use of open standards from the World Wide Web Commission (W3C) (i.e. RDF and SPARQL) to identify things, so that people can point to your data and metadata. Five stars: All the above plus link your data to other people's data to provide context Here we present work building on the SeaDataNet common vocabularies served by the NERC Vocabulary Server, connecting projects such as the Rolling Deck to Repository (R2R) and the Biological and Chemical Oceanography Data Management Office (BCO-DMO) and other vocabularies such as the Marine Metadata Interoperability Ontology Register and Repository and the NASA Global Change Master Directory to create a Linked Ocean Data cloud. Publishing the vocabularies and metadata in standard RDF XML and exposing SPARQL endpoints renders them five-star Linked

Assessing the relative stabilities of engineered hemoglobins using electrospray mass spectrometry.

Science.gov (United States)

Apostol, I

1999-07-15

An ion trap mass spectrometer equipped with an electrospray source was used to examine the relative thermodynamic stabilities of various hemoglobins with respect to both tetramer dissociation and hemin dissociation. The results demonstrated that the stability of hemoglobin molecules can be differentiated by the amount of applied collision-induced dissociation (CID) energy necessary to break up the intact tetramer into its constituent globins. The stability of the intact tetramer was affected by single mutations in the beta-globins. The stabilities of the constituent hologlobins were assessed via trap CID of selected ions. The results demonstrated the importance of the contributions of the hologlobin components to the stability of the intact tetramer. Genetic fusion of two alpha-globins, through the introduction of a single glycine residue between the C-terminus of one alpha-chain and the N-terminus of the second, significantly increased the stability of the hemoglobin pseudo-tetramer. Chemical crosslinking of the beta-globins in addition to genetic fusion of alpha-globins further stabilized the hemoglobin molecule. A dihemoglobin molecule produced by the genetic fusion of two di-alpha-globins with a flexible linker demonstrated a decreased stability relative to the corresponding monohemoglobin. Copyright 1999 Academic Press.

Visualisierung von typisierten Links in Linked Data

Directory of Open Access Journals (Sweden)

Georg Neubauer

2017-09-01

Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

Identification of a negative allosteric site on human α4β2 and α3β4 neuronal nicotinic acetylcholine receptors.

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Ryan E Pavlovicz

Full Text Available Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs. These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological

Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

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Keyan Chen

2018-04-01

Full Text Available Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR on postoperative cognitive dysfunction (POCD and intestinal injury induced by cardiopulmonary bypass (CPB and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

LinkMind: Link Optimization in Swarming Mobile Sensor Networks

DEFF Research Database (Denmark)

Ngo, Trung Dung

2012-01-01

of the most advantageous properties of the swarming wireless sensor network is that mobile nodes can work cooperatively to organize an ad-hoc network and optimize the network link capacity to maximize the transmission of gathered data from a source to a target. This paper describes a new method of link...... optimization of swarming mobile sensor networks. The new method is based on combination of the artificial potential force guaranteeing connectivities of the mobile sensor nodes and the max-flow min-cut theorem of graph theory ensuring optimization of the network link capacity. The developed algorithm...

29 CFR 24.104 - Investigation.

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2010-07-01

... be dismissed unless the complainant has made a prima facie showing that protected activity was a... to make a prima facie showing as follows: (i) The employee engaged in a protected activity; (ii) The... be dismissed unless the complainant has made a prima facie showing that protected activity was a...

76 FR 13937 - Rules of Practice in Proceedings Relative to False Representation and Lottery Orders

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2011-03-15

... Officer shall review the complaint and any supporting information and determine whether a prima facie... by 39 U.S.C. 3005(a). Where the Judicial Officer concludes that a prima facie showing has not been made the complaint shall be dismissed. Where the Judicial Officer concludes that a prima facie showing...

8 CFR 245a.13 - During pendency of application.

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2010-01-01

... States submits a prima facie application for adjustment of status under LIFE Legalization during the... inadmissibility, an application for adjustment of status shall be treated as a prima facie application during the... eligible alien who submits a prima facie application for adjustment of status under this Subpart B shall be...

A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways

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Phillips, Martin B.; Leonard, Jeremy A.; Grulke, Christopher M.; Chang, Daniel T.; Edwards, Stephen W.; Brooks, Raina; Goldsmith, Michael-Rock; El-Masri, Hisham; Tan, Yu-Mei

2015-01-01

Background Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals. Objectives We developed a conceptual workflow to examine exposure and ADME properties in relation to an MIE. The utility of this workflow was evaluated using a previously established AOP, acetylcholinesterase (AChE) inhibition. Methods Thirty chemicals found to inhibit human AChE in the ToxCast™ assay were examined with respect to their exposure, absorption potential, and ability to cross the blood–brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites. Results Application of the workflow screened 10 “low-priority” chemicals of 30 active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold of ≥ 75% with their nearest active neighbors. Of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or as a result of metabolic activation. Conclusions The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 “low-priority” chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible “false negatives.” Citation Phillips MB, Leonard JA, Grulke CM, Chang DT, Edwards SW, Brooks R, Goldsmith MR, El-Masri H, Tan YM. 2016. A workflow to investigate exposure and pharmacokinetic influences on high-throughput in vitro chemical screening based on adverse outcome pathways. Environ

