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Sample records for hybrid aggregation inhibitor

  1. Novel hybrids of oxoisoaporphine-tryptamine as acetylcholinesterase-induced β-amyloid aggregation inhibitors with improved antioxidant properties

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    Zhao Hai-Tao

    2015-01-01

    Full Text Available A series of dual binding site acetylcholinesterase (AChE inhibitors have been designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced b-amyloid (Ab aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tryptamine or its derivative, connected through a a,w - alkyldiamide bridge. These hybrids exhibit moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity toward the AChE-induced Ab aggregation. Moreover, six out of the nine hybrids of this series exhibit a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.

  2. O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation.

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    Mao, Fei; Huang, Ling; Luo, Zonghua; Liu, Anqiu; Lu, Chuanjun; Xie, Zhiyong; Li, Xingshu

    2012-10-01

    In an effort to identify novel multifunctional drug candidates for the treatment of Alzheimer's disease (AD), a series of hybrid molecules were synthesised by reacting N-(aminoalkyl)tacrine with salicylic aldehyde or derivatives of 2-aminobenzaldehyde. These compounds were then evaluated as multifunctional anti-Alzheimer's disease agents. All of the hybrids are potential biometal chelators, and in addition, most of them were better antioxidants and inhibitors of cholinesterases and amyloid-β (Aβ) aggregation than the lead compound tacrine. Compound 7c has the potential to be a candidate for AD therapy: it is a much better inhibitor of acetylcholinesterase (AChE) than tacrine (IC(50): 0.55 nM vs 109 nM), has good biometal chelation ability, is able to inhibit Aβ aggregation and has moderate antioxidant activity (1.22 Trolox equivalents). Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. DL-3-n-butylphthalide-Edaravone hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer's therapy.

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    Qiang, Xiaoming; Li, Yan; Yang, Xia; Luo, Li; Xu, Rui; Zheng, Yunxiaozhu; Cao, Zhongcheng; Tan, Zhenghuai; Deng, Yong

    2017-02-15

    Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, compounds 9a-d exhibited good inhibition of self-induced Aβ 1-42 aggregation with inhibition ratio 57.7-71.5%. For MAO, these new hybrids exhibited good balance of inhibition for MAO-A and MAO-B. In addition, all target compounds retained the antioxidant activity of edaravone, showed equal or better antioxidant activity than edaravone. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that compounds 9a-d would be able to cross the blood-brain barrier and reach their biological targets in the central nervous system. The promising results in all assays demonstrated that the strategy behind the designing of compounds was rational and favourable. Taken together, these preliminary findings suggested that the compounds with the strongest bioactivity deserves further investigated for pharmacological development in AD therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. (-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-β aggregation with high antioxidant potency for Alzheimer's therapy.

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    Cheng, Shaobing; Zheng, Wei; Gong, Ping; Zhou, Qiang; Xie, Qiong; Yu, Lining; Zhang, Peiyi; Chen, Liangkang; Li, Juan; Chen, Jianxing; Chen, Hailin; Chen, Hongzhuan

    2015-07-01

    The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Advances toward multifunctional cholinesterase and β-amyloid aggregation inhibitors.

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    Panek, Dawid; Wichur, Tomasz; Godyń, Justyna; Pasieka, Anna; Malawska, Barbara

    2017-10-01

    The emergence of a multitarget design approach in the development of new potential anti-Alzheimer's disease agents has resulted in the discovery of many multifunctional compounds focusing on various targets. Among them the largest group comprises inhibitors of both cholinesterases, with additional anti-β-amyloid aggregation activity. This review describes recent advances in this research area and presents the most interesting compounds reported over a 2-year span (2015-2016). The majority of hybrids possess heterodimeric structures obtained by linking structurally active fragments interacting with different targets. Multipotent cholinesterase inhibitors with β-amyloid antiaggregating activity may additionally possess antioxidative, neuroprotective or metal-chelating properties or less common features such as anti-β-secretase or τ-antiaggregation activity.

  6. Aggregation of trypsin and trypsin inhibitor by Al cation.

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    Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

    2017-04-01

    Al cation may trigger protein structural changes such as aggregation and fibrillation, causing neurodegenerative diseases. We report the effect of Al cation on the solution structures of trypsin (try) and trypsin inhibitor (tryi), using thermodynamic analysis, UV-Visible, Fourier transform infrared (FTIR) spectroscopic methods and atomic force microscopy (AFM). Thermodynamic parameters showed Al-protein bindings occur via H-bonding and van der Waals contacts for trypsin and trypsin inhibitor. AFM showed that Al cations are able to force trypsin into larger or more robust aggregates than trypsin inhibitor, with trypsin 5±1 SE (n=52) proteins per aggregate and for trypsin inhibitor 8.3±0.7 SE (n=118). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced more alterations of trypsin inhibitor conformation than trypsin. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Novel β-amyloid aggregation inhibitors possessing a turn mimic.

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    Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

    2015-04-01

    Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. New pyridine derivatives as inhibitors of acetylcholinesterase and amyloid aggregation.

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    Pandolfi, Fabiana; De Vita, Daniela; Bortolami, Martina; Coluccia, Antonio; Di Santo, Roberto; Costi, Roberta; Andrisano, Vincenza; Alabiso, Francesco; Bergamini, Christian; Fato, Romana; Bartolini, Manuela; Scipione, Luigi

    2017-12-01

    A new series of pyridine derivatives with carbamic or amidic function has been designed and synthesized to act as cholinesterase inhibitors. The synthesized compounds were tested toward EeAChE and hAChE and toward eqBChE and hBChE. The carbamate 8 was the most potent hAChE inhibitor (IC 50  = 0.153 ± 0.016 μM) while the carbamate 11 was the most potent inhibitor of hBChE (IC 50  = 0.828 ± 0.067 μM). A molecular docking study indicated that the carbamate 8 was able to bind AChE by interacting with both CAS and PAS, in agreement with the mixed inhibition mechanism. Furthermore, the carbamates 8, 9 and 11 were able to inhibit Aβ 42 self-aggregation and possessed quite low toxicity against human astrocytoma T67 and HeLa cell lines, being the carbamate 8 the less toxic compound on both cell lines. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.

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    Michiaki Okuda

    Full Text Available In tauopathies, a neural microtubule-associated protein tau (MAPT is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.

  10. Structure activity relationship study of curcumin analogues toward the amyloid-beta aggregation inhibitor.

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    Endo, Hitoshi; Nikaido, Yuri; Nakadate, Mamiko; Ise, Satomi; Konno, Hiroyuki

    2014-12-15

    Inhibition of the amyloid β aggregation process could possibly prevent the onset of Alzheimer's disease. In this article, we report a structure-activity relationship study of curcumin analogues for anti amyloid β aggregation activity. Compound 7, the ideal amyloid β aggregation inhibitor in vitro among synthesized curcumin analogues, has not only potent anti amyloid β aggregation effects, but also water solubility more than 160 times that of curcumin. In addition, new approaches to improve water solubility of curcumin-type compounds are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Cellular Models of Aggregation-dependent Template-directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer Disease.

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    Harrington, Charles R; Storey, John M D; Clunas, Scott; Harrington, Kathleen A; Horsley, David; Ishaq, Ahtsham; Kemp, Steven J; Larch, Christopher P; Marshall, Colin; Nicoll, Sarah L; Rickard, Janet E; Simpson, Michael; Sinclair, James P; Storey, Lynda J; Wischik, Claude M

    2015-04-24

    Alzheimer disease (AD) is a degenerative tauopathy characterized by aggregation of Tau protein through the repeat domain to form intraneuronal paired helical filaments (PHFs). We report two cell models in which we control the inherent toxicity of the core Tau fragment. These models demonstrate the properties of prion-like recruitment of full-length Tau into an aggregation pathway in which template-directed, endogenous truncation propagates aggregation through the core Tau binding domain. We use these in combination with dissolution of native PHFs to quantify the activity of Tau aggregation inhibitors (TAIs). We report the synthesis of novel stable crystalline leucomethylthioninium salts (LMTX®), which overcome the pharmacokinetic limitations of methylthioninium chloride. LMTX®, as either a dihydromesylate or a dihydrobromide salt, retains TAI activity in vitro and disrupts PHFs isolated from AD brain tissues at 0.16 μM. The Ki value for intracellular TAI activity, which we have been able to determine for the first time, is 0.12 μM. These values are close to the steady state trough brain concentration of methylthioninium ion (0.18 μM) that is required to arrest progression of AD on clinical and imaging end points and the minimum brain concentration (0.13 μM) required to reverse behavioral deficits and pathology in Tau transgenic mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. [Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey].

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    Dangers, L; Similowski, T; Chenivesse, C

    2016-01-01

    When pleural procedures (thoracocentesis, blind pleural biopsies and chest tube insertion) are required in patients taking long-term platelet aggregation inhibitors, the risk of bleeding must be balanced against the risk of arterial thrombosis. Currently, the bleeding risk of pleural procedures is poorly understood. The objective of the survey was to gather the opinion of respiratory physicians regarding the bleeding risk of pleural procedures in patients taking platelet aggregation inhibitors. We emailed a standardized questionnaire designed by the French National Authority for Health to 2697 French respiratory physicians. One hundred and eighty-eight of the 2697 questionnaires were returned (response rate: 7 %). The respiratory physicians declared that they performed an average of 8 pleural procedures per month. One hundred and seventy-five responders (95 %) practised pleural procedures in patients receiving platelet aggregation inhibitors; 68 of them (39 %) reported experiencing haemorrhagic complications. The bleeding risk associated with thoracentesis and chest tube insertion was considered minor by 97.8 and 65 % of responders respectively, whereas it was considered major for blind pleural biopsies by 73.4 %. Respiratory physicians were more reticent about performing pleural procedures in patients treated with clopidogrel than in those taking aspirin. This study provides an overview of how respiratory physicians perceive the bleeding risk associated with pleural procedures in patients taking platelet aggregation inhibitors. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Use of selective-serotonin reuptake inhibitors and platelet aggregation inhibitors among individuals with co-occurring atherosclerotic cardiovascular disease and depression or anxiety

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    J Douglas Thornton

    2016-12-01

    Full Text Available Objective: Medications commonly used to treat heart disease, anxiety, and depression can interact resulting in an increased risk of bleeding, warranting a cautious approach in medical decision making. This retrospective, descriptive study examined the prevalence and the factors associated with the use of both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor among individuals with co-occurring atherosclerotic cardiovascular disease and anxiety or depression. Methods: Respondents aged 22 years and older, alive throughout the study period, and diagnosed with co-occurring atherosclerotic cardiovascular disease and anxiety or depression (n = 1507 in years 2007 through 2013 of the Medical Expenditures Panel Survey were included. The use of treatment was grouped as follows: selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Results: Overall, 16.5% used both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, 61.2% used selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and 22.3% used neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Respondents aged over 65 years (adjusted odds ratio = 1.93 (95% confidence interval = 1.08–3.45 and having a diagnosis of diabetes (adjusted odds ratio = 1.63 (95% confidence interval = 1.15–2.31 and hypertension (adjusted odds ratio = 1.84 (95% confidence interval = 1.04–3.27 were more likely to be prescribed the combination. Conclusion: The drug interaction was prevalent in patients who are already at higher risk of health disparities and worse outcomes thus requiring vigilant evaluation.

  14. Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.

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    Aslam, Sana; Zaib, Sumera; Ahmad, Matloob; Gardiner, John M; Ahmad, Aqeel; Hameed, Abdul; Furtmann, Norbert; Gütschow, Michael; Bajorath, Jürgen; Iqbal, Jamshed

    2014-05-06

    Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compounds 12d and 12k were the most potent AChE inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17 nM) proved to be the most active inhibitor against BuChE with remarkable selectivity for BuChE over AChE. Molecular docking studies were also performed on human AChE and BuChE to suggest possible binding modes in which the inhibitor's extended structure is accommodated along the active site gorge of both enzymes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Oxindole based oxadiazole hybrid analogs: Novel α-glucosidase inhibitors.

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    Taha, Muhammad; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Khan, Khalid Mohammed

    2018-02-01

    Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. Beside these α-glucosidase inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in view the greater importance of α-glucosidase inhibitors here in this study we are presenting oxindole based oxadiazoles hybrid analogs (1-20) synthesis, characterized by different spectroscopic techniques including 1 H NMR and EI-MS and their α-glucosidase inhibitory activity. All compounds were found potent inhibitors for the enzyme with IC 50 values ranging between 1.25 ± 0.05 and 268.36 ± 4.22 µM when compared with the standard drug acarbose having IC 50 value 895.09 ± 2.04 µM. Our study identifies novel series of potent α-glucosidase inhibitors and further investigation on this may led to the lead compounds. A structure activity relationship has been established for all compounds. The interactions of the active compounds and enzyme active site were established with the help of molecular docking studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Novel hybrid coatings with controlled wettability by composite nanoparticle aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Hritcu, Doina, E-mail: dhritcu@ch.tuiasi.ro; Dodi, Gianina; Iordache, Mirabela L.; Draganescu, Dan; Sava, Elena; Popa, Marcel I.

    2016-11-30

    Highlights: • Magnetite-grafted chitosan composite nanoparticles were synthesized. • The particles are able to assemble under the influence of a silane derivative. • Thin films containing composites, chitosan and hydrolyzed silane were optimized. • The novel hybrid coatings show hierarchical roughness and high wetting angle. - Abstract: The aim of this study is to evaluate novel hybrid materials as potential candidates for producing coatings with hierarchical roughness and controlled wetting behaviour. Magnetite (Fe{sub 3}O{sub 4}) nanoparticles obtained by co-precipitation were embedded in matrices synthesized by radical graft co-polymerization of butyl acrylate (BA), butyl methacrylate (BMA), hexyl acrylate (HA) or styrene (ST) with ethylene glycol di-methacrylate (EGDMA) onto previously modified chitosan bearing surface vinyl groups. The resulting composite particles were characterized regarding their average size, composition and magnetic properties. Hybrid thin films containing suspension of composite particles in ethanol and pre-hydrolysed hexadecyltrimethoxysilane (HDTS) as a coupling/crosslinking agent were deposited by spin coating or spraying. The films were cured by heating and subsequently characterized regarding their morphology (scanning electron microscopy), contact angle with water and adhesion to substrate (scratch test). The structure-property relationship is discussed.

  17. Electrochemical Performance of Low-Carbon Steel in Alkaline Model Solutions Containing Hybrid Aggregates

    NARCIS (Netherlands)

    Koleva, D.A.; Hu, J.; De Wit, J.H.W.; Boshkov, N.; Radeva, T.; Milkova, V.; Van Breugel, K.

    2010-01-01

    This work reports on the electrochemical performance of low-carbon steel electrodes in model alkaline solutions in the presence of 4.9.10-4 g/l hybrid aggregates i.e. cement extract, containing PDADMAC (poly (diallyl, dimethyl ammonium chloride) / PAA (Poly (acrylic acid)/ PDADMAC over a CaO core.

  18. β-Hairpin of Islet Amyloid Polypeptide Bound to an Aggregation Inhibitor

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    Mirecka, Ewa A.; Feuerstein, Sophie; Gremer, Lothar; Schröder, Gunnar F.; Stoldt, Matthias; Willbold, Dieter; Hoyer, Wolfgang

    2016-01-01

    In type 2 diabetes, the formation of islet amyloid consisting of islet amyloid polypeptide (IAPP) is associated with reduction in β-cell mass and contributes to the failure of islet cell transplantation. Rational design of inhibitors of IAPP amyloid formation has therapeutic potential, but is hampered by the lack of structural information on inhibitor complexes of the conformationally flexible, aggregation-prone IAPP. Here we characterize a β-hairpin conformation of IAPP in complex with the engineered binding protein β-wrapin HI18. The β-strands correspond to two amyloidogenic motifs, 12-LANFLVH-18 and 22-NFGAILS-28, which are connected by a turn established around Ser-20. Besides backbone hydrogen bonding, the IAPP:HI18 interaction surface is dominated by non-polar contacts involving hydrophobic side chains of the IAPP β-strands. Apart from monomers, HI18 binds oligomers and fibrils and inhibits IAPP aggregation and toxicity at low substoichiometric concentrations. The IAPP β-hairpin can serve as a molecular recognition motif enabling control of IAPP aggregation. PMID:27641459

  19. Differential stress response of Saccharomyces hybrids revealed by monitoring Hsp104 aggregation and disaggregation.

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    Kempf, Claudia; Lengeler, Klaus; Wendland, Jürgen

    2017-07-01

    Proteotoxic stress may occur upon exposure of yeast cells to different stress conditions. The induction of stress response mechanisms is important for cells to adapt to changes in the environment and ensure survival. For example, during exposure to elevated temperatures the expression of heat shock proteins such as Hsp104 is induced in yeast. Hsp104 extracts misfolded proteins from aggregates to promote their refolding. We used an Hsp104-GFP reporter to analyze the stress profiles of Saccharomyces species hybrids. To this end a haploid S. cerevisiae strain, harboring a chromosomal HSP104-GFP under control of its endogenous promoter, was mated with stable haploids of S. bayanus, S. cariocanus, S. kudriavzevii, S. mikatae, S. paradoxus and S. uvarum. Stress response behaviors in these hybrids were followed over time by monitoring the appearance and dissolution of Hsp104-GFP foci upon heat shock. General stress tolerance of these hybrids was related to the growth rate detected during exposure to e.g. ethanol and oxidizing agents. We observed that hybrids were generally more resistant to high temperature and ethanol stress compared to their parental strains. Amongst the hybrids differential responses regarding the appearance of Hsp104-foci and the time required for dissolving these aggregates were observed. The S. cerevisiae/S. paradoxus hybrid, combining the two most closely related strains, performed best under these conditions. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Impact Resistance of Recycled Aggregate Concrete with Single and Hybrid Fibers

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    Ismail Sallehan

    2016-01-01

    Full Text Available This paper presents a recycled aggregate concrete (RAC mix that has been modified by adding treated recycled concrete aggregate (RCA and various types of fiber-reinforced systems. The effectiveness of these modifications in terms of energy absorption and impact resistance was evaluated and compared with that of the corresponding regular concrete, as well as with unmodified RAC specimens. Results clearly indicate that although modification of the RAC mix with treated RCA significantly enhances the impact resistance of RAC, further diversification with additional fiber, particularly those in hybrid form, can optimize the results.

  1. A microliter-scale high-throughput screening system with quantum-dot nanoprobes for amyloid-β aggregation inhibitors.

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    Yukako Ishigaki

    Full Text Available The aggregation of amyloid β protein (Aβ is a key step in the pathogenesis of Alzheimer's disease (AD, and therefore inhibitory substances for Aβ aggregation may have preventive and/or therapeutic potential for AD. Here we report a novel microliter-scale high-throughput screening system for Aβ aggregation inhibitors based on fluorescence microscopy-imaging technology with quantum-dot Nanoprobes. This screening system could be analyzed with a 5-µl sample volume when a 1536-well plate was used, and the inhibitory activity could be estimated as half-maximal effective concentrations (EC50. We attempted to comprehensively screen Aβ aggregation inhibitors from 52 spices using this system to assess whether this novel screening system is actually useful for screening inhibitors. Screening results indicate that approximately 90% of the ethanolic extracts from the spices showed inhibitory activity for Aβ aggregation. Interestingly, spices belonging to the Lamiaceae, the mint family, showed significantly higher activity than the average of tested spices. Furthermore, we tried to isolate the main inhibitory compound from Saturejahortensis, summer savory, a member of the Lamiaceae, using this system, and revealed that the main active compound was rosmarinic acid. These results demonstrate that this novel microliter-scale high-throughput screening system could be applied to the actual screening of Aβ aggregation inhibitors. Since this system can analyze at a microscopic scale, it is likely that further minimization of the system would easily be possible such as protein microarray technology.

  2. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    International Nuclear Information System (INIS)

    Amin, D.

    1986-01-01

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with ( 14 C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A 2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  3. Formation of hybrid gold nanoparticle network aggregates by specific host-guest interactions in a turbulent flow reactor

    NARCIS (Netherlands)

    Weinhart-Mejia, R.; Huskens, Jurriaan

    2014-01-01

    A multi-inlet vortex mixer (MIVM) was used to investigate the formation of hybrid gold nanoparticle network aggregates under highly turbulent flow conditions. To form aggregates, gold nanoparticles were functionalized with β-cyclodextrin (CD) and mixed with adamantyl (Ad)-terminated

  4. Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease.

    Science.gov (United States)

    Xie, Sai-Sai; Wang, Xiao-Bing; Li, Jiang-Yan; Yang, Lei; Kong, Ling-Yi

    2013-06-01

    A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

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    Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

    2015-11-13

    The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Rationally Designed Peptides and Peptidomimetics as Inhibitors of Amyloid-β (Aβ) Aggregation: Potential Therapeutics of Alzheimer's Disease.

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    Goyal, Deepti; Shuaib, Suniba; Mann, Sukhmani; Goyal, Bhupesh

    2017-02-13

    Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The worldwide effort to develop peptide-based inhibitors of amyloid-β (Aβ) aggregation can be considered an unplanned combinatorial experiment. An understanding of what has been done and achieved may advance our understanding of AD pathology and the discovery of effective therapeutic agents. We review here the history of such peptide-based inhibitors, including those based on the Aβ sequence and those not derived from that sequence, containing both natural and unnatural amino acid building blocks. Peptide-based aggregation inhibitors hold significant promise for future AD therapy owing to their high selectivity, effectiveness, low toxicity, good tolerance, low accumulation in tissues, high chemical and biological diversity, possibility of rational design, and highly developed methods for analyzing their mode of action, proteolytic stability (modified peptides), and blood-brain barrier (BBB) permeability.

  7. Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

    Science.gov (United States)

    Chen, Yao; Zhu, Jie; Mo, Jun; Yang, Hongyu; Jiang, Xueyang; Lin, Hongzhi; Gu, Kai; Pei, Yuqiong; Wu, Liang; Tan, Renxiang; Hou, Jing; Chen, Jingyi; Lv, Yang; Bian, Yaoyao; Sun, Haopeng

    2018-12-01

    Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC 50  = 10.2 ± 1.2, 16.5 ± 1.7, and 15.3 ± 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.

  8. Antibacterial activity of berberine-NorA pump inhibitor hybrids with a methylene ether linking group.

    Science.gov (United States)

    Samosorn, Siritron; Tanwirat, Bongkot; Muhamad, Nussara; Casadei, Gabriele; Tomkiewicz, Danuta; Lewis, Kim; Suksamrarn, Apichart; Prammananan, Therdsak; Gornall, Karina C; Beck, Jennifer L; Bremner, John B

    2009-06-01

    Conjugation of the NorA substrate berberine and the NorA inhibitor 5-nitro-2-phenyl-1H-indole via a methylene ether linking group gave the 13-substituted berberine-NorA inhibitor hybrid, 3. A series of simpler arylmethyl ether hybrid structures were also synthesized. The hybrid 3 showed excellent antibacterial activity (MIC Staphylococcus aureus, 1.7 microM), which was over 382-fold more active than the parent antibacterial berberine, against this bacterium. This compound was also shown to block the NorA efflux pump in S. aureus.

  9. HWDA: A coherence recognition and resolution algorithm for hybrid web data aggregation

    Science.gov (United States)

    Guo, Shuhang; Wang, Jian; Wang, Tong

    2017-09-01

    Aiming at the object confliction recognition and resolution problem for hybrid distributed data stream aggregation, a distributed data stream object coherence solution technology is proposed. Firstly, the framework was defined for the object coherence conflict recognition and resolution, named HWDA. Secondly, an object coherence recognition technology was proposed based on formal language description logic and hierarchical dependency relationship between logic rules. Thirdly, a conflict traversal recognition algorithm was proposed based on the defined dependency graph. Next, the conflict resolution technology was prompted based on resolution pattern matching including the definition of the three types of conflict, conflict resolution matching pattern and arbitration resolution method. At last, the experiment use two kinds of web test data sets to validate the effect of application utilizing the conflict recognition and resolution technology of HWDA.

  10. Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

    Science.gov (United States)

    Zhu, Jie; Yang, Hongyu; Chen, Yao; Lin, Hongzhi; Li, Qi; Mo, Jun; Bian, Yaoyao; Pei, Yuqiong; Sun, Haopeng

    2018-12-01

    The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC 50 ) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC 50  = 101.40 nM). Besides, it inhibited amyloid β-protein self-aggregation by 65.49% at 25 μM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD.

  11. ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Cistanches) growing in Xinjiang

    Science.gov (United States)

    Xing, Yachao; Liao, Jing; Tang, Yingzhan; Zhang, Peng; Tan, Chengyu; Ni, Hui; Wu, Xueqin; Li, Ning; Jia, Xiaoguang

    2014-01-01

    Background: Tamarix hohenackeri Bunge is a salt cedar that grows widespread in the desert mountains in Xinjiang. T. hohenackeri has not been investigated earlier, although there are many reports of phytochemical work on other Tamarix species. Materials and Methods: To find out natural angiotensin-converting enzyme (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were investigated. The active fraction was purified by repeated column chromatography, including silica gel, Sephadex LH-20 column, medium-pressure liquid chromatography (MPLC) (polyamide column) and high-performance liquid chromatography (HPLC). The isolated major constituents were tested for their anti-platelet aggregation activity. Results: Bioassay-directed separation of the EtOAc fraction of the 70% ethanol extract from the air-dried aerial parts of T. hohenackeri led to the isolation of a new triterpenoid lactone (1), together with 13 known compounds (2-14). It was the first time to focus on screening bioactive constituents for this plant. The chemical structures were established on the basis of spectral data (ESI-MS and NMR). The results showed that the flavonoid compounds (7 and 8) and phenolic compounds (9, 10, 11, and 14) were potential ACE inhibitors. And the flavonoid compounds (5 and 7) showed significant anti-platelet aggregation activities. Conclusion: On the basis of the chemical and biological data, the material basis of ACE inhibitory activity for the active part was the phenolic constituents. However, the flavonoid compounds were responsible for the anti-platelet aggregation. The primary structure and activity relationship were also discussed respectively. PMID:24914275

  12. Tyrosinase Inhibitor Activity of Coumarin-Resveratrol Hybrids

    Directory of Open Access Journals (Sweden)

    Giovanna Delogu

    2009-07-01

    Full Text Available In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC50 values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3’,4’,5’-trihydroxyphenyl-6,8-dihydroxycoumarin (8is the most potentcompound (0.27 mM, more so than umbelliferone (0.42 mM, used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

  13. Tyrosinase inhibitor activity of coumarin-resveratrol hybrids.

    Science.gov (United States)

    Fais, Antonella; Corda, Marcella; Era, Benedetta; Fadda, M Benedetta; Matos, Maria Joao; Quezada, Elias; Santana, Lourdes; Picciau, Carmen; Podda, Gianni; Delogu, Giovanna

    2009-07-13

    In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC(50) values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3',4',5'-trihydroxyphenyl)-6,8-dihydroxycoumarin (8)is the most potentcompound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

  14. Platelet aggregation inhibitors in primary and secondary prevention of ischemic stroke

    Directory of Open Access Journals (Sweden)

    von der Schulenburg, Johann-Matthias

    2006-04-01

    Full Text Available Background: The ischaemic stroke (IS is one of the most frequent cause of death in Germany. Besides of non-drug many drug-based interventions are used in primary or secondary prevention of IS, among them the thrombocyte aggregation inhibitors (TAI. Objectives: The evaluation addresses the questions on medical efficacy and cost-effectiveness of the TAI administration in the prevention of IS as compared to the management of risk factors alone as well as to the use of anticoagulant drugs. Methods: The literature search for articles published after 1997 was conducted in December 2003 in the most important medical and economic databases. The medical analysis was performed on the basis of the most up-to date meta-analyses of randomised controlled trials (RCT as well as of new published RCT. The data from the studies for stroke, bleeding complications as well as for the combined endpoint "severe vascular events" (SVE: death or stroke or myocardial infarction were summarised in meta-analyses.In order to include grey literature contact has been taken up with the pharmaceutical manufacturers of TAI. Results are presented in a descriptive way. Results: The medical analysis included data from 184 RCT (vs. placebo and from 22 RCT (vs. anticoagulant drugs. The absolute reduction of IS (4.8% vs. 6.6%; p<0,00001 and SVE (10.0% vs. 12.4%; p<0,00001 were definitely higher than the absolute increase of bleeding complications (1.6% vs. 0.9%; p<0,00001, but relatively similar to this absolute increase in a subpopulation with a low risk for SVE. With regard to the stroke prevention, evidence of efficacy could be yielded for acetylsalicil acid (ASA, dipyridamole, cilostazol, ridogrel and the combination ASA with dipyridamole. ASA is less effective than anticoagulants in the prevention of ischaemic stroke in atrial fibrillation, however, it causes fewer bleeding complications.Low dosed ASA can be considered cost-effective in secondary prevention of ischemic stroke

  15. Exploring the structural diversity in inhibitors of α-synuclein amyloidogenic folding, aggregation and neurotoxicity

    Science.gov (United States)

    Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

    2018-05-01

    Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson’s disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2', 3', 4' trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favourable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 hrs incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that i

  16. Purification and characterization of a platelet aggregation inhibitor and anticoagulant Cc 5_NTase, CD 73-like, from Cerastes cerastes venom.

    Science.gov (United States)

    Saoud, Samah; Chérifi, Fatah; Benhassine, Traki; Laraba-Djebari, Fatima

    2017-05-01

    The present study is the first attempt to report the characterization of a nucleotidase from Cerastes cerastes venom. A 70 kDa 5'-nucleotidase (Cc-5'NTase) was purified to homogeneity. The amino acid sequence of Cc-5'NTase displayed high homology with many nucleotidases. Its activity was optimal at pH 7 with a specific hydrolytic activity toward mono-, di-, and triphosphate adenylated nucleotides. Cc-5'NTase preferentially hydrolyzed ADP and obeyed Michaelis-Menten kinetics. Among the metals and inhibitors tested, Ni 2+ and Mg 2+ completely potentiated enzyme activity, whereas EGTA, PMSF, iodoacetamide, vanillic acid, vanillyl mandelic acid, and 1,10-phenanthroline partially abolished its activity. Cc-5'NTase was not lethal for mice at 5 mg/kg and exhibited in vivo anticoagulant effect. It also dose-dependently inhibited adenosine diphosphate-induced platelet aggregation by converting adenosine diphosphate to adenosine and prohibited arachidonic acid-induced aggregation but was not effective on fibrinogen-induced aggregation. Cc-5'NTase could be a good tool as pharmacological molecule in thrombosis diagnostic and/or therapy. © 2016 Wiley Periodicals, Inc.

  17. Engineered aggregation inhibitor fusion for production of highly amyloidogenic human islet amyloid polypeptide.

    Science.gov (United States)

    Mirecka, Ewa Agnieszka; Gremer, Lothar; Schiefer, Stephanie; Oesterhelt, Filipp; Stoldt, Matthias; Willbold, Dieter; Hoyer, Wolfgang

    2014-12-10

    Human islet amyloid polypeptide (IAPP) is the major component of pancreatic amyloid deposits in type 2 diabetes. The structural conversion of IAPP from a monomeric state into amyloid assemblies is the subject of intense research. Recombinant production of IAPP is, however, difficult due to its extreme aggregation propensity. Here we describe a novel strategy for expression of IAPP in Escherichia coli, based on an engineered protein tag, which sequesters IAPP monomers and prevents IAPP aggregation. The IAPP-binding protein HI18 was selected by phage display from a β-wrapin library. Fusion of HI18 to IAPP enabled the soluble expression of the construct. IAPP was cleaved from the fusion construct and purified to homogeneity with a yield of 3mg of isotopically labeled peptide per liter of culture. In the monomeric state, IAPP was largely disordered as evidenced by far-UV CD and liquid-state NMR spectroscopy but competent to form amyloid fibrils according to atomic force microscopy. These results demonstrate the ability of the engineered β-wrapin HI18 for shielding the hydrophobic sequence of IAPP during expression and purification. Fusion of aggregation-inhibiting β-wrapins is a suitable approach for the recombinant production of aggregation-prone proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Piceatannol and Other Wine Stilbenes: A Pool of Inhibitors against α-Synuclein Aggregation and Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Hamza Temsamani

    2016-06-01

    Full Text Available The aggregation of α-synuclein is one on the key pathogenic events in Parkinson’s disease. In the present study, we investigated the inhibitory capacities of stilbenes against α-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate the inhibitory effects of three stilbenes against α-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated α-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against α-synuclein-induced toxicity. Piceatannol inhibited the formation of α synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against α-synuclein-induced damage. Finally, piceatannol protected cells against α-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol were less active.

  19. Plasminogen-induced aggregation of PANC-1 cells requires conversion to plasmin and is inhibited by endogenous plasminogen activator inhibitor-1.

    Science.gov (United States)

    Deshet, Naamit; Lupu-Meiri, Monica; Espinoza, Ingrid; Fili, Oded; Shapira, Yuval; Lupu, Ruth; Gershengorn, Marvin C; Oron, Yoram

    2008-09-01

    PANC-1 cells express proteinase-activated receptors (PARs)-1, -2, and respond to their activation by transient elevation of cytosolic [Ca(2+)] and accelerated aggregation (Wei et al., 2006, J Cell Physiol 206:322-328). We studied the effect of plasminogen (PGN), an inactive precursor of the PAR-1-activating protease, plasmin (PN) on aggregation of pancreatic adenocarcinoma (PDAC) cells. A single dose of PGN time- and dose-dependently promoted PANC-1 cells aggregation in serum-free medium, while PN did not. PANC-1 cells express urokinase plasminogen activator (uPA), which continuously converted PGN to PN. This activity and PGN-induced aggregation were inhibited by the uPA inhibitor amiloride. PGN-induced aggregation was also inhibited by alpha-antiplasmin and by the PN inhibitor epsilon-aminocaproic acid (EACA). Direct assay of uPA activity revealed very low rate, markedly enhanced in the presence of PGN. Moreover, in PGN activator inhibitor 1-deficient PANC-1 cells, uPA activity and PGN-induced aggregation were markedly potentiated. Two additional human PDAC cell lines, MiaPaCa and Colo347, were assayed for PGN-induced aggregation. Both cell lines responded by aggregation and exhibited PGN-enhanced uPA activity. We hypothesized that the continuous conversion of PGN to PN by endogenous uPA is limited by PN's degradation and negatively controlled by endogenously produced PAI-1. Indeed, we found that PANC-1 cells inactivate PN with t1/2 of approximately 7 h, while the continuous addition of PN promoted aggregation. Our data suggest that PANC-1 cells possess intrinsic, PAI-1-sensitive mechanism for promotion of aggregation and differentiation by prolonged exposure to PGN and, possibly, additional precursors of PARs agonists.

  20. Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation.

    Science.gov (United States)

    Li, Yan-Ping; Ning, Fang-Xian; Yang, Meng-Bi; Li, Yong-Cheng; Nie, Min-Hua; Ou, Tian-Miao; Tan, Jia-Heng; Huang, Shi-Liang; Li, Ding; Gu, Lian-Quan; Huang, Zhi-Shu

    2011-05-01

    A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid β (Aβ) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Aβ self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  1. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    International Nuclear Information System (INIS)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho

    2013-01-01

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC 50 = 2.3 ± 0.7 μM) and AChE (IC 50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K i ) value to BuChE is 2.91 ± 0.15 μM

  2. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

    2013-11-15

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

  3. Computational Selection of Inhibitors of A-beta Aggregation and Neuronal Toxicity

    Science.gov (United States)

    Chen, Deliang; Martin, Zane S.; Soto, Claudio; Schein, Catherine H.

    2009-01-01

    Alzheimer’s Disease (AD) is characterized by the cerebral accumulation of misfolded and aggregated amyloid-β protein (Aβ). Disease symptoms can be alleviated, in vitro and in vivo, by “β-sheet breaker” pentapeptides that reduce plaque volume. However the peptide nature of these compounds, made them biologically unstable and unable to penetrate membranes with high efficiency. The main goal of this study was to use computational methods to identify small molecule mimetics with better drug-like properties. For this purpose, the docked conformations of the active peptides were used to identify compounds with similar activities. A series of related β-sheet breaker peptides were docked to solid state NMR structures of a fibrillar form of Aβ. The lowest energy conformations of the active peptides were used to design three dimensional (3D)-pharmacophores, suitable for screening the NCI database with Unity. Small molecular weight compounds with physicochemical features in a conformation similar to the active peptides were selected, ranked by docking solubility parameters. Of 16 diverse compounds selected for experimental screening, 2 prevented and reversed Aβ aggregation at 2–3 μM concentration, as measured by Thioflavin T (ThT) fluorescence and ELISA assays. They also prevented the toxic effects of aggregated Aβ on neuroblastoma cells. Their low molecular weight and aqueous solubility makes them promising lead compounds for treating AD. PMID:19540126

  4. Molecular modeling of cationic porphyrin-anthraquinone hybrids as DNA topoisomerase IIβ inhibitors.

    Science.gov (United States)

    Arba, Muhammad; Ruslin; Ihsan, Sunandar; Tri Wahyudi, Setyanto; Tjahjono, Daryono H

    2017-12-01

    Human DNA Topoisomerase II has been regarded as a promising target in anticancer drug discovery. In the present study, we designed six porphyrin-anthraquinone hybrids bearing pyrazole or pyridine group as meso substituents and evaluated their potentials as DNA Topoisomerase IIβ inhibitor. First, we investigated the binding orientation of porphyrin hybrids into DNA topoisomerase IIβ employing AutoDock 4.2 and then performed 20-ns molecular dynamics simulations to see the dynamic stability of each porphyrin-Topo IIβ complex using Amber 14. We found that the binding of porphyrin hybrids occured through intercalation and groove binding mode in addition interaction with the amino acid residues constituting the active cavity of Topo IIβ. Each porphyrin-Topo IIβ complex was stabilized during 20-ns dynamics simulations. The MM-PBSA free energy calculation shows that the binding affinities of porphyrin hybrids were modified with the number of meso substituent. Interestingly, the affinity of all porphyrin hybrids to Topo IIβ was stronger than that of native ligand (EVP), indicating the potential of the designed porphyrin to be considered in experimental research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Disease-modifying anti-Alzheimer's drugs: inhibitors of human cholinesterases interfering with β-amyloid aggregation.

    Science.gov (United States)

    Brogi, Simone; Butini, Stefania; Maramai, Samuele; Colombo, Raffaella; Verga, Laura; Lanni, Cristina; De Lorenzi, Ersilia; Lamponi, Stefania; Andreassi, Marco; Bartolini, Manuela; Andrisano, Vincenza; Novellino, Ettore; Campiani, Giuseppe; Brindisi, Margherita; Gemma, Sandra

    2014-07-01

    We recently described multifunctional tools (2a-c) as potent inhibitors of human Cholinesterases (ChEs) also able to modulate events correlated with Aβ aggregation. We herein propose a thorough biological and computational analysis aiming at understanding their mechanism of action at the molecular level. We determined the inhibitory potency of 2a-c on Aβ1-42 self-aggregation, the interference of 2a with the toxic Aβ oligomeric species and with the postaggregation states by capillary electrophoresis analysis and transmission electron microscopy. The modulation of Aβ toxicity was assessed for 2a and 2b on human neuroblastoma cells. The key interactions of 2a with Aβ and with the Aβ-preformed fibrils were computationally analyzed. 2a-c toxicity profile was also assessed (human hepatocytes and mouse fibroblasts). Our prototypical pluripotent analogue 2a interferes with Aβ oligomerization process thus reducing Aβ oligomers-mediated toxicity in human neuroblastoma cells. 2a also disrupts preformed fibrils. Computational studies highlighted the bases governing the diversified activities of 2a. Converging analytical, biological, and in silico data explained the mechanism of action of 2a on Aβ1-42 oligomers formation and against Aβ-preformed fibrils. This evidence, combined with toxicity data, will orient the future design of safer analogues. © 2014 John Wiley & Sons Ltd.

  6. Design, Synthesis, and Herbicidal Activity of Pyrimidine-Biphenyl Hybrids as Novel Acetohydroxyacid Synthase Inhibitors.

    Science.gov (United States)

    Li, Ke-Jian; Qu, Ren-Yu; Liu, Yu-Chao; Yang, Jing-Fang; Devendar, Ponnam; Chen, Qiong; Niu, Cong-Wei; Xi, Zhen; Yang, Guang-Fu

    2018-04-18

    The issue of weed resistance to acetohydroxyacid synthase (EC 2.2.1.6, AHAS) inhibitors has become one of the largest obstacles for the application of this class of herbicides. In a continuing effort to discover novel AHAS inhibitors to overcome weed resistance, a series of pyrimidine-biphenyl hybrids (4aa-bb and 5aa-ah) were designed and synthesized via a scaffold hopping strategy. Among these derivatives, compounds 4aa ( K i = 0.09 μM) and 4bb ( K i = 0.02 μM) displayed higher inhibitory activities against Arabidopsis thaliana AHAS than those of the controls bispyribac ( K i = 0.54 μM) and flumetsulam ( K i = 0.38 μM). Remarkably, compounds 4aa, 4bb, 5ah, and 5ag exhibited excellent postemergence herbicidal activity and a broad spectrum of weed control at application rates of 37.5-150 g of active ingredient (ai)/ha. Furthermore, 4aa and 4bb showed higher herbicidal activity against AHAS inhibitor-resistant Descurainia sophia, Ammannia arenaria, and the corresponding sensitive weeds than that of bispyribac at 0.94-0.235 g ai/ha. Therefore, the pyrimidine-biphenyl motif and lead compounds 4aa and 4bb have great potential for the discovery of novel AHAS inhibitors to combat AHAS-inhibiting herbicide-resistant weeds.

  7. Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line

    Directory of Open Access Journals (Sweden)

    ANDRÉA C PAULA LIMA

    2008-01-01

    Full Text Available We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the β-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh, CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levéis ([Ca2+]¡. Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca2+]¡. Results indícate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells.

  8. High-Performance Doping-Free Hybrid White OLEDs Based on Blue Aggregation-Induced Emission Luminogens.

    Science.gov (United States)

    Liu, Baiquan; Nie, Han; Lin, Gengwei; Hu, Shiben; Gao, Dongyu; Zou, Jianhua; Xu, Miao; Wang, Lei; Zhao, Zujin; Ning, Honglong; Peng, Junbiao; Cao, Yong; Tang, Ben Zhong

    2017-10-04

    Doping-free white organic light-emitting diodes (DF-WOLEDs) have aroused research interest because of their simple properties. However, to achieve doping-free hybrid WOLEDs (DFH-WOLEDs), avoiding aggregation-caused quenching is challenging. Herein, blue luminogens with aggregation-induced emission (AIE) characteristics, for the first time, have been demonstrated to develop DFH-WOLEDs. Unlike previous DFH-WOLEDs, both thin (10 nm) AIE luminogen (AIEgen) can be used for devices, enhancing the flexibility. Two-color devices show (i) pure-white emission, (ii) high CRI (85), and (iii) high efficiency. Particularly, 19.0 lm W 1- is the highest for pure-white DF-WOLEDs, while 35.0 lm W 1- is the best for two-color hybrid WOLEDs with CRI ≥ 80. A three-color DFH-WOLED shows broad color-correlated temperature span (2301-11628 K), (i) the first sunlight-like OLED (2500-8000 K) operating at low voltages, (ii) the broadest span among sunlight-like OLED, and (iii) possesses comparable efficiency with the best doping counterpart. Another three-color DFH-WOLED exhibits CRI > 90 at ≥3000 cd m -2 , (i) the first DF-WOLED with CRI ≥ 90 at high luminances, and (ii) the CRI (92.8) is not only the highest among AIE-based WOLEDs but also the highest among DF-WOLEDs. Such findings may unlock an alternative concept to develop DFH-WOLEDs.

  9. Hybrid Tunable Wideband Single Feed Antenna Element for Smartphones supporting Carrier Aggregation

    DEFF Research Database (Denmark)

    Stanev, Simon Peter; Tatomirescu, Alexandru

    2016-01-01

    This paper presents a single feed antenna with a dual branch matching circuit combined with a 3dB microstrip power divider to support the carrier aggregation in LTE advanced mobile handsets. By the use of the matching circuits, an independent and versatile broadband antenna is achieved. Hence, th...

  10. Data Aggregation in Multi-Agent Systems in the Presence of Hybrid Faults

    Science.gov (United States)

    Srinivasan, Satish Mahadevan

    2010-01-01

    Data Aggregation (DA) is a set of functions that provide components of a distributed system access to global information for purposes of network management and user services. With the diverse new capabilities that networks can provide, applicability of DA is growing. DA is useful in dealing with multi-value domain information and often requires…

  11. Semisynthesis and Structure-Activity Studies of Uncarinic Acid C Isolated from Uncaria rhynchophylla as a Specific Inhibitor of the Nucleation Phase in Amyloid β42 Aggregation.

    Science.gov (United States)

    Yoshioka, Takuya; Murakami, Kazuma; Ido, Kyohei; Hanaki, Mizuho; Yamaguchi, Kanoko; Midorikawa, Satohiro; Taniwaki, Shinji; Gunji, Hiroki; Irie, Kazuhiro

    2016-10-28

    Oligomers of the 42-mer amyloid-β protein (Aβ42), rather than fibrils, cause synaptic dysfunction in the pathology of Alzheimer's disease (AD). The nucleation phase in a nucleation-dependent aggregation model of Aβ42 is related to the formation of oligomers. Uncaria rhynchophylla is one component of "Yokukansan", a Kampo medicine, which is widely used for treating AD symptoms. Previously, an extract of U. rhynchophylla was found to reduce the aggregation of Aβ42, but its active principles have yet to be identified. In the present work, uncarinic acid C (3) was identified as an inhibitor of Aβ42 aggregation that is present in U. rhynchophylla. Moreover, compound 3 acted as a specific inhibitor of the nucleation phase of Aβ42 aggregation. Compound 3 was synthesized from saponin A (10), an abundant byproduct of rutin purified from Uncaria elliptica. Comprehensive structure-activity studies on 3 suggest that both a C-27 ferulate and a C-28 carboxylic acid group are required for its inhibitory activity. These findings may aid the development of oligomer-specific inhibitors for AD therapy.

  12. Dynamic Control of Plasmon-Exciton Coupling in Au Nanodisk–J-Aggregate Hybrid Nanostructure Arrays

    KAUST Repository

    Zheng, Yue Bing; Juluri, Bala Krishna; Jensen, Linlin; Jensen, Lasse; Huang, Tony Jun

    2009-01-01

    We report the dynamic control of plasmon-exciton coupling in Au nanodisk arrays adsorbed with J-aggregate molecules by incident angle of light. The angle-resolved spectra of an array of bare Au nanodisks exhibit continuous shifting of localized surface plasmon resonances. This characteristic enables the production of real-time, controllable spectral overlaps between molecular and plasmonic resonances, and the efficient measurement of plasmon-exciton coupling as a function of wavelength with one or fewer nanodisk arrays. Experimental observations of varying plasmon-exciton coupling match with coupled dipole approximation calculations.

  13. Larger spontaneous polarization ferroelectric inorganic-organic hybrids: [PbI3](infinity) chains directed organic cations aggregation to Kagomé-shaped tubular architecture.

    Science.gov (United States)

    Zhao, Hai-Rong; Li, Dong-Ping; Ren, Xiao-Ming; Song, You; Jin, Wan-Qin

    2010-01-13

    Four isostructural inorganic-organic hybrid ferroelectric compounds, assembled from achiral 3-R-benzylidene-1-aminopyridiniums (R = NO(2), Br, Cl, or F for 1-4, respectively) and [PbI(3)](-) anions with the chiral Kagomé-shaped tubular aggregating architecture, show larger spontaneous polarizations.

  14. Inhibitors

    Science.gov (United States)

    ... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

  15. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate, Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy

    Directory of Open Access Journals (Sweden)

    Karima Schwab

    2018-01-01

    Full Text Available α-Synuclein (α-Syn aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson’s disease (PD. We have tested whether N,N,N′,N′-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate (leuco-methylthioninium bis(hydromethanesulfonate; LMTM, a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62 transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation.

  16. The difference in association between aspirin use and other thrombocyte aggregation inhibitors and survival in patients with colorectal cancer.

    Science.gov (United States)

    Frouws, M A; Rademaker, E; Bastiaannet, E; van Herk-Sukel, M P P; Lemmens, V E; Van de Velde, C J H; Portielje, J E A; Liefers, G J

    2017-05-01

    Several studies have suggested that the association between aspirin and improved cancer survival is mediated through the mechanism of aspirin as thrombocyte aggregation inhibitors (TAI). The aim of this study was to provide epidemiological evidence for this mechanism assessing the association between overall survival and the use of aspirin and non-aspirin TAI in patients with colorectal cancer. In this observational study, data from the Netherlands Comprehensive Cancer Organisation were linked to PHARMO Database Network. Patients using aspirin or aspirin in combination with non-aspirin TAI (dual users) were selected and compared with non-users. The association between overall survival and the use of (non-)aspirin TAI was analysed using Cox regression models with the use of (non-)aspirin TAI as a time-varying covariate. In total, 9196 patients were identified with colorectal cancer and 1766 patients used TAI after diagnosis. Non-aspirin TAI were mostly clopidogrel and dipyridamole. Aspirin use was associated with a significant increased overall survival and hazard ratio (HR) 0.41 (95% confidence interval [CI] 0.37-0.47), and the use of non-aspirin TAI was not associated with survival of HR 0.92 (95% CI 0.70-1.22). Dual users did not have an improved overall survival when compared with patients using solely aspirin. Aspirin use after diagnosis of colorectal cancer was associated with significantly lower mortality rates and this effect remained significant after adjusting for potential confounders. No additional survival benefit was observed in patients using both aspirin and another TAI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Use of a specific MMP inhibitor (Galardin) for preservation of hybrid layer

    Science.gov (United States)

    Breschi, Lorenzo; Martin, Patrizia; Mazzoni, Annalisa; Nato, Fernando; Carrilho, Marcela; Tjäderhane, Leo; Visintini, Erika; Cadenaro, Milena; Tay, Franklin R; De Stefano Dorigo, Elettra; Pashley, David H

    2013-01-01

    Objective Dentinal MMPs have been claimed to contribute to the auto-degradation of collagen fibrils within incompletely resin-infiltrated hybrid layers and their inhibition may, therefore, slow the degradation of hybrid layer. This study aimed to determine the contribution of a synthetic MMPs inhibitor (Galardin) to the proteolytic activity of dentinal MMPs and to the morphological and mechanical features of hybrid layers after aging. Methods Dentin powder obtained from human molars was treated with Galardin or chlorhexidine digluconate and zymographically analyzed. Microtensile bond strength was also evaluated in extracted human teeth. Exposed dentin was etched with 35% phosphoric acid and specimens were assigned to (1) pre-treatment with Galardin as additional primer for 30s; (2) no pre-treatment. A two-step etch-and-rinse adhesive (Adper Scotchbond 1XT, 3M ESPE) was then applied in accordance with manufacturer's instructions and resin composite build-ups were created. Specimens were immediately tested for their microtensile bond strength or stored in artificial saliva for 12 months prior to being tested. Data were evaluated by two-way ANOVA and Tukey's tests (〈=0.05). Additional specimens were prepared for interfacial nanoleakage analysis under light microscopy and TEM, quantified by two independent observers and statistically analyzed (|2 test, 〈=0.05). Results The inhibitory effect of Galardin on dentinal MMPs was confirmed by zymographic analysis, as complete inhibition of both MMP-2 and -9 was observed. The use of Galardin had no effect on immediate bond strength, while it significantly decreased bond degradation after 1 year (padhesive after artificial aging. PMID:20299089

  18. Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining.

    Science.gov (United States)

    Ring, Hans Christian; Theut Riis, Peter; Bay, Lene; Kallenbach, Klaus; Bjarnsholt, Thomas; Jemec, Gregor B E

    2017-10-01

    Although peptide nucleic acid (PNA), fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) are the reference tools in the study of bacterial aggregates/biofilms, it may also be rather time-consuming. This study aimed to investigate the sensitivity and specificity between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively. The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid and practical low-cost tool to evaluate bacterial aggregates. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Multitarget Therapeutic Leads for Alzheimer's Disease: Quinolizidinyl Derivatives of Bi- and Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation.

    Science.gov (United States)

    Tonelli, Michele; Catto, Marco; Tasso, Bruno; Novelli, Federica; Canu, Caterina; Iusco, Giovanna; Pisani, Leonardo; Stradis, Angelo De; Denora, Nunzio; Sparatore, Anna; Boido, Vito; Carotti, Angelo; Sparatore, Fabio

    2015-06-01

    Multitarget therapeutic leads for Alzheimer's disease were designed on the models of compounds capable of maintaining or restoring cell protein homeostasis and of inhibiting β-amyloid (Aβ) oligomerization. Thirty-seven thioxanthen-9-one, xanthen-9-one, naphto- and anthraquinone derivatives were tested for the direct inhibition of Aβ(1-40) aggregation and for the inhibition of electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBChE). These compounds are characterized by basic side chains, mainly quinolizidinylalkyl moieties, linked to various bi- and tri-cyclic (hetero)aromatic systems. With very few exceptions, these compounds displayed inhibitory activity on both AChE and BChE and on the spontaneous aggregation of β-amyloid. In most cases, IC50 values were in the low micromolar and sub-micromolar range, but some compounds even reached nanomolar potency. The time course of amyloid aggregation in the presence of the most active derivative (IC50 =0.84 μM) revealed that these compounds might act as destabilizers of mature fibrils rather than mere inhibitors of fibrillization. Many compounds inhibited one or both cholinesterases and Aβ aggregation with similar potency, a fundamental requisite for the possible development of therapeutics exhibiting a multitarget mechanism of action. The described compounds thus represent interesting leads for the development of multitarget AD therapeutics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Synthesis of novel disulfide and sulfone hybrid scaffolds as potent β-glucuronidase inhibitor.

    Science.gov (United States)

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Al Muqarrabin, Laode Muhammad Ramadhan; Zaki, Hamizah Mohd; Ahmat, Norizan; Nasir, Abdul; Khan, Fahad

    2016-10-01

    Novel series of disulfide and sulfone hybrid analogs (1-20) were synthesized and characterized through EI-MS and (1)H NMR and evaluated for β-glucuronidase inhibitory potential. All synthesized analogs except 13 and 15 showed excellent β-glucuronidase inhibitory potential with IC50 value ranging in between 2.20-88.16μM as compared to standard d-saccharic acid 1,4 lactone (48.4±1.25μM). Analogs 19, 16, 4, 1, 17, 6, 10, 3, 18, 2, 11, 14 and 5 showed many fold potent activity against β-glucuronidase inhibitor. Structure activity relationship showed that substitution of electron withdrawing groups at ortho as well as para position on phenyl ring increase potency. Electron withdrawing groups at meta position on phenyl ring showed slightly low potency as compared to ortho and para position. The binding interactions were confirmed through molecular docking studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Ceria nanoparticles vis-à-vis cerium nitrate as corrosion inhibitors for silica-alumina hybrid sol-gel coating

    Energy Technology Data Exchange (ETDEWEB)

    Lakshmi, R.V. [Surface Engineering Division, Council of Scientific and Industrial Research – National Aerospace Laboratories, HAL Airport Road, Kodihalli, Bengaluru 560017 (India); Aruna, S.T., E-mail: staruna194@gmail.com [Surface Engineering Division, Council of Scientific and Industrial Research – National Aerospace Laboratories, HAL Airport Road, Kodihalli, Bengaluru 560017 (India); Sampath, S. [Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bengaluru 560012 (India)

    2017-01-30

    Highlights: • Corrosion protection efficiency comparison of ceria nanoparticles and cerium nitrate. • Silica-alumina hybrid coating exhibited good barrier protection. • Detailed XPS study confirm the hybrid structure and presence of Ce species in coating. • Loss of cerium ions not prevalent in ceria doped coating unlike that of cerium nitrate. • Ceria increased the coating integrity, corrosion inhibition and barrier protection. - Abstract: The present work provides a comparative study on the corrosion protection efficiency of defect free sol-gel hybrid coating containing ceria nanoparticles and cerium nitrate ions as corrosion inhibitors. Less explored organically modified alumina-silica hybrid sol-gel coatings are synthesized from 3-glycidoxypropyltrimethoxysilane and aluminium-tri-sec-butoxide. The microemulsion derived nanoparticles and the hybrid coatings are characterized and compared with coatings containing cerium nitrate. Corrosion inhibiting capability is assessed using electrochemical impedance spectroscopy. Scanning Kelvin probe measurements are also conducted on the coatings for identifying the apparent corrosion prone regions. Detailed X-ray photoelectron spectroscopy (XPS) analysis is carried out to comprehend the bonding and corrosion protection rendered by the hybrid coatings.

  2. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties.

    Science.gov (United States)

    Guzior, Natalia; Bajda, Marek; Skrok, Mirosław; Kurpiewska, Katarzyna; Lewiński, Krzysztof; Brus, Boris; Pišlar, Anja; Kos, Janko; Gobec, Stanislav; Malawska, Barbara

    2015-03-06

    The presented study describes the synthesis, pharmacological evaluation (AChE and BuChE inhibition, beta amyloid anti-aggregation effect and neuroprotective effect), molecular modeling and crystallographic studies of a novel series of isoindoline-1,3-dione derivatives. The target compounds were designed as dual binding site acetylcholinesterase inhibitors with an arylalkylamine moiety binding at the catalytic site of the enzyme and connected via an alkyl chain to a heterocyclic fragment, capable of binding at the peripheral anionic site of AChE. Among these molecules, compound 15b was found to be the most potent and selective AChE inhibitor (IC50EeAChE = 0.034 μM). Moreover, compound 13b in addition to AChE inhibition (IC50 EeAChE = 0.219 μM) possesses additional properties, such as the ability to inhibit Aβ aggregation (65.96% at 10 μM) and a neuroprotective effect against Aβ toxicity at 1 and 3 μM. Compound 13b emerges as a promising multi-target ligand for the further development of the therapy for age-related neurodegenerative disorders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Discovery of novel PDE9 inhibitors capable of inhibiting Aβ aggregation as potential candidates for the treatment of Alzheimer’s disease

    Science.gov (United States)

    Su, Tao; Zhang, Tianhua; Xie, Shishun; Yan, Jun; Wu, Yinuo; Li, Xingshu; Huang, Ling; Luo, Hai-Bin

    2016-02-01

    Recently, phosphodiesterase-9 (PDE9) inhibitors and biometal-chelators have received much attention as potential therapeutics for the treatment of Alzheimer’s disease (AD). Here, we designed, synthesized, and evaluated a novel series of PDE9 inhibitors with the ability to chelate metal ions. The bioassay results showed that most of these molecules strongly inhibited PDE9 activity. Compound 16 showed an IC50 of 34 nM against PDE9 and more than 55-fold selectivity against other PDEs. In addition, this compound displayed remarkable metal-chelating capacity and a considerable ability to halt copper redox cycling. Notably, in comparison to the reference compound clioquinol, it inhibited metal-induced Aβ1-42 aggregation more effectively and promoted greater disassembly of the highly structured Aβ fibrils generated through Cu2+-induced Aβ aggregation. These activities of 16, together with its favorable blood-brain barrier permeability, suggest that 16 may be a promising compound for treatment of AD.

  4. Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-β-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Li, Yuxing; Qiang, Xiaoming; Li, Yan; Yang, Xia; Luo, Li; Xiao, Ganyuan; Cao, Zhongcheng; Tan, Zhenghuai; Deng, Yong

    2016-04-15

    A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Aβ1-42 aggregation and HuAChE-induced Aβ1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50=0.06 μM) and good inhibition of BuChE (IC50=28.04 μM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Aβ aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. In vitro evaluation of the contact angle formed between AH Plus, Hybrid Root Seal and mineral trioxide aggregate Plus sealer with dentin and gutta-percha.

    Science.gov (United States)

    Nikhil, Vineeta; Jaiswal, Shikha; Bajpai, Gauravi

    2018-01-01

    The purpose of this study was evaluation and comparison of the contact angle of new root canal sealers - Hybrid Root Seal, mineral trioxide aggregate (MTA) Plus, and the conventional AH Plus sealer with dentin and gutta-percha. Two groups (Group D - dentin and Group G - gutta-percha) of 18 samples each were further randomly divided into 3 subgroups based on the type of sealer used, that is, AH Plus, Hybrid Root Seal, and MTA Plus. Contact angle measurement device (Phoenix 300) was used to measure the contact angle of the sealers on both dentin and gutta-percha. The results thus obtained were analyzed using one-way analysis of variance and Student's t -test. MTA Plus recorded significantly higher values of contact angle on both the substrates, that is, dentin and gutta-percha when compared to AH Plus and Hybrid root canal sealer. The lowest value of contact angle in gutta-percha and dentin was shown by Hybrid root canal sealer and AH Plus, respectively. Both AH Plus and Hybrid Root Seal exhibited lower contact angle values, and hence, better wettability on both dentin and gutta-percha as compared to MTA Plus.

  6. 7-Methoxytacrine-p-Anisidine Hybrids as Novel Dual Binding Site Acetylcholinesterase Inhibitors for Alzheimer’s Disease Treatment

    Directory of Open Access Journals (Sweden)

    Jan Korabecny

    2015-12-01

    Full Text Available Alzheimer’s disease (AD is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient’s death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds’ behavior was confirmed in the subsequent molecular modeling studies.

  7. High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

    Science.gov (United States)

    Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

    2016-10-01

    Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

  8. Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

    Science.gov (United States)

    Dgachi, Youssef; Ismaili, Lhassane; Knez, Damijan; Benchekroun, Mohamed; Martin, Hélène; Szałaj, Natalia; Wehle, Sarah; Bautista-Aguilera, Oscar M; Luzet, Vincent; Bonnet, Alexandre; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Decker, Michael; Chabchoub, Fakher; Marco-Contelles, José

    2016-06-20

    Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1-42 antiaggregating power (40.3 %). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. [Design, synthesis and evaluation of bis-nicotine derivatives as inhibitors of cholinesterases and beta-amyloid aggregation].

    Science.gov (United States)

    Luo, Wen; Zhao, Yong-mei; Tian, Run-guo; Su, Ya-bin; Hong, Chen

    2013-11-01

    A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).

  10. Protein Colloidal Aggregation Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  11. Novel histone deacetylase 8-selective inhibitor 1,3,4-oxadiazole-alanine hybrid induces apoptosis in breast cancer cells.

    Science.gov (United States)

    Pidugu, Vijaya Rao; Yarla, Nagendra Sastry; Bishayee, Anupam; Kalle, Arunasree M; Satya, Alapati Krishna

    2017-11-01

    Identification of isoform-specific histone deacetylase inhibitors (HDACi) is a significant advantage to overcome the adverse side effects of pan-HDACi for the treatment of various diseases, including cancer. We have designed, and synthesized novel 1,3,4 oxadiazole with glycine/alanine hybrids as HDAC8-specific inhibitors and preliminary evaluation has indicated that 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)propanamide (10b)] to be a potent HDAC8 inhibitor. In the present study, the in vitro efficacy of the molecule in inhibiting the cancer cell proliferation and the underlying molecular mechanism was studied. 10b inhibited the growth of MDA-MB-231 and MCF7 breast cancer cells, with a lower IC 50 of 230 and 1000 nM, respectively, compared to K562, COLO-205 and HepG2 cells and was not cytotoxic to normal breast epithelial cells, MCF10A. 10b was specific to HDAC8 and did not affect the expression of other class I HDACs. Further, a dose-dependent increase in H3K9 acetylation levels demonstrated the HDAC-inhibitory activity of 10b in MDA-MB-231 cells. Flow cytometric analysis indicated a dose-dependent increase and decrease in the percent apoptotic cells and mitochondrial membrane potential, respectively, when treated with 10b. Immunoblot analysis showed a modulation of Bax/Bcl2 ratio with a decrease in Bcl2 expression and no change in Bax expression. 10b treatment resulted in induction of p21 and inhibition of CDK1 proteins along with cytochrome c release from mitochondria, activation of caspases-3 and -9 and cleavage of poly ADP-ribose polymerase leading to apoptotic death of MDA-MB-231 and MCF7 cells. In conclusion, our results clearly demonstrated the efficacy of 10b as an anticancer agent against breast cancer.

  12. Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Montero, Ana; Leman, Luke J.

    2012-01-01

    We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC...

  13. Synthesis and Characterization of Hybrid Silica-Zirconia Coatings with Cerium Inhibitor on Aluminum 6061

    Directory of Open Access Journals (Sweden)

    M. Bahrami

    2016-12-01

    Full Text Available Organic–inorganic hybrid coatings were prepared by sol–gel method and deposited on aluminum alloy 6061. Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR spectroscopy and Scanning Electron Microscopy (SEM were used for structural study of the hybrid coatings. Adhesive strength of sol–gel coatings to the substrate was evaluated quantitatively and qualitatively. Corrosion behavior of the samples was studied by cyclic potentiodynamic and linear polarization tests. Results showed that adhesion strength of the coatings to the substrates was increased with increasing tetrapropoxide of zirconium (TPOZ and cerium content. Corrosion tests showed that corrosion current density of coated samples were decreased three to seven orders of magnitude in comparison with uncoated aluminum alloy 6061. Decreasing in corrosion current density and increasing in polarization resistance was observed by increasing zirconia and cerium content. Unlike the uncoated aluminum alloy 6061, the crack-free coatings did not show pitting tendency. 

  14. Cost- and reliability-oriented aggregation point association in long-term evolution and passive optical network hybrid access infrastructure for smart grid neighborhood area network

    Science.gov (United States)

    Cheng, Xiao; Feng, Lei; Zhou, Fanqin; Wei, Lei; Yu, Peng; Li, Wenjing

    2018-02-01

    With the rapid development of the smart grid, the data aggregation point (AP) in the neighborhood area network (NAN) is becoming increasingly important for forwarding the information between the home area network and wide area network. Due to limited budget, it is unable to use one-single access technology to meet the ongoing requirements on AP coverage. This paper first introduces the wired and wireless hybrid access network with the integration of long-term evolution (LTE) and passive optical network (PON) system for NAN, which allows a good trade-off among cost, flexibility, and reliability. Then, based on the already existing wireless LTE network, an AP association optimization model is proposed to make the PON serve as many APs as possible, considering both the economic efficiency and network reliability. Moreover, since the features of the constraints and variables of this NP-hard problem, a hybrid intelligent optimization algorithm is proposed, which is achieved by the mixture of the genetic, ant colony and dynamic greedy algorithm. By comparing with other published methods, simulation results verify the performance of the proposed method in improving the AP coverage and the performance of the proposed algorithm in terms of convergence.

  15. Haematoxylin and eosin staining identifies medium to large bacterial aggregates with a reliable specificity: A comparative analysis of follicular bacterial aggregates in axillary biopsies using peptide nucleic acid-fluorescence in situ hybridization and haematoxylin and eosin staining

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Riis, Peter Theut; Bay, Lene

    2017-01-01

    between bacterial aggregates identified by haematoxylin and eosin (HE) staining vs bacterial aggregates in corresponding PNA-FISH samples. Axillary biopsies were obtained in 24 healthy controls. HE-stained and PNA-FISH samples were investigated using traditional light microscopy and CLSM, respectively....... The data demonstrate that HE staining identifies large bacterial aggregates (>10 μm) with a sensitivity of 0.43 and specificity of 1. The methods, however, are not equivalent as demonstrated by a McNemar's test (P=.04). Where bacterial aggregates >10 μm in diameter, HE staining may offer a rapid...... and practical low-cost tool to evaluate bacterial aggregates....

  16. Transurethral bipolar plasmakinetic vapo-enucleation of the prostate: Is it safe for patients on chronic oral anticoagulants and/or platelet aggregation inhibitors?

    Directory of Open Access Journals (Sweden)

    Waleed El-Shaer

    2017-12-01

    Full Text Available Objectives: To assess the safety and efficacy of bipolar plasmakinetic enucleation and resection of the prostate (PKERP for the management of benign prostatic hyperplasia (BPH in patients on oral anticoagulant (OAC therapy and/or platelet aggregation inhibitors (PAIs. Patients and methods: In all, 91 patients were recruited and underwent PKERP whilst they were receiving PAIs (aspirin, 56 patients; clopidogrel, three; aspirin and clopidogrel, 11. In all, 15 patients were receiving an OAC drug perioperatively, whilst another six patients were on dual PAIs and OACs. The primary outcomes were the perioperative morbidity and mortality rates. The secondary outcomes were functional outcomes including maximum urinary flow rate (Qmax, International Prostate Symptoms Score (IPSS, and post-void residual urine volume (PVR. Results: The mean (SD age of the patients was 65 (5.9 years, preoperative adenoma volume was 80.9 (30.4 mL, and the operative time was 67 (23 min. No patient developed serious perioperative cardiovascular complications. The mean (SD duration of hospital stay was 1.79 (1 days and the postoperative catheterisation time was 1.14 (0.76 days. The mean (SD haemoglobin drop was 0.74 (0.61 g/dL, blood transfusion rate was 2.2%, and the clot retention rate was 2.2%. The mean (SD postoperative Qmax was 18.6 (4.37 mL/s as compared to 7.2 (3.2 mL/s preoperatively (P < 0.001, and the preoperative IPSS was reduced from 24.3 (6.1 to 5.7 (2.3 postoperatively (P < 0.05. Prostate volume measured by transrectal ultrasonography was significantly reduced from a mean (SD of 80.9 (30.4 mL preoperatively to 29.5 (10.6 mL postoperatively (P < 0.001. Conclusion: Minimally invasive PKERP may be considered as a safe and effective treatment option for managing patients with BPH receiving OAC/PAI drugs. Keywords: Anticoagulant, BPH, LUTS, PKERP

  17. De-optical-line-terminal hybrid access-aggregation optical network for time-sensitive services based on software-defined networking orchestration

    Science.gov (United States)

    Bai, Wei; Yang, Hui; Xiao, Hongyun; Yu, Ao; He, Linkuan; Zhang, Jie; Li, Zhen; Du, Yi

    2017-11-01

    With the increase in varieties of services in network, time-sensitive services (TSSs) appear and bring forward an impending need for delay performance. Ultralow-latency communication has become one of the important development goals for many scenarios in the coming 5G era (e.g., robotics and driverless cars). However, the conventional methods, which decrease delay by promoting the available resources and the network transmission speed, have limited effect; a new breakthrough for ultralow-latency communication is necessary. We propose a de-optical-line-terminal (De-OLT) hybrid access-aggregation optical network (DAON) for TSS based on software-defined networking (SDN) orchestration. In this network, low-latency all-optical communication based on optical burst switching can be achieved by removing OLT. For supporting this network and guaranteeing the quality of service for TSSs, we design SDN-driven control method and service provision method. Numerical results demonstrate the proposed DAON promotes network service efficiency and avoids traffic congestion.

  18. Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

    Science.gov (United States)

    Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

    2017-04-15

    Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids.

    Science.gov (United States)

    Bautista-Aguilera, Oscar M; Esteban, Gerard; Chioua, Mourad; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Soriano, Elena; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, José

    2014-01-01

    The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs) as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM) was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE) inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE). Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for hBuChE. Concerning human monoamine oxidase (hMAO) A inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent (IC50 [MAO A] =5,700±2,100 nM). For hMAO B, only DPHs 13 and 14 were moderate inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950±940 nM). Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode with an extended conformation, interacting simultaneously with both catalytic and peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion, distribution, metabolism, excretion and toxicity analysis showed that structures lacking phenyl-substituent show better druglikeness profiles; in particular, DPHs13-15 showed the most suitable absortion, distribution, metabolism, excretion and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent, moderately selective h

  20. Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.

    Graph aggregation is the process of computing a single output graph that constitutes a good compromise between several input graphs, each provided by a different source. One needs to perform graph aggregation in a wide variety of situations, e.g., when applying a voting rule (graphs as preference

  1. Rydberg aggregates

    Science.gov (United States)

    Wüster, S.; Rost, J.-M.

    2018-02-01

    We review Rydberg aggregates, assemblies of a few Rydberg atoms exhibiting energy transport through collective eigenstates, considering isolated atoms or assemblies embedded within clouds of cold ground-state atoms. We classify Rydberg aggregates, and provide an overview of their possible applications as quantum simulators for phenomena from chemical or biological physics. Our main focus is on flexible Rydberg aggregates, in which atomic motion is an essential feature. In these, simultaneous control over Rydberg-Rydberg interactions, external trapping and electronic energies, allows Born-Oppenheimer surfaces for the motion of the entire aggregate to be tailored as desired. This is illustrated with theory proposals towards the demonstration of joint motion and excitation transport, conical intersections and non-adiabatic effects. Additional flexibility for quantum simulations is enabled by the use of dressed dipole-dipole interactions or the embedding of the aggregate in a cold gas or Bose-Einstein condensate environment. Finally we provide some guidance regarding the parameter regimes that are most suitable for the realization of either static or flexible Rydberg aggregates based on Li or Rb atoms. The current status of experimental progress towards enabling Rydberg aggregates is also reviewed.

  2. Crystallization and preliminary X-ray diffraction studies of BmooPLA2-I, a platelet-aggregation inhibitor and hypotensive phospholipase A2 from Bothrops moojeni venom

    International Nuclear Information System (INIS)

    Salvador, Guilherme H. M.; Marchi-Salvador, Daniela P.; Silveira, Lucas B.; Soares, Andreimar M.; Fontes, Marcos R. M.

    2011-01-01

    BmooPLA 2 -I, an acidic, catalytic and nontoxic phospholipase A 2 from B. moojeni venom that is able to inhibit platelet aggregation and induce a hypotensive effect, has been crystallized. An X-ray diffraction data set was collected to 1.6 Å resolution and a molecular-replacement solution was obtained. Phospholipases A 2 (PLA 2 s) are enzymes that cause the liberation of fatty acids and lysophospholipids by the hydrolysis of membrane phospholipids. In addition to their catalytic action, a wide variety of pharmacological activities have been described for snake-venom PLA 2 s. BmooPLA 2 -I is an acidic, nontoxic and catalytic PLA 2 isolated from Bothrops moojeni snake venom which exhibits an inhibitory effect on platelet aggregation, an immediate decrease in blood pressure, inducing oedema at a low concentration, and an effective bactericidal effect. BmooPLA 2 -I has been crystallized and X-ray diffraction data have been collected to 1.6 Å resolution using a synchrotron-radiation source. The crystals belonged to space group C222 1 , with unit-cell parameters a = 39.7, b = 53.2, c = 89.2 Å. The molecular-replacement solution of BmooPLA 2 -I indicated a monomeric conformation, which is in agreement with nondenaturing electrophoresis and dynamic light-scattering experiments. A comparative study of this enzyme with the acidic PLA 2 from B. jararacussu (BthA-I) and other toxic and nontoxic PLA 2 s may provide important insights into the functional aspects of this class of proteins

  3. HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?

    Science.gov (United States)

    Maksimovic-Ivanic, Danijela; Fagone, Paolo; McCubrey, James; Bendtzen, Klaus; Mijatovic, Sanja; Nicoletti, Ferdinando

    2017-04-15

    The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this article, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer. © 2016 UICC.

  4. Caspase-1 Specific Light-Up Probe with Aggregation-Induced Emission Characteristics for Inhibitor Screening of Coumarin-Originated Natural Products.

    Science.gov (United States)

    Lin, Hao; Yang, Haitao; Huang, Shuai; Wang, Fujia; Wang, Dong-Mei; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

    2018-04-18

    Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is found to be beneficial to various diseases. Coumarin-originated natural products have an anti-inflammation function, but their direct inhibition effect to caspase-1 remains unexplored. To evaluate their interactions, the widely used commercial coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from coumarin-originated natural products could interfere with the screening results. Therefore, fluorescent probes using a large Stokes shift could help solve this problem. In this work, we chose the fluorophore of tetraphenylethylene-thiophene (TPETH) with aggregation-induced emission characteristics and a large Stokes shift of about 200 nm to develop a molecular probe. Bioconjugation between TPETH and hydrophilic peptides (DDYVADC) through a thiol-ene reaction generated a light-up probe, C1-P3. The probe has little background signal in aqueous media and exerts a fluorescent turn-on effect in the presence of caspase-1. Moreover, when evaluating the inhibition potency of coumarin-originated natural products, the new probe could generate a true and objective result but not for the commercial probe (Ac-YVAD-AMC), which is evidenced by HPLC analysis. The quick light-up response and accurate screening results make C1-P3 very useful in fundamental study and inhibitior screening toward caspase-1.

  5. Purification and characterization of Cc-Lec, C-type lactose-binding lectin: A platelet aggregation and blood-clotting inhibitor from Cerastes cerastes venom.