Detection and clinical significance of serum autoantibodies in patients with myasthenia gravis

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Yun LIU

2016-10-01

Full Text Available Objective To investigate the expressions and clinical significance of serum anti - acetylcholine receptor antibodies (AChR-Ab, anti-Titin antibodies (Titin-Ab, and anti-Ryanodine receptor antibodies (RyR-Ab in patients with myasthenia gravis (MG. Methods Serum AChR-Ab, Titin-Ab and RyR-Ab were detected with enzyme-linked immunosorbent assay (ELISA in 182 MG patients, 105 patients of other neurological diseases (OND and 62 normal controls. Results Serum AChR-Ab, Titin-Ab and RyR-Ab were detected positive respectively in 68.13% (124/182, 64.29% (117/182 and 67.03% (122/182 of patients in MG group. The positive rates of those antibodies in MG group were significantly higher than those in OND group (P = 0.000, for all and control group (P = 0.000, for all. When 3 antibodies coexisted, the sensitivity in the diagnosis of MG was 41.21%, with 99.40% of specificity. There was no significant difference in the positive rate of serum AChR-Ab, Titin-Ab and RyR-Ab between early-onset MG subgroup and late-onset MG subgroup (P > 0.05, for all. The positive rates of AChR-Ab were significantly higher in MG patients with thymoma than in those without thymoma (P = 0.004. There was no significant difference in the positive rate of Titin-Ab and RyR-Ab between MG with thymoma subgroup and MG without thymoma subgroup (P > 0.05, for all. The prevalence of AChR-Ab in generalized MG (GMG atients (Ⅱa and Ⅱb was higher than those in ocular MG (OMG patients (typeⅠ; P = 0.005, 0.012. There was no significant difference in the positive rate of Titin-Ab and RyR-Ab between GMG subgroup and OMG subgroup (P > 0.05, for all. Conclusions Serum AChR-Ab, Titin-Ab and RyR-Ab can be used as ndicators of the diagnosis of MG. Patients with 3 coexisted positive antibodies are highly suspected as MG. Higher AChR-Ab level in serum of OMG patients indicates the possibility of progressing to GMG. DOI: 10.3969/j.issn.1672-6731.2016.10.007

Wallops' Low Elevation Link Analysis for the Constellation Launch/Ascent Links

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Cheung, Kar-Ming; Ho, Christian; Kantak, Anil; Lee, Charles; Tye, Robert; Richards, Edger; Sham, Catherine; Schlesinger, Adam; Barritt, Brian

2011-01-01

Prior to the redirection of the Constellation Program, the Wallops 11.3-meter ground station was tasked to support the Orion's Dissimilar Voice (DV) link and the Ares's Development Flight Instrument (DFI) link. Detailed analysis of the launch trajectories indicates that during the launch and ascent operation, the critical events of Orion-Ares main engine cut off (MECO) and Separation occur at low elevation angle. We worked with engineers from both Wallops Flight Facility (WFF) and Johnson Space Center (JSC) to perform an intensive measurement and link analysis campaign on the DV and DFI links. The main results were as follows: (1) The DV links have more than 3 dB margin at MECO and Separation. (2) The DFI links have 0 dB margin at Separation during certain weather condition in summer season. (3) Tropospheric scintillation loss is the major impairment at low elevation angle. (4) The current scintillation models in the Recommendation ITU-R P.618 (Propagation data and prediction methods required for the design of Earth-space telecommunication systems), which are based on limited experimental and theoretical work, exhibit idiosyncratic behaviors. We developed an improved model based on the measurements of recent Shuttle mission launch and ascent links and the ITU propagation data. (5) Due to the attitude uncertainty of the Orion-Ares stack, the high dynamics of the launch and ascent trajectory, and the irregularity of the Orion and Ares antenna patterns, we employed new link analysis approach to model the spacecraft antenna gain. In this paper we discuss the details of the aforementioned results.

Khovanov homology of graph-links

Energy Technology Data Exchange (ETDEWEB)

Nikonov, Igor M [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

2012-08-31

Graph-links arise as the intersection graphs of turning chord diagrams of links. Speaking informally, graph-links provide a combinatorial description of links up to mutations. Many link invariants can be reformulated in the language of graph-links. Khovanov homology, a well-known and useful knot invariant, is defined for graph-links in this paper (in the case of the ground field of characteristic two). Bibliography: 14 titles.

76 FR 71375 - Scott D. Fedosky, M.D.; Denial of Application

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2011-11-17

... statement of position and supporting letter, I conclude that the Government has made out a prima facie case... inconsistent with the public interest. However, where the Government makes out a prima facie case to deny an... the public interest. In this matter, I conclude that the Government has established a prima facie case...