    Science.gov (United States)

    Samah, Saoud; Fatah, Chérifi; Jean-Marc, Berjeaud; Safia, Kellou-Taîri; Fatima, Laraba-Djebari

    2017-09-01

    In this study, we reported for the first time the biochemical and structural characterization of Cc-Lec, a C-type lectin purified from Cerastes cerastes venom by affinity chromatography. This lectin was homogeneous by SDS-PAGE, and was shown to be a 34 271.59Da polypeptide by Electrospray mass spectrometry MS-ES-TOF. Its identified sequence of 160 amino acids corresponding to one subunit, revealed a high identity with other related proteins. Cc-Lec modeled 3D structure appeared as homodimer cross-linked by one disulfide bridge. Cc-Lec exhibited a calcium dependent hemagglutinating activity against human group O erythrocytes. Cc-Lec inhibited platelet aggregation induced by ADP, arachidonic acid or fibrinogen suggesting its interaction with their specific receptors namely P2Y1 and/or P2Y12, GPIIb/IIIa and TPα respectively. Cc-Lec was not lethal for mice until 10mg/kg administered by i.p. route. The lectin displayed a lasting anticoagulation on mice plasma even two days post-injection. This anticoagulation seems to be related to its interaction with coagulation factors Xa and IXa. Therefore, Cc-Lec prevented FXa amidolytic activity with Km=4.3310 -4 μg/mL and ki=14.4μg/mL. It seems to interact with these targets through CRD domain which could make it a good target as a pharmacological promising molecule in thrombosis diagnosis and therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Is hybridization involved in the evolution of the Chenopodium album aggregate? An analysis based on chromosome counts and genome size estimation

    Czech Academy of Sciences Publication Activity Database

    Mandák, Bohumil; Trávníček, Pavel; Paštová, Ladislava; Kořínková, Dana

    2012-01-01

    Roč. 270, č. 7 (2012), s. 530-540 ISSN 0367-2530 R&D Projects: GA ČR GA206/09/1126 Institutional support: RVO:67985939 Keywords : Chenopodium * hybridization * polyploidization Subject RIV: EF - Botanics Impact factor: 1.716, year: 2012

  7. Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking.

    Science.gov (United States)

    Saeed, Aamer; Mahesar, Parvez Ali; Channar, Pervaiz Ali; Larik, Fayaz Ali; Abbas, Qamar; Hassan, Mubashir; Raza, Hussain; Seo, Sung-Yum

    2017-08-01

    The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a - 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3-(2-oxo-2H-chromen-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (5n) was found to be superior agent in the series with an IC 50  = 0.358 ± 0.017 μm compared to standard thiourea with an IC 50  = 4720 ± 174 μm. To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non-competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  8. Protein Aggregation Inhibitors for ALS Therapy

    Science.gov (United States)

    2013-07-01

    time (2, 5, 10, 15, and 30 min), and disappearance was monitored by HPLC -UV-Vis278nm analysis (Figure 33). Following 10 min irradiation at 312 nm, the...and irradiated with UV light (312 nm, 6W, 4 cm). Photolysis was monitored by HPLC -UV-Vis278nm. Photoaffinity labeling Studies in Whole Cell...well-known compounds resveratrol (57) and curcumin (58), as well as a large family of flavonoids such as quercitin (59) and epicatechin (60), have

  9. Taurine and platelet aggregation

    International Nuclear Information System (INIS)

    Nauss-Karol, C.; VanderWende, C.; Gaut, Z.N.

    1986-01-01

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 μM/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na + and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with 14 C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 μM, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet

  10. Design, synthesis and biological evaluation of benzo[e][1,2,4]triazin-7(1H)-one and [1,2,4]-triazino[5,6,1-jk]carbazol-6-one derivatives as dual inhibitors of beta-amyloid aggregation and acetyl/butyryl cholinesterase.

    Science.gov (United States)

    Catto, Marco; Berezin, Andrey A; Lo Re, Daniele; Loizou, Georgia; Demetriades, Marina; De Stradis, Angelo; Campagna, Francesco; Koutentis, Panayiotis A; Carotti, Angelo

    2012-12-01

    Alzheimer's disease (AD) onset and progression are associated with the dysregulation of multiple and complex physiological processes and a successful therapeutic approach should therefore address more than one target. Two new chemical entities, the easily accessible heterocyclic scaffolds 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (benzotriazinone I) and 2-phenyl-6H-[1,2,4]triazino[5,6,1-jk]carbazol-6-one (triazafluoranthenone II), were explored for their multitarget-directed inhibition of beta-amyloid (Aβ) fibrillization and acetyl- (AChE) and/or butyryl- (BChE) cholinesterase, three valuable targets for AD therapy. Introduction of appropriate amine substituents at positions 6 and 5 on scaffold I and II, respectively, allowed the preparation of a series of compounds that were tested as Aβ(1-40) aggregation and cholinesterase inhibitors. Potent inhibitors of Aβ self-aggregation were discovered and among them benzotriazinone 7 exhibited an outstanding IC(50) equal to 0.37 μM. Compounds bearing a basic amine linked to the heterocyclic scaffold through a linear alkyl chain of varying length also afforded good ChE inhibitors. In particular, benzotriazinone 24 and triazafluoranthenone 38 were endowed with an interesting multiple activity, the former displaying IC(50) values of 1.4, 1.5 and 1.9 μM on Aβ aggregation and AChE and BChE inhibition, respectively, and the latter showing IC(50) values of 1.4 and an outstanding 0.025 μM in the Aβ aggregation and BChE inhibition, respectively. Benzotriazinone 24 and triazafluoranthenone 29, selected owing to their suitable aqueous solubility and Aβ aggregation inhibition, were submitted to a time course kinetic assay followed with thioflavin T (ThT) spectrofluorimetry, circular dichroism (CD) and transmission electron microscopy (TEM). Experimental data indicated that 24 acted at a low concentration ratio (10 μM 24 vs. 50 μM Aβ), stabilizing the unstructured Aβ peptide and inhibiting fibrillogenesis, and that 29

  11. Probability Aggregates in Probability Answer Set Programming

    OpenAIRE

    Saad, Emad

    2013-01-01

    Probability answer set programming is a declarative programming that has been shown effective for representing and reasoning about a variety of probability reasoning tasks. However, the lack of probability aggregates, e.g. {\\em expected values}, in the language of disjunctive hybrid probability logic programs (DHPP) disallows the natural and concise representation of many interesting problems. In this paper, we extend DHPP to allow arbitrary probability aggregates. We introduce two types of p...

  12. A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD).

    Science.gov (United States)

    Shaltiel-Karyo, Ronit; Frenkel-Pinter, Moran; Rockenstein, Edward; Patrick, Christina; Levy-Sakin, Michal; Schiller, Abigail; Egoz-Matia, Nirit; Masliah, Eliezer; Segal, Daniel; Gazit, Ehud

    2013-06-14

    The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease.

  13. ALPHA-SYNUCLEIN STRUCTURE, AGGREGATION AND MODULATORS

    Directory of Open Access Journals (Sweden)

    Pinakin K. Makwana

    2016-06-01

    Full Text Available Alpha-synuclein is an intrinsically unstructured protein, involved in various neurodegenerative disorders. In vitro/in vivo experiments, as well as genetic mutation studies establish a direct link between alphasynuclein and synucleinopathies. Due to its natively unfolded state, alpha synuclein can adopt numerous conformations upon interaction with its partners and cellular factors, offering explanation for its diverse interactions. Aggregated form of alpha-synuclein has been observed in the brain of patients with synucleinopathies, a hallmark of neurodegeneration, and cell death has been attributed to aggregation induced toxicity. The process of aggregation involves nucleation, followed by intermediate oligomeric states, and finally the fibrillar amyloids. Of the various conformations/species that alpha-synuclein assumes before it transforms into mature amyloid fibrils, the oligomeric species is the most toxic. Thus, an effective way to limit disease progression is by modifying/slowing down protein aggregation/deposition in the brain. Various small natural products, synthetic chemicals, peptides and antibodies specific to alpha-synuclein have been designed/identified to reduce its rate of aggregation. Unfortunately, not even a handful of the molecules have cleared the clinical trials. Even today, medications available for Parkinson’s patients are mostly the drugs that adjust for loss of dopamine in the brain, and hence do not stop the progression of the disease or cure the symptoms. Thus, more molecular level studies are warranted to fully elucidate the process of alpha-synuclein aggregation, which in turn could help in identifying novel therapeutics and preventives. The present review summarizes the insights gained into the structure, in vitro aggregation and inhibitors/modulators of alpha-synuclein aggregation, that can be used to design better and effective inhibitors against the diseases.

  14. Information Aggregation in Organizations

    OpenAIRE

    Schulte, Elisabeth

    2006-01-01

    This dissertation contributes to the analysis of information aggregation procedures within organizations. Facing uncertainty about the consequences of a collective decision, information has to be aggregated before making a choice. Two main questions are addressed. Firstly, how well is an organization suited for the aggregation of decision-relevant information? Secondly, how should an organization be designed in order to aggregate information efficiently? The main part deals with information a...

  15. Towards General Temporal Aggregation

    DEFF Research Database (Denmark)

    Boehlen, Michael H.; Gamper, Johann; Jensen, Christian Søndergaard

    2008-01-01

    associated with the management of temporal data. Indeed, temporal aggregation is complex and among the most difficult, and thus interesting, temporal functionality to support. This paper presents a general framework for temporal aggregation that accommodates existing kinds of aggregation, and it identifies...

  16. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids

    Directory of Open Access Journals (Sweden)

    Bautista-Aguilera OM

    2014-10-01

    Full Text Available Oscar M Bautista-Aguilera,1,* Gerard Esteban,2,* Mourad Chioua,1 Katarina Nikolic,3 Danica Agbaba,3 Ignacio Moraleda,4 Isabel Iriepa,4 Elena Soriano,5 Abdelouahid Samadi,1 Mercedes Unzeta,2 José Marco-Contelles1 1Laboratory of Medicinal Chemistry (Institute of General Organic Chemistry [IQOG], National Research Council [CSIC], Madrid, Spain; 2Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Autonomous Barcelona University, Barcelona, Spain; 3Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia; 4Department of Organic Chemistry, Faculty of Pharmacy, University of Alcalá, Ctra Barcelona, Alcalá de Henares, Spain; 5Synthesis, and Structure of Organic Compounds (SEPCO (IQOG, CSIC, Madrid, Spain *These authors have equally contributed to this work Abstract: The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs as multipotent cholinesterase (ChE and monoamine oxidase (MAO inhibitors for the potential treatment of Alzheimer’s disease (AD is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE, and butyrylcholinesterase (BuChE enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (­Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE. Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for h

  17. Solid supported microwave induced synthesis of imidazole–pyrimidine hybrids: Antimicrobial evaluation and docking study as 14DM-CPY51 inhibitors

    Directory of Open Access Journals (Sweden)

    Naziyanaz B. Pathan

    2016-09-01

    Full Text Available As part of our exploration for new antifungal agents, substituted 4,5-diphenyl imidazolyl pyrimidine hybrids were synthesized. A series of substituted ethyl 1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1-(4,5-diphenyl-1-H-imidazol-2-yl pyrimidine-5-carboxylates have been studied for their binding active sites of cytochrome P450 14α-sterol demethylase CPY51 enzyme. For comparison, the binding behavior of known 14DM selective (Fluconazole and non-selective (Clotrimazole, Miconazole, Griesofulvin drugs has also been studied. Synthesized compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aurogenosa and Klebsiella pneumonae and also antifungal activity against the opportunistic pathogens Candida albicans.

  18. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten

    2013-01-01

    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...

  19. Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.

    Science.gov (United States)

    Zha, Xiaoming; Lamba, Doriano; Zhang, Lili; Lou, Yinghan; Xu, Changxu; Kang, Di; Chen, Li; Xu, Yungen; Zhang, Luyong; De Simone, Angela; Samez, Sarah; Pesaresi, Alessandro; Stojan, Jure; Lopez, Manuela G; Egea, Javier; Andrisano, Vincenza; Bartolini, Manuela

    2016-01-14

    Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.

  20. Aggregates from mineral wastes

    Directory of Open Access Journals (Sweden)

    Baic Ireneusz

    2016-01-01

    Full Text Available The problem concerning the growing demand for natural aggregates and the need to limit costs, including transportation from remote deposits, cause the increase in growth of interest in aggregates from mineral wastes as well as in technologies of their production and recovery. The paper presents the issue related to the group of aggregates other than natural. A common name is proposed for such material: “alternative aggregates”. The name seems to be fully justified due to adequacy of this term because of this raw materials origin and role, in comparison to the meaning of natural aggregates based on gravel and sand as well as crushed stones. The paper presents characteristics of the market and basic application of aggregates produced from mineral wastes, generated in the mining, power and metallurgical industries as well as material from demolished objects.

  1. Marine Synechococcus Aggregation

    Science.gov (United States)

    Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.

    2016-02-01

    Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

  2. Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

    Science.gov (United States)

    Bautista-Aguilera, Oscar M; Esteban, Gerard; Bolea, Irene; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Samadi, Abdelouahid; Soriano, Elena; Unzeta, Mercedes; Marco-Contelles, José

    2014-03-21

    The design, synthesis, and pharmacological evaluation of donepezil-indolyl based amines 7-10, amides 12-16, and carboxylic acid derivatives 5 and 11, as multipotent ASS234 analogs, able to inhibit simultaneously cholinesterase (ChE) and monoamine oxidase (MAO) enzymes for the potential treatment of Alzheimer's disease (AD), is reported. Theoretical studies using 3D-Quantitative Structure-Activity Relationship (3D-QSAR) was used to define 3D-pharmacophores for inhibition of MAO A/B, AChE, and BuChE enzymes. We found that, in general, and for the same substituent, amines are more potent ChE inhibitors (see compounds 12, 13 versus 7 and 8) or equipotent (see compounds 14, 15 versus 9 and 10) than the corresponding amides, showing a clear EeAChE inhibition selectivity. For the MAO inhibition, amides were not active, and among the amines, compound 14 was totally MAO A selective, while amines 15 and 16 were quite MAO A selective. Carboxylic acid derivatives 5 and 11 showed a multipotent moderate selective profile as EeACE and MAO A inhibitors. Propargylamine 15 [N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)prop-2-yn-1-amine] resulted in the most potent hMAO A (IC50 = 5.5 ± 1.4 nM) and moderately potent hMAO B (IC50 = 150 ± 31 nM), EeAChE (IC50 = 190 ± 10 nM), and eqBuChE (IC50 = 830 ± 160 nM) inhibitor. However, the analogous N-allyl and the N-morpholine derivatives 16 and 14 deserve also attention as they show an attractive multipotent profile. To sum up, donepezil-indolyl hybrid 15 is a promising drug for further development for the potential prevention and treatment of AD. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Aluminum induces lipid peroxidation and aggregation of human blood platelets

    Directory of Open Access Journals (Sweden)

    T.J.C. Neiva

    1997-05-01

    Full Text Available Aluminum (Al3+ intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 µM stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA (100 µM and n-propyl gallate (NPG (100 µM, inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA (100 µM, an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation

  4. Aggregated Computational Toxicology Online Resource

    Data.gov (United States)

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  5. Recycled aggregates concrete: aggregate and mix properties

    Directory of Open Access Journals (Sweden)

    González-Fonteboa, B.

    2005-09-01

    Full Text Available This study of structural concrete made with recycled concrete aggregate focuses on two issues: 1. The characterization of such aggregate on the Spanish market. This involved conducting standard tests to determine density, water absorption, grading, shape, flakiness and hardness. The results obtained show that, despite the considerable differences with respect to density and water absorption between these and natural aggregates, on the whole recycled aggregate is apt for use in concrete production. 2. Testing to determine the values of basic concrete properties: mix design parameters were established for structural concrete in non-aggressive environments. These parameters were used to produce conventional concrete, and then adjusted to manufacture recycled concrete aggregate (RCA concrete, in which 50% of the coarse aggregate was replaced by the recycled material. Tests were conducted to determine the physical (density of the fresh and hardened material, water absorption and mechanical (compressive strength, splitting tensile strength and modulus of elasticity properties. The results showed that, from the standpoint of its physical and mechanical properties, concrete in which RCA accounted for 50% of the coarse aggregate compared favourably to conventional concrete.

    Se aborda el estudio de hormigones estructurales fabricados con áridos reciclados procedentes de hormigón, incidiéndose en dos aspectos: 1. Caracterización de tales áridos, procedentes del mercado español. Para ello se llevan a cabo ensayos de densidad, absorción, granulometría, coeficiente de forma, índice de lajas y dureza. Los resultados obtenidos han puesto de manifiesto que, a pesar de que existen diferencias notables (sobre todo en cuanto a densidad y absorción con los áridos naturales, las características de los áridos hacen posible la fabricación de hormigones. 2. Ensayos sobre propiedades básicas de los hormigones: se establecen parámetros de dosificaci

  6. (E)-4-Methyl-N-((quinolin-2-yl)ethylidene)aniline as ligand for IIB supramolecular complexes: synthesis, structure, aggregation-induced emission enhancement and application in PMMA-doped hybrid material.

    Science.gov (United States)

    Wang, Ani; Fan, Ruiqing; Dong, Yuwei; Chen, Wei; Song, Yang; Wang, Ping; Hao, Sue; Liu, Zhigang; Yang, Yulin

    2016-12-20

    Judicious structural design employing 2-quinolinecarboxaldehyde and 4-methylaniline was used to generate the Schiff base ligand (E)-4-methyl-N-((quinolin-2-yl)ethylidene)aniline (L). Five IIB complexes, namely, [ZnLCl 2 ] (1), [ZnL(NO 3 ) 2 ] (2), [ZnL(OAc) 2 ] 3 (3), [CdL(OAc) 2 ] 3 (4), and [HgLCl 2 ] (5) have been synthesized based on L. Single-crystal X-ray diffraction analysis indicates that complexes 1, 3 and 4 exhibit 3D networks, whereas 2 and 5 form 2D layers and 1D chains, respectively. TD-DFT calculations show a good correlation with the UV-vis absorption assigned to π → π* intraligand transitions. Furthermore, complexes 1-5 displayed strong greenish luminescent emissions (518-524 nm) in the aggregate state but weak emissions in solution (aggregation-induced emission enhancement), which may be due to the existence of C-HCl/O hydrogen bonding and ππ stacking interactions, resulting in restriction of intramolecular rotation (RIR). Variable-concentration 1 H NMR studies suggested that the aggregates undergo intramolecular changes in conformation due to intermolecular interactions. Moreover, the emission intensity and lifetime exhibited obvious increases induced by mechanical grinding and temperature reduction, which were also attributed to AIEE properties. Subsequently, complex 1 was incorporated into poly(methyl methacrylate) (PMMA), whereby 1-PMMA exhibited enhanced emission intensity (20-fold increase in comparison with that of 1), which offers opportunities for use in plastic greenhouses to increase leaf photosynthesis.

  7. Observing Convective Aggregation

    Science.gov (United States)

    Holloway, Christopher E.; Wing, Allison A.; Bony, Sandrine; Muller, Caroline; Masunaga, Hirohiko; L'Ecuyer, Tristan S.; Turner, David D.; Zuidema, Paquita

    2017-11-01

    Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.

  8. Fly ash aggregates. Vliegaskunstgrind

    Energy Technology Data Exchange (ETDEWEB)

    1983-03-01

    A study has been carried out into artificial aggregates made from fly ash, 'fly ash aggregates'. Attention has been drawn to the production of fly ash aggregates in the Netherlands as a way to obviate the need of disposal of fly ash. Typical process steps for the manufacturing of fly ash aggregates are the agglomeration and the bonding of fly ash particles. Agglomeration techniques are subdivided into agitation and compaction, bonding methods into sintering, hydrothermal and 'cold' bonding. In sintering no bonding agent is used. The fly ash particles are more or less welded together. Sintering in general is performed at a temperature higher than 900 deg C. In hydrothermal processes lime reacts with fly ash to a crystalline hydrate at temperatures between 100 and 250 deg C at saturated steam pressure. As a lime source not only lime as such, but also portland cement can be used. Cold bonding processes rely on reaction of fly ash with lime or cement at temperatures between 0 and 100 deg C. The pozzolanic properties of fly ash are used. Where cement is applied, this bonding agent itself contributes also to the strength development of the artificial aggregate. Besides the use of lime and cement, several processes are known which make use of lime containing wastes such as spray dry absorption desulfurization residues or fluid bed coal combustion residues. (In Dutch)

  9. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders

    2014-01-01

    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...... aggregation response and ISS. Higher TRAP values were associated with death due to cerebral injuries (P 

  10. Erosion of dust aggregates

    NARCIS (Netherlands)

    Seizinger, A.; Krijt, S.; Kley, W.

    2013-01-01

    Aims: The aim of this work is to gain a deeper insight into how much different aggregate types are affected by erosion. Especially, it is important to study the influence of the velocity of the impacting projectiles. We also want to provide models for dust growth in protoplanetary disks with simple

  11. Aggregates, broccoli and cauliflower

    Science.gov (United States)

    Grey, Francois; Kjems, Jørgen K.

    1989-09-01

    Naturally grown structures with fractal characters like broccoli and cauliflower are discussed and compared with DLA-type aggregates. It is suggested that the branching density can be used to characterize the growth process and an experimental method to determine this parameter is proposed.

  12. Sustainable aggregates production : green applications for aggregate by-products.

    Science.gov (United States)

    2015-06-01

    Increased emphasis in the construction industry on sustainability and recycling requires production of : aggregate gradations with lower dust (cleaner aggregates) and smaller maximum sizeshence, increased : amount of quarry by-products (QBs). QBs ...

  13. Concrete produced with recycled aggregates

    Directory of Open Access Journals (Sweden)

    J. J. L. Tenório

    Full Text Available This paper presents the analysis of the mechanical and durable properties of recycled aggregate concrete (RAC for using in concrete. The porosity of recycled coarse aggregates is known to influence the fresh and hardened concrete properties and these properties are related to the specific mass of the recycled coarse aggregates, which directly influences the mechanical properties of the concrete. The recycled aggregates were obtained from construction and demolition wastes (CDW, which were divided into recycled sand (fine and coarse aggregates. Besides this, a recycled coarse aggregate of a specific mass with a greater density was obtained by mixing the recycled aggregates of the CDW with the recycled aggregates of concrete wastes (CW. The concrete was produced in laboratory by combining three water-cement ratios, the ratios were used in agreement with NBR 6118 for structural concretes, with each recycled coarse aggregates and recycled sand or river sand, and the reference concrete was produced with natural aggregates. It was observed that recycled aggregates can be used in concrete with properties for structural concrete. In general, the use of recycled coarse aggregate in combination with recycled sand did not provide good results; but when the less porous was used, or the recycled coarse aggregate of a specific mass with a greater density, the properties of the concrete showed better results. Some RAC reached bigger strengths than the reference concrete.

  14. Aggregation Algorithms in Heterogeneous Tables

    Directory of Open Access Journals (Sweden)

    Titus Felix FURTUNA

    2006-01-01

    Full Text Available The heterogeneous tables are most used in the problem of aggregation. A solution for this problem is to standardize these tables of figures. In this paper, we proposed some methods of aggregation based on the hierarchical algorithms.

  15. Familial Aggregation of Insomnia.

    Science.gov (United States)

    Jarrin, Denise C; Morin, Charles M; Rochefort, Amélie; Ivers, Hans; Dauvilliers, Yves A; Savard, Josée; LeBlanc, Mélanie; Merette, Chantal

    2017-02-01

    There is little information about familial aggregation of insomnia; however, this type of information is important to (1) improve our understanding of insomnia risk factors and (2) to design more effective treatment and prevention programs. This study aimed to investigate evidence of familial aggregation of insomnia among first-degree relatives of probands with and without insomnia. Cases (n = 134) and controls (n = 145) enrolled in a larger epidemiological study were solicited to invite their first-degree relatives and spouses to complete a standardized sleep/insomnia survey. In total, 371 first-degree relatives (Mage = 51.9 years, SD = 18.0; 34.3% male) and 138 spouses (Mage = 55.5 years, SD = 12.2; 68.1% male) completed the survey assessing the nature, severity, and frequency of sleep disturbances. The dependent variable was insomnia in first-degree relatives and spouses. Familial aggregation was claimed if the risk of insomnia was significantly higher in the exposed (relatives of cases) compared to the unexposed cohort (relatives of controls). The risk of insomnia was also compared between spouses in the exposed (spouses of cases) and unexposed cohort (spouses of controls). The risk of insomnia in exposed and unexposed biological relatives was 18.6% and 10.4%, respectively, yielding a relative risk (RR) of 1.80 (p = .04) after controlling for age and sex. The risk of insomnia in exposed and unexposed spouses was 9.1% and 4.2%, respectively; however, corresponding RR of 2.13 (p = .28) did not differ significantly. Results demonstrate evidence of strong familial aggregation of insomnia. Additional research is warranted to further clarify and disentangle the relative contribution of genetic and environmental factors in insomnia. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  16. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  17. Bacterial Aggregates Establish at the Edges of Acute Epidermal Wounds

    DEFF Research Database (Denmark)

    Bay, Lene; Kragh, Kasper N.; Eickhardt, Steffen R.

    2018-01-01

    for culturing from the wounds and adjacent skin, and the wounds including adjacent skin were excised. Tissue sections were stained with peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) probes, counterstained by 4′,6-diamidino-2-phenylindole, and evaluated by confocal laser scanning...... microscopy (CLSM). Results: No bacterial aggregates were detected at day 0. At day 4, coagulase-negative staphylococci (CoNS) were the sole bacteria identified by CLSM/PNA-FISH and culturing. CoNS was isolated from 78% of the wound swabs and 48% of the skin swabs. Bacterial aggregates (5–150 μm) were...

  18. Concrete = aggregate, cement, water?

    International Nuclear Information System (INIS)

    Jelinek, J.

    1990-01-01

    Concrete for the Temelin nuclear power plant is produced to about 70 different formulae. For quality production, homogeneous properties of aggregates, accurate proportioning devices, technological discipline and systematic inspections and tests should be assured. The results are reported of measuring compression strength after 28 days for different concrete samples. The results of such tests allow reducing the proportion of cement, which brings about considerable savings. Reduction in cement quantities can also be achieved by adding ash to the concrete mixes. Ligoplast, a plasticizer addition is used for improving workability. (M.D). 8 figs

  19. [Syk inhibitors].

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

    2013-07-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk.

  20. Syk inhibitors.

    Science.gov (United States)

    Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

    2013-01-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

  1. Research on Judgment Aggregation Based on Logic

    Directory of Open Access Journals (Sweden)

    Li Dai

    2014-05-01

    Full Text Available Preference aggregation and judgment aggregation are two basic research models of group decision making. And preference aggregation has been deeply studied in social choice theory. However, researches of social choice theory gradually focus on judgment aggregation which appears recently. Judgment aggregation focuses on how to aggregate many consistent logical formulas into one, from the perspective of logic. We try to start with judgment aggregation model based on logic and then explore different solutions to problem of judgment aggregation.

  2. Lysosomal enzyme cathepsin B enhances the aggregate forming activity of exogenous α-synuclein fibrils.

    Science.gov (United States)

    Tsujimura, Atsushi; Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tatebe, Harutsugu; Tokuda, Takahiko; Mizuno, Toshiki; Tanaka, Masaki

    2015-01-01

    The formation of intracellular aggregates containing α-synuclein (α-Syn) is one of the key steps in the progression of Parkinson's disease and dementia with Lewy bodies. Recently, it was reported that pathological α-Syn fibrils can undergo cell-to-cell transmission and form Lewy body-like aggregates. However, little is known about how they form α-Syn aggregates from fibril seeds. Here, we developed an assay to study the process of aggregate formation using fluorescent protein-tagged α-Syn-expressing cells and examined the aggregate forming activity of exogenous α-Syn fibrils. α-Syn fibril-induced formation of intracellular aggregates was suppressed by a cathepsin B specific inhibitor, but not by a cathepsin D inhibitor. α-Syn fibrils pretreated with cathepsin B in vitro enhanced seeding activity in cells. Knockdown of cathepsin B also reduced fibril-induced aggregate formation. Moreover, using LAMP-1 immunocytochemistry and live-cell imaging, we observed that these aggregates initially occurred in the lysosome. They then rapidly grew larger and moved outside the boundary of the lysosome within one day. These results suggest that the lysosomal protease cathepsin B is involved in triggering intracellular aggregate formation by α-Syn fibrils. Copyright © 2015. Published by Elsevier Inc.

  3. Proteins aggregation and human diseases

    International Nuclear Information System (INIS)

    Hu, Chin-Kun

    2015-01-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease. (paper)

  4. Information Aggregation and Investment Decisions

    OpenAIRE

    Christian Hellwig; Aleh Tsyvinski; Elias Albagli

    2010-01-01

    This paper studies an environment in which information aggregation interacts with investment decisions. The first contribution of the paper is to develop a tractable model of such interactions. The second contribution is to solve the model in closed form and derive a series of implications that result from the interplay between information aggregation and the value of market information for the firms' decision problem. We show that the model generates an information aggregation wedge between ...

  5. Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

    Science.gov (United States)

    Estrada, L D; Soto, C

    2007-01-01

    Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

  6. [Inhibitory mechanism of ifenprodil tartrate on rabbit platelet aggregation].

    Science.gov (United States)

    Irino, O; Saitoh, K; Hayashi, T; Ohkubo, K

    1985-05-01

    The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.

  7. Topics in Probabilistic Judgment Aggregation

    Science.gov (United States)

    Wang, Guanchun

    2011-01-01

    This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

  8. Collective Rationality in Graph Aggregation

    NARCIS (Netherlands)

    Endriss, U.; Grandi, U.; Schaub, T.; Friedrich, G.; O'Sullivan, B.

    2014-01-01

    Suppose a number of agents each provide us with a directed graph over a common set of vertices. Graph aggregation is the problem of computing a single “collective” graph that best represents the information inherent in this profile of individual graphs. We consider this aggregation problem from the

  9. Orthogonal flexible Rydberg aggregates

    Science.gov (United States)

    Leonhardt, K.; Wüster, S.; Rost, J. M.

    2016-02-01

    We study the link between atomic motion and exciton transport in flexible Rydberg aggregates, assemblies of highly excited light alkali-metal atoms, for which motion due to dipole-dipole interaction becomes relevant. In two one-dimensional atom chains crossing at a right angle adiabatic exciton transport is affected by a conical intersection of excitonic energy surfaces, which induces controllable nonadiabatic effects. A joint exciton-motion pulse that is initially governed by a single energy surface is coherently split into two modes after crossing the intersection. The modes induce strongly different atomic motion, leading to clear signatures of nonadiabatic effects in atomic density profiles. We have shown how this scenario can be exploited as an exciton switch, controlling direction and coherence properties of the joint pulse on the second of the chains [K. Leonhardt et al., Phys. Rev. Lett. 113, 223001 (2014), 10.1103/PhysRevLett.113.223001]. In this article we discuss the underlying complex dynamics in detail, characterize the switch, and derive our isotropic interaction model from a realistic anisotropic one with the addition of a magnetic bias field.

  10. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

    Directory of Open Access Journals (Sweden)

    Laura C. López

    2016-06-01

    Full Text Available Human Amylin, or islet amyloid polypeptide (hIAPP, is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin.

  11. Kinetics of aggregation with choice.

    Science.gov (United States)

    Ben-Naim, E; Krapivsky, P L

    2016-12-01

    We generalize the ordinary aggregation process to allow for choice. In ordinary aggregation, two random clusters merge and form a larger aggregate. In our implementation of choice, a target cluster and two candidate clusters are randomly selected and the target cluster merges with the larger of the two candidate clusters. We study the long-time asymptotic behavior and find that as in ordinary aggregation, the size density adheres to the standard scaling form. However, aggregation with choice exhibits a number of different features. First, the density of the smallest clusters exhibits anomalous scaling. Second, both the small-size and the large-size tails of the density are overpopulated, at the expense of the density of moderate-size clusters. We also study the complementary case where the smaller candidate cluster participates in the aggregation process and find an abundance of moderate clusters at the expense of small and large clusters. Additionally, we investigate aggregation processes with choice among multiple candidate clusters and a symmetric implementation where the choice is between two pairs of clusters.

  12. Nickel aggregates produced by radiolysis

    International Nuclear Information System (INIS)

    Marignier, J.L.; Belloni, J.

    1988-01-01

    Nickel aggregates with subcolloidal size and stable in water have been synthesized by inhibiting the corrosion by the medium. The protective effect of the surfactant is discussed in relation with the characteristics of various types of polyvinyl alcohol studied. The reactivity of aggregates towards oxidizing compounds, nitro blue tetrazolium, methylene blue, silver ions, oxygen, methylviologen, enables an estimation of the redox potential of nickel aggregates (E = - 04 ± 0.05 V). It has been applied to quantitative analysis of the particles in presence of nickel ions. 55 refs [fr

  13. Aggregating and Disaggregating Flexibility Objects

    DEFF Research Database (Denmark)

    Siksnys, Laurynas; Valsomatzis, Emmanouil; Hose, Katja

    2015-01-01

    In many scientific and commercial domains we encounter flexibility objects, i.e., objects with explicit flexibilities in a time and an amount dimension (e.g., energy or product amount). Applications of flexibility objects require novel and efficient techniques capable of handling large amounts...... and aiming at energy balancing during aggregation. In more detail, this paper considers the complete life cycle of flex-objects: aggregation, disaggregation, associated requirements, efficient incremental computation, and balance aggregation techniques. Extensive experiments based on real-world data from...

  14. Electrochemical sensors and biosensors based on less aggregated graphene.

    Science.gov (United States)

    Bo, Xiangjie; Zhou, Ming; Guo, Liping

    2017-03-15

    As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Hybrid reactors

    International Nuclear Information System (INIS)

    Moir, R.W.

    1980-01-01

    The rationale for hybrid fusion-fission reactors is the production of fissile fuel for fission reactors. A new class of reactor, the fission-suppressed hybrid promises unusually good safety features as well as the ability to support 25 light-water reactors of the same nuclear power rating, or even more high-conversion-ratio reactors such as the heavy-water type. One 4000-MW nuclear hybrid can produce 7200 kg of 233 U per year. To obtain good economics, injector efficiency times plasma gain (eta/sub i/Q) should be greater than 2, the wall load should be greater than 1 MW.m -2 , and the hybrid should cost less than 6 times the cost of a light-water reactor. Introduction rates for the fission-suppressed hybrid are usually rapid

  16. Aggregated Computational Toxicology Resource (ACTOR)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Aggregated Computational Toxicology Resource (ACTOR) is a database on environmental chemicals that is searchable by chemical name and other identifiers, and by...

  17. Laser characterization of fine aggregate.

    Science.gov (United States)

    2012-12-01

    This report describes the results of a research effort to establish the feasibility of using a laser monitoring system to provide real-time data to characterize aggregate properties in a laboratory or field environment. This was accomplished by using...

  18. Aggregate Supply and Potential Output

    OpenAIRE

    Razin, Assaf

    2004-01-01

    The New-Keynesian aggregate supply derives from micro-foundations an inflation-dynamics model very much like the tradition in the monetary literature. Inflation is primarily affected by: (i) economic slack; (ii) expectations; (iii) supply shocks; and (iv) inflation persistence. This paper extends the New Keynesian aggregate supply relationship to include also fluctuations in potential output, as an additional determinant of the relationship. Implications for monetary rules and to the estimati...

  19. Glycation precedes lens crystallin aggregation

    International Nuclear Information System (INIS)

    Swamy, M.S.; Perry, R.E.; Abraham, E.C.

    1987-01-01

    Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both [ 3 H]NaBH 4 reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated

  20. Model for amorphous aggregation processes

    Science.gov (United States)

    Stranks, Samuel D.; Ecroyd, Heath; van Sluyter, Steven; Waters, Elizabeth J.; Carver, John A.; von Smekal, Lorenz

    2009-11-01

    The amorphous aggregation of proteins is associated with many phenomena, ranging from the formation of protein wine haze to the development of cataract in the eye lens and the precipitation of recombinant proteins during their expression and purification. While much literature exists describing models for linear protein aggregation, such as amyloid fibril formation, there are few reports of models which address amorphous aggregation. Here, we propose a model to describe the amorphous aggregation of proteins which is also more widely applicable to other situations where a similar process occurs, such as in the formation of colloids and nanoclusters. As first applications of the model, we have tested it against experimental turbidimetry data of three proteins relevant to the wine industry and biochemistry, namely, thaumatin, a thaumatinlike protein, and α -lactalbumin. The model is very robust and describes amorphous experimental data to a high degree of accuracy. Details about the aggregation process, such as shape parameters of the aggregates and rate constants, can also be extracted.

  1. Identification of fermentation inhibitors in wood hydrolyzates and removal of inhibitors by ion exchange and liquid-liquid extraction

    Science.gov (United States)

    Luo, Caidian

    1998-12-01

    Common methods employed in the ethanol production from biomass consist of chemical or enzymatic degradation of biomass into sugars and then fermentation of sugars into ethanol or other chemicals. However, some degradation products severely inhibit the fermentation processes and substantially reduce the efficiency of ethanol production. How to remove inhibitors from the reaction product mixture and increase the production efficiency are critical in the commercialization of any processes of energy from biomass. The present study has investigated anion exchange and liquid-liquid extraction as potential methods for inhibitor removal. An analytical method has been developed to identify the fermentation inhibitors in a hydrolyzate. The majority of inhibitors present in hybrid poplar hydrolyzate have positively been identified. Ion exchange with weak basic Dowex-MWA-1 resin has been proved to be an effective mean to remove fermentation inhibitors from hybrid poplar hydrolyzate and significantly increase the fermentation productivity. Extraction with n-butanol might be a preferred way to remove inhibitors from wood hydrolyzates and improve the fermentability of sugars in the hydrolyzates. n-Butanol also removes some glucose, mannose and xylose from the hydrolyzate. Inhibitor identification reveals that lignin and sugar degradation compounds including both aromatic and aliphatic aldehydes and carboxylic acids formed in hydrolysis, plus fatty acids and other components from wood extractives are major fermentation inhibitors in Sacchromyces cerevisiae fermentation. There are 35 components identified as fermentation inhibitors. Among them, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, syringic acid, syringaldehyde, and ferulic acid are among the most abundant aromatic inhibitors in hybrid poplar hydrolyzate. The conversion of aldehyde groups into carboxylic acid groups in the nitric acid catalyzed hydrolysis reduces the toxicity of the hydrolyzate. A wide spectrum of

  2. Aggregate size and architecture determine biomass activity for one-stage partial nitritation and anammox

    DEFF Research Database (Denmark)

    Vlaeminck, S.; Terada, Akihiko; Smets, Barth F.

    2010-01-01

    to the inoculation and operation of the reactors. Fluorescent in-situ hybridization (FISH) was applied on aggregate sections to quantify AerAOB and AnAOB, as well as to visualize the aggregate architecture. The activity balance of the aggregates was calculated as the nitrite accumulation rate ratio (NARR), i...... and nitrite sources (NARR, > 1.7). Large A and C aggregates were granules capable of autonomous nitrogen removal (NARR, 0.6 to 1.1) with internal AnAOB zones surrounded by an AerAOB rim. Around 50% of the autotrophic space in these granules consisted of AerAOB- and AnAOB-specific EPS. Large B aggregates were...... thin film-like nitrite sinks (NARR,

  3. Effect of physicochemical action on the aggregative properties of detonation-synthesized nanodiamonds

    Science.gov (United States)

    Fan, Z. W.; Ilnitska, H.; Lysakovskyi, V.; Ivakhnenko, S.; Kovalenko, T.

    2018-01-01

    The results of researches of physicochemical action on aggregate properties of nanodiamond are presented. The kinetics of aggregation of nanodiamond powder was studied as a function of time, temperature, and pH of the solution. The effect of the sp2-sp3 hybridization ratio of carbon in nanodiamond powders on their aggregation was studied. It is shown that the presence of non-diamond carbon in detonation synthesis nanodiamond powders leads to the increase of the mean diameters of particles, i.e., their agglomeration. The theoretical justification of the aggregation mechanism is proposed. It is shown that it is possible to control aggregative properties of nanodiamond powders by physicochemical influences, e.g., gas-phase thermal treatment to reduce the size of agglomerates and to create a well-developed reconstructed surface of diamond particles with a low content of functional groups on their surface.

  4. Hybrid composites

    CSIR Research Space (South Africa)

    Jacob John, Maya

    2009-04-01

    Full Text Available mixed short sisal/glass hybrid fibre reinforced low density polyethylene composites was investigated by Kalaprasad et al [25].Chemical surface modifications such as alkali, acetic anhydride, stearic acid, permanganate, maleic anhydride, silane...

  5. Hybrid intermediaries

    OpenAIRE

    Cetorelli, Nicola

    2014-01-01

    I introduce the concept of hybrid intermediaries: financial conglomerates that control a multiplicity of entity types active in the "assembly line" process of modern financial intermediation, a system that has become known as shadow banking. The complex bank holding companies of today are the best example of hybrid intermediaries, but I argue that financial firms from the "nonbank" space can just as easily evolve into conglomerates with similar organizational structure, thus acquiring the cap...

  6. Aggregated recommendation through random forests.

    Science.gov (United States)

    Zhang, Heng-Ru; Min, Fan; He, Xu

    2014-01-01

    Aggregated recommendation refers to the process of suggesting one kind of items to a group of users. Compared to user-oriented or item-oriented approaches, it is more general and, therefore, more appropriate for cold-start recommendation. In this paper, we propose a random forest approach to create aggregated recommender systems. The approach is used to predict the rating of a group of users to a kind of items. In the preprocessing stage, we merge user, item, and rating information to construct an aggregated decision table, where rating information serves as the decision attribute. We also model the data conversion process corresponding to the new user, new item, and both new problems. In the training stage, a forest is built for the aggregated training set, where each leaf is assigned a distribution of discrete rating. In the testing stage, we present four predicting approaches to compute evaluation values based on the distribution of each tree. Experiments results on the well-known MovieLens dataset show that the aggregated approach maintains an acceptable level of accuracy.

  7. Fractal Aggregates in Tennis Ball Systems

    Science.gov (United States)

    Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

    2009-01-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

  8. A Functional Reference Architecture for Aggregators

    DEFF Research Database (Denmark)

    Bondy, Daniel Esteban Morales; Heussen, Kai; Gehrke, Oliver

    2015-01-01

    Aggregators are considered to be a key enabling technology for harvesting power system services from distributed energy resources (DER). As a precondition for more widespread use of aggregators in power systems, methods for comparing and validating aggregator designs must be established. This paper...... proposes a functional reference architecture for aggregators to address this requirement....

  9. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon; Røpke, Stefan

    Aggregating formulations is a powerful approach for problems to take on tractable forms. Aggregation may lead to loss of information, i.e. the aggregated formulation may be an approximation of the original problem. In branch-and-bound context, aggregation can also complicate branching, e.g. when...... optimality cannot be guaranteed by branching on aggregated variables. We present a generic exact solution method to remedy the drawbacks of aggregation. It combines the original and aggregated formulations and applies Benders' decomposition. We apply the method to the Split Delivery Vehicle Routing Problem....

  10. Balancing energy flexibilities through aggregation

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Hose, Katja; Pedersen, Torben Bach

    2014-01-01

    One of the main goals of recent developments in the Smart Grid area is to increase the use of renewable energy sources. These sources are characterized by energy fluctuations that might lead to energy imbalances and congestions in the electricity grid. Exploiting inherent flexibilities, which exist...... in both energy production and consumption, is the key to solving these problems. Flexibilities can be expressed as flex-offers, which due to their high number need to be aggregated to reduce the complexity of energy scheduling. In this paper, we discuss balance aggregation techniques that already during...... aggregation aim at balancing flexibilities in production and consumption to reduce the probability of congestions and reduce the complexity of scheduling. We present results of our extensive experiments....

  11. Turbulent breakage of ductile aggregates.

    Science.gov (United States)

    Marchioli, Cristian; Soldati, Alfredo

    2015-05-01

    In this paper we study breakage rate statistics of small colloidal aggregates in nonhomogeneous anisotropic turbulence. We use pseudospectral direct numerical simulation of turbulent channel flow and Lagrangian tracking to follow the motion of the aggregates, modeled as sub-Kolmogorov massless particles. We focus specifically on the effects produced by ductile rupture: This rupture is initially activated when fluctuating hydrodynamic stresses exceed a critical value, σ>σ(cr), and is brought to completion when the energy absorbed by the aggregate meets the critical breakage value. We show that ductile rupture breakage rates are significantly reduced with respect to the case of instantaneous brittle rupture (i.e., breakage occurs as soon as σ>σ(cr)). These discrepancies are due to the different energy values at play as well as to the statistical features of energy distribution in the anisotropic turbulence case examined.

  12. SHAPE CHARACTERIZATION OF CONCRETE AGGREGATE

    Directory of Open Access Journals (Sweden)

    Jing Hu

    2011-05-01

    Full Text Available As a composite material, the performance of concrete materials can be expected to depend on the properties of the interfaces between its two major components, aggregate and cement paste. The microstructure at the interfacial transition zone (ITZ is assumed to be different from the bulk material. In general, properties of conventional concrete have been found favoured by optimum packing density of the aggregate. Particle size is a common denominator in such studies. Size segregation in the ITZ among the binder particles in the fresh state, observed in simulation studies by concurrent algorithm-based SPACE system, additionally governs density as well as physical bonding capacity inside these shell-like zones around aggregate particles. These characteristics have been demonstrated qualitatively pertaining also after maturation of the concrete. Such properties of the ITZs have direct impact on composite properties. Despite experimental approaches revealed effects of aggregate grain shape on different features of material structure (among which density, and as a consequence on mechanical properties, it is still an underrated factor in laboratory studies, probably due to the general feeling that a suitable methodology for shape characterization is not available. A scientific argument hindering progress is the interconnected nature of size and shape. Presently, a practical problem preventing shape effects to be emphasized is the limitation of most computer simulation systems in concrete technology to spherical particles. New developments at Delft University of Technology will make it possible in the near future to generate jammed states, or other high-density fresh particle mixtures of non-spherical particles, which thereupon can be subjected to hydration algorithms. This paper will sketch the outlines of a methodological approach for shape assessment of loose (non-embedded aggregate grains, and demonstrate its use for two types of aggregate, allowing

  13. Customer Aggregation: An Opportunity for Green Power?

    Energy Technology Data Exchange (ETDEWEB)

    Holt, E.; Bird, L.

    2001-02-26

    We undertook research into the experience of aggregation groups to determine whether customer aggregation offers an opportunity to bring green power choices to more customers. The objectives of this report, therefore, are to (1) identify the different types of aggregation that are occurring today, (2) learn whether aggregation offers an opportunity to advance sales of green power, and (3) share these concepts and approaches with potential aggregators and green power advocates.

  14. Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Nielsen, Christian; Söderström, Anna Cecilia

    2017-01-01

    Dabigatran is an oral anticoagulant and a reversible inhibitor of thrombin. Further, dabigatran might affect platelet function through a direct effect on platelet thrombin receptors. The aim was to investigate the effect of dabigatran on platelet activation and platelet aggregation. Healthy donor...

  15. Environmentalism and natural aggregate mining

    Science.gov (United States)

    Drew, L.J.; Langer, W.H.; Sachs, J.S.

    2002-01-01

    Sustaining a developed economy and expanding a developing one require the use of large volumes of natural aggregate. Almost all human activity (commercial, recreational, or leisure) is transacted in or on facilities constructed from natural aggregate. In our urban and suburban worlds, we are almost totally dependent on supplies of water collected behind dams and transported through aqueducts made from concrete. Natural aggregate is essential to the facilities that produce energy-hydroelectric dams and coal-fired powerplants. Ironically, the utility created for mankind by the use of natural aggregate is rarely compared favorably with the environmental impacts of mining it. Instead, the empty quarries and pits are seen as large negative environmental consequences. At the root of this disassociation is the philosophy of environmentalism, which flavors our perceptions of the excavation, processing, and distribution of natural aggregate. The two end-member ideas in this philosophy are ecocentrism and anthropocentrism. Ecocentrism takes the position that the natural world is a organism whose arteries are the rivers-their flow must not be altered. The soil is another vital organ and must not be covered with concrete and asphalt. The motto of the ecocentrist is "man must live more lightly on the land." The anthropocentrist wants clean water and air and an uncluttered landscape for human use. Mining is allowed and even encouraged, but dust and noise from quarry and pit operations must be minimized. The large volume of truck traffic is viewed as a real menace to human life and should be regulated and isolated. The environmental problems that the producers of natural aggregate (crushed stone and sand and gravel) face today are mostly difficult social and political concerns associated with the large holes dug in the ground and the large volume of heavy truck traffic associated with quarry and pit operations. These concerns have increased in recent years as society's demand for

  16. Irreversible colloidal agglomeration in presence of associative inhibitors: Computer simulation study

    International Nuclear Information System (INIS)

    Barcenas, Mariana; Duda, Yurko

    2007-01-01

    Monte Carlo simulation is employed to study the irreversible particle-cluster agglomeration of valence-limited colloids affected by associative inhibitors. The cluster size distribution and number of connections between colloids are analyzed as a function of density and inhibitor concentration. The influence of colloid functionality on its aggregation is discussed

  17. NABi, a novel β-sheet breaker, inhibits Aβ aggregation and neuronal toxicity: Therapeutic implications for Alzheimer's disease.

    Science.gov (United States)

    Jang, Ja-Young; Rhim, Hyangshuk; Kang, Seongman

    2018-01-01

    Amyloid beta (Aβ) aggregates are an important therapeutic target for Alzheimer's disease (AD), a fatal neurodegenerative disease. To date, AD still remains a big challenge due to no effective treatments. Based on the property that Aβ aggregates have the cross-β-structure, a common structural feature in amyloids, we systemically designed the Aβ-aggregation inhibitor that maintains Aβ-interacting ability but removes toxic part from SOD1 (superoxide dismutase 1)-G93A. We identified NABi (Natural Aβ Binder and Aβ-aggregation inhibitor) composed of β2-3 strands, a novel breaker of Aβ aggregation, which does not self-aggregate and has no cytotoxicity at all. The NABi blocks Aβ-fibril formation in vitro and in vivo and prevents neuronal cell death, a hallmark of AD pathogenesis. Such anti-amyloidogenic properties can provide novel strategies for treating AD. Furthermore, our study provides molecular insights into the design of amyloidogenic inhibitors to cure various neurodegenerative and amyloid-associated diseases, as NABi would regulate aggregation of other toxic β-sheet proteins other than Aβ. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Acetylcholinesterase triggers the aggregation of PrP 106-126

    International Nuclear Information System (INIS)

    Pera, M.; Roman, S.; Ratia, M.; Camps, P.; Munoz-Torrero, D.; Colombo, L.; Manzoni, C.; Salmona, M.; Badia, A.; Clos, M.V.

    2006-01-01

    Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-β-protein (Aβ) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Aβ aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs

  19. Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form.

    Science.gov (United States)

    Kato, Eisuke; Kawakami, Kazuhiro; Kawabata, Jun

    2018-12-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range. Evaluation of macrocarpal C solution by turbidity, nuclear magnetic resonance spectroscopy and mass spectrometry indicated its aggregation, which may explain the characteristics of the inhibition curve. These findings will be valuable for further study of potential small molecule DPP-4 inhibitors.

  20. Shape characterization of concrete aggregate

    NARCIS (Netherlands)

    Stroeven, P.; Hu, J.

    2006-01-01

    As a composite material, the performance of concrete materials can be expected to depend on the properties of the interfaces between its two major components, aggregate and cement paste. The microstructure at the interfacial transition zone (ITZ) is assumed to be different from the bulk material. In

  1. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.; Kempf, K.G.; Keskinocak, P.; Uzsoy, R.

    2011-01-01

    In this chapter we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  2. The Aggregate Dutch Historical Censuses

    NARCIS (Netherlands)

    Ashkpour, Ashkan; Meroño-Peñuela, Albert; Mandemakers, Kees

    2015-01-01

    Historical censuses have an enormous potential for research. In order to fully use this potential, harmonization of these censuses is essential. During the last decades, enormous efforts have been undertaken in digitizing the published aggregated outcomes of the Dutch historical censuses

  3. The Aggregate Dutch Historical Censuses

    NARCIS (Netherlands)

    A. Ashkpour (Ashkan); A. Meronõ-Peñuela (Albert); C.A. Mandemakers (Kees)

    2015-01-01

    textabstractHistorical censuses have an enormous potential for research. In order to fully use this potential, harmonization of these censuses is essential. During the last decades, enormous efforts have been undertaken in digitizing the published aggregated outcomes of the Dutch historical censuses

  4. Aggregate modeling of manufacturing systems

    NARCIS (Netherlands)

    Lefeber, A.A.J.; Armbruster, H.D.

    2007-01-01

    In this report we will present three approaches to model manufacturing systems in an aggregate way leading to fast and effective (i.e., scalable) simulations that allow the development of simulation tools for rapid exploration of different production scenarios in a factory as well as in a whole

  5. Diversity, intent, and aggregated search

    NARCIS (Netherlands)

    de Rijke, M.

    2014-01-01

    Diversity, intent and aggregated search are three core retrieval concepts that receive significant attention. In search result diversification one typically considers the relevance of a document in light of other retrieved documents. The goal is to identify the probable "aspects" of an ambiguous

  6. Studies on recycled aggregates-based concrete.

    Science.gov (United States)

    Rakshvir, Major; Barai, Sudhirkumar V

    2006-06-01

    Reduced extraction of raw materials, reduced transportation cost, improved profits, reduced environmental impact and fast-depleting reserves of conventional natural aggregates has necessitated the use of recycling, in order to be able to conserve conventional natural aggregate. In this study various physical and mechanical properties of recycled concrete aggregates were examined. Recycled concrete aggregates are different from natural aggregates and concrete made from them has specific properties. The percentages of recycled concrete aggregates were varied and it was observed that properties such as compressive strength showed a decrease of up to 10% as the percentage of recycled concrete aggregates increased. Water absorption of recycled aggregates was found to be greater than natural aggregates, and this needs to be compensated during mix design.

  7. NOSH–aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model

    International Nuclear Information System (INIS)

    Chattopadhyay, Mitali; Kodela, Ravinder; Olson, Kenneth R.; Kashfi, Khosrow

    2012-01-01

    Highlights: ► NOSH–aspirin is the first dual acting NO and H 2 S releasing hybrid. ► Its IC 50 for cell growth inhibition is in the low nano-molar range. ► Structure–activity studies show that the sum of the parts does not equal the whole. ► NOSH–aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H 2 S) can increase mucosal defense mechanisms has led to the development of NO- and H 2 S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH–aspirin, which is an NO- and H 2 S-releasing agent. NOSH–aspirin inhibited HT-29 colon cancer growth with IC 50 s of 45.5 ± 2.5, 19.7 ± 3.3, and 7.7 ± 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH–aspirin inhibited cell proliferation, induced apoptosis, and caused G 0 /G 1 cell cycle block. Reconstitution and structure–activity studies representing a fairly close approximation to the intact molecule showed that NOSH–aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH–aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH–ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH–aspirin has strong anti-cancer potential and merits further evaluation.

  8. Costs and utilization of hemophilia A and B patients with and without inhibitors.

    Science.gov (United States)

    Armstrong, Edward P; Malone, Daniel C; Krishnan, Sangeeta; Wessler, Maj Jacob

    2014-11-01

    To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors.

  9. Whispering gallery mode emission from a composite system of J-aggregates and photonic microcavity

    Energy Technology Data Exchange (ETDEWEB)

    Melnikau, Dzmitry; Savateeva, Diana [Centro de Física de Materiales (MPC, CSIC-UPV/EHU) and Donostia International Physics Center (DIPC), Po Manuel de Lardizabal 5, Donostia, San Sebastian 20018 (Spain); Rusakov, Konstantin I. [Department of Physics, Brest State Technical University, Brest 224017 (Belarus); Rakovich, Yury P., E-mail: Yury.Rakovich@ehu.es [Centro de Física de Materiales (MPC, CSIC-UPV/EHU) and Donostia International Physics Center (DIPC), Po Manuel de Lardizabal 5, Donostia, San Sebastian 20018 (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain)

    2014-01-15

    We report on development and characterization of Whispering Gallery Modes spherical microcavities integrated with organic dye molecules in a J-aggregate state. The microcavities are studied using micro-photoluminescence spectroscopy, and fluorescence lifetime imaging confocal microscopy. Directional emission of light from the microcavity is also experimentally demonstrated and attributed to the photonic jets generated in the microsphere. -- Highlights: • Report on the development and characterization of hybrid system consisting of thin shell of J-aggregates and spherical Whispering Gallery Mode microcavity. • An investigation of spontaneous emission rate in the shell of J-aggregates integrated with a Whispering Gallery Mode cavity. • Demonstration of directional emission from Whispering Gallery Mode cavity with J-aggregates which is highly desirable functionality for both micro- and nano-scale cavities.

  10. Hybrid stars

    Indian Academy of Sciences (India)

    Hybrid stars. AsHOK GOYAL. Department of Physics and Astrophysics, University of Delhi, Delhi 110 007, India. Abstract. Recently there have been important developments in the determination of neutron ... number and the electric charge. ... available to the system to rearrange concentration of charges for a given fraction of.

  11. ROCK and PRK-2 Mediate the Inhibitory Effect of Y-27632 on Polyglutamine Aggregation

    Science.gov (United States)

    Shao, Jieya; Welch, William J.; Diamond, Marc I.

    2009-01-01

    Polyglutamine expansion in huntingtin (Htt) and the androgen receptor (AR) causes untreatable neurodegenerative diseases. Y-27632, a therapeutic lead, reduces Htt and AR aggregation in cultured cells, and Htt-induced neurodegeneration in Drosophila. Y-27632 inhibits both Rho-associated kinases ROCK and PRK-2, making its precise intracellular target uncertain. Over-expression of either kinase increases Htt and AR aggregation. Three ROCK inhibitors (Y-27632, H-1077, HA-1152), and a specific ROCK inhibitory peptide reduce polyglutamine protein aggregation, as does knockdown of ROCK or PRK-2 by RNAi. RNAi also indicates that each kinase is required for the inhibitory effects of Y-27632 to manifest fully. These two actin regulatory kinases are thus involved in polyglutamine aggregation, and their simultaneous inhibition may be an important therapeutic goal. PMID:18423405

  12. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Chattopadhyay, Mitali; Kodela, Ravinder [Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031 (United States); Olson, Kenneth R. [Department of Physiology, Indiana University School of Medicine, South Bend, IN 46617 (United States); Kashfi, Khosrow, E-mail: kashfi@med.cuny.edu [Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031 (United States)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer NOSH-aspirin is the first dual acting NO and H{sub 2}S releasing hybrid. Black-Right-Pointing-Pointer Its IC{sub 50} for cell growth inhibition is in the low nano-molar range. Black-Right-Pointing-Pointer Structure-activity studies show that the sum of the parts does not equal the whole. Black-Right-Pointing-Pointer NOSH-aspirin reduced tumor growth by 85% in mice bearing a colon cancer xenograft. -- Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H{sub 2}S) can increase mucosal defense mechanisms has led to the development of NO- and H{sub 2}S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H{sub 2}S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC{sub 50}s of 45.5 {+-} 2.5, 19.7 {+-} 3.3, and 7.7 {+-} 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G{sub 0}/G{sub 1} cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation.

  13. Catanionic aggregates stability and structure

    International Nuclear Information System (INIS)

    Vautrin, Claire

    2004-01-01

    The catanionic system cetyl-trimethyl-ammonium hydroxide - myristic acid - water studied here has the advantage to produce aggregates with controlled charge. So, the ternary phase diagram presents some interesting aggregates (micelle, vesicle, disc, lamellar phase). The study of the CMC put in evidence some strong interactions between monomers: the interaction parameter is equal to -10 kT. On a microscopic point of view, the alkyl chains packing is hexagonal and we proved by WAXS and WANS that the head groups are liquid ordered. Moreover, the hydrogen bonds participate to the bilayer cohesion. The mechanical properties of the catanionic membrane are similar to the properties of phospholipids. We estimated the Young modulus to 100 MPa by compressibility measurements (acoustic propagation and Langmuir trough). The thermodynamic properties studied by DSC showed that the chain melting transition depends on the sample composition. (author) [fr

  14. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model.

    Science.gov (United States)

    Chattopadhyay, Mitali; Kodela, Ravinder; Olson, Kenneth R; Kashfi, Khosrow

    2012-03-16

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical anti-cancer agents. However, their long-term use is associated with adverse gastrointestinal effects. Recognition that endogenous gaseous mediators, nitric oxide (NO) and hydrogen sulfide (H(2)S) can increase mucosal defense mechanisms has led to the development of NO- and H(2)S-releasing NSAIDs with increased safety profiles. Here we report on a new hybrid, NOSH-aspirin, which is an NO- and H(2)S-releasing agent. NOSH-aspirin inhibited HT-29 colon cancer growth with IC(50)s of 45.5 ± 2.5, 19.7 ± 3.3, and 7.7 ± 2.2 nM at 24, 48, and 72 h, respectively. This is the first NSAID based agent with such high degree of potency. NOSH-aspirin inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-aspirin was 9000-fold more potent than the sum of its parts towards growth inhibition. NOSH-aspirin inhibited ovine COX-1 more than ovine COX-2. NOSH-ASA treatment of mice bearing a human colon cancer xenograft caused a reduction in volume of 85%. Taken together, these results demonstrate that NOSH-aspirin has strong anti-cancer potential and merits further evaluation. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Utilization of unbound aggregates for road construction

    OpenAIRE

    Fladvad, Marit

    2017-01-01

    Crushed rock aggregate is a non-renewable resource of great interest in road construction and other branches of the construction industry. To prevent resource scarcity, utilization of aggregates should be considered carefully. © 2016 Norsk Bergforening

  16. Recycled concrete aggregate in portland cement concrete.

    Science.gov (United States)

    2013-01-01

    Aggregates can be produced by crushing hydraulic cement concrete and are known as recycled concrete : aggregates (RCA). This report provides results from a New Jersey Department of Transportation study to identify : barriers to the use of RCA in new ...

  17. Aggregate Uncertainty, Money and Banking

    OpenAIRE

    Hongfei Sun

    2006-01-01

    This paper studies the problem of monitoring the monitor in a model of money and banking with aggregate uncertainty. It shows that when inside money is required as a means of bank loan repayment, a market of inside money is entailed at the repayment stage and generates information-revealing prices that perfectly discipline the bank. The incentive problem of a bank is costlessly overcome simply by involving inside money in repayment. Inside money distinguishes itself from outside money by its ...

  18. Intuitionistic fuzzy aggregation and clustering

    CERN Document Server

    Xu, Zeshui

    2012-01-01

    This book offers a systematic introduction to the clustering algorithms for intuitionistic fuzzy values, the latest research results in intuitionistic fuzzy aggregation techniques, the extended results in interval-valued intuitionistic fuzzy environments, and their applications in multi-attribute decision making, such as supply chain management, military system performance evaluation, project management, venture capital, information system selection, building materials classification, and operational plan assessment, etc.

  19. Aspirin-Mediated Acetylation Protects Against Multiple Neurodegenerative Pathologies by Impeding Protein Aggregation.

    Science.gov (United States)

    Ayyadevara, Srinivas; Balasubramaniam, Meenakshisundaram; Kakraba, Samuel; Alla, Ramani; Mehta, Jawahar L; Shmookler Reis, Robert J

    2017-12-10

    Many progressive neurological disorders, including Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease (PD), are characterized by accumulation of insoluble protein aggregates. In prospective trials, the cyclooxygenase inhibitor aspirin (acetylsalicylic acid) reduced the risk of AD and PD, as well as cardiovascular events and many late-onset cancers. Considering the role played by protein hyperphosphorylation in aggregation and neurodegenerative diseases, and aspirin's known ability to donate acetyl groups, we asked whether aspirin might reduce both phosphorylation and aggregation by acetylating protein targets. Aspirin was substantially more effective than salicylate in reducing or delaying aggregation in human neuroblastoma cells grown in vitro, and in Caenorhabditis elegans models of human neurodegenerative diseases in vivo. Aspirin acetylates many proteins, while reducing phosphorylation, suggesting that acetylation may oppose phosphorylation. Surprisingly, acetylated proteins were largely excluded from compact aggregates. Molecular-dynamic simulations indicate that acetylation of amyloid peptide energetically disfavors its association into dimers and octamers, and oligomers that do form are less compact and stable than those comprising unacetylated peptides. Hyperphosphorylation predisposes certain proteins to aggregate (e.g., tau, α-synuclein, and transactive response DNA-binding protein 43 [TDP-43]), and it is a critical pathogenic marker in both cardiovascular and neurodegenerative diseases. We present novel evidence that acetylated proteins are underrepresented in protein aggregates, and that aggregation varies inversely with acetylation propensity after diverse genetic and pharmacologic interventions. These results are consistent with the hypothesis that aspirin inhibits protein aggregation and the ensuing toxicity of aggregates through its acetyl-donating activity. This mechanism may contribute to the neuro-protective, cardio

  20. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition.

    Science.gov (United States)

    Moll, Lorna; Ben-Gedalya, Tziona; Reuveni, Hadas; Cohen, Ehud

    2016-04-01

    The discovery that the alteration of aging by reducing the activity of the insulin/IGF-1 signaling (IIS) cascade protects nematodes and mice from neurodegeneration-linked, toxic protein aggregation (proteotoxicity) raises the prospect that IIS inhibitors bear therapeutic potential to counter neurodegenerative diseases. Recently, we reported that NT219, a highly efficient IGF-1 signaling inhibitor, protects model worms from the aggregation of amyloid β peptide and polyglutamine peptides that are linked to the manifestation of Alzheimer's and Huntington's diseases, respectively. Here, we employed cultured cell systems to investigate whether NT219 promotes protein homeostasis (proteostasis) in mammalian cells and to explore its underlying mechanisms. We found that NT219 enhances the aggregation of misfolded prion protein and promotes its deposition in quality control compartments known as "aggresomes." NT219 also elevates the levels of certain molecular chaperones but, surprisingly, reduces proteasome activity and impairs autophagy. Our findings show that IGF-1 signaling inhibitors in general and NT219 in particular can promote proteostasis in mammalian cells by hyperaggregating hazardous proteins, thereby bearing the potential to postpone the onset and slow the progression of neurodegenerative illnesses in the elderly.-Moll, L., Ben-Gedalya, T., Reuveni, H., Cohen, E. The inhibition of IGF-1 signaling promotes proteostasis by enhancing protein aggregation and deposition. © FASEB.

  1. Defining and systematic analyses of aggregation indices to evaluate degree of calcium oxalate crystal aggregation

    Science.gov (United States)

    Chaiyarit, Sakdithep; Thongboonkerd, Visith

    2017-12-01

    Crystal aggregation is one of the most crucial steps in kidney stone pathogenesis. However, previous studies of crystal aggregation were rarely done and quantitative analysis of aggregation degree was handicapped by a lack of the standard measurement. We thus performed an in vitro assay to generate aggregation of calcium oxalate monohydrate (COM) crystals with various concentrations (25-800 µg/ml) in saturated aggregation buffer. The crystal aggregates were analyzed by microscopic examination, UV-visible spectrophotometry, and GraphPad Prism6 software to define a total of 12 aggregation indices (including number of aggregates, aggregated mass index, optical density, aggregation coefficient, span, number of aggregates at plateau time-point, aggregated area index, aggregated diameter index, aggregated symmetry index, time constant, half-life, and rate constant). The data showed linear correlation between crystal concentration and almost all of these indices, except only for rate constant. Among these, number of aggregates provided the greatest regression coefficient (r=0.997; pr=0.993; pr=‑0.993; pr=0.991; p<0.001 for both). These five indices are thus recommended as the most appropriate indices for quantitative analysis of COM crystal aggregation in vitro.

  2. α-Synuclein aggregation, seeding and inhibition by scyllo-inositol

    Energy Technology Data Exchange (ETDEWEB)

    Ibrahim, Tarek [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada); McLaurin, JoAnne, E-mail: jmclaurin@sri.utoronto.ca [Biological Sciences, Sunnybrook Research Institute (Canada); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M4N 3M5, ON (Canada)

    2016-01-15

    Recent literature demonstrates the accelerated aggregation of α-synuclein, a protein implicated in the pathogenesis of Parkinson's disease (PD), by the presence of preformed fibrillar conformers in vitro. Furthermore, these preformed fibrillar seeds are suggested to accelerate pathological induction in vivo when injected into the brains of mice. Variation in the results of in vivo studies is proposed to be caused by α-synuclein conformational variants. To investigate the impact of amino acid sequence on seeding efficiency, human and mouse α-synuclein seeds, which vary at 7 amino acid residues, were generated and cross-seeding kinetics studied. Using transmission electron microscopy (TEM), we confirmed that mouse α-synuclein aggregated more rapidly than human α-synuclein. Subsequently, we determined that seeding of human and mouse α-synuclein was more rapid in the presence of seeds generated from the same species. In addition, an established amyloid inhibitor, scyllo-inositol, was examined for potential inhibitory effects on α-synuclein aggregation. TEM analysis of protein:inhibitor assays demonstrated that scyllo-inositol inhibits the aggregation of α-synuclein, suggesting the therapeutic potential of the small molecule in PD. - Highlights: • Mouse α-syn fibrillizes in a significantly shorter timeframe than human α-syn. • Seeding of monomers is more efficient when seeds originate from the same species. • scyllo-Inositol has anti-aggregation effects on mouse and human α-syn.

  3. Heating of Porous Icy Dust Aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Sirono, Sin-iti [Earth and Environmental Sciences, Nagoya University, Tikusa-ku, Furo-cho, Nagoya 464-8601 (Japan)

    2017-06-10

    At the beginning of planetary formation, highly porous dust aggregates are formed through coagulation of dust grains. Outside the snowline, the main component of an aggregate is H{sub 2}O ice. Because H{sub 2}O ice is formed in amorphous form, its thermal conductivity is extremely small. Therefore, the thermal conductivity of an icy dust aggregate is low. There is a possibility of heating inside an aggregate owing to the decay of radionuclides. It is shown that the temperature increases substantially inside an aggregate, leading to crystallization of amorphous ice. During the crystallization, the temperature further increases sufficiently to continue sintering. The mechanical properties of icy dust aggregates change, and the collisional evolution of dust aggregates is affected by the sintering.

  4. What favors convective aggregation and why?

    Science.gov (United States)

    Muller, Caroline; Bony, Sandrine

    2015-07-01

    The organization of convection is ubiquitous, but its physical understanding remains limited. One particular type of organization is the spatial self-aggregation of convection, taking the form of cloud clusters, or tropical cyclones in the presence of rotation. We show that several physical processes can give rise to self-aggregation and highlight the key features responsible for it, using idealized simulations. Longwave radiative feedbacks yield a "radiative aggregation." In that case, sufficient spatial variability of radiative cooling rates yields a low-level circulation, which induces the upgradient energy transport and radiative-convective instability. Not only do vertically integrated radiative budgets matter but the vertical profile of cooling is also crucial. Convective aggregation is facilitated when downdrafts below clouds are weak ("moisture-memory aggregation"), and this is sufficient to trigger aggregation in the absence of longwave radiative feedbacks. These results shed some light on the sensitivity of self-aggregation to various parameters, including resolution or domain size.

  5. A Method Based on Intuitionistic Fuzzy Dependent Aggregation Operators for Supplier Selection

    Directory of Open Access Journals (Sweden)

    Fen Wang

    2013-01-01

    Full Text Available Recently, resolving the decision making problem of evaluation and ranking the potential suppliers have become as a key strategic factor for business firms. In this paper, two new intuitionistic fuzzy aggregation operators are developed: dependent intuitionistic fuzzy ordered weighed averaging (DIFOWA operator and dependent intuitionistic fuzzy hybrid weighed aggregation (DIFHWA operator. Some of their main properties are studied. A method based on the DIFHWA operator for intuitionistic fuzzy multiple attribute decision making is presented. Finally, an illustrative example concerning supplier selection is given.

  6. Fabrication of fluorescent silica nanoparticles with aggregation-induced emission luminogens for cell imaging.

    Science.gov (United States)

    Chen, Sijie; Lam, Jacky W Y; Tang, Ben Zhong

    2013-01-01

    Fluorescence-based techniques have found wide applications in life science. Among various luminogenic materials, fluorescent nanoparticles have attracted much attention due to their fabulous emission properties and potential applications as sensors. Here, we describe the fabrication of fluorescent silica nanoparticles (FSNPs) containing aggregation-induced emission (AIE) luminogens. By employing surfactant-free sol-gel reaction, FSNPs with uniform size and high surface charge and colloidal stability are generated. The FSNPs emit strong light upon photoexcitation, due to the AIE characteristic of the silole -aggregates in the hybrid nanoparticles. The FSNPs are cytocompatible and can be utilized as fluorescent visualizer for intracellular imaging for HeLa cells.

  7. Effects of Polymer Hydrophobicity on Protein Structure and Aggregation Kinetics in Crowded Milieu.

    Science.gov (United States)

    Breydo, Leonid; Sales, Amanda E; Frege, Telma; Howell, Mark C; Zaslavsky, Boris Y; Uversky, Vladimir N

    2015-05-19

    We examined the effects of water-soluble polymers of various degrees of hydrophobicity on the folding and aggregation of proteins. The polymers we chose were polyethylene glycol (PEG) and UCON (1:1 copolymer of ethylene glycol and propylene glycol). The presence of additional methyl groups in UCON makes it more hydrophobic than PEG. Our earlier analysis revealed that similarly sized PEG and UCON produced different changes in the solvent properties of water in their solutions and induced morphologically different α-synuclein aggregates [Ferreira, L. A., et al. (2015) Role of solvent properties of aqueous media in macromolecular crowding effects. J. Biomol. Struct. Dyn., in press]. To improve our understanding of molecular mechanisms defining behavior of proteins in a crowded environment, we tested the effects of these polymers on secondary and tertiary structure and aromatic residue solvent accessibility of 10 proteins [five folded proteins, two hybrid proteins; i.e., protein containing ordered and disordered domains, and three intrinsically disordered proteins (IDPs)] and on the aggregation kinetics of insulin and α-synuclein. We found that effects of both polymers on secondary and tertiary structures of folded and hybrid proteins were rather limited with slight unfolding observed in some cases. Solvent accessibility of aromatic residues was significantly increased for the majority of the studied proteins in the presence of UCON but not PEG. PEG also accelerated the aggregation of protein into amyloid fibrils, whereas UCON promoted aggregation to amyloid oligomers instead. These results indicate that even a relatively small change in polymer structure leads to a significant change in the effect of this polymer on protein folding and aggregation. This is an indication that protein folding and especially aggregation are highly sensitive to the presence of other macromolecules, and an excluded volume effect is insufficient to describe their effect.

  8. Asphaltene Aggregation and Fouling Behavior

    Science.gov (United States)

    Derakhshesh, Marzie

    This thesis explored the properties of asphaltene nano-aggregates in crude oil and toluene based solutions and fouling at process furnace temperatures, and the links between these two phenomena. The link between stability of asphaltenes at ambient conditions and fouling at the conditions of a delayed coker furnace, at over 450 °C, was examined by blending crude oil with an aliphatic diluent in different ratios. The stability of the blends were measured using a S-value analyzer, then fouling rates were measured on electrically heated stainless steel 316 wires in an autoclave reactor. The less stable the blend, the greater the rate and extent of fouling. The most severe fouling occurred with the unstable asphaltenes. SEM imaging of the foulant illustrates very different textures, with the structure becoming more porous with lower stability. Under cross-polarized light, the coke shows the presence of mesophase in the foulant layer. These data suggest a correlation between the fouling rate at high temperature furnace conditions and the stability index of the crude oil. Three organic polysulfides were introduced to the crude oil to examine their effect on fouling. The polysulfides are able to reduce coking and carbon monoxide generation in steam crackers. The fouling results demonstrated that polysulfide with more sulfur content increased the amount of corrosion-fouling of the wire. Various additives, solvents, ultrasound, and heat were employed to attempt to completely disaggregate the asphaltene nano-aggregates in solution at room temperature. The primary analytical technique used to monitor the nano-aggregation state of the asphaltenes in solution was the UV-visible spectroscopy. The results indicate that stronger solvents, such as pyridine and quinoline, combined with ionic liquids yield a slight reduction in the apparent absorbance at longer wavelengths, indicative of a decrease in the nano-aggregate size although the magnitude of the decrease is not significant

  9. Hybrid Qualifications

    DEFF Research Database (Denmark)

    Against the background of increasing qualification needs there is a growing awareness of the challenge to widen participation in processes of skill formation and competence development. At the same time, the issue of permeability between vocational education and training (VET) and general education...... has turned out as a major focus of European education and training policies and certainly is a crucial principle underlying the European Qualifications Framework (EQF). In this context, «hybrid qualifications» (HQ) may be seen as an interesting approach to tackle these challenges as they serve «two...

  10. Hybrid Gear

    Science.gov (United States)

    Handschuh, Robert F. (Inventor); Roberts, Gary D. (Inventor)

    2016-01-01

    A hybrid gear consisting of metallic outer rim with gear teeth and metallic hub in combination with a composite lay up between the shaft interface (hub) and gear tooth rim is described. The composite lay-up lightens the gear member while having similar torque carrying capability and it attenuates the impact loading driven noise/vibration that is typical in gear systems. The gear has the same operational capability with respect to shaft speed, torque, and temperature as an all-metallic gear as used in aerospace gear design.

  11. Role of Multicellular Aggregates in Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Kasper N. Kragh

    2016-03-01

    Full Text Available In traditional models of in vitro biofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process. This makes it likely that biofilms are often seeded by aggregates and single cells, yet how these aggregates impact biofilm initiation and development is not known. Here we use a combination of experimental and computational approaches to determine the relative fitness of single cells and preformed aggregates during early development of Pseudomonas aeruginosa biofilms. We find that the relative fitness of aggregates depends markedly on the density of surrounding single cells, i.e., the level of competition for growth resources. When competition between aggregates and single cells is low, an aggregate has a growth disadvantage because the aggregate interior has poor access to growth resources. However, if competition is high, aggregates exhibit higher fitness, because extending vertically above the surface gives cells at the top of aggregates better access to growth resources. Other advantages of seeding by aggregates, such as earlier switching to a biofilm-like phenotype and enhanced resilience toward antibiotics and immune response, may add to this ecological benefit. Our findings suggest that current models of biofilm formation should be reconsidered to incorporate the role of aggregates in biofilm initiation.

  12. Intuitionistic hybrid logic

    DEFF Research Database (Denmark)

    Braüner, Torben

    2011-01-01

    Intuitionistic hybrid logic is hybrid modal logic over an intuitionistic logic basis instead of a classical logical basis. In this short paper we introduce intuitionistic hybrid logic and we give a survey of work in the area.......Intuitionistic hybrid logic is hybrid modal logic over an intuitionistic logic basis instead of a classical logical basis. In this short paper we introduce intuitionistic hybrid logic and we give a survey of work in the area....

  13. Aggregation server for grid-integrated vehicles

    Science.gov (United States)

    Kempton, Willett

    2015-05-26

    Methods, systems, and apparatus for aggregating electric power flow between an electric grid and electric vehicles are disclosed. An apparatus for aggregating power flow may include a memory and a processor coupled to the memory to receive electric vehicle equipment (EVE) attributes from a plurality of EVEs, aggregate EVE attributes, predict total available capacity based on the EVE attributes, and dispatch at least a portion of the total available capacity to the grid. Power flow may be aggregated by receiving EVE operational parameters from each EVE, aggregating the received EVE operational parameters, predicting total available capacity based on the aggregated EVE operational parameters, and dispatching at least a portion of the total available capacity to the grid.

  14. Aggregated particles caused by instrument artifact

    Science.gov (United States)

    Pierce, Ashley M.; Loría-Salazar, S. Marcela; Arnott, W. Patrick; Edwards, Grant C.; Miller, Matthieu B.; Gustin, Mae S.

    2018-04-01

    Previous studies have indicated that superaggregates, clusters of aggregates of soot primary particles, can be formed in large-scale turbulent fires. Due to lower effective densities, higher porosity, and lower aerodynamic diameters, superaggregates may pass through inlets designed to remove particles 2.5 µm in aerodynamic diameter were collected on 36 out of 158 sample days. On preliminary analysis, it was thought that these aggregated particles were superaggregates, depositing past PM10 (particles wind speeds, as well as the use of generators on site. Samples with aggregated particles, referred to as aggregates, were analyzed using a scanning electron microscope for size and shape and energy dispersive X-ray spectroscopy was used for elemental analysis. It was determined, based on the high amounts of aluminum present in the aggregate samples, that a sampling artifact associated with the sample inlet and prolonged, high wind events was the probable reason for the observed aggregates.

  15. Colloid Release from Soil Aggregates

    DEFF Research Database (Denmark)

    Vendelboe, Anders Lindblad; Møldrup, Per; Schjønning, Per

    2012-01-01

    The content of water-dispersible colloids (WDC) has a major impact on soil functions and structural stability. In addition, the presence of mobile colloids may increase the risk of colloid-facilitated transport of strongly sorbing environmental contaminants. The WDC content was measured in 39 soils......, using laser diffraction, by agitating the samples using a wet-dispersion unit. This approach eliminated the need for long sedimentation times required by the more classical end-over-end shaking approach and provided information about the time-dependent release of WDC. The total clay content of the soils...... ranged from 0.1 to 0.44 kg kg−1. The WDC content was measured on air-dry and moist 1- to 2-mm aggregates. The WDC content at a reference time was highly correlated to the total clay content (r > 0.91, P soils. Only for two sites was the WDC content correlated to the content of clay...

  16. Aggregate assessments support improved operational decision making

    International Nuclear Information System (INIS)

    Bauer, R.

    2003-01-01

    At Darlington Nuclear aggregate assessment of plant conditions is carried out in support of Operational Decision Making. This paper discusses how aggregate assessments have been applied to Operator Workarounds leading to improved prioritisation and alignment of work programs in different departments. As well, aggregate assessment of plant and human performance factors has been carried out to identify criteria which support conservative decision making in the main control room during unit transients. (author)

  17. Using Multifunctional Peptide Conjugated Au Nanorods for Monitoring β-amyloid Aggregation and Chemo-Photothermal Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Li, Meng; Guan, Yijia; Zhao, Andong; Ren, Jinsong; Qu, Xiaogang

    2017-01-01

    Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibit Aβ aggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from Aβ-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the Aβ aggregates. This is the first report to integrate 3 segments, an Aβ-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment.

  18. Inhibition of αIIbβ3 Ligand Binding by an αIIb Peptide that Clasps the Hybrid Domain to the βI Domain of β3.

    Directory of Open Access Journals (Sweden)

    Wen Hwa Lee

    Full Text Available Agonist-stimulated platelet activation triggers conformational changes of integrin αIIbβ3, allowing fibrinogen binding and platelet aggregation. We have previously shown that an octapeptide, p1YMESRADR8, corresponding to amino acids 313-320 of the β-ribbon extending from the β-propeller domain of αIIb, acts as a potent inhibitor of platelet aggregation. Here we have performed in silico modelling analysis of the interaction of this peptide with αIIbβ3 in its bent and closed (not swing-out conformation and show that the peptide is able to act as a substitute for the β-ribbon by forming a clasp restraining the β3 hybrid and βI domains in a closed conformation. The involvement of species-specific residues of the β3 hybrid domain (E356 and K384 and the β1 domain (E297 as well as an intrapeptide bond (pE315-pR317 were confirmed as important for this interaction by mutagenesis studies of αIIbβ3 expressed in CHO cells and native or substituted peptide inhibitory studies on platelet functions. Furthermore, NMR data corroborate the above results. Our findings provide insight into the important functional role of the αIIb β-ribbon in preventing integrin αIIbβ3 head piece opening, and highlight a potential new therapeutic approach to prevent integrin ligand binding.

  19. Internal water curing with Liapor aggregates

    DEFF Research Database (Denmark)

    Lura, Pietro

    2005-01-01

    Internal water curing is a very efficient way to counteract self-desiccation and autogenous shrinkage in high performance concrete, thereby reducing the likelihood of early-age cracking. This paper deals with early-age volume changes and moisture transport in lightweight aggregate concrete realized...... with wet lightweight aggregates. Lightweight aggregate concrete mixtures with different degree of saturation and different particle size of the lightweight aggregates were studied and compared to normal weight concrete. Autogenous deformations, selfinduced stresses in fully restrained conditions, elastic...

  20. Macroeconomic susceptibility, inflation, and aggregate supply

    Science.gov (United States)

    Hawkins, Raymond J.

    2017-03-01

    We unify aggregate-supply dynamics as a time-dependent susceptibility-mediated relationship between inflation and aggregate economic output. In addition to representing well various observations of inflation-output dynamics this parsimonious formalism provides a straightforward derivation of popular representations of aggregate-supply dynamics and a natural basis for economic-agent expectations as an element of inflation formation. Our formalism also illuminates questions of causality and time-correlation that challenge central banks for whom aggregate-supply dynamics is a key constraint in their goal of achieving macroeconomic stability.

  1. Pre-aggregation for Probability Distributions

    DEFF Research Database (Denmark)

    Timko, Igor; Dyreson, Curtis E.; Pedersen, Torben Bach

    Motivated by the increasing need to analyze complex uncertain multidimensional data (e.g., in order to optimize and personalize location-based services), this paper proposes novel types of {\\em probabilistic} OLAP queries that operate on aggregate values that are probability distributions...... and the techniques to process these queries. The paper also presents the methods for computing the probability distributions, which enables pre-aggregation, and for using the pre-aggregated distributions for further aggregation. In order to achieve good time and space efficiency, the methods perform approximate...... multidimensional data analysis that is considered in this paper (i.e., approximate processing of probabilistic OLAP queries over probability distributions)....

  2. Hybridized Tetraquarks

    CERN Document Server

    Esposito, A.; Polosa, A.D.

    2016-01-01

    We propose a new interpretation of the neutral and charged X, Z exotic hadron resonances. Hybridized-tetraquarks are neither purely compact tetraquark states nor bound or loosely bound molecules. The latter would require a negative or zero binding energy whose counterpart in h-tetraquarks is a positive quantity. The formation mechanism of this new class of hadrons is inspired by that of Feshbach metastable states in atomic physics. The recent claim of an exotic resonance in the Bs pi+- channel by the D0 collaboration and the negative result presented subsequently by the LHCb collaboration are understood in this scheme, together with a considerable portion of available data on X, Z particles. Considerations on a state with the same quantum numbers as the X(5568) are also made.

  3. Input-output analysis of CO2 emissions embodied in trade. The effects of sector aggregation

    International Nuclear Information System (INIS)

    Su, Bin; Huang, H.C.; Ang, B.W.; Zhou, P.

    2010-01-01

    Energy-related CO 2 emissions embodied in international trade have been widely studied by researchers using the input-output analysis framework. These studies are often conducted at a specific level of sector aggregation and the choice made to a large extent is dictated by economic and energy data availability. We investigate analytically the possible effects of sector aggregation on the study results. We conduct empirical studies using the data of China and Singapore where energy-related CO 2 emissions embodied in their exports are estimated at different levels of sector aggregation. A finding from the studies is that levels around 40 sectors appear to be sufficient to capture the overall share of emissions embodied in a country's exports. Another finding is that in approximating the 'ideal' situation the hybrid data treatment approach produces better results than the uniformly distributed data treatment approach. Other findings and some recommendations are also presented. (author)

  4. Selective inhibition of aggregation/fibrillation of bovine serum albumin by osmolytes: Mechanistic and energetics insights.

    Directory of Open Access Journals (Sweden)

    Moumita Dasgupta

    Full Text Available Bovine serum albumin (BSA is an important transport protein of the blood and its aggregation/fibrillation would adversely affect its transport ability leading to metabolic disorder. Therefore, understanding the mechanism of fibrillation/aggregation of BSA and design of suitable inhibitor molecules for stabilizing its native conformation, are of utmost importance. The qualitative and quantitative aspects of the effect of osmolytes (proline, hydroxyproline, glycine betaine, sarcosine and sorbitol on heat induced aggregation/fibrillation of BSA at physiological pH (pH 7.4 have been studied employing a combination of fluorescence spectroscopy, Rayleigh scattering, isothermal titration calorimetry (ITC, dynamic light scattering (DLS and transmission electron microscopy (TEM. Formation of fibrils by BSA under the given conditions was confirmed from increase in fluorescence emission intensities of Thioflavin T over a time period of 600 minutes and TEM images. Absence of change in fluorescence emission intensities of 8-Anilinonaphthalene-1-sulfonic acid (ANS in presence of native and aggregated BSA signify the absence of any amorphous aggregates. ITC results have provided important insights on the energetics of interaction of these osmolytes with different stages of the fibrillar aggregates of BSA, thereby suggesting the possible modes/mechanism of inhibition of BSA fibrillation by these osmolytes. The heats of interaction of the osmolytes with different stages of fibrillation of BSA do not follow a trend, suggesting that the interactions of stages of BSA aggregates are osmolyte specific. Among the osmolytes used here, we found glycine betaine to be supporting and promoting the aggregation process while hydroxyproline to be maximally efficient in suppressing the fibrillation process of BSA, followed by sorbitol, sarcosine and proline in the following order of their decreasing potency: Hydroxyproline> Sorbitol> Sarcosine> Proline> Glycine betaine.

  5. There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study

    DEFF Research Database (Denmark)

    Dall, M; Schaffalitzky de Muckadell, O B; Lassen, Annmarie Touborg

    2010-01-01

    Persons who use serotonin reuptake inhibitors (SSRIs) seem to be at increased risk of having serious upper gastrointestinal bleeding. In vitro studies have shown that SSRIs inhibit platelet aggregation. It remains unknown if SSRIs have a direct ulcerogenic effect....

  6. RELATIONSHIPS BETWEEN SOIL MICROBIAL BIOMASS, AGGREGATE STABILITY AND AGGREGATE ASSOCIATED-C: A MECHANISTIC APPROACH

    Directory of Open Access Journals (Sweden)

    Patrizia Guidi

    2014-01-01

    Full Text Available For the identification of C pools involved in soil aggregation, a physically-based aggregate fractionation was proposed, and  additional pretreatments were used in the measurement of the 1-2 mm aggregate stability in order to elucidate the relevance of the role of soil microorganisms with respect to the different aggregate breakdown mechanisms. The study was carried out on three clay loam Regosols, developed on calcareous shales, known history of organic cultivation.Our results showed that the soil C pool controlling the process of stabilisation of aggregates was related to the microbial community. We identified the resistance to fast wetting as the major mechanism of aggregate stability driven by microorganims. The plausible hypothesis is that organic farming promotes fungi growth, improving water repellency of soil aggregates by fungal hydrophobic substances. By contrast, we failed in the identification of C pools controlling the formation of aggregates, probably because of the disturbance of mechanical tillage which contributes to the breakdown of soil aggregates.The physically-based aggregate fractionation proposed in this study resulted useful in the  mechanistically understanding of the role of microorganisms in soil aggregation and it might be suggested for studying the impact of management on C pools, aggregates properties and their relationships in agricultural soils.

  7. Continuity controlled Hybrid Automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation

  8. Continuity Controlled Hybrid Automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2004-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of

  9. Continuity controlled hybrid automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2004-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of

  10. Continuity controlled hybrid automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2006-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of

  11. Rules for aggregated satisfaction with work commutes

    NARCIS (Netherlands)

    Suzuki, Haruna; Fujii, Satoshi; Gärling, Tommy; Ettema, Dick|info:eu-repo/dai/nl/114422729; Olsson, Lars E.; Friman, Margareta

    In general trips frequently entail several stages varying in mode, duration, and other factors. In some way travelers aggregate their satisfaction with the stages to satisfaction with the whole trip. In this paper we address the question of how this aggregation is made. We use data from a Swedish

  12. Teaching Aggregate Demand and Supply Models

    Science.gov (United States)

    Wells, Graeme

    2010-01-01

    The author analyzes the inflation-targeting model that underlies recent textbook expositions of the aggregate demand-aggregate supply approach used in introductory courses in macroeconomics. He shows how numerical simulations of a model with inflation inertia can be used as a tool to help students understand adjustments in response to demand and…

  13. Biomass round bales infield aggregation logistic scenarios

    Science.gov (United States)

    Biomass bales often need to be aggregated (collected into groups and transported) to a field-edge stack for temporary storage for feedlots or processing facilities. Aggregating the bales with the least total distance involved is a goal of producers and bale handlers. Several logistics scenarios for ...

  14. Reuse of industrial sludge as construction aggregates.

    Science.gov (United States)

    Tay, J H; Show, K Y; Hong, S Y

    2001-01-01

    Industrial wastewater sludge and dredged marine clay are high volume wastes that needed enormous space at landfill disposal sites. Due to the limitation of land space, there is an urgent need for alternative disposal methods for these two wastes. This study investigates the possibility of using the industrial sludge in combination with marine clay as construction aggregates. Different proportions of sludge and clay were made into round and angular aggregates. It was found that certain mix proportions could provide aggregates of adequate strength, comparable to that of conventional aggregates. Concrete samples cast from the sludge-clay aggregates yield compressive strengths in the range of 31.0 to 39.0 N/mm2. The results showed that the round aggregates of 100% sludge and the crush aggregates of sludge with up to 20% clay produced concrete of compressive strengths which are superior to that of 38.0 N/mm2 for conventional aggregate. The study indicates that the conversion of high volume wastes into construction materials is a potential option for waste management.

  15. Aggregation and fibrillation of bovine serum albumin

    DEFF Research Database (Denmark)

    Holm, NK; Jespersen, SK; Thomassen, LV

    2007-01-01

    The all-alpha helix multi-domain protein bovine serum albumin (BSA) aggregates at elevated temperatures. Here we show that these thermal aggregates have amyloid properties. They bind the fibril-specific dyes Thioflavin T and Congo Red, show elongated although somewhat worm-like morphology...

  16. Determinants of Aggregate Agricultural Productivity among High ...

    African Journals Online (AJOL)

    African Journal of Food, Agriculture, Nutrition and Development ... Determinants of Aggregate Agricultural Productivity among High External Input Technology Farms in a ... of aggregate agricultural productivity in an environment where policy on ... to increase the farm sizes through re-examination of the existing land laws.

  17. Monoamine Oxidase Inhibitors (MAOIs)

    Science.gov (United States)

    ... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Monoamine oxidase inhibitors (MAOIs) for ... www.uptodate.com/home. Accessed May 16, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

  18. Ratio-Based Gradual Aggregation of Data

    DEFF Research Database (Denmark)

    Iftikhar, Nadeem

    2012-01-01

    cause data management and data storage issues. However, non-flexible and ineffective means of data aggregation not only reduce performance of database queries but also lead to erroneous reporting. This paper presents flexible and effective ratio-based methods for gradual data aggregation in databases....... Gradual data aggregation is a process that reduces data volume by converting the detailed data into multiple levels of summarized data as the data gets older. This paper also describes implementation strategies of the proposed methods based on standard database technology.......Majority of databases contain large amounts of data, gathered over long intervals of time. In most cases, the data is aggregated so that it can be used for analysis and reporting purposes. The other reason of data aggregation is to reduce data volume in order to avoid over-sized databases that may...

  19. Energy challenges in optical access and aggregation networks.

    Science.gov (United States)

    Kilper, Daniel C; Rastegarfar, Houman

    2016-03-06

    Scalability is a critical issue for access and aggregation networks as they must support the growth in both the size of data capacity demands and the multiplicity of access points. The number of connected devices, the Internet of Things, is growing to the tens of billions. Prevailing communication paradigms are reaching physical limitations that make continued growth problematic. Challenges are emerging in electronic and optical systems and energy increasingly plays a central role. With the spectral efficiency of optical systems approaching the Shannon limit, increasing parallelism is required to support higher capacities. For electronic systems, as the density and speed increases, the total system energy, thermal density and energy per bit are moving into regimes that become impractical to support-for example requiring single-chip processor powers above the 100 W limit common today. We examine communication network scaling and energy use from the Internet core down to the computer processor core and consider implications for optical networks. Optical switching in data centres is identified as a potential model from which scalable access and aggregation networks for the future Internet, with the application of integrated photonic devices and intelligent hybrid networking, will emerge. © 2016 The Author(s).

  20. In vitro model of platelet aggregation in stenotic arteries

    International Nuclear Information System (INIS)

    Morley, D.; Santamore, W.P.

    1988-01-01

    Clinical and experimental evidence suggest a strong relationship between arterial stenosis, platelet aggregation, and subsequent thrombus formation. To facilitate the study of platelet accumulation in stenotic arteries, we developed an in vitro preparation. Arterial segments were perfused with whole citrated blood. A stenosis was created by applying an external plastic constrictor to the artery. Platelet accumulation within the stenosis was assessed by scanning electron microscopy and by radioactive counts from Indium-111 labeled platelets. Utilizing this preparation, 30 carotid arterial segments from 10 mongrel dogs were perfused at 100 mmHg for 15 min. In 10 arteries without a stenosis, scanning electron microscopy and radioactive counts demonstrated little platelet accumulation. In contrast, extensive platelet aggregation was observed in 10 arteries with stenoses. Moreover, in 10 stenotic arteries exposed to the thromboxane mimetic, U46619 (Upjohn Diagnostic Group), scanning electron microscopy and radioactive counts demonstrated a significant increase in platelet deposition. Conversely, we demonstrated a dimunition of platelet accumulation in stenosed arterial segments exposed to the prostacyclin analogue platelet inhibitor, Iloprost. The in vitro preparation allows precise control of hemodynamic variables and makes it possible to perform multiple tests on segments of the same vessel from the same animal

  1. Sans study of asphaltene aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Overfield, R.E.; Sheu, E.Y.; Sinha, S.K.; Liang, K.S. (Esso Resources Canada Ltd., 339-50 Avenue S.E., Calgary, Alberta T2G 2B3 (CA))

    1988-06-01

    The colloidal properties of asphaltenes have long been recognized from peculiarities in their solubility and colligative properties. A layered micellar model or asphaltenes was proposed by others in which a highly condensed alkyl aromatic formed the central part, and molecules of decreasingly aromatic character (resins) clustered around them. Numerous studies, based on a variety of techniques such as ultracentrifugation and electron microscopy indicated a particulate nature for asphaltenes with size 20-40 A diameter. Others have proposed a refined model based on x-ray diffraction and small angle scattering. In this model, interactions between flat sheets of condensed aromatic rings form the central ''crystallite'' part of a spherical particle with the outer part being comprised of the aliphatic positions of the same molecules. These particles are bunched together with some degree of entanglement into ''micelles''. Concentration and solvent dependent radii of gyration, ranging from 30-50 A were reported. The aggregation creates a good deal of uncertainty as to the true molecular size or weight of asphaltenes. Neutron scattering offers novel contrast relative to light scattering (refractive index) and x-ray scattering (electron density). This is because the scattering length of proton is negative, whereas that from deuterium and other nuclei such as C, S, O, and N are positive. Thus by replacing hydrogen with deuterium in either the solvent or the scatterer the contrast can be varied, and different parts of the molecule can be highlighted.

  2. Congested Aggregation via Newtonian Interaction

    Science.gov (United States)

    Craig, Katy; Kim, Inwon; Yao, Yao

    2018-01-01

    We consider a congested aggregation model that describes the evolution of a density through the competing effects of nonlocal Newtonian attraction and a hard height constraint. This provides a counterpoint to existing literature on repulsive-attractive nonlocal interaction models, where the repulsive effects instead arise from an interaction kernel or the addition of diffusion. We formulate our model as the Wasserstein gradient flow of an interaction energy, with a penalization to enforce the constraint on the height of the density. From this perspective, the problem can be seen as a singular limit of the Keller-Segel equation with degenerate diffusion. Two key properties distinguish our problem from previous work on height constrained equations: nonconvexity of the interaction kernel (which places the model outside the scope of classical gradient flow theory) and nonlocal dependence of the velocity field on the density (which causes the problem to lack a comparison principle). To overcome these obstacles, we combine recent results on gradient flows of nonconvex energies with viscosity solution theory. We characterize the dynamics of patch solutions in terms of a Hele-Shaw type free boundary problem and, using this characterization, show that in two dimensions patch solutions converge to a characteristic function of a disk in the long-time limit, with an explicit rate on the decay of the energy. We believe that a key contribution of the present work is our blended approach, combining energy methods with viscosity solution theory.

  3. Hybrid-Based Dense Stereo Matching

    Science.gov (United States)

    Chuang, T. Y.; Ting, H. W.; Jaw, J. J.

    2016-06-01

    Stereo matching generating accurate and dense disparity maps is an indispensable technique for 3D exploitation of imagery in the fields of Computer vision and Photogrammetry. Although numerous solutions and advances have been proposed in the literature, occlusions, disparity discontinuities, sparse texture, image distortion, and illumination changes still lead to problematic issues and await better treatment. In this paper, a hybrid-based method based on semi-global matching is presented to tackle the challenges on dense stereo matching. To ease the sensitiveness of SGM cost aggregation towards penalty parameters, a formal way to provide proper penalty estimates is proposed. To this end, the study manipulates a shape-adaptive cross-based matching with an edge constraint to generate an initial disparity map for penalty estimation. Image edges, indicating the potential locations of occlusions as well as disparity discontinuities, are approved by the edge drawing algorithm to ensure the local support regions not to cover significant disparity changes. Besides, an additional penalty parameter 𝑃𝑒 is imposed onto the energy function of SGM cost aggregation to specifically handle edge pixels. Furthermore, the final disparities of edge pixels are found by weighting both values derived from the SGM cost aggregation and the U-SURF matching, providing more reliable estimates at disparity discontinuity areas. Evaluations on Middlebury stereo benchmarks demonstrate satisfactory performance and reveal the potency of the hybrid-based dense stereo matching method.

  4. Corporate Hybrid Bonds

    OpenAIRE

    Ahlberg, Johan; Jansson, Anton

    2016-01-01

    Hybrid securities do not constitute a new phenomenon in the Swedish capital markets. Most commonly, hybrids issued by Swedish real estate companies in recent years are preference shares. Corporate hybrid bonds on the other hand may be considered as somewhat of a new-born child in the family of hybrid instruments. These do, as all other hybrid securities, share some equity-like and some debt-like characteristics. Nevertheless, since 2013 the interest for the instrument has grown rapidly and ha...

  5. Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

    International Nuclear Information System (INIS)

    Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G.

    1991-01-01

    The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor

  6. Curcumin inhibits aggregation of alpha-synuclein.

    Science.gov (United States)

    Pandey, Neeraj; Strider, Jeffrey; Nolan, William C; Yan, Sherry X; Galvin, James E

    2008-04-01

    Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

  7. Hybrid XRF

    International Nuclear Information System (INIS)

    Heckel, J.

    2002-01-01

    Full text: In the last 10 years significant innovations of EDXRF, e.g. total reflection XRF or polarized beam XRF, were utilized in different industrial applications. The decrease of background within the spectra was the goal of these developments. Excellent detection limits and sensitivities demonstrate the success of these new techniques. Nevertheless, further improvements are possible by using Si drift detectors. These detectors allow the processing of input count rates up to 10 6 cps in comparison to 10 5 of Si(Li) detectors. New excitation optics are necessary to produce such count rates. One possibility is the use of doubly curved crystals between tube and sample. These crystals enable the reflection of the primary beam within the given solid angle (0.4π) of an end window tube to the sample. Using such brightness optics excellent sensitivities mainly for light elements are achievable. The combination of a BRAGG crystal as a wavelength dispersive component and a solid state detector as an energy dispersive component creates a new technique: hybrid XRF. Copyright (2002) Australian X-ray Analytical Association Inc. Copyright (2002) Australian X-ray Analytical Association Inc

  8. Hybrid mimics and hybrid vigor in Arabidopsis

    Science.gov (United States)

    Wang, Li; Greaves, Ian K.; Groszmann, Michael; Wu, Li Min; Dennis, Elizabeth S.; Peacock, W. James

    2015-01-01

    F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID:26283378

  9. Product Aggregation Bias as a Specification Error in Demand Systems

    OpenAIRE

    George C. Davis

    1997-01-01

    Inherent in all demand studies is some form of product aggregation which can lead to product aggregation bias. This article develops a simple procedure for incorporating product aggregation bias in demand systems that permits testing of product aggregation bias with a standard likelihood ratio test. An empirical illustration of the procedure demonstrates the importance of proper product aggregation. Copyright 1997, Oxford University Press.

  10. Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

    Directory of Open Access Journals (Sweden)

    Massimo Stefani

    2013-06-01

    Full Text Available Amyloid aggregation is a hallmark of several degenerative diseases affecting the brain or peripheral tissues, whose intermediates (oligomers, protofibrils and final mature fibrils display different toxicity. Consequently, compounds counteracting amyloid aggregation have been investigated for their ability (i to stabilize toxic amyloid precursors; (ii to prevent the growth of toxic oligomers or speed that of fibrils; (iii to inhibit fibril growth and deposition; (iv to disassemble preformed fibrils; and (v to favor amyloid clearance. Natural phenols, a wide panel of plant molecules, are one of the most actively investigated categories of potential amyloid inhibitors. They are considered responsible for the beneficial effects of several traditional diets being present in green tea, extra virgin olive oil, red wine, spices, berries and aromatic herbs. Accordingly, it has been proposed that some natural phenols could be exploited to prevent and to treat amyloid diseases, and recent studies have provided significant information on their ability to inhibit peptide/protein aggregation in various ways and to stimulate cell defenses, leading to identify shared or specific mechanisms. In the first part of this review, we will overview the significance and mechanisms of amyloid aggregation and aggregate toxicity; then, we will summarize the recent achievements on protection against amyloid diseases by many natural phenols.

  11. Compressive strength improvement for recycled concrete aggregate

    Directory of Open Access Journals (Sweden)

    Mohammed Dhiyaa

    2018-01-01

    Full Text Available Increasing amount of construction waste and, concrete remnants, in particular pose a serious problem. Concrete waste exist in large amounts, do not decay and need long time for disintegration. Therefore, in this work old demolished concrete is crashed and recycled to produce recycled concrete aggregate which can be reused in new concrete production. The effect of using recycled aggregate on concrete compressive strength has been experimentally investigated; silica fume admixture also is used to improve recycled concrete aggregate compressive strength. The main parameters in this study are recycled aggregate and silica fume admixture. The percent of recycled aggregate ranged from (0-100 %. While the silica fume ranged from (0-10 %. The experimental results show that the average concrete compressive strength decreases from 30.85 MPa to 17.58 MPa when the recycled aggregate percentage increased from 0% to 100%. While, when silica fume is used the concrete compressive strength increase again to 29.2 MPa for samples with 100% of recycled aggregate.

  12. Learning about individuals' health from aggregate data.

    Science.gov (United States)

    Colbaugh, Rich; Glass, Kristin

    2017-07-01

    There is growing awareness that user-generated social media content contains valuable health-related information and is more convenient to collect than typical health data. For example, Twitter has been employed to predict aggregate-level outcomes, such as regional rates of diabetes and child poverty, and to identify individual cases of depression and food poisoning. Models which make aggregate-level inferences can be induced from aggregate data, and consequently are straightforward to build. In contrast, learning models that produce individual-level (IL) predictions, which are more informative, usually requires a large number of difficult-to-acquire labeled IL examples. This paper presents a new machine learning method which achieves the best of both worlds, enabling IL models to be learned from aggregate labels. The algorithm makes predictions by combining unsupervised feature extraction, aggregate-based modeling, and optimal integration of aggregate-level and IL information. Two case studies illustrate how to learn health-relevant IL prediction models using only aggregate labels, and show that these models perform as well as state-of-the-art models trained on hundreds or thousands of labeled individuals.

  13. Discrete stochastic charging of aggregate grains

    Science.gov (United States)

    Matthews, Lorin S.; Shotorban, Babak; Hyde, Truell W.

    2018-05-01

    Dust particles immersed in a plasma environment become charged through the collection of electrons and ions at random times, causing the dust charge to fluctuate about an equilibrium value. Small grains (with radii less than 1 μm) or grains in a tenuous plasma environment are sensitive to single additions of electrons or ions. Here we present a numerical model that allows examination of discrete stochastic charge fluctuations on the surface of aggregate grains and determines the effect of these fluctuations on the dynamics of grain aggregation. We show that the mean and standard deviation of charge on aggregate grains follow the same trends as those predicted for spheres having an equivalent radius, though aggregates exhibit larger variations from the predicted values. In some plasma environments, these charge fluctuations occur on timescales which are relevant for dynamics of aggregate growth. Coupled dynamics and charging models show that charge fluctuations tend to produce aggregates which are much more linear or filamentary than aggregates formed in an environment where the charge is stationary.

  14. Efficient clustering aggregation based on data fragments.

    Science.gov (United States)

    Wu, Ou; Hu, Weiming; Maybank, Stephen J; Zhu, Mingliang; Li, Bing

    2012-06-01

    Clustering aggregation, known as clustering ensembles, has emerged as a powerful technique for combining different clustering results to obtain a single better clustering. Existing clustering aggregation algorithms are applied directly to data points, in what is referred to as the point-based approach. The algorithms are inefficient if the number of data points is large. We define an efficient approach for clustering aggregation based on data fragments. In this fragment-based approach, a data fragment is any subset of the data that is not split by any of the clustering results. To establish the theoretical bases of the proposed approach, we prove that clustering aggregation can be performed directly on data fragments under two widely used goodness measures for clustering aggregation taken from the literature. Three new clustering aggregation algorithms are described. The experimental results obtained using several public data sets show that the new algorithms have lower computational complexity than three well-known existing point-based clustering aggregation algorithms (Agglomerative, Furthest, and LocalSearch); nevertheless, the new algorithms do not sacrifice the accuracy.

  15. Aggregated particles caused by instrument artifact

    Directory of Open Access Journals (Sweden)

    A. M. Pierce

    2018-04-01

    Full Text Available Previous studies have indicated that superaggregates, clusters of aggregates of soot primary particles, can be formed in large-scale turbulent fires. Due to lower effective densities, higher porosity, and lower aerodynamic diameters, superaggregates may pass through inlets designed to remove particles  <  2.5 µm in aerodynamic diameter (PM2.5. Ambient particulate matter samples were collected at Peavine Peak, NV, USA (2515 m northwest of Reno, NV, USA from June to November 2014. The Teledyne Advanced Pollution Instrumentation (TAPI 602 BetaPlus particulate monitor was used to collect PM2.5 on two filter types. During this time, aggregated particles  >  2.5 µm in aerodynamic diameter were collected on 36 out of 158 sample days. On preliminary analysis, it was thought that these aggregated particles were superaggregates, depositing past PM10 (particles  <  10 µm in aerodynamic diameter pre-impactors and PM2.5 cyclones. However, further analysis revealed that these aggregated particles were dissimilar to superaggregates observed in previous studies, both in morphology and in elemental composition. To determine if the aggregated particles were superaggregates or an instrument artifact, samples were investigated for the presence of certain elements, the occurrence of fires, high relative humidity and wind speeds, as well as the use of generators on site. Samples with aggregated particles, referred to as aggregates, were analyzed using a scanning electron microscope for size and shape and energy dispersive X-ray spectroscopy was used for elemental analysis. It was determined, based on the high amounts of aluminum present in the aggregate samples, that a sampling artifact associated with the sample inlet and prolonged, high wind events was the probable reason for the observed aggregates.

  16. Microbial Ecology of Soil Aggregation in Agroecosystems

    Science.gov (United States)

    Hofmockel, K. S.; Bell, S.; Tfailly, M.; Thompson, A.; Callister, S.

    2017-12-01

    Crop selection and soil texture influence the physicochemical attributes of the soil, which structures microbial communities and influences soil C cycling storage. At the molecular scale, microbial metabolites and necromass alter the soil environment, which creates feedbacks that influence ecosystem functions, including soil C accumulation. By integrating lab to field studies we aim to identify the molecules, organisms and metabolic pathways that control carbon cycling and stabilization in bioenergy soils. We investigated the relative influence of plants, microbes, and minerals on soil aggregate ecology at the Great Lakes Bioenergy Research experiment. Sites in WI and MI, USA have been in corn and switchgrass cropping systems for a decade. By comparing soil aggregate ecology across sites and cropping systems we are able to test the relative importance of plant, microbe, mineral influences on soil aggregate dynamics. Soil microbial communities (16S) differ in diversity and phylogeny among sites and cropping systems. FT-ICR MS revealed differences in the molecular composition of water-soluble fraction of soil organic matter for cropping systems and soil origin for both relative abundance of assigned formulas and biogeochemical classes of compounds. We found the degree of aggregation, measured by mean weighted diameter of aggregate fractions, is influenced by plant-soil interactions. Similarly, the proportion of soil aggregate fractions varied by both soil and plant factors. Differences in aggregation were reflected in differences in bacterial, but not fungal community composition across aggregate fractions, within each soil. Scanning electron microscopy revealed stark differences in mineral-organic interactions that influence the microbial niche and the accessibility of substrates within the soil. The clay soils show greater surface heterogeneity, enabling interactions with organic fraction of the soil. This is consistent with molecular data that reveal differences

  17. Path coupling and aggregate path coupling

    CERN Document Server

    Kovchegov, Yevgeniy

    2018-01-01

    This book describes and characterizes an extension to the classical path coupling method applied to statistical mechanical models, referred to as aggregate path coupling. In conjunction with large deviations estimates, the aggregate path coupling method is used to prove rapid mixing of Glauber dynamics for a large class of statistical mechanical models, including models that exhibit discontinuous phase transitions which have traditionally been more difficult to analyze rigorously. The book shows how the parameter regions for rapid mixing for several classes of statistical mechanical models are derived using the aggregate path coupling method.

  18. Entanglement dynamics of J-aggregate systems

    Energy Technology Data Exchange (ETDEWEB)

    Thilagam, A, E-mail: Thilagam.Lohe@unisa.edu.au [Information Technology, Engineering and the Environment, Mawson Institute, University of South Australia, South Australia 5095 (Australia)

    2011-04-01

    The entanglement dynamics of one-dimensional J-aggregate systems are examined using entanglement measures such as the von Neumann entropy and Wootters concurrence. The effect of dispersion and resonance terms associated with the exciton-phonon interaction are analyzed using Green's function formalism. A probability propagator term, derived using the Markovian approximation, presents J-aggregate systems as potential channels for large scale energy propagation for a select range of parameters. We highlight the role of a critical number of coherently coupled monomer sites and two-exciton states in determining superradiance in J-aggregate systems.

  19. Programming spiders, bots, and aggregators in Java

    CERN Document Server

    Heaton, Jeff

    2006-01-01

    The content and services available on the web continue to be accessed mostly through direct human control. But this is changing. Increasingly, users rely on automated agents that save them time and effort by programmatically retrieving content, performing complex interactions, and aggregating data from diverse sources. Programming Spiders, Bots, and Aggregators in Java teaches you how to build and deploy a wide variety of these agents-from single-purpose bots to exploratory spiders to aggregators that present a unified view of information from multiple user accounts. You will quickly build on

  20. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    Aggregating formulations is a powerful approach for transforming problems into taking more tractable forms. Aggregated formulations can, though, have drawbacks: some information may get lost in the aggregation and { put in a branch-and-bound context { branching may become very di_cult and even....... The paper includes general considerations on types of problems for which the method is of particular interest. Furthermore, we prove the correctness of the procedure and consider how to include extensions such as cutting planes and advanced branching strategies....

  1. Reusing recycled aggregates in structural concrete

    Science.gov (United States)

    Kou, Shicong

    The utilization of recycled aggregates in concrete can minimize environmental impact and reduce the consumption of natural resources in concrete applications. The aim of this thesis is to provide a scientific basis for the possible use of recycled aggregates in structure concrete by conducting a comprehensive programme of laboratory study to gain a better understanding of the mechanical, microstructure and durability properties of concrete produced with recycled aggregates. The study also explored possible techniques to of improve the properties of recycled aggregate concrete that is produced with high percentages (≧ 50%) of recycled aggregates. These techniques included: (a) using lower water-to-cement ratios in the concrete mix design; (b) using fly ash as a cement replacement or as an additional mineral admixture in the concrete mixes, and (c) precasting recycled aggregate concrete with steam curing regimes. The characteristics of the recycled aggregates produced both from laboratory and a commercially operated pilot construction and demolition (C&D) waste recycling plant were first studied. A mix proportioning procedure was then established to produce six series of concrete mixtures using different percentages of recycled coarse aggregates with and without the use of fly ash. The water-to-cement (binder) ratios of 0.55, 0.50, 0.45 and 0.40 were used. The fresh properties (including slump and bleeding) of recycled aggregate concrete (RAC) were then quantified. The effects of fly ash on the fresh and hardened properties of RAC were then studied and compared with those RAC prepared with no fly ash addition. Furthermore, the effects of steam curing on the hardened properties of RAC were investigated. For micro-structural properties, the interfacial transition zones of the aggregates and the mortar/cement paste were analyzed by SEM and EDX-mapping. Moreover, a detailed set of results on the fracture properties for RAC were obtained. Based on the experimental

  2. SGLT2 inhibitors.

    Science.gov (United States)

    Dardi, I; Kouvatsos, T; Jabbour, S A

    2016-02-01

    Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Aromatase inhibitors in pediatrics.

    Science.gov (United States)

    Wit, Jan M; Hero, Matti; Nunez, Susan B

    2011-10-25

    Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts; hyperandrogenism, for example, testotoxicosis (also known as familial male-limited precocious puberty) and congenital adrenal hyperplasia; pubertal gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that aromatase inhibitors are probably effective in the treatment of patients with aromatase excess syndrome or testotoxicosis, partially effective in Peutz-Jeghers and McCune-Albright syndrome, but probably ineffective in gynecomastia. Insufficient data are available in patients with congenital adrenal hyperplasia or functional ovarian cysts. Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution.

  4. Patterns of [PSI+] aggregation allow insights into cellular organization of yeast prion aggregates

    Science.gov (United States)

    Tyedmers, Jens

    2012-01-01

    The yeast prion phenomenon is very widespread and mounting evidence suggests that it has an impact on cellular regulatory mechanisms related to phenotypic responses to changing environments. Studying the aggregation patterns of prion amyloids during different stages of the prion life cycle is a first key step to understand major principles of how and where cells generate, organize and turn-over prion aggregates. The induction of the [PSI+] state involves the actin cytoskeleton and quality control compartments such as the Insoluble Protein Deposit (IPOD). An initially unstable transitional induction state can be visualized by overexpression of the prion determinant and displays characteristic large ring- and ribbon-shaped aggregates consisting of poorly fragmented bundles of very long prion fibrils. In the mature prion state, the aggregation pattern is characterized by highly fragmented, shorter prion fibrils that form aggregates, which can be visualized through tagging with fluorescent proteins. The number of aggregates formed varies, ranging from a single large aggregate at the IPOD to multiple smaller ones, depending on several parameters discussed. Aggregate units below the resolution of light microscopy that are detectable by fluorescence correlation spectroscopy are in equilibrium with larger aggregates in this stage and can mediate faithful inheritance of the prion state. Loss of the prion state is often characterized by reduced fragmentation of prion fibrils and fewer, larger aggregates. PMID:22449721

  5. p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53.

    Directory of Open Access Journals (Sweden)

    Karolyn J Forget

    Full Text Available Prion diseases are unique pathologies in which the infectious particles are prions, a protein aggregate. The prion protein has many particular features, such as spontaneous aggregation, conformation transmission to other native PrP proteins and transmission from an individual to another. Protein aggregation is now frequently associated to many human diseases, for example Alzheimer's disease, Parkinson's disease or type 2 diabetes. A few proteins associated to these conformational diseases are part of a new category of proteins, called prionoids: proteins that share some, but not all, of the characteristics associated with prions. The p53 protein, a transcription factor that plays a major role in cancer, has recently been suggested to be a possible prionoid. The protein has been shown to accumulate in multiple cancer cell types, and its aggregation has also been reproduced in vitro by many independent groups. These observations suggest a role for p53 aggregates in cancer development. This study aims to test the «prion-like» features of p53. Our results show in vitro aggregation of the full length and N-terminally truncated protein (p53C, and penetration of these aggregates into cells. According to our findings, the aggregates enter cells using macropinocytosis, a non-specific pathway of entry. Lastly, we also show that once internalized by the cell, p53C aggregates can co-aggregate with endogenous p53 protein. Together, these findings suggest prion-like characteristics for p53 protein, based on the fact that p53 can spontaneously aggregate, these aggregates can penetrate cells and co-aggregate with cellular p53.

  6. Effect of aggregate graining compositions on skid resistance of Exposed Aggregate Concrete pavement

    Science.gov (United States)

    Wasilewska, Marta; Gardziejczyk, Wladysław; Gierasimiuk, Pawel

    2018-05-01

    The paper presents the evaluation of skid resistance of EAC (Exposed Aggregate Concrete) pavements which differ in aggregate graining compositions. The tests were carried out on concrete mixes with a maximum aggregate size of 8 mm. Three types of coarse aggregates were selected depending on their resistance to polishing which was determined on the basis of the PSV (Polished Stone Value). Basalt (PSV 48), gabbro (PSV 50) and trachybasalt (PSV 52) aggregates were chosen. For each type of aggregate three graining compositions were designed, which differed in the content of coarse aggregate > 4mm. Their content for each series was as follows: A - 38%, B - 50% and C - 68%. Evaluation of the skid resistance has been performed using the FAP (Friction After Polishing) test equipment also known as the Wehner/Schulze machine. Laboratory method enables to compare the skid resistance of different types of wearing course under specified conditions simulating polishing processes. In addition, macrotexture measurements were made on the surface of each specimen using the Elatexure laser profile. Analysis of variance showed that at significance level α = 0.05, aggregate graining compositions as well as the PSV have a significant influence on the obtained values of the friction coefficient μm of the tested EAC pavements. The highest values of the μm have been obtained for EAC with the lowest amount of coarse aggregates (compositions A). In these cases the resistance to polishing of the aggregate does not significantly affect the friction coefficients. This is related to the large areas of cement mortar between the exposed coarse grains. Based on the analysis of microscope images, it was observed that the coarse aggregates were not sufficiently exposed. It has been proved that PSV significantly affected the coefficient of friction in the case of compositions B and C. This is caused by large areas of exposed coarse aggregate. The best parameters were achieved for the EAC pavements

  7. Geopolymerization of lightweight aggregate waste

    Directory of Open Access Journals (Sweden)

    Labrincha, J. A.

    2008-09-01

    Full Text Available Geopolymerization is a viable way to process and re-use alumino-silicate industrial waste while producing highstrength, high chemical inertia materials that can effectively immobilize other industrial by-products, and even hazardous waste. In this study industrial waste from different stages of the manufacture of lightweight expanded clay aggregate was characterized for its possible transformation, via alkali activation, to geopolymers. The ultimate aim was to assess the possibility of using such geopolymers to develop thermal and acoustic insulation panels. The containment of hazardous materials is another important application for these new materials. Geopolymers were prepared for this study with different particles size distributions and activator concentrations. Their mechanical properties, composition and microstructure were characterized and a material with promising insulating properties was produced. A preliminary analysis was conducted of the salt formation observed in these geopolymers, the chief drawback to their use.La geopolimerización es una manera viable para procesar y agregar valor a los residuos industriales de alumino-silicato dando lugar a materiales con elevadas resistencias mecánmicas, alta inercia química y que permiten encapsular otros residuos, incluso peligrosos. Los residuos industriales que proceden de diversos tipos de arcillas para la fabricación de áridos ligeros se han caracterizado para la producción de geopolímeros mediante el proceso de ataque alcalino. Su incorporación en una matriz geopolimérica permite la posibilidad de desarrollo de paneles de aislamiento (térmico y acústico. Además, la inmovilización de materiales peligrosos es un logro adicional importante. Los geopolímeros se han producido con fórmulas diferentes y se han caracterizado sus propiedades mecánicas, composición y microestructura, para dar lugar a una composición interesante con propiedades aislantes. Se ha llevado a cabo

  8. Characterization of fine aggregates in concrete by different experimental approaches

    OpenAIRE

    He, Huan; Courard, Luc; Pirard, Eric; Michel, Frédéric

    2011-01-01

    Being its major component, aggregate can occupy up to three-quarter of the volume of concrete. The structure of aggregate formed in hardened state impacts largely on mechanical and durability properties of concrete. On another hand, physical characteristics of aggregate are primarily assumed to be relevant to granular behavior of aggregate. Therefore, characterization of aggregate is of high relevance to concrete studies. In this study, different types of fine aggregate used in concrete, name...

  9. Wind energy aggregation: A coalitional game approach

    KAUST Repository

    Baeyens, E.; Bitar, E.Y.; Khargonekar, P.P.; Poolla, K.

    2011-01-01

    power output as single entity into a forward energy market. We prove that wind power generators will always improve their expected profit when they aggregate their generated power and use tools from coalitional game theory to design fair sharing

  10. GPP Webinar: The Power of Aggregated Purchasing

    Science.gov (United States)

    Green Power Partnership webinar examining the use of an aggregated model for renewable energy purchases which can lead to significant energy, environmental and financial benefits by addressing administrative cost barriers and leveraging the shared purchasi

  11. Alkali-aggregate reactivity (AAR) facts book.

    Science.gov (United States)

    2013-03-01

    This document provides detailed information on alkali-aggregate reactivity (AAR). It primarily discusses alkali-silica reaction (ASR), covering the chemistry, symptoms, test methods, prevention, specifications, diagnosis and prognosis, and mitigation...

  12. Modeling Generational Transitions from Aggregate Data

    NARCIS (Netherlands)

    Ph.H.B.F. Franses (Philip Hans); S. Stremersch (Stefan)

    2002-01-01

    textabstractUsing only aggregate sales data, the model we propose decomposes the diffusion processes of the respective technological generations and tests if different technological generations have different diffusion parameters. It also estimates the location of the generational transition from

  13. Salt-induced aggregation of stiff polyelectrolytes

    International Nuclear Information System (INIS)

    Fazli, Hossein; Mohammadinejad, Sarah; Golestanian, Ramin

    2009-01-01

    Molecular dynamics simulation techniques are used to study the process of aggregation of highly charged stiff polyelectrolytes due to the presence of multivalent salt. The dominant kinetic mode of aggregation is found to be the case of one end of one polyelectrolyte meeting others at right angles, and the kinetic pathway to bundle formation is found to be similar to that of flocculation dynamics of colloids as described by Smoluchowski. The aggregation process is found to favor the formation of finite bundles of 10-11 filaments at long times. Comparing the distribution of the cluster sizes with the Smoluchowski formula suggests that the energy barrier for the aggregation process is negligible. Also, the formation of long-lived metastable structures with similarities to the raft-like structures of actin filaments is observed within a range of salt concentration.

  14. HDR-Aggregate Read Service (ARS)

    Data.gov (United States)

    Department of Veterans Affairs — ARS is a SOAP web service exposed over HTTPS that provides an aggregated (report) view of HTH Survey, DMP and Census data stored in the HDR DB. ARS is deployed in...

  15. Protein aggregation and misfolding: good or evil?

    Science.gov (United States)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-06-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open.

  16. Protein aggregation and misfolding: good or evil?

    International Nuclear Information System (INIS)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-01-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open. (topical review)

  17. Model of fractal aggregates induced by shear

    Directory of Open Access Journals (Sweden)

    Wan Zhanhong

    2013-01-01

    Full Text Available It is an undoubted fact that particle aggregates from marine, aerosol, and engineering systems have fractal structures. In this study, fractal geometry is used to describe the morphology of irregular aggregates. The mean-field theory is employed to solve coagulation kinetic equation of aggregates. The Taylor-expansion method of moments in conjunction with the self-similar fractal characteristics is used to represent the particulate field. The effect of the target fractal dimensions on zeroth-order moment, second-order moment, and geometric standard deviation of the aggregates is explored. Results show that the developed moment method is an efficient and powerful approach to solving such evolution equations.

  18. Suspensions of colloidal particles and aggregates

    CERN Document Server

    Babick, Frank

    2016-01-01

    This book addresses the properties of particles in colloidal suspensions. It has a focus on particle aggregates and the dependency of their physical behaviour on morphological parameters. For this purpose, relevant theories and methodological tools are reviewed and applied to selected examples. The book is divided into four main chapters. The first of them introduces important measurement techniques for the determination of particle size and interfacial properties in colloidal suspensions. A further chapter is devoted to the physico-chemical properties of colloidal particles—highlighting the interfacial phenomena and the corresponding interactions between particles. The book’s central chapter examines the structure-property relations of colloidal aggregates. This comprises concepts to quantify size and structure of aggregates, models and numerical tools for calculating the (light) scattering and hydrodynamic properties of aggregates, and a discussion on van-der-Waals and double layer interactions between ...

  19. Engineering Performance of Polyurethane Bonded Aggregates

    Directory of Open Access Journals (Sweden)

    Haimin WU

    2017-08-01

    Full Text Available In this paper the engineering performance of polyurethane (PUR bonded aggregate were studied. The engineering performance, including compressive and flexural mechanical properties, void ratio, and coefficient of permeability were determined through laboratory tests. Moreover, the effects of two different curing conditions on the compressive strength properties of a PUR bonded aggregate were also evaluated. The compressive strengths of PUR bonded aggregates were found to be lower than that of conventional porous concrete, which is a commonly used cushion material. However, experimental results indicated a higher void ratio and coefficient of permeability, lower elasticity modulus, better toughness, and stronger adaptability to flexural deformation compared to porous concrete. Consequently, PUR bonded aggregate is a better solution than porous concrete when used as the cushion material of a geomembrane surface barrier for a high rock-fill dam.DOI: http://dx.doi.org/10.5755/j01.ms.23.2.15798

  20. Modeling In-Network Aggregation in VANETs

    NARCIS (Netherlands)

    Dietzel, Stefan; Kargl, Frank; Heijenk, Geert; Schaub, Florian

    2011-01-01

    The multitude of applications envisioned for vehicular ad hoc networks requires efficient communication and dissemination mechanisms to prevent network congestion. In-network data aggregation promises to reduce bandwidth requirements and enable scalability in large vehicular networks. However, most

  1. Fish Aggregation Sites in the Florida Keys

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Spawning aggregations are an important event in the life-history of many coral reef fish species. During short time periods (typically during full moons), fish will...

  2. Cellular strategies to cope with protein aggregation

    NARCIS (Netherlands)

    Scior, Annika; Juenemann, Katrin; Kirstein, Janine

    2016-01-01

    Nature has evolved several mechanisms to detoxify intracellular protein aggregates that arise upon proteotoxic challenges. These include the controlled deposition of misfolded proteins at distinct cellular sites, the protein disaggregation and refolding by molecular chaperones and/or degradation of

  3. Multitarget Molecular Hybrids of Cinnamic Acids

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2014-12-01

    Full Text Available In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX inhibition and analgesic activity (IC50 = 0.34 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ and the highest anti-proteolytic activity (IC50= 5 μΜ. The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91% and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.

  4. Platelet GP II b/III a inhibitors in neurointervention therapeutics

    International Nuclear Information System (INIS)

    Wang Kuizhong; Huang Qinghai; Liu Jianmin

    2007-01-01

    The platelet glucoprotein (GP) II b/III a inhibitors prossess inhibiting platelet aggregation effectly. As new drugs of antiplatelet, they are different in mechanism with action, application and dosage between the II b/III a inhibitors and other tradional antiplatelet drugs such as aspirin or clopidogrel. In familiar with the pharmacologic action and clinical application of II b/III a inhibitors is important for endovascular interventional radiology, especially with important significance for obtaining high quality neuro-endovascular stenting in the perioperative period. (authors)

  5. Photoacoustic signal amplification through plasmonic nanoparticle aggregation

    OpenAIRE

    Bayer, Carolyn L.; Nam, Seung Yun; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-01-01

    Photoacoustic imaging, using targeted plasmonic metallic nanoparticles, is a promising noninvasive molecular imaging method. Analysis of the photoacoustic signal generated by plasmonic metallic nanoparticles is complex because of the dependence upon physical properties of both the nanoparticle and the surrounding environment. We studied the effect of the aggregation of gold nanoparticles on the photoacoustic signal amplitude. We found that the photoacoustic signal from aggregated silica-coate...

  6. Aggregating Local Descriptors for Epigraphs Recognition

    OpenAIRE

    Amato, Giuseppe; Falchi, Fabrizio; Rabitti, Fausto; Vadicamo, Lucia

    2014-01-01

    In this paper, we consider the task of recognizing epigraphs in images such as photos taken using mobile devices. Given a set of 17,155 photos related to 14,560 epigraphs, we used a k-NearestNeighbor approach in order to perform the recognition. The contribution of this work is in evaluating state-of-the-art visual object recognition techniques in this specific context. The experimental results conducted show that Vector of Locally Aggregated Descriptors obtained aggregating SIFT descriptors ...

  7. Underground mining of aggregates. Main report

    OpenAIRE

    Brown, Teresa J.; Coggan, John S.; Evans, David J.; Foster, Patrick J.; Hewitt, Jeremy; Kruyswijk, Jacob B.; Smith, Nigel; Steadman, Ellie J.

    2010-01-01

    This report examines the economic feasibility of underground mining for crushed rock aggregates in the UK, but particularly in the London, South East and East of England regions (the South East area of England). These regions import substantial volumes of crushed rock, primarily from the East Midlands and South West regions, requiring relatively long transport distances to market for this bulk commodity. A key part of the research was to determine whether or not aggregate could be produced an...

  8. Smooth generalized linear models for aggregated data

    OpenAIRE

    Ayma Anza, Diego Armando

    2016-01-01

    Mención Internacional en el título de doctor Aggregated data commonly appear in areas such as epidemiology, demography, and public health. Generally, the aggregation process is done to protect the privacy of patients, to facilitate compact presentation, or to make it comparable with other coarser datasets. However, this process may hinder the visualization of the underlying distribution that follows the data. Also, it prohibits the direct analysis of relationships between ag...

  9. JAK inhibitors in autoinflammation.

    Science.gov (United States)

    Hoffman, Hal M; Broderick, Lori

    2018-06-11

    Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.

  10. Cathepsin D inhibitors

    Directory of Open Access Journals (Sweden)

    M. Gacko

    2007-11-01

    Full Text Available Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirectproduct, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes withcathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme.Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeuticapplications are discussed.

  11. Growth hormone aggregates in the rat adenohypophysis

    Science.gov (United States)

    Farrington, M.; Hymer, W. C.

    1990-01-01

    Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro.

  12. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  13. Enhanced emission of nile red fluorescent nanoparticles embedded in hybrid sol-gel glasses.

    Science.gov (United States)

    Ferrer, Maria L; del Monte, Francisco

    2005-01-13

    Highly fluorescent Nile Red (NR) nanoparticles embedded in a hybrid sol-gel glass are reported. The crystallite growth within the confined system created by the porous hybrid matrix results in NR nanoparticles of averaged dimensions below 36 nm. The preparation process allows for the control of both the conformation adopted by single NR molecules prior to aggregation (e.g., near planar) and the configuration of the aggregates (e.g., oblique with phi architecture which ultimately forms the nanoparticles. The full preservation of the fluorescent configuration of the aggregates in the nanoparticles is confirmed through the application of the exciton theory, and it is responsible for the significant increase of the fluorescence emission intensity (e.g., up to 525- and 70-fold as compared to that obtained for single NR molecules embedded in pure and hybrid silica glasses, respectively).

  14. Hybrid Management in Hospitals

    DEFF Research Database (Denmark)

    Byrkjeflot, Haldor; Jespersen, Peter Kragh

    2010-01-01

    Artiklen indeholder et litteraturbaseret studium af ledelsesformer i sygehuse, hvor sundhedsfaglig ledelse og generel ledelse mikses til hybride ledelsesformer......Artiklen indeholder et litteraturbaseret studium af ledelsesformer i sygehuse, hvor sundhedsfaglig ledelse og generel ledelse mikses til hybride ledelsesformer...

  15. Hydraulic Hybrid Vehicles

    Science.gov (United States)

    EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.

  16. Mesoscale hybrid calibration artifact

    Science.gov (United States)

    Tran, Hy D.; Claudet, Andre A.; Oliver, Andrew D.

    2010-09-07

    A mesoscale calibration artifact, also called a hybrid artifact, suitable for hybrid dimensional measurement and the method for make the artifact. The hybrid artifact has structural characteristics that make it suitable for dimensional measurement in both vision-based systems and touch-probe-based systems. The hybrid artifact employs the intersection of bulk-micromachined planes to fabricate edges that are sharp to the nanometer level and intersecting planes with crystal-lattice-defined angles.

  17. Hybrid quantum information processing

    Energy Technology Data Exchange (ETDEWEB)

    Furusawa, Akira [Department of Applied Physics, School of Engineering, The University of Tokyo (Japan)

    2014-12-04

    I will briefly explain the definition and advantage of hybrid quantum information processing, which is hybridization of qubit and continuous-variable technologies. The final goal would be realization of universal gate sets both for qubit and continuous-variable quantum information processing with the hybrid technologies. For that purpose, qubit teleportation with a continuousvariable teleporter is one of the most important ingredients.

  18. Adaptive enhanced sampling with a path-variable for the simulation of protein folding and aggregation

    Science.gov (United States)

    Peter, Emanuel K.

    2017-12-01

    In this article, we present a novel adaptive enhanced sampling molecular dynamics (MD) method for the accelerated simulation of protein folding and aggregation. We introduce a path-variable L based on the un-biased momenta p and displacements dq for the definition of the bias s applied to the system and derive 3 algorithms: general adaptive bias MD, adaptive path-sampling, and a hybrid method which combines the first 2 methodologies. Through the analysis of the correlations between the bias and the un-biased gradient in the system, we find that the hybrid methodology leads to an improved force correlation and acceleration in the sampling of the phase space. We apply our method on SPC/E water, where we find a conservation of the average water structure. We then use our method to sample dialanine and the folding of TrpCage, where we find a good agreement with simulation data reported in the literature. Finally, we apply our methodologies on the initial stages of aggregation of a hexamer of Alzheimer's amyloid β fragment 25-35 (Aβ 25-35) and find that transitions within the hexameric aggregate are dominated by entropic barriers, while we speculate that especially the conformation entropy plays a major role in the formation of the fibril as a rate limiting factor.

  19. Transglutaminase inhibitor from milk

    NARCIS (Netherlands)

    Jong, G.A.H. de; Wijngaards, G.; Koppelman, S.J.

    2003-01-01

    Cross-linking experiments of skimmed bovine milk with bacterial transglutaminase isolated from Streptoverticillium mobaraense showed only some degree of formation of high-molecular-weight casein polymers. Studies on the nature of this phenomenon revealed that bovine milk contains an inhibitor of

  20. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H

    2011-01-01

    Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the i...

  1. A battery-fuel cell hybrid auxiliary power unit for trucks: Analysis of direct and indirect hybrid configurations

    International Nuclear Information System (INIS)

    Samsun, Remzi Can; Krupp, Carsten; Baltzer, Sidney; Gnörich, Bruno; Peters, Ralf; Stolten, Detlef

    2016-01-01

    Highlights: • A battery-fuel cell hybrid auxiliary power unit for heavy duty vehicles is reported. • Comparison of direct and indirect hybrids using representative load profiles. • Evaluation based on validated fuel cell system and battery models. • Indirect hybrid with constant fuel cell load yields 29.3% hybrid system efficiency. • Fuel cell should be pre-heated using waste heat from the diesel engine during drive. - Abstract: The idling operation of engines in heavy duty vehicles to cover electricity demand during layovers entails significant fuel consumption and corresponding emissions. Indeed, this mode of operation is highly inefficient and a noteworthy contributor to the transportation sector’s aggregate carbon dioxide emissions. Here, a potential solution to this wasteful practice is outlined in the form of a hybrid battery-fuel cell system for application as an auxiliary power unit for trucks. Drawing on experimentally-validated fuel cell and battery models, several possible hybrid concepts are evaluated and direct and indirect hybrid configurations analyzed using a representative load profile. The results indicate that a direct hybrid configuration is only applicable if the load demand profile does not deviate strongly from the assumed profile. Operation of an indirect hybrid with a constant fuel cell load yields the greatest hybrid system efficiency, at 29.3%, while battery size could be reduced by 87% if the fuel cell is operated at the highest dynamics. Maximum efficiency in truck applications can be achieved by pre-heating the system prior to operation using exhaust heat from the motor, which increased system efficiency from 25.3% to 28.1%, including start-up. These findings confirm that hybrid systems could offer enormous fuel savings and constitute a sizeable step on the path toward energy-efficient and environmentally-friendly heavy duty vehicles that does not necessitate a fuel switch.

  2. Automated Image Analysis for Quantitative Fluorescence In Situ Hybridization with Environmental Samples▿ †

    OpenAIRE

    Zhou, Zhi; Pons, Marie Noëlle; Raskin, Lutgarde; Zilles, Julie L.

    2007-01-01

    When fluorescence in situ hybridization (FISH) analyses are performed with complex environmental samples, difficulties related to the presence of microbial cell aggregates and nonuniform background fluorescence are often encountered. The objective of this study was to develop a robust and automated quantitative FISH method for complex environmental samples, such as manure and soil. The method and duration of sample dispersion were optimized to reduce the interference of cell aggregates. An au...

  3. Hybrid stochastic simplifications for multiscale gene networks

    Directory of Open Access Journals (Sweden)

    Debussche Arnaud

    2009-09-01

    Full Text Available Abstract Background Stochastic simulation of gene networks by Markov processes has important applications in molecular biology. The complexity of exact simulation algorithms scales with the number of discrete jumps to be performed. Approximate schemes reduce the computational time by reducing the number of simulated discrete events. Also, answering important questions about the relation between network topology and intrinsic noise generation and propagation should be based on general mathematical results. These general results are difficult to obtain for exact models. Results We propose a unified framework for hybrid simplifications of Markov models of multiscale stochastic gene networks dynamics. We discuss several possible hybrid simplifications, and provide algorithms to obtain them from pure jump processes. In hybrid simplifications, some components are discrete and evolve by jumps, while other components are continuous. Hybrid simplifications are obtained by partial Kramers-Moyal expansion 123 which is equivalent to the application of the central limit theorem to a sub-model. By averaging and variable aggregation we drastically reduce simulation time and eliminate non-critical reactions. Hybrid and averaged simplifications can be used for more effective simulation algorithms and for obtaining general design principles relating noise to topology and time scales. The simplified models reproduce with good accuracy the stochastic properties of the gene networks, including waiting times in intermittence phenomena, fluctuation amplitudes and stationary distributions. The methods are illustrated on several gene network examples. Conclusion Hybrid simplifications can be used for onion-like (multi-layered approaches to multi-scale biochemical systems, in which various descriptions are used at various scales. Sets of discrete and continuous variables are treated with different methods and are coupled together in a physically justified approach.

  4. Nanoscale Organic−Inorganic Hybrid Lubricants

    KAUST Repository

    Kim, Daniel

    2011-03-15

    Silica (SiO2) nanoparticles densely grafted with amphiphilic organic chains are used to create a family of organic-inorganic hybrid lubricants. Short sulfonate-functionalized alkylaryl chains covalently tethered to the particles form a dense corona brush that stabilizes them against aggregation. When these hybrid particles are dispersed in poly-α-olefin (PAO) oligomers, they form homogeneous nanocomposite fluids at both low and high particle loadings. By varying the volume fraction of the SiO2 nanostructures in the PAO nanocomposites, we show that exceptionally stable hybrid lubricants can be created and that their mechanical properties can be tuned to span the spectrum from simple liquids to complex gels. We further show that these hybrid lubricants simultaneously exhibit lower interfacial friction coefficients, enhanced wear and mechanical properties, and superior thermal stability in comparison with either PAO or its nanocomposites created at low nanoparticle loadings. Profilometry and energy dispersive X-ray spectroscopic analysis of the wear track show that the enhanced wear characteristics in PAO-SiO2 composite lubricants originate from two sources: localization of the SiO2 particles into the wear track and extension of the elastohydrodynamic lubrication regime to Sommerfeld numbers more than an order of magnitude larger than for PAO. © 2011 American Chemical Society.

  5. Silt-clay aggregates on Mars

    International Nuclear Information System (INIS)

    Greeley, R.

    1979-01-01

    Viking observations suggest abundant silt and clay particles on Mars. It is proposed that some of these particles agglomerate to form sand size aggregates that are redeposited as sandlike features such as drifts and dunes. Although the binding for the aggregates could include salt cementation or other mechanisms, electrostatic bonding is considered to be a primary force holding the aggregates together. Various laboratory experiments conducted since the 19th century, and as reported here for simulated Martian conditions, show that both the magnitude and sign of electrical charges on windblown particles are functions of particle velocity, shape and composition, atmospheric pressure, atmospheric composition, and other factors. Electrical charges have been measured for saltating particles in the wind tunnel and in the field, on the surfaces of sand dunes, and within dust clouds on earth. Similar, and perhaps even greater, charges are proposed to occur on Mars, which could form aggregates of silt and clay size particles. Electrification is proposed to occur within Martian dust clouds, generating silt-clay aggregates which would settle to the surface where they may be deposited in the form of sandlike structures. By analog, silt-clay dunes are known in many parts of the earth where silt-clay aggregated were transported by saltation and deposited as 'sand.' In these structures the binding forces were later destroyed, and the particles reassumed the physical properties of silt and clay, but the sandlike bedding structure within the 'dunes' was preserved. The bedding observed in drifts at the Viking landing site is suggested to result from a similar process involving silt-clay aggregates on Mars

  6. A Novel Method to Quantify Soil Aggregate Stability by Measuring Aggregate Bond Energies

    Science.gov (United States)

    Efrat, Rachel; Rawlins, Barry G.; Quinton, John N.; Watts, Chris W.; Whitmore, Andy P.

    2016-04-01

    Soil aggregate stability is a key indicator of soil quality because it controls physical, biological and chemical functions important in cultivated soils. Micro-aggregates are responsible for the long term sequestration of carbon in soil, therefore determine soils role in the carbon cycle. It is thus vital that techniques to measure aggregate stability are accurate, consistent and reliable, in order to appropriately manage and monitor soil quality, and to develop our understanding and estimates of soil as a carbon store to appropriately incorporate in carbon cycle models. Practices used to assess the stability of aggregates vary in sample preparation, operational technique and unit of results. They use proxies and lack quantification. Conflicting results are therefore drawn between projects that do not provide methodological or resultant comparability. Typical modern stability tests suspend aggregates in water and monitor fragmentation upon exposure to an un-quantified amount of ultrasonic energy, utilising a laser granulometer to measure the change in mean weight diameter. In this project a novel approach has been developed based on that of Zhu et al., (2009), to accurately quantify the stability of aggregates by specifically measuring their bond energies. The bond energies are measured operating a combination of calorimetry and a high powered ultrasonic probe, with computable output function. Temperature change during sonication is monitored by an array of probes which enables calculation of the energy spent heating the system (Ph). Our novel technique suspends aggregates in heavy liquid lithium heteropolytungstate, as opposed to water, to avoid exposing aggregates to an immeasurable disruptive energy source, due to cavitation, collisions and clay swelling. Mean weight diameter is measured by a laser granulometer to monitor aggregate breakdown after successive periods of calculated ultrasonic energy input (Pi), until complete dispersion is achieved and bond

  7. Synthesis of Novel Chalcones as Acetylcholinesterase Inhibitors

    Directory of Open Access Journals (Sweden)

    Thanh-Dao Tran

    2016-07-01

    Full Text Available A new series of benzylaminochalcone derivatives with different substituents on ring B were synthesized and evaluated as inhibitors of acetylcholinesterase. The study is aimed at identification of novel benzylaminochalcones capable of blocking acetylcholinesterase activity for further development of an approach to Alzheimer’s disease treatment. These compounds were produced in moderate to good yields via Claisen-Schmidt condensation and subjected to an in vitro acetylcholinesterase inhibition assay, using Ellman’s method. The in silico docking procedure was also employed to identify molecular interactions between the chalcone compounds and the enzyme. Compounds with ring B bearing pyridin-4-yl, 4-nitrophenyl, 4-chlorophenyl and 3,4-dimethoxyphenyl moieties were discovered to exhibit significant inhibitory activities against acetylcholinesterase, with IC50 values ranging from 23 to 39 µM. The molecular modeling studies are consistent with the hypothesis that benzylaminochalcones could exert their effects as dual-binding-site acetylcholinesterase inhibitors, which might simultaneously enhance cholinergic neurotransmission and inhibit β-amyloid aggregation through binding to both catalytic and peripheral sites of the enzyme. These derivatives could be further developed to provide novel leads for the discovery of new anti-Alzheimer drugs in the future.

  8. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  9. Soil aggregation under different management systems

    Directory of Open Access Journals (Sweden)

    Cibele Mascioli Rebello Portella

    2012-12-01

    Full Text Available Considering that the soil aggregation reflects the interaction of chemical, physical and biological soil factors, the aim of this study was evaluate alterations in aggregation, in an Oxisol under no-tillage (NT and conventional tillage (CT, since over 20 years, using as reference a native forest soil in natural state. After analysis of the soil profile (cultural profile in areas under forest management, samples were collected from the layers 0-5, 5-10, 10-20 and 20-40 cm, with six repetitions. These samples were analyzed for the aggregate stability index (ASI, mean weighted diameter (MWD, mean geometric diameter (MGD in the classes > 8, 8-4, 4-2, 2-1, 1-0.5, 0.5-0.25, and < 0.25 mm, and for physical properties (soil texture, water dispersible clay (WDC, flocculation index (FI and bulk density (Bd and chemical properties (total organic carbon - COT, total nitrogen - N, exchangeable calcium - Ca2+, and pH. The results indicated that more intense soil preparation (M < NT < PC resulted in a decrease in soil stability, confirmed by all stability indicators analyzed: MWD, MGD, ASI, aggregate class distribution, WDC and FI, indicating the validity of these indicators in aggregation analyses of the studied soil.

  10. The Mechanisms of Aberrant Protein Aggregation

    Science.gov (United States)

    Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

    2012-02-01

    We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

  11. Aspects Concerning the Use of Recycled Concrete Aggregates

    Science.gov (United States)

    Robu, I.; Mazilu, C.; Deju, R.

    2016-11-01

    Natural aggregates (gravel and crushed) are essential non-renewable resources which are used for infrastructure works and civil engineering. Using recycled concrete aggregates (RCA) is a matter of high priority in the construction industry worldwide. This paper presents a study on the use of recycled aggregates, from a concrete of specified class, to acquire new cement concrete with different percentages of recycled aggregates.

  12. Oil-Price Shocks: Beyond Standard Aggregate Demand/Aggregate Supply Analysis.

    Science.gov (United States)

    Elwood, S. Kirk

    2001-01-01

    Explores the problems of portraying oil-price shocks using the aggregate demand/aggregate supply model. Presents a simple modification of the model that differentiates between production and absorption of goods, which enables it to better reflect the effects of oil-price shocks on open economies. (RLH)

  13. Self-organizing bioinspired oligothiophene–oligopeptide hybrids

    Directory of Open Access Journals (Sweden)

    Alexey K. Shaytan

    2011-09-01

    Full Text Available In this minireview, we survey recent advances in the synthesis, characterization, and modeling of new oligothiophene–oligopeptide hybrids capable of forming nanostructured fibrillar aggregates in solution and on solid substrates. Compounds of this class are promising for applications because their self-assembly and stimuli-responsive properties, provided by the peptide moieties combined with the semiconducting properties of the thiophene blocks, can result in novel opportunities for the design of advanced smart materials. These bio-inspired molecular hybrids are experimentally shown to form stable fibrils as visualized by AFM and TEM. While the experimental evidence alone is not sufficient to reveal the exact molecular organization of the fibrils, theoretical approaches based on quantum chemistry calculations and large-scale atomistic molecular dynamics simulations are attempted in an effort to reveal the structure of the fibrils at the nanoscale. Based on the combined theoretical and experimental analysis, the most likely models of fibril formation and aggregation are suggested.

  14. Marine Fish Hybridization

    KAUST Repository

    He, Song

    2017-04-01

    Natural hybridization is reproduction (without artificial influence) between two or more species/populations which are distinguishable from each other by heritable characters. Natural hybridizations among marine fishes were highly underappreciated due to limited research effort; it seems that this phenomenon occurs more often than is commonly recognized. As hybridization plays an important role in biodiversity processes in the marine environment, detecting hybridization events and investigating hybridization is important to understand and protect biodiversity. The first chapter sets the framework for this disseration study. The Cohesion Species Concept was selected as the working definition of a species for this study as it can handle marine fish hybridization events. The concept does not require restrictive species boundaries. A general history and background of natural hybridization in marine fishes is reviewed during in chapter as well. Four marine fish hybridization cases were examed and documented in Chapters 2 to 5. In each case study, at least one diagnostic nuclear marker, screened from among ~14 candidate markers, was found to discriminate the putative hybridizing parent species. To further investigate genetic evidence to support the hybrid status for each hybrid offspring in each case, haploweb analysis on diagnostic markers (nuclear and/or mitochondrial) and the DAPC/PCA analysis on microsatellite data were used. By combining the genetic evidences, morphological traits, and ecological observations together, the potential reasons that triggered each hybridization events and the potential genetic/ecology effects could be discussed. In the last chapter, sequences from 82 pairs of hybridizing parents species (for which COI barcoding sequences were available either on GenBank or in our lab) were collected. By comparing the COI fragment p-distance between each hybridizing parent species, some general questions about marine fish hybridization were discussed: Is

  15. Nafion–clay hybrids with a network structure

    KAUST Repository

    Burgaz, Engin; Lian, Huiqin; Alonso, Rafael Herrera; Estevez, Luis; Kelarakis, Antonios; Giannelis, Emmanuel P.

    2009-01-01

    Nafion-clay hybrid membranes with a unique microstructure were synthesized using a fundamentally new approach. The new approach is based on depletion aggregation of suspended particles - a well-known phenomenon in colloids. For certain concentrations of clay and polymer, addition of Nafion solution to clay suspensions in water leads to a gel. Using Cryo-TEM we show that the clay particles in the hybrid gels form a network structure with an average cell size in the order of 500 nm. The hybrid gels are subsequently cast to produce hybrid Nafion-clay membranes. Compared to pure Nafion the swelling of the hybrid membranes in water and methanol is dramatically reduced while their selectivity (ratio of conductivity over permeability) increases. The small decrease of ionic conductivity for the hybrid membranes is more than compensated by the large decrease in methanol permeability. Lastly the hybrid membranes are much stiffer and can withstand higher temperatures compared to pure Nafion. Both of these characteristics are highly desirable for use in fuel cell applications, since a) they will allow the use of a thinner membrane circumventing problems associated with the membrane resistance and b) enable high temperature applications. © 2009 Elsevier Ltd. All rights reserved.

  16. Nafion–clay hybrids with a network structure

    KAUST Repository

    Burgaz, Engin

    2009-05-01

    Nafion-clay hybrid membranes with a unique microstructure were synthesized using a fundamentally new approach. The new approach is based on depletion aggregation of suspended particles - a well-known phenomenon in colloids. For certain concentrations of clay and polymer, addition of Nafion solution to clay suspensions in water leads to a gel. Using Cryo-TEM we show that the clay particles in the hybrid gels form a network structure with an average cell size in the order of 500 nm. The hybrid gels are subsequently cast to produce hybrid Nafion-clay membranes. Compared to pure Nafion the swelling of the hybrid membranes in water and methanol is dramatically reduced while their selectivity (ratio of conductivity over permeability) increases. The small decrease of ionic conductivity for the hybrid membranes is more than compensated by the large decrease in methanol permeability. Lastly the hybrid membranes are much stiffer and can withstand higher temperatures compared to pure Nafion. Both of these characteristics are highly desirable for use in fuel cell applications, since a) they will allow the use of a thinner membrane circumventing problems associated with the membrane resistance and b) enable high temperature applications. © 2009 Elsevier Ltd. All rights reserved.

  17. 9,10-Anthraquinone hinders β-aggregation: How does a small molecule interfere with Aβ-peptide amyloid fibrillation?

    Science.gov (United States)

    Convertino, Marino; Pellarin, Riccardo; Catto, Marco; Carotti, Angelo; Caflisch, Amedeo

    2009-01-01

    Amyloid aggregation is linked to a number of neurodegenerative syndromes, the most prevalent one being Alzheimer's disease. In this pathology, the β-amyloid peptides (Aβ) aggregate into oligomers, protofibrils, and fibrils and eventually into plaques, which constitute the characteristic hallmark of Alzheimer's disease. Several low-molecular-weight compounds able to impair the Aβ aggregation process have been recently discovered; yet, a detailed description of their interactions with oligomers and fibrils is hitherto missing. Here, molecular dynamics simulations are used to investigate the influence of two relatively similar tricyclic, planar compounds, that is, 9, 10-anthraquinone (AQ) and anthracene (AC), on the early phase of the aggregation of the Aβ heptapeptide segment H14QKLVFF20, the hydrophobic stretch that promotes the Aβ self-assembly. The simulations show that AQ interferes with β-sheet formation more than AC. In particular, AQ intercalates into the β-sheet because polar interactions between the compound and the peptide backbone destabilize the interstrand hydrogen bonds, thereby favoring disorder. The thioflavin T-binding assay indicates that AQ, but not AC, sensibly reduces the amount of aggregated Aβ1–40 peptide. Taken together, the in silico and in vitro results provide evidence that structural perturbations by AQ can remarkably affect ordered oligomerization. Moreover, the simulations shed light at the atomic level on the interactions between AQ and Aβ oligomers, providing useful insights for the design of small-molecule inhibitors of aggregation with therapeutic potential in Alzheimer's disease. PMID:19309732

  18. Aloe emodin, an anthroquinone from Aloe vera acts as an anti aggregatory agent to the thermally aggregated hemoglobin

    Science.gov (United States)

    Furkan, Mohammad; Alam, Md Tauqir; Rizvi, Asim; Khan, Kashan; Ali, Abad; Shamsuzzaman; Naeem, Aabgeena

    2017-05-01

    Aggregation of proteins is a physiological process which contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. In this study we have reported that aloe emodin (AE), an anthroquinone, which is one of the active components of the Aloe vera plant, acts as an inhibitor of hemoglobin (Hb) aggregation. Hb was thermally aggregated at 60 °C for four days as evident by increased thioflavin T and ANS fluorescence, shifted congo red absorbance, appearance of β sheet structure, increase in turbidity and presence of oligomeric aggregates. Increasing concentration of AE partially reverses the aggregation of the model heme protein (hemoglobin). The maximum effect of AE was observed at 100 μM followed by saturation at 125 μM. The results were confirmed by UV-visible spectrometry, intrinsic fluorescence, ThT, ANS, congo red assay as well as transmission electron microscopy (TEM). These results were also supported by fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) which shows the disappearance of β sheet structure and appearance of α helices. This study will serve as baseline for translatory research and the development of AE based therapeutics for diseases attributed to protein aggregation.

  19. A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake Venom

    Directory of Open Access Journals (Sweden)

    Bruna Barbosa de Sousa

    2017-01-01

    Full Text Available This work reports the purification and functional characterization of BmooPAi, a platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The toxin was purified by a combination of three chromatographic steps (ion-exchange on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity chromatography on HiTrap™ Heparin HP. BmooPAi was found to be a single-chain protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic, defibrinating, or coagulant activities and induced no significant oedema or hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin-induced platelet aggregation in human platelet-rich plasma, whereas it had little or no effect on platelet aggregation induced by collagen and adenosine diphosphate. The results presented in this work suggest that BmooPAi is a toxin comprised of disintegrin-like and cysteine-rich domains, originating from autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may be of medical interest because it is a platelet aggregation inhibitor, which could potentially be developed as a novel therapeutic agent to prevent and/or treat patients with thrombotic disorders.

  20. Acid corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, N G

    1964-04-28

    An acid corrosion inhibitor is prepared by a 2-stage vacuum evaporation of effluents obtained from the ammonia columns of the coking oven plant. The effluent, leaving a scrubber in which the phenols are removed at a temperature of 98$C, passes through a quartz filter and flows into a heated chamber in which it is used for preheating a solution circulating through a vacuum unit, maintaining the temperature of the solution at 55$ to 60$C. The effluent enters a large tank in which it is boiled at 55$ to 60$C under 635 to 640 mm Hg pressure. Double evaporation of this solution yields a very effective acid corrosion inhibitor. Its corrosion-preventing effect is 97.9% compared with 90.1% for thiourea and 88.5% for urotropin under identical conditions.

  1. Benzoylurea Chitin Synthesis Inhibitors.

    Science.gov (United States)

    Sun, Ranfeng; Liu, Chunjuan; Zhang, Hao; Wang, Qingmin

    2015-08-12

    Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs.

  2. Relationship between macroeconomic aggregates and bank performance

    Directory of Open Access Journals (Sweden)

    Mitrović Ranka

    2016-01-01

    Full Text Available The aim of the paper is relations between some macroeconomic aggregates and performance of banks. This paper show analysis of trends in gross domestic product, exchange rates, interest rates, inflation load, developments in the balance of payments. On the business side, performance is achieved insight into the liquidity, capital adequacy, and the amount of non-performable loans. The aim of the research is to refute or confirm the interconnectedness of movement values of macroeconomic aggregates and bank performance. The analysis confirmed the association of two set variables. The negative value movements of macroeconomic aggregates directly or indirectly have an impact on the quality of performance of the banking sector. Therefore, it is necessary to define an adequate strategy of the economy, would not it safer to carry out the process of adapting to new developments in the market, such as the global financial crisis, the rise in unproductive enterprises, distrust customers etc.

  3. Building energy demand aggregation and simulation tools

    DEFF Research Database (Denmark)

    Gianniou, Panagiota; Heller, Alfred; Rode, Carsten

    2015-01-01

    to neighbourhoods and cities. Buildings occupy a key place in the development of smart cities as they represent an important potential to integrate smart energy solutions. Building energy consumption affects significantly the performance of the entire energy network. Therefore, a realistic estimation...... of the aggregated building energy use will not only ensure security of supply but also enhance the stabilization of national energy balances. In this study, the aggregation of building energy demand was investigated for a real case in Sønderborg, Denmark. Sixteen single-family houses -mainly built in the 1960s......- were examined, all connected to the regional district heating network. The aggregation of building energy demands was carried out according to typologies, being represented by archetype buildings. These houses were modelled with dynamic energy simulation software and with a simplified simulation tool...

  4. Aggregation kinetics and structure of cryoimmunoglobulins clusters

    CERN Document Server

    De Spirito, M; Bassi, F A; Di Stasio, E; Giardina, B; Arcovito, G

    2002-01-01

    Cryoimmunoglobulins are pathological antibodies characterized by a temperature-dependent reversible insolubility. Rheumatoid factors (RF) are immunoglobulins possessing anti-immunoglobulin activity and usually consist of an IgM antibody that recognizes IgG as antigen. These proteins are present in sera of patients affected by a large variety of different pathologies, such as HCV infection, neoplastic and autoimmune diseases. Aggregation and precipitation of cryoimmunoglobulins, leading to vasculiti, are physical phenomena behind such pathologies. A deep knowledge of the physico-chemical mechanisms regulating such phenomena plays a fundamental role in biological and clinical applications. In this work, a preliminary investigation of the aggregation kinetics and of the final macro- molecular structure of the aggregates is presented. Through static light scattering techniques, the gyration radius R/sub g/ and the fractal dimension D/sub m/ of the growing clusters have been determined. However, while the initial ...

  5. Principles of Need and the Aggregation Thesis.

    Science.gov (United States)

    Gustavsson, Erik; Juth, Niklas

    2017-09-02

    Principles of need are constantly referred to in health care priority setting. The common denominator for any principle of need is that it will ascribe some kind of special normative weight to people being worse off. However, this common ground does not answer the question how a plausible principle of need should relate to the aggregation of benefits across individuals. Principles of need are sometimes stated as being incompatible with aggregation and sometimes characterized as accepting aggregation in much the same way as utilitarians do. In this paper we argue that if one wants to take principles of need seriously both of these positions have unreasonable implications. We then characterize and defend a principle of need consisting of sufficientarian elements as well as prioritarian which avoids these unreasonable implications.

  6. Wind energy aggregation: A coalitional game approach

    KAUST Repository

    Baeyens, E.

    2011-12-01

    In this paper we explore the extent to which a group of N wind power producers can exploit the statistical benefits of aggregation and quantity risk sharing by forming a willing coalition to pool their variable power to jointly offer their aggregate power output as single entity into a forward energy market. We prove that wind power generators will always improve their expected profit when they aggregate their generated power and use tools from coalitional game theory to design fair sharing mechanisms to allocate the payoff among the coalition participants. We show that the corresponding coalitional game is super-additive and has a nonempty core. Hence, there always exists a mechanism for profit-sharing that makes the coalition stable. However, the game is not convex and the celebrated Shapley value may not belong to the core of the game. An allocation mechanism that minimizes the worst-case dissatisfaction is proposed. © 2011 IEEE.

  7. Inflammation Induces TDP-43 Mislocalization and Aggregation.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

  8. Use of molecular hybridization to explore genetic relationships. Progress report, July 1, 1974--March 31, 1975

    International Nuclear Information System (INIS)

    Atwood, K.C.

    1975-01-01

    Progress is reported on DNA distribution in pygmy chimpanzees, mountain gorillas, Catarrhine monkeys, baboons, spider monkeys, and marmosets; chromosome mapping of human 5S RNA using 3 H or 125 I labelled RNA; hybridization of 125 I-RNA to chromosomes in mice; mapping of low-multiplicity genes by hybridization in situ; technical improvements in iodination of RNA; formation of RNA aggregates; genetics of DNA and RNA in Drosophila; and x-radioinduced chromosomal aberrations in Drosophila. (U.S.)

  9. New Acetylcholinesterase Inhibitors for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Mona Mehta

    2012-01-01

    Full Text Available Acetylcholinesterase (AChE remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

  10. A method for minimum risk portfolio optimization under hybrid uncertainty

    Science.gov (United States)

    Egorova, Yu E.; Yazenin, A. V.

    2018-03-01

    In this paper, we investigate a minimum risk portfolio model under hybrid uncertainty when the profitability of financial assets is described by fuzzy random variables. According to Feng, the variance of a portfolio is defined as a crisp value. To aggregate fuzzy information the weakest (drastic) t-norm is used. We construct an equivalent stochastic problem of the minimum risk portfolio model and specify the stochastic penalty method for solving it.

  11. Heat-shock protein dysregulation is associated with functional and pathological TDP-43 aggregation

    Science.gov (United States)

    Chang, Hsiang-Yu; Hou, Shin-Chen; Way, Tzong-Der; Wong, Chi-Huey; Wang, I.-Fan

    2013-11-01

    Conformational disorders are involved in various neurodegenerative diseases. Reactive oxygen species (ROS) are the major contributors to neurodegenerative disease; however, ROS that affect the structural changes in misfolded disease proteins have yet to be well characterized. Here we demonstrate that the intrinsic propensity of TDP-43 to aggregate drives the assembly of TDP-43-positive stress granules and soluble toxic TDP-43 oligomers in response to a ROS insult via a disulfide crosslinking-independent mechanism. Notably, ROS-induced TDP-43 protein assembly correlates with the dynamics of certain TDP-43-associated chaperones. The heat-shock protein (HSP)-90 inhibitor 17-AAG prevents ROS-induced TDP-43 aggregation, alters the type of TDP-43 multimers and reduces the severity of pathological TDP-43 inclusions. In summary, our study suggests that a common mechanism could be involved in the pathogenesis of conformational diseases that result from HSP dysregulation.

  12. Recycled aggregates in concrete production: engineering properties and environmental impact

    OpenAIRE

    Seddik Meddah Mohammed

    2017-01-01

    Recycled concrete aggregate is considered as the most abundant and used secondary aggregate in concrete production, other types of solid waste are also being used in concrete for specific purposes and to achieve some desired properties. Recycled aggregates and particularly, recycled concrete aggregate substantially affect the properties and mix design of concrete both at fresh and hardened states since it is known by high porosity due to the adhered layer of old mortar on the aggregate which ...

  13. Customer Aggregation: An Opportunity for Green Power?; TOPICAL

    International Nuclear Information System (INIS)

    Holt, E.; Bird, L.

    2001-01-01

    We undertook research into the experience of aggregation groups to determine whether customer aggregation offers an opportunity to bring green power choices to more customers. The objectives of this report, therefore, are to (1) identify the different types of aggregation that are occurring today, (2) learn whether aggregation offers an opportunity to advance sales of green power, and (3) share these concepts and approaches with potential aggregators and green power advocates

  14. Avoiding deontic explosion by contextually restricting aggregation

    OpenAIRE

    Meheus, Joke; Beirlaen, Mathieu; Van De Putte, Frederik

    2010-01-01

    In this paper, we present an adaptive logic for deontic conflicts, called P2.1(r), that is based on Goble's logic SDLaPe-a bimodal extension of Goble's logic P that invalidates aggregation for all prima facie obligations. The logic P2.1(r) has several advantages with respect to SDLaPe. For consistent sets of obligations it yields the same results as Standard Deontic Logic and for inconsistent sets of obligations, it validates aggregation "as much as possible". It thus leads to a richer conseq...

  15. PUREX source Aggregate Area management study report

    International Nuclear Information System (INIS)

    1993-03-01

    This report presents the results of an aggregate area management study (AAMS) for the PUREX Plant Aggregate Area in the 200 Areas of the US Department of Energy (DOE)Hanford Site in Washington State. This scoping level study provides the basis for initiating Remedial Investigation/Feasibility Study (RI/FS) activities under the comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) or Resource Conservation and Recovery Act (RCRA) Facility Investigations (RFI) and Corrective Measures Studies (CMS) under RCRA. This report also integrates select RCRA treatment, storage, or disposal (TSD) closure activities with CERCLA and RCRA past-practice investigations

  16. Multi-Dimensional Aggregation for Temporal Data

    DEFF Research Database (Denmark)

    Böhlen, M. H.; Gamper, J.; Jensen, Christian Søndergaard

    2006-01-01

    Business Intelligence solutions, encompassing technologies such as multi-dimensional data modeling and aggregate query processing, are being applied increasingly to non-traditional data. This paper extends multi-dimensional aggregation to apply to data with associated interval values that capture...... that the data holds for each point in the interval, as well as the case where the data holds only for the entire interval, but must be adjusted to apply to sub-intervals. The paper reports on an implementation of the new operator and on an empirical study that indicates that the operator scales to large data...

  17. Relative aggregation operator in database fuzzy querying

    Directory of Open Access Journals (Sweden)

    Luminita DUMITRIU

    2005-12-01

    Full Text Available Fuzzy selection criteria querying relational databases include vague terms; they usually refer linguistic values form the attribute linguistic domains, defined as fuzzy sets. Generally, when a vague query is processed, the definitions of vague terms must already exist in a knowledge base. But there are also cases when vague terms must be dynamically defined, when a particular operation is used to aggregate simple criteria in a complex selection. The paper presents a new aggregation operator and the corresponding algorithm to evaluate the fuzzy query.

  18. Does it Matter How to Measure Aggregates?

    DEFF Research Database (Denmark)

    Beyer, Andreas; Juselius, Katarina

    Beyer, Doornik and Hendry (2000, 2001) show analytically that three out of four aggregation methods yield problematic results when exchange rate shifts induce relative-price changes between individual countries and found the least problematic method to be the variable weight method of growth rate...... the impact on the cointegration properties in empirical modelling, the monetary model in Coenen & Vega (2001) based on fixed weights was re-estimated using flexible real and nominal GDP weights. In general, the results remained reasonably robust to the choice of aggregation method...

  19. 200 North Aggregate Area source AAMS report

    International Nuclear Information System (INIS)

    1993-06-01

    This report presents the results of an aggregate area management study (AAMS) for the 200 North Aggregate Area in the 200 Areas of the US Department of Energy (DOE) Hanford Site in Washington State. This scoping level study provides the basis for initiating Remedial Investigation/Feasibility Study (RI/FS) activities under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) or Resource Conservation and Recovery Act (RCRA) Facility Investigations (RFI) and Corrective Measures Studies (CMS) under RCRA. This report also integrates select RCRA treatment, storage, or disposal (TSD) closure activities with CERCLA and RCRA past practice investigations

  20. Interface-Based Service Composition with Aggregation

    DEFF Research Database (Denmark)

    Dalla Preda, Mila; Gabbrielli, Maurizio; Guidi, Claudio

    2012-01-01

    Service-oriented architectures (SOAs) usually comprehend in-the-middle entities such as proxies or service mediators that compose services abstracting from the order in which they exchange messages. Although widely used, these entities are usually implemented by means of ad-hoc solutions....... In this paper we generalise this composition mechanism by identifying the primitive notion of aggregation. We formally define the semantics of aggregation in terms of a process calculus. We also provide a reference implementation for this primitive by extending the Jolie language, thus allowing...

  1. 200 North Aggregate Area source AAMS report

    Energy Technology Data Exchange (ETDEWEB)

    1993-06-01

    This report presents the results of an aggregate area management study (AAMS) for the 200 North Aggregate Area in the 200 Areas of the US Department of Energy (DOE) Hanford Site in Washington State. This scoping level study provides the basis for initiating Remedial Investigation/Feasibility Study (RI/FS) activities under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) or Resource Conservation and Recovery Act (RCRA) Facility Investigations (RFI) and Corrective Measures Studies (CMS) under RCRA. This report also integrates select RCRA treatment, storage, or disposal (TSD) closure activities with CERCLA and RCRA past practice investigations.

  2. Aggregate hierarchy and chemical exchange reactions

    International Nuclear Information System (INIS)

    Gerzabek, M.H.

    1994-01-01

    Recent publications show that macroaggregates (> 250 μm) may consist of microaggregates (20-250 μm) in soils, which contain organic colloids. Roots and hyphae have a potential role in the formation of macroaggregates. Fragments of roots and hyphae may serve as nuclei for smaller aggregates. This implicates that aggregate factions contain organic material of different characteristics. Especially humus in microaggregates may play a keyrole for the mobility of elements in the soil. E.g. radiocaesium extractability in the silt fraction of a Calcic Chemozem and soil-to-plant transfer was distinctly enhanced due to seven times higher C org -contents as compared to an Eutric Cambisol

  3. Fault tolerant aggregation for power system services

    DEFF Research Database (Denmark)

    Kosek, Anna Magdalena; Gehrke, Oliver; Kullmann, Daniel

    2013-01-01

    number of small units. A common approach is to aggregate a portfolio of such units together and expose them to the power system as a single large virtual unit. In order to realize the vision of a Smart Grid, concepts for flexible, resilient and reliable aggregation infrastructures are required......Exploiting the flexibility in distributed energy resources (DER) is seen as an important contribution to allow high penetrations of renewable generation in electrical power systems. However, the present control infrastructure in power systems is not well suited for the integration of a very large...

  4. Location Aggregation of Spatial Population CTMC Models

    Directory of Open Access Journals (Sweden)

    Luca Bortolussi

    2016-10-01

    Full Text Available In this paper we focus on spatial Markov population models, describing the stochastic evolution of populations of agents, explicitly modelling their spatial distribution, representing space as a discrete, finite graph. More specifically, we present a heuristic approach to aggregating spatial locations, which is designed to preserve the dynamical behaviour of the model whilst reducing the computational cost of analysis. Our approach combines stochastic approximation ideas (moment closure, linear noise, with computational statistics (spectral clustering to obtain an efficient aggregation, which is experimentally shown to be reasonably accurate on two case studies: an instance of epidemic spreading and a London bike sharing scenario.

  5. Protein carbonylation, protein aggregation and neuronal cell death in a murine model of multiple sclerosis

    Science.gov (United States)

    Dasgupta, Anushka

    /spatial relationship between carbonylation, protein aggregation and cellular apoptosis. Furthermore, the effectiveness of the carbonyl scavenger hydralazine, histidine hydrazide and methoxylamine at preventing cell death identifies protein carbonyls as the toxic species. Experiments using well-characterized apoptosis inhibitors place protein carbonylation downstream of the mitochondrial transition pore opening and upstream of caspase activation. These in vitro studies demonstrate for the first time a causal relationship between carbonylation, protein aggregation and apoptosis of neurons undergoing oxidative damage. This relationship was further strengthened with the experiments carried out in chapter 4, which show that inhibition of protein aggregation with congo red (CR) or 2-hydroxypropyl beta-cyclodextrin (HPCD) significantly reduced neuronal cell death without affecting the levels of oxidized proteins. Interestingly, large, juxta-nuclear aggregates are not formed upon GSH depletion, suggesting that the small protein aggregates are the cytotoxic species. Together, our data suggest that protein carbonylation causes protein aggregation to mediate neuronal apoptosis in vitro and that a similar mechanism might be contributing to neuronal/glial apoptosis in EAE. These studies provide the basis for testing protein carbonylation scavengers and protein aggregation inhibitors for the treatment of inflammatory demyelinating disorders.

  6. Amyloidogenic peptides for design of inhibitors of peptide aggregation and as templates for new bionanomaterials

    NARCIS (Netherlands)

    Elgersma, R.C.

    2008-01-01

    Misfolding of proteins from their soluble form into highly insoluble fibrillar deposits can lead to (non-)neurodegenerative disorders or systemic amyloidosis. This class of diseases (for which no therapy is available yet) is called amyloid diseases. Amyloid refers to the extracellular proteinaceous

  7. On the Mechanism of Berberine-INF55 (5-Nitro-2-phenylindole) Hybrid Antibacterials.

    Science.gov (United States)

    Dolla, Naveen K; Chen, Chao; Larkins-Ford, Jonah; Rajamuthiah, Rajmohan; Jagadeesan, Sakthimala; Conery, Annie L; Ausubel, Frederick M; Mylonakis, Eleftherios; Bremner, John B; Lewis, Kim; Kelso, Michael J

    Berberine-INF55 hybrids are a promising class of antibacterials that combine berberine and the NorA multidrug resistance pump inhibitor INF55 (5-nitro-2-phenylindole) together in one molecule via a chemically stable linkage. Previous studies demonstrated the potential of these compounds for countering efflux-mediated antibacterial drug resistance but they didn't establish whether the compounds function as originally intended, i.e. with the berberine moiety providing antibacterial activity and the attached INF55 component independently blocking multidrug resistance pumps, thereby enhancing the activity of berberine by reducing its efflux. We hypothesised that if the proposed mechanism is correct, then hybrids carrying more potent INF55 pump inhibitor structures should show enhanced antibacterial effects relative to those bearing weaker inhibitors. Two INF55 analogues showing graded reductions in NorA inhibitory activity compared with INF55 were identified and their corresponding berberine-INF55 hybrids carrying equivalent INF55 inhibitor structures synthesised. Multiple assays comparing the antibacterial effects of the hybrids and their corresponding berberine-INF55 analogue combinations showed that the three hybrids all show very similar activities, leading us to conclude that the antibacterial mechanism(s) of berberine-INF55 hybrids is different from berberine-INF55 combinations.

  8. New Detection Modality for Label-Free Quantification of DNA in Biological Samples via Superparamagnetic Bead Aggregation

    Science.gov (United States)

    Leslie, Daniel C.; Li, Jingyi; Strachan, Briony C.; Begley, Matthew R.; Finkler, David; Bazydlo, Lindsay L.; Barker, N. Scott; Haverstick, Doris; Utz, Marcel; Landers, James P.

    2012-01-01

    Combining DNA and superparamagnetic beads in a rotating magnetic field produces multiparticle aggregates that are visually striking, and enables label-free optical detection and quantification of DNA at levels in the picogram per microliter range. DNA in biological samples can be quantified directly by simple analysis of optical images of microfluidic wells placed on a magnetic stirrer without DNA purification. Aggregation results from DNA/bead interactions driven either by the presence of a chaotrope (a nonspecific trigger for aggregation) or by hybridization with oligonucleotides on functionalized beads (sequence-specific). This paper demonstrates quantification of DNA with sensitivity comparable to that of the best currently available fluorometric assays. The robustness and sensitivity of the method enable a wide range of applications, illustrated here by counting eukaryotic cells. Using widely available and inexpensive benchtop hardware, the approach provides a highly accessible low-tech microscale alternative to more expensive DNA detection and cell counting techniques. PMID:22423674

  9. H-aggregate analysis of P3HT thin films-Capability and limitation of photoluminescence and UV/Vis spectroscopy.

    Science.gov (United States)

    Ehrenreich, Philipp; Birkhold, Susanne T; Zimmermann, Eugen; Hu, Hao; Kim, Kwang-Dae; Weickert, Jonas; Pfadler, Thomas; Schmidt-Mende, Lukas

    2016-09-01

    Polymer morphology and aggregation play an essential role for efficient charge carrier transport and charge separation in polymer-based electronic devices. It is a common method to apply the H-aggregate model to UV/Vis or photoluminescence spectra in order to analyze polymer aggregation. In this work we present strategies to obtain reliable and conclusive information on polymer aggregation and morphology based on the application of an H-aggregate analysis on UV/Vis and photoluminescence spectra. We demonstrate, with P3HT as model system, that thickness dependent reflection behavior can lead to misinterpretation of UV/Vis spectra within the H-aggregate model. Values for the exciton bandwidth can deviate by a factor of two for polymer thicknesses below 150 nm. In contrast, photoluminescence spectra are found to be a reliable basis for characterization of polymer aggregation due to their weaker dependence on the wavelength dependent refractive index of the polymer. We demonstrate this by studying the influence of surface characteristics on polymer aggregation for spin-coated thin-films that are commonly used in organic and hybrid solar cells.

  10. Influence of Aggregate Wettability with Different Lithology Aggregates on Concrete Drying Shrinkage

    Directory of Open Access Journals (Sweden)

    Yuanchen Guo

    2015-01-01

    Full Text Available The correlation of the wettability of different lithology aggregates and the drying shrinkage of concrete materials is studied, and some influential factors such as wettability and wetting angle are analyzed. A mercury porosimeter is used to measure the porosities of different lithology aggregates accurately, and the pore size ranges that significantly affect the drying shrinkage of different lithology aggregate concretes are confirmed. The pore distribution curve of the different coarse aggregates is also measured through a statistical method, and the contact angle of different coarse aggregates and concrete is calculated according to the linear fitting relationship. Research shows that concrete strength is determined by aggregate strength. Aggregate wettability is not directly correlated with concrete strength, but wettability significantly affects concrete drying shrinkage. In all types’ pores, the greatest impacts on wettability are capillary pores and gel pores, especially for the pores of the size locating 2.5–50 nm and 50–100 nm two ranges.

  11. Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

    Science.gov (United States)

    Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

    2016-01-20

    The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

  12. Henkin and Hybrid Logic

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Huertas, Antonia; Manzano, Maria

    2014-01-01

    Leon Henkin was not a modal logician, but there is a branch of modal logic that has been deeply influenced by his work. That branch is hybrid logic, a family of logics that extend orthodox modal logic with special proposition symbols (called nominals) that name worlds. This paper explains why...... Henkin’s techniques are so important in hybrid logic. We do so by proving a completeness result for a hybrid type theory called HTT, probably the strongest hybrid logic that has yet been explored. Our completeness result builds on earlier work with a system called BHTT, or basic hybrid type theory...... is due to the first-order perspective, which lies at the heart of Henin’s best known work and hybrid logic....

  13. Chromosomal localization of the human diazepam binding inhibitor gene

    International Nuclear Information System (INIS)

    DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.

    1988-01-01

    The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes

  14. Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

    Science.gov (United States)

    Kurokawa, Yoshika; Sone, Hideko; Win-Shwe, Tin-Tin; Zeng, Yang; Kimura, Hiroyuki; Koyama, Yosuke; Yagi, Yusuke; Matsui, Yasuto; Yamazaki, Masashi; Hirano, Seishiro

    2017-01-01

    Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD), an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB) in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau– Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media) confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis suggested that this was largely attributable to the reduced BBB permeability arising from the propensity of the particles to promptly aggregate upon mixing with body fluids. PMID:28579780

  15. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

  16. Nanoscale Organic Hybrid Electrolytes

    KAUST Repository

    Nugent, Jennifer L.

    2010-08-20

    Nanoscale organic hybrid electrolytes are composed of organic-inorganic hybrid nanostructures, each with a metal oxide or metallic nanoparticle core densely grafted with an ion-conducting polyethylene glycol corona - doped with lithium salt. These materials form novel solvent-free hybrid electrolytes that are particle-rich, soft glasses at room temperature; yet manifest high ionic conductivity and good electrochemical stability above 5V. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Nanoscale Organic Hybrid Electrolytes

    KAUST Repository

    Nugent, Jennifer L.; Moganty, Surya S.; Archer, Lynden A.

    2010-01-01

    Nanoscale organic hybrid electrolytes are composed of organic-inorganic hybrid nanostructures, each with a metal oxide or metallic nanoparticle core densely grafted with an ion-conducting polyethylene glycol corona - doped with lithium salt. These materials form novel solvent-free hybrid electrolytes that are particle-rich, soft glasses at room temperature; yet manifest high ionic conductivity and good electrochemical stability above 5V. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. HYBRID VEHICLE CONTROL SYSTEM

    Directory of Open Access Journals (Sweden)

    V. Dvadnenko

    2016-06-01

    Full Text Available The hybrid vehicle control system includes a start–stop system for an internal combustion engine. The system works in a hybrid mode and normal vehicle operation. To simplify the start–stop system, there were user new possibilities of a hybrid car, which appeared after the conversion. Results of the circuit design of the proposed system of basic blocks are analyzed.

  19. Hybrid radiator cooling system

    Science.gov (United States)

    France, David M.; Smith, David S.; Yu, Wenhua; Routbort, Jules L.

    2016-03-15

    A method and hybrid radiator-cooling apparatus for implementing enhanced radiator-cooling are provided. The hybrid radiator-cooling apparatus includes an air-side finned surface for air cooling; an elongated vertically extending surface extending outwardly from the air-side finned surface on a downstream air-side of the hybrid radiator; and a water supply for selectively providing evaporative cooling with water flow by gravity on the elongated vertically extending surface.

  20. Kinetics of fibrilar aggregation of food proteins

    NARCIS (Netherlands)

    Arnaudov, L.N.

    2005-01-01

    In this thesis we study the kinetics of fibrilar aggregation of two model proteins widely used in the food industry -b-lactoglobulin (b-lg) and hen

  1. Information security risk assessment, aggregation, and mitigation

    NARCIS (Netherlands)

    Lenstra, A.K.; Voss, T.; Wang, H.; Pieprzyk, J.; Varadharajan, V.

    2004-01-01

    As part of their compliance process with the Basel 2 operational risk management requirements, banks must define how they deal with information security risk management. In this paper we describe work in progress on a new quantitative model to assess and aggregate information security risks that is

  2. Role of end effects in helical aggregation

    NARCIS (Netherlands)

    Gestel, van J.A.M.; Schoot, van der P.P.A.M.; Michels, M.A.J.

    2003-01-01

    End effects are known to play a pivotal role in equilibrium polymerization. To investigate their role in detail, we apply constraints to the first and last bonds of model linear aggregates that exhibit a helix-coil type configurational transition. Three different classes of behavior manifest

  3. Aggregate Unemployment Decreases Individual Returns to Education

    Science.gov (United States)

    Ammermueller, Andreas; Kuckulenz, Anja; Zwick, Thomas

    2009-01-01

    Aggregate unemployment may affect individual returns to education through qualification-specific responses in participation and wage bargaining. This paper shows that an increase in regional unemployment by 1% decreases returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour…

  4. Synchronized Data Aggregation for Wireless Sensor Network

    DEFF Research Database (Denmark)

    Dnyaneshwar, Mantri; Prasad, Neeli R.; Prasad, Ramjee

    2014-01-01

    Wireless Sensor Networks (WSNs) are used for monitoring and data collection purposes. A key challenge in effective data collection is to schedule and synchronize the activities of the nodes with global clock. This paper proposes the Synchronized Data Aggregation Algorithm (SDA) using spanning tree...

  5. Aggregation of log-linear risks

    DEFF Research Database (Denmark)

    Embrechts, Paul; Hashorva, Enkeleijd; Mikosch, Thomas Valentin

    2014-01-01

    In this paper we work in the framework of a k-dimensional vector of log-linear risks. Under weak conditions on the marginal tails and the dependence structure of a vector of positive risks, we derive the asymptotic tail behaviour of the aggregated risk {and present} an application concerning log...

  6. Quasi-Species and Aggregate Dynamics

    DEFF Research Database (Denmark)

    Eriksson, Anders; Görnerup, Olof; Jacobi, Martin Nilsson

    2005-01-01

    a partial differential equation that describes the system. We find that the relative prevalence of fast and slow replicators is determined by the relative strength of selection at the aggregate level to the selection strength at the molecular level. The analysis is concluded by a preliminary treatment...

  7. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  8. Globalization and Aggregate Employment Nexus: A Recent ...

    African Journals Online (AJOL)

    Since Nigeria is monotonically dependent on external trade for survival, globalization measured by the ratio of export plus import to GDP soared for the period. Coincidentally, aggregate employment in the industrial sector also rose, at least from liturgical observation. This paper therefore examined this relationship using ...

  9. Utilitarian Aggregation of Beliefs and Tastes.

    Science.gov (United States)

    Gilboa, Itzhak; Samet, Dov; Schmeidler, David

    2004-01-01

    Harsanyi's utilitarianism is extended here to Savage's framework. We formulate a Pareto condition that implies that both society's utility function and its probability measure are linear combinations of those of the individuals. An indiscriminate Pareto condition has been shown to contradict linear aggregation of beliefs and tastes. We argue that…

  10. Aggregate stability in soils cultivated with eucalyptus

    Science.gov (United States)

    Eucalyptus cultivation has increased in many Brazilian regions. In order to recommend good management practices, it is necessary to understand changes in soil properties where eucalyptus is planted. Aggregate stability analyses have proved to be a useful tool to measure soil effects caused by change...

  11. Aggregation of MBP in chronic demyelination.

    Science.gov (United States)

    Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

    2015-07-01

    Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer's diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS.

  12. A vertically resolved model for phytoplankton aggregation

    Indian Academy of Sciences (India)

    pellets (Smith et al 1998), or in large, fast-settling aggregates, which are often ...... the Arabian Sea, and its ability to graze upon natural assemblages of diatoms e.g. off the ... the amount and quality of food that supplies benthic organisms.

  13. A kinetic equation for irreversible aggregation

    International Nuclear Information System (INIS)

    Zanette, D.H.

    1990-09-01

    We introduce a kinetic equation for describing irreversible aggregation in the ballistic regime, including velocity distributions. The associated evolution for the macroscopic quantities is studied, and the general solution for Maxwell interaction models is obtained in the Fourier representation. (author). 23 refs

  14. Studies of the aggregation of RNase Sa

    DEFF Research Database (Denmark)

    Khasa, Harshit; Kramer, Ryan; Maddux, Nathan

    2014-01-01

    Thirty-eight mutants of RNase Sa (ribonuclease from Streptomyces aureofaciens) were examined for their structure, thermal sensitivity, and tendency to aggregate. Although a biphasic correlation was seen between the effect of temperature on structure and the free energy of transfer changes in many...

  15. Comparative evaluation of mineral trioxide aggregate and ...

    African Journals Online (AJOL)

    MTA) as an apical barrier material are limited, and no studies have so far examined the clinical performance of BioAggregate as apical barrier material in nonvital immature teeth. Aim: This study was aimed to provide a comparative evaluation of ...

  16. Software quality metrics aggregation in industry

    NARCIS (Netherlands)

    Mordal, K.; Anquetil, N.; Laval, J.; Serebrenik, A.; Vasilescu, B.N.; Ducasse, S.

    2013-01-01

    With the growing need for quality assessment of entire software systems in the industry, new issues are emerging. First, because most software quality metrics are defined at the level of individual software components, there is a need for aggregation methods to summarize the results at the system

  17. Lattice modeling of aggregate interlocking in concrete

    DEFF Research Database (Denmark)

    Eliáš, Jan; Stang, Henrik

    2012-01-01

    roughness, i.e.what is termed aggregate interlocking. We demonstrate this enhancement via the simulation of mixed-mode experiments on concrete performed at a laboratory at the Technical University of Denmark. Double notched concrete specimens were initially pre-cracked in tension. Then, various combinations...

  18. Stay connected: Electrical conductivity of microbial aggregates.

    Science.gov (United States)

    Li, Cheng; Lesnik, Keaton Larson; Liu, Hong

    2017-11-01

    The discovery of direct extracellular electron transfer offers an alternative to the traditional understanding of diffusional electron exchange via small molecules. The establishment of electronic connections between electron donors and acceptors in microbial communities is critical to electron transfer via electrical currents. These connections are facilitated through conductivity associated with various microbial aggregates. However, examination of conductivity in microbial samples is still in its relative infancy and conceptual models in terms of conductive mechanisms are still being developed and debated. The present review summarizes the fundamental understanding of electrical conductivity in microbial aggregates (e.g. biofilms, granules, consortia, and multicellular filaments) highlighting recent findings and key discoveries. A greater understanding of electrical conductivity in microbial aggregates could facilitate the survey for additional microbial communities that rely on direct extracellular electron transfer for survival, inform rational design towards the aggregates-based production of bioenergy/bioproducts, and inspire the construction of new synthetic conductive polymers. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Aggregate Measures of Watershed Health from Reconstructed ...

    Science.gov (United States)

    Risk-based indices such as reliability, resilience, and vulnerability (R-R-V), have the potential to serve as watershed health assessment tools. Recent research has demonstrated the applicability of such indices for water quality (WQ) constituents such as total suspended solids and nutrients on an individual basis. However, the calculations can become tedious when time-series data for several WQ constituents have to be evaluated individually. Also, comparisons between locations with different sets of constituent data can prove difficult. In this study, data reconstruction using relevance vector machine algorithm was combined with dimensionality reduction via variational Bayesian noisy principal component analysis to reconstruct and condense sparse multidimensional WQ data sets into a single time series. The methodology allows incorporation of uncertainty in both the reconstruction and dimensionality-reduction steps. The R-R-V values were calculated using the aggregate time series at multiple locations within two Indiana watersheds. Results showed that uncertainty present in the reconstructed WQ data set propagates to the aggregate time series and subsequently to the aggregate R-R-V values as well. serving as motivating examples. Locations with different WQ constituents and different standards for impairment were successfully combined to provide aggregate measures of R-R-V values. Comparisons with individual constituent R-R-V values showed that v

  20. Assays for alpha-synuclein aggregation

    DEFF Research Database (Denmark)

    Giehm, Lise; Lorenzen, Nikolai; Otzen, Daniel

    2011-01-01

    Over the last few decades, protein aggregation gone from being an irritating side product in the test tube to becoming a subject of great interest. This has been stimulated by the realization that a large and growing number of diseases is associated with the formation and accumulation of proteins...

  1. Aggregation process, application to nuclear multifragmentation

    International Nuclear Information System (INIS)

    Garcia, Jean-Baptiste

    1995-01-01

    It is depicted an aggregation model (applied to nuclear multifragmentation) which I have elaborated and validated. This model contains an aggregation procedure, allowing one to determine the aggregation state of a given system. It takes into account spatial and kinetic nucleonic information, as well as in-medium effects. It is made of several energetic linkage criterions, all based on a single quantity: the energy of a system computed in its center of mass frame. This procedure has been applied to nuclear physics, assuming nucleus as a mix of two Fermi gas, interacting via the Yukawa potential (plus Coulomb in between protons) and obeying to a classical exclusion principle. The general trends of the model match with those of nuclear physics. Moreover, two comparisons between the model and nuclear multifragmentation experiments (ALADIN, then FOPI) exhibit nice agreements. The FOPI one, shows that fragments are bound to be formed at the beginning of the expansion phase (Au + Au at 150 MeV/nuc, for central collisions). This work ends with a study of the main ingredients included in the model. It reveals that in-medium effects, exclusion principle as well as the shape of the potential have a non negligible influence on the studied nuclear aggregation process. (author) [fr

  2. Aggregation of ALS-linked FUS mutant sequesters RNA binding proteins and impairs RNA granules formation

    Energy Technology Data Exchange (ETDEWEB)

    Takanashi, Keisuke; Yamaguchi, Atsushi, E-mail: atsyama@restaff.chiba-u.jp

    2014-09-26

    Highlights: • Aggregation of ALS-linked FUS mutant sequesters ALS-associated RNA-binding proteins (FUS wt, hnRNP A1, and hnRNP A2). • Aggregation of ALS-linked FUS mutant sequesters SMN1 in the detergent-insoluble fraction. • Aggregation of ALS-linked FUS mutant reduced the number of speckles in the nucleus. • Overproduced ALS-linked FUS mutant reduced the number of processing-bodies (PBs). - Abstract: Protein aggregate/inclusion is one of hallmarks for neurodegenerative disorders including amyotrophic lateral sclerosis (ALS). FUS/TLS, one of causative genes for familial ALS, encodes a multifunctional DNA/RNA binding protein predominantly localized in the nucleus. C-terminal mutations in FUS/TLS cause the retention and the inclusion of FUS/TLS mutants in the cytoplasm. In the present study, we examined the effects of ALS-linked FUS mutants on ALS-associated RNA binding proteins and RNA granules. FUS C-terminal mutants were diffusely mislocalized in the cytoplasm as small granules in transiently transfected SH-SY5Y cells, whereas large aggregates were spontaneously formed in ∼10% of those cells. hnRNP A1, hnRNP A2, and SMN1 as well as FUS wild type were assembled into stress granules under stress conditions, and these were also recruited to FUS mutant-derived spontaneous aggregates in the cytoplasm. These aggregates stalled poly(A) mRNAs and sequestered SMN1 in the detergent insoluble fraction, which also reduced the number of nuclear oligo(dT)-positive foci (speckles) in FISH (fluorescence in situ hybridization) assay. In addition, the number of P-bodies was decreased in cells harboring cytoplasmic granules of FUS P525L. These findings raise the possibility that ALS-linked C-terminal FUS mutants could sequester a variety of RNA binding proteins and mRNAs in the cytoplasmic aggregates, which could disrupt various aspects of RNA equilibrium and biogenesis.

  3. Effects of chlorpyrifos on soil carboxylesterase activity at an aggregate-size scale.

    Science.gov (United States)

    Sanchez-Hernandez, Juan C; Sandoval, Marco

    2017-08-01

    The impact of pesticides on extracellular enzyme activity has been mostly studied on the bulk soil scale, and our understanding of the impact on an aggregate-size scale remains limited. Because microbial processes, and their extracellular enzyme production, are dependent on the size of soil aggregates, we hypothesized that the effect of pesticides on enzyme activities is aggregate-size specific. We performed three experiments using an Andisol to test the interaction between carboxylesterase (CbE) activity and the organophosphorus (OP) chlorpyrifos. First, we compared esterase activity among aggregates of different size spiked with chlorpyrifos (10mgkg -1 wet soil). Next, we examined the inhibition of CbE activity by chlorpyrifos and its metabolite chlorpyrifos-oxon in vitro to explore the aggregate size-dependent affinity of the pesticides for the active site of the enzyme. Lastly, we assessed the capability of CbEs to alleviate chlorpyrifos toxicity upon soil microorganisms. Our principal findings were: 1) CbE activity was significantly inhibited (30-67% of controls) in the microaggregates (1.0mm) compared with the corresponding controls (i.e., pesticide-free aggregates), 2) chlorpyrifos-oxon was a more potent CbE inhibitor than chlorpyrifos; however, no significant differences in the CbE inhibition were found between micro- and macroaggregates, and 3) dose-response relationships between CbE activity and chlorpyrifos concentrations revealed the capability of the enzyme to bind chlorpyrifos-oxon, which was dependent on the time of exposure. This chemical interaction resulted in a safeguarding mechanism against chlorpyrifos-oxon toxicity on soil microbial activity, as evidenced by the unchanged activity of dehydrogenase and related extracellular enzymes in the pesticide-treated aggregates. Taken together, these results suggest that environmental risk assessments of OP-polluted soils should consider the fractionation of soil in aggregates of different size to measure

  4. Toronto hybrid taxi pilot

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, M. [CrossChasm Technologies, Cambridge, ON (Canada); Marans, B. [Toronto Atmospheric Fund, ON (Canada)

    2009-10-15

    This paper provided details of a hybrid taxi pilot program conducted to compare the on-road performance of Toyota Camry hybrid vehicles against conventional vehicles over a 1-year period in order to determine the business case and air emission reductions associated with the use of hybrid taxi cabs. Over 750,000 km worth of fuel consumption was captured from 10 Toyota Camry hybrids, a Toyota Prius, and 5 non-hybrid Camry vehicles over an 18-month period. The average real world fuel consumption for the taxis demonstrated that the Toyota Prius has the lowest cost of ownership, while the non-hybrid Camry has the highest cost of ownership. Carbon dioxide (CO{sub 2}) reductions associated with the 10 Camry hybrid taxis were calculated at 236 tonnes over a 7-year taxi service life. Results suggested that the conversion of Toronto's 5680 taxis would yield annual CO{sub 2} emission reductions of over 19,000 tonnes. All hybrid purchasers identified themselves as highly likely to purchase a hybrid again. 5 tabs., 9 figs.

  5. Managing hybrid marketing systems.

    Science.gov (United States)

    Moriarty, R T; Moran, U

    1990-01-01

    As competition increases and costs become critical, companies that once went to market only one way are adding new channels and using new methods - creating hybrid marketing systems. These hybrid marketing systems hold the promise of greater coverage and reduced costs. But they are also hard to manage; they inevitably raise questions of conflict and control: conflict because marketing units compete for customers; control because new indirect channels are less subject to management authority. Hard as they are to manage, however, hybrid marketing systems promise to become the dominant design, replacing the "purebred" channel strategy in all kinds of businesses. The trick to managing the hybrid is to analyze tasks and channels within and across a marketing system. A map - the hybrid grid - can help managers make sense of their hybrid system. What the chart reveals is that channels are not the basic building blocks of a marketing system; marketing tasks are. The hybrid grid forces managers to consider various combinations of channels and tasks that will optimize both cost and coverage. Managing conflict is also an important element of a successful hybrid system. Managers should first acknowledge the inevitability of conflict. Then they should move to bound it by creating guidelines that spell out which customers to serve through which methods. Finally, a marketing and sales productivity (MSP) system, consisting of a central marketing database, can act as the central nervous system of a hybrid marketing system, helping managers create customized channels and service for specific customer segments.

  6. Toronto hybrid taxi pilot

    International Nuclear Information System (INIS)

    Stevens, M.; Marans, B.

    2009-10-01

    This paper provided details of a hybrid taxi pilot program conducted to compare the on-road performance of Toyota Camry hybrid vehicles against conventional vehicles over a 1-year period in order to determine the business case and air emission reductions associated with the use of hybrid taxi cabs. Over 750,000 km worth of fuel consumption was captured from 10 Toyota Camry hybrids, a Toyota Prius, and 5 non-hybrid Camry vehicles over an 18-month period. The average real world fuel consumption for the taxis demonstrated that the Toyota Prius has the lowest cost of ownership, while the non-hybrid Camry has the highest cost of ownership. Carbon dioxide (CO 2 ) reductions associated with the 10 Camry hybrid taxis were calculated at 236 tonnes over a 7-year taxi service life. Results suggested that the conversion of Toronto's 5680 taxis would yield annual CO 2 emission reductions of over 19,000 tonnes. All hybrid purchasers identified themselves as highly likely to purchase a hybrid again. 5 tabs., 9 figs.

  7. Hybrid FOSS Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Armstrong researchers are continuing their efforts to further develop FOSS technologies. A hybrid FOSS technique (HyFOSS) employs conventional continuous grating...

  8. Live Cell Characterization of DNA Aggregation Delivered through Lipofection.

    Science.gov (United States)

    Mieruszynski, Stephen; Briggs, Candida; Digman, Michelle A; Gratton, Enrico; Jones, Mark R

    2015-05-27

    DNA trafficking phenomena, such as information on where and to what extent DNA aggregation occurs, have yet to be fully characterised in the live cell. Here we characterise the aggregation of DNA when delivered through lipofection by applying the Number and Brightness (N&B) approach. The N&B analysis demonstrates extensive aggregation throughout the live cell with DNA clusters in the extremity of the cell and peri-nuclear areas. Once within the nucleus aggregation had decreased 3-fold. In addition, we show that increasing serum concentration of cell media results in greater cytoplasmic aggregation. Further, the effects of the DNA fragment size on aggregation was explored, where larger DNA constructs exhibited less aggregation. This study demonstrates the first quantification of DNA aggregation when delivered through lipofection in live cells. In addition, this study has presents a model for alternative uses of this imaging approach, which was originally developed to study protein oligomerization and aggregation.

  9. Single particle detection and characterization of synuclein co-aggregation

    International Nuclear Information System (INIS)

    Giese, Armin; Bader, Benedikt; Bieschke, Jan; Schaffar, Gregor; Odoy, Sabine; Kahle, Philipp J.; Haass, Christian; Kretzschmar, Hans

    2005-01-01

    Protein aggregation is the key event in a number of human diseases such as Alzheimer's and Parkinson's disease. We present a general method to quantify and characterize protein aggregates by dual-colour scanning for intensely fluorescent targets (SIFT). In addition to high sensitivity, this approach offers a unique opportunity to study co-aggregation processes. As the ratio of two fluorescently labelled components can be analysed for each aggregate separately in a homogeneous assay, the molecular composition of aggregates can be studied even in samples containing a mixture of different types of aggregates. Using this method, we could show that wild-type α-synuclein forms co-aggregates with a mutant variant found in familial Parkinson's disease. Moreover, we found a striking increase in aggregate formation at non-equimolar mixing ratios, which may have important therapeutic implications, as lowering the relative amount of aberrant protein may cause an increase of protein aggregation leading to adverse effects

  10. Transportation and utilization of aggregates for road construction

    Science.gov (United States)

    Fladvad, Marit; Wigum, Børge Johannes; Aurstad, Joralf

    2017-04-01

    Road construction relies on non-renewable aggregate resources as the main construction material. Sources for high-quality aggregate resources are scattered, and requirements for aggregate quality can cause long transport distances between quarry and road construction site. In European countries, the average aggregate consumption per capita is 5 tonnes per year (European Aggregates Association, 2016), while the corresponding figure for Norway is 11 tonnes (Neeb, 2015). Half the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction. In Norway, aggregate resources have been considered abundant. However, stricter requirement for aggregate quality, and increased concern for sustainability and environmental issues have spurred focus on reduction of transport lengths through better utilization of local aggregate materials. In this research project, information about pavement design and aggregate quality requirements were gathered from a questionnaire sent to selected experts from the World Road Organization (PIARC), European Committee for Standardization (CEN), and Nordic Road Association (NVF). The gathered data was compared to identify differences and similarities for aggregate use in the participating countries. Further, the data was compared to known data from Norway regarding: - amount of aggregates required for a road structure - aggregate transport lengths and related costs A total of 18 countries participated in the survey, represented by either road authorities, research institutions, or contractors. There are large variations in practice for aggregate use among the represented countries, and the selection of countries is sufficient to illustrate a variety in pavement designs, aggregate sizes, and quality requirements for road construction. There are considerable differences in both pavement thickness and aggregate sizes used in the studied countries. Total thicknesses for pavement structures varies from 220 mm to 2400 mm

  11. Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

    Czech Academy of Sciences Publication Activity Database

    Šebestík, Jaroslav; Marques, S. M.; Falé, P. L.; Santos, S.; Arduíno, D. M.; Cardoso, S. M.; Oliveira, S. M.; Serralheiro, M. L. M.; Santos, A. M.

    Roč. 26, č. 4 (485), s. 497 ISSN 1475-6366 Institutional research plan: CEZ:AV0Z40550506 Keywords : acetylcholinesterase inhibitors * antioxidants * hybrid ligands * anti-neurodegeneratives * Alzheimer´s disease Subject RIV: CC - Organic Chemistry

  12. DGAT inhibitors for obesity.

    Science.gov (United States)

    Matsuda, Daisuke; Tomoda, Hiroshi

    2007-10-01

    Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Diacylglycerol acyltransferase (DGAT) catalyzes the final reaction of triacylgycerol synthesis. Two isozymes of DGAT, DGAT1 and DGAT2, have been reported. Increased DGAT2 activity has a role in steatosis, while DGAT1 plays a role in very (V)LDL synthesis; increased plasma VLDL concentrations may promote obesity and thus DGAT1 is considered a potential therapeutic target of inhibition for obesity control. Several DGAT inhibitors of natural and synthetic origin have been reported, and their future prospect as anti-obesity drugs is discussed in this review.

  13. Chemoproteomics-Aided Medicinal Chemistry for the Discovery of EPHA2 Inhibitors.

    Science.gov (United States)

    Heinzlmeir, Stephanie; Lohse, Jonas; Treiber, Tobias; Kudlinzki, Denis; Linhard, Verena; Gande, Santosh Lakshmi; Sreeramulu, Sridhar; Saxena, Krishna; Liu, Xiaofeng; Wilhelm, Mathias; Schwalbe, Harald; Kuster, Bernhard; Médard, Guillaume

    2017-06-21

    The receptor tyrosine kinase EPHA2 has gained attention as a therapeutic drug target for cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small-molecule inhibitors. Herein we report the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor dasatinib as a lead structure. We designed hybrid structures of dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955, and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2. Medicinal chemistry and inhibitor design were guided by a chemical proteomics approach, allowing early selectivity profiling of the newly synthesized inhibitor candidates. Concomitant protein crystallography of 17 inhibitor co-crystals delivered detailed insight into the atomic interactions that underlie the structure-affinity relationship. Finally, the anti-proliferative effect of the inhibitor candidates was confirmed in the glioblastoma cell line SF-268. In this work, we thus discovered a novel EPHA2 inhibitor candidate that features an improved selectivity profile while maintaining potency against EPHA2 and anticancer activity in SF-268 cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. From hybrid swarms to swarms of hybrids

    Science.gov (United States)

    Stohlgren, Thomas J.; Szalanski, Allen L; Gaskin, John F.; Young, Nicholas E.; West, Amanda; Jarnevich, Catherine S.; Tripodi, Amber

    2014-01-01

    Science has shown that the introgression or hybridization of modern humans (Homo sapiens) with Neanderthals up to 40,000 YBP may have led to the swarm of modern humans on earth. However, there is little doubt that modern trade and transportation in support of the humans has continued to introduce additional species, genotypes, and hybrids to every country on the globe. We assessed the utility of species distributions modeling of genotypes to assess the risk of current and future invaders. We evaluated 93 locations of the genus Tamarix for which genetic data were available. Maxent models of habitat suitability showed that the hybrid, T. ramosissima x T. chinensis, was slightly greater than the parent taxa (AUCs > 0.83). General linear models of Africanized honey bees, a hybrid cross of Tanzanian Apis mellifera scutellata and a variety of European honey bee including A. m. ligustica, showed that the Africanized bees (AUC = 0.81) may be displacing European honey bees (AUC > 0.76) over large areas of the southwestern U.S. More important, Maxent modeling of sub-populations (A1 and A26 mitotypes based on mDNA) could be accurately modeled (AUC > 0.9), and they responded differently to environmental drivers. This suggests that rapid evolutionary change may be underway in the Africanized bees, allowing the bees to spread into new areas and extending their total range. Protecting native species and ecosystems may benefit from risk maps of harmful invasive species, hybrids, and genotypes.

  15. Hybrid protocols plus natural treatments for inflammatory conditions.

    Science.gov (United States)

    1998-01-01

    Hybrid protocols combine one, two, or three pharmaceutical drugs with several nutritional or immune-based therapies. These protocols are not limited solely to FDA-approved drugs or strictly to alternative therapies. The rationale for using a hybrid protocol is to find an effective antiviral regimen that also restores immune function. The goal is to obtain the benefits of protease inhibitors without viral resistance and side effects which include problems with fat metabolism and cholesterol levels. Natural treatments for inflammatory conditions are also described. Options include licorice root, ginger root, and slippery elm.

  16. Small file aggregation in a parallel computing system

    Science.gov (United States)

    Faibish, Sorin; Bent, John M.; Tzelnic, Percy; Grider, Gary; Zhang, Jingwang

    2014-09-02

    Techniques are provided for small file aggregation in a parallel computing system. An exemplary method for storing a plurality of files generated by a plurality of processes in a parallel computing system comprises aggregating the plurality of files into a single aggregated file; and generating metadata for the single aggregated file. The metadata comprises an offset and a length of each of the plurality of files in the single aggregated file. The metadata can be used to unpack one or more of the files from the single aggregated file.

  17. Probabilistic Analysis of Structural Member from Recycled Aggregate Concrete

    Science.gov (United States)

    Broukalová, I.; Šeps, K.

    2017-09-01

    The paper aims at the topic of sustainable building concerning recycling of waste rubble concrete from demolition. Considering demands of maximising recycled aggregate use and minimising of cement consumption, composite from recycled concrete aggregate was proposed. The objective of the presented investigations was to verify feasibility of the recycled aggregate cement based fibre reinforced composite in a structural member. Reliability of wall from recycled aggregate fibre reinforced composite was assessed in a probabilistic analysis of a load-bearing capacity of the wall. The applicability of recycled aggregate fibre reinforced concrete in structural applications was demonstrated. The outcomes refer to issue of high scatter of material parameters of recycled aggregate concretes.

  18. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates

    Science.gov (United States)

    Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B.

    2015-01-01

    Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA. PMID:26161440

  19. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates.

    Science.gov (United States)

    Siringi, Gideon; Abolmaali, Ali; Aswath, Pranesh B

    2015-01-01

    Tire derived aggregate (TDA) has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA) and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength) based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA.

  20. Protein aggregate turbidity: Simulation of turbidity profiles for mixed-aggregation reactions.

    Science.gov (United States)

    Hall, Damien; Zhao, Ran; Dehlsen, Ian; Bloomfield, Nathaniel; Williams, Steven R; Arisaka, Fumio; Goto, Yuji; Carver, John A

    2016-04-01

    Due to their colloidal nature, all protein aggregates scatter light in the visible wavelength region when formed in aqueous solution. This phenomenon makes solution turbidity, a quantity proportional to the relative loss in forward intensity of scattered light, a convenient method for monitoring protein aggregation in biochemical assays. Although turbidity is often taken to be a linear descriptor of the progress of aggregation reactions, this assumption is usually made without performing the necessary checks to provide it with a firm underlying basis. In this article, we outline utilitarian methods for simulating the turbidity generated by homogeneous and mixed-protein aggregation reactions containing fibrous, amorphous, and crystalline structures. The approach is based on a combination of Rayleigh-Gans-Debye theory and approximate forms of the Mie scattering equations. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  1. Properties of Concrete with Tire Derived Aggregate Partially Replacing Coarse Aggregates

    Directory of Open Access Journals (Sweden)

    Gideon Siringi

    2015-01-01

    Full Text Available Tire derived aggregate (TDA has been proposed as a possible lightweight replacement for mineral aggregate in concrete. The role played by the amount of TDA replacing coarse aggregate as well as different treatment and additives in concrete on its properties is examined. Conventional concrete (without TDA and concrete containing TDA are compared by examining their compressive strength based on ASTM C39, workability based on ASTM C143, splitting tensile strength based on ASTM C496, modulus of rupture (flexural strength based on ASTM C78, and bond stress based on ASTM C234. Results indicate that while replacement of coarse aggregates with TDA results in reduction in strength, it may be mitigated with addition of silica fume to obtain the desired strength. The greatest benefit of using TDA is in the development of a higher ductile product while utilizing recycled TDA.

  2. Mechanical properties of concrete containing recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate replacement

    Science.gov (United States)

    Khalid, Faisal Sheikh; Azmi, Nurul Bazilah; Sumandi, Khairul Azwa Syafiq Mohd; Mazenan, Puteri Natasya

    2017-10-01

    Many construction and development activities today consume large amounts of concrete. The amount of construction waste is also increasing because of the demolition process. Much of this waste can be recycled to produce new products and increase the sustainability of construction projects. As recyclable construction wastes, concrete and ceramic can replace the natural aggregate in concrete because of their hard and strong physical properties. This research used 25%, 35%, and 45% recycled concrete aggregate (RCA) and ceramic waste as coarse aggregate in producing concrete. Several tests, such as concrete cube compression and splitting tensile tests, were also performed to determine and compare the mechanical properties of the recycled concrete with those of the normal concrete that contains 100% natural aggregate. The concrete containing 35% RCA and 35% ceramic waste showed the best properties compared with the normal concrete.

  3. Influence of granitic aggregates from Northeast Brazil on the alkali-aggregate reaction

    Energy Technology Data Exchange (ETDEWEB)

    Gomes Neto, David de Paiva; Santana, Rodrigo Soares de; Barreto, Ledjane Silva, E-mail: pvgomes@uol.com.br [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Dept. de Ciencias dos Materiais e Engenharia; Conceicao, Herbert; Lisboa, Vinicios Anselmo Carvalho [Universidade Federal de Sergipe (UFS), Sao Cristovao, SE (Brazil). Dept. de Geologia

    2014-08-15

    The alkali-aggregate reaction (AAR) in concrete structures is a problem that has concerned engineers and researchers for decades. This reaction occurs when silicates in the aggregates react with the alkalis, forming an expanded gel that can cause cracks in the concrete and reduce its lifespan. The aim of this study was to characterize three coarse granitic aggregates employed in concrete production in northeastern Brazil, correlating petrographic analysis with the kinetics of silica dissolution and the evolution of expansions in mortar bars, assisted by SEM/EDS, XRD, and EDX. The presence of grains showing recrystallization into individual microcrystalline quartz subgrains was associated with faster dissolution of silica and greater expansion in mortar bars. Aggregates showing substantial deformation, such as stretched grains of quartz with strong undulatory extinction, experienced slower dissolution, with reaction and expansion occurring over longer periods that could not be detected using accelerated tests with mortar bars. (author)

  4. Selective serotonin reuptake inhibitors and risk for gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Batić-Mujanović Olivera

    2014-01-01

    Full Text Available The most of the known effects of selective serotonin reuptake inhibitors, beneficial or harmful, are associated with the inhibitory action of the serotonin reuptake transporter. This mechanism is present not only in neurons, but also in other cells such as platelets. Serotoninergic mechanism seems to have an important role in hemostasis, which has long been underestimated. Abnormal activation may lead to a prothrombotic state in patients treated with selective serotonin reuptake inhibitors. On one hand there may be an increased risk of bleeding, and on the other hand reduction in thrombotic risk may be possible. Serotonin is critical to maintain a platelet haemostatic function, such as platelet aggregation. Evidences from the studies support the hypothesis that antidepressants with a relevant blockade of action of serotonin reuptake mechanism may increase the risk of bleeding, which can occur anywhere in the body. Epidemiological evidences are, however, the most robust for upper gastrointestinal bleeding. It is estimated that this bleeding can occur in 1 in 100 to 1 in 1.000 patient-years of exposure to the high-affinity selective serotonin reuptake inhibitors, with very old patients at the highest risk. The increased risk may be of particular relevance when selective serotonin reuptake inhibitors are taken simultaneously with nonsteroidal anti-inflammatory drugs, low dose of aspirin or warfarin.

  5. Effect of the Aggregate Size on Strength Properties of Recycled Aggregate Concrete

    Directory of Open Access Journals (Sweden)

    Ma Kang

    2018-01-01

    Full Text Available The study on preparation technology of recycled concrete with economical and technical feasibility has gained more serious attention in each country due to its involvement and effect on the environment protection and the sustainable development of human society. In this study, we conducted a control variable test to investigate and assess the influence of the aggregate size on the strength characteristics of concrete with different diameters of recycled aggregates. Concrete with recycled aggregates of 5∼15 mm (A, 15∼20 mm (B, 20∼30 mm (C, and their combinations were subjected to a series of unconfined pressure tests after curing for 28 days. Based on the results obtained from the tests, an effort was made to study the relationship between the mechanical characteristics of recycled aggregate concrete and aggregate particle size. Also, a regression model of recycled concrete was proposed to predict the elasticity modulus and to adjust the design of mixture proportion. It is believed that these experiment results would contribute to adjust the remediation mixture for recycling plants by considering the influence of recycled aggregate size.

  6. Prediction of the aggregation propensity of proteins from the primary sequence: aggregation properties of proteomes.

    Science.gov (United States)

    Castillo, Virginia; Graña-Montes, Ricardo; Sabate, Raimon; Ventura, Salvador

    2011-06-01

    In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Foam stabilization by solid particle aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Guignot, S.; Faure, S. [CEA Marcoule, Lab. des Procedes Avances de Decontamination, 30 (France); Pitois, O. [UniversiteParis-Est Marne-La-Valle, Lab. Physique des Materiaux Divises et des Interfaces (LPMDI), 77 - Marne la Vallee (France)

    2008-07-01

    During the dismantling of nuclear facilities, radioactive deposits on exposed areas are removed and solubilized by successive rinses of reactive liquid. Using this liquid in a foam state reduces the amount of resulting wastes. During the required decontamination time (1 to 5 hours) the foam has to be sufficiently wet (1). In the Laboratory of Advanced Processes for Decontamination, new formulations are currently studied to slow down the drainage kinetics of these foams, by adding colloidal particles of hydrophilic fumed silica into the classical mixtures of well-defined non ionic foaming surfactants previously used (2). The objective of our study is to shed light on the foam surprising stability induced by these particles. The study focuses on drainage of foams generated by air sparging through a suspension lying on a porous glass. The foaming suspensions contain between 0 and 70 g.L-1 of a fumed silica (Aerosil 380) which is well-known to form gels for concentrations above 200 g.L{sup -1}. In the studied solutions this silica builds up into aggregates of dozens of microns, whose volume-averaged mean diameter after sonication is centred around 300 nm. Under gentle stirring, they display no sign of re-aggregation during 24 h. On a free drainage configuration, a foam that contains particles keeps a significant amount of its initial liquid: up to 60 % during up to 5 hours, in contrast to classical foams that drain out all of their liquid in about 20 minutes. From a rheological point of view, the most concentrated suspensions display a yield stress behaviour. This evidences the structuring of the aggregates into a coherent network that might explain the incomplete drainage of the solutions. For the lowest concentrated solutions, such rheological properties have not been observed although the corresponding foams can retain large amount of solution. This suggests that local concentrations of aggregates can rise owing to their retention by foam channels, until they form

  8. Hybridization in geese

    NARCIS (Netherlands)

    Ottenburghs, Jente; Hooft, van Pim; Wieren, van Sipke E.; Ydenberg, Ronald C.; Prins, Herbert H.T.

    2016-01-01

    The high incidence of hybridization in waterfowl (ducks, geese and swans) makes this bird group an excellent study system to answer questions related to the evolution and maintenance of species boundaries. However, knowledge on waterfowl hybridization is biased towards ducks, with a large

  9. Mirror hybrid reactor studies

    International Nuclear Information System (INIS)

    Bender, D.J.

    1978-01-01

    The hybrid reactor studies are reviewed. The optimization of the point design and work on a reference design are described. The status of the nuclear analysis of fast spectrum blankets, systems studies for fissile fuel producing hybrid reactor, and the mechanical design of the machine are reviewed

  10. Hybrid Universities in Malaysia

    Science.gov (United States)

    Lee, Molly; Wan, Chang Da; Sirat, Morshidi

    2017-01-01

    Are Asian universities different from those in Western countries? Premised on the hypothesis that Asian universities are different because of hybridization between Western academic models and local traditional cultures, this paper investigates the hybrid characteristics in Malaysian universities resulting from interaction between contemporary…

  11. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-05-15

    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  12. Hybrid job shop scheduling

    NARCIS (Netherlands)

    Schutten, Johannes M.J.

    1995-01-01

    We consider the problem of scheduling jobs in a hybrid job shop. We use the term 'hybrid' to indicate that we consider a lot of extensions of the classic job shop, such as transportation times, multiple resources, and setup times. The Shifting Bottleneck procedure can be generalized to deal with

  13. Hybrid Shipboard Microgrids

    DEFF Research Database (Denmark)

    Othman @ Marzuki, Muzaidi Bin; Anvari-Moghaddam, Amjad; Guerrero, Josep M.

    2017-01-01

    Strict regulation on emissions of air pollutants imposed by the maritime authorities has led to the introduction of hybrid microgrids to the shipboard power systems (SPSs) which acts toward energy efficient ships with less pollution. A hybrid energy system can include different means of generation...

  14. Hybrid intelligent engineering systems

    CERN Document Server

    Jain, L C; Adelaide, Australia University of

    1997-01-01

    This book on hybrid intelligent engineering systems is unique, in the sense that it presents the integration of expert systems, neural networks, fuzzy systems, genetic algorithms, and chaos engineering. It shows that these new techniques enhance the capabilities of one another. A number of hybrid systems for solving engineering problems are presented.

  15. Editorial: Hybrid Systems

    DEFF Research Database (Denmark)

    Olderog, Ernst-Rüdiger; Ravn, Anders Peter

    2007-01-01

    An introduction to three papers in a special issue on Hybrid Systems. These paper were first presented at an IFIP WG 2.2 meeting in Skagen 2005.......An introduction to three papers in a special issue on Hybrid Systems. These paper were first presented at an IFIP WG 2.2 meeting in Skagen 2005....

  16. Pulmonary Toxicity of Cholinesterase Inhibitors

    National Research Council Canada - National Science Library

    Hilmas, Corey; Adler, Michael; Baskin, Steven I; Gupta, Ramesh C

    2006-01-01

    .... Whereas nerve agents were produced primarily for military deployment, other cholinesterase inhibitors were used for treating conditions such as myasthenia gravis and as pretreaunents for nerve agent exposure...

  17. Course on hybrid calculation

    International Nuclear Information System (INIS)

    Weill, J.; Tellier; Bonnemay; Craigne; Chareton; Di Falco

    1969-02-01

    After a definition of hybrid calculation (combination of analogue and digital calculation) with a distinction between series and parallel hybrid computing, and a description of a hybrid computer structure and of task sharing between computers, this course proposes a description of hybrid hardware used in Saclay and Cadarache computing centres, and of operations performed by these systems. The next part addresses issues related to programming languages and software. The fourth part describes how a problem is organised for its processing on these computers. Methods of hybrid analysis are then addressed: resolution of optimisation problems, of partial differential equations, and of integral equations by means of different methods (gradient, maximum principle, characteristics, functional approximation, time slicing, Monte Carlo, Neumann iteration, Fischer iteration)

  18. Hybrid functional pseudopotentials

    Science.gov (United States)

    Yang, Jing; Tan, Liang Z.; Rappe, Andrew M.

    2018-02-01

    The consistency between the exchange-correlation functional used in pseudopotential construction and in the actual density functional theory calculation is essential for the accurate prediction of fundamental properties of materials. However, routine hybrid density functional calculations at present still rely on generalized gradient approximation pseudopotentials due to the lack of hybrid functional pseudopotentials. Here, we present a scheme for generating hybrid functional pseudopotentials, and we analyze the importance of pseudopotential density functional consistency for hybrid functionals. For the PBE0 hybrid functional, we benchmark our pseudopotentials for structural parameters and fundamental electronic gaps of the Gaussian-2 (G2) molecular dataset and some simple solids. Our results show that using our PBE0 pseudopotentials in PBE0 calculations improves agreement with respect to all-electron calculations.

  19. Avoiding Deontic Explosion by Contextually Restricting Aggregation

    Science.gov (United States)

    Meheus, Joke; Beirlaen, Mathieu; van de Putte, Frederik

    In this paper, we present an adaptive logic for deontic conflicts, called P2.1 r , that is based on Goble's logic SDL a P e - a bimodal extension of Goble's logic P that invalidates aggregation for all prima facie obligations. The logic P2.1 r has several advantages with respect to SDL a P e. For consistent sets of obligations it yields the same results as Standard Deontic Logic and for inconsistent sets of obligations, it validates aggregation "as much as possible". It thus leads to a richer consequence set than SDL a P e. The logic P2.1 r avoids Goble's criticisms against other non-adjunctive systems of deontic logic. Moreover, it can handle all the 'toy examples' from the literature as well as more complex ones.

  20. Modeling decisions information fusion and aggregation operators

    CERN Document Server

    Torra, Vicenc

    2007-01-01

    Information fusion techniques and aggregation operators produce the most comprehensive, specific datum about an entity using data supplied from different sources, thus enabling us to reduce noise, increase accuracy, summarize and extract information, and make decisions. These techniques are applied in fields such as economics, biology and education, while in computer science they are particularly used in fields such as knowledge-based systems, robotics, and data mining. This book covers the underlying science and application issues related to aggregation operators, focusing on tools used in practical applications that involve numerical information. Starting with detailed introductions to information fusion and integration, measurement and probability theory, fuzzy sets, and functional equations, the authors then cover the following topics in detail: synthesis of judgements, fuzzy measures, weighted means and fuzzy integrals, indices and evaluation methods, model selection, and parameter extraction. The method...

  1. COSMIC DUST AGGREGATION WITH STOCHASTIC CHARGING

    International Nuclear Information System (INIS)

    Matthews, Lorin S.; Hyde, Truell W.; Shotorban, Babak

    2013-01-01

    The coagulation of cosmic dust grains is a fundamental process which takes place in astrophysical environments, such as presolar nebulae and circumstellar and protoplanetary disks. Cosmic dust grains can become charged through interaction with their plasma environment or other processes, and the resultant electrostatic force between dust grains can strongly affect their coagulation rate. Since ions and electrons are collected on the surface of the dust grain at random time intervals, the electrical charge of a dust grain experiences stochastic fluctuations. In this study, a set of stochastic differential equations is developed to model these fluctuations over the surface of an irregularly shaped aggregate. Then, employing the data produced, the influence of the charge fluctuations on the coagulation process and the physical characteristics of the aggregates formed is examined. It is shown that dust with small charges (due to the small size of the dust grains or a tenuous plasma environment) is affected most strongly

  2. Important Features of Sustainable Aggregate Resource Management

    Directory of Open Access Journals (Sweden)

    Slavko V. Šolar

    2004-06-01

    Full Text Available Every society, whether developed, developing or in a phase of renewal following governmental change, requires stable, adequate and secure supplies of natural resources. In the latter case, there could be significant need for construction materials for rebuilding infrastructure, industrial capacity, and housing. It is essential that these large-volume materials be provided in a rational manner that maximizes their societal contribution and minimizes environmental impacts. We describe an approach to resource management based on the principles of sustainable development. Sustainable Aggregate Resource Management offers a way of addressing the conflicting needs and interests of environmental, economic, and social systems. Sustainability is an ethics based concept that utilizes science and democratic processes to reach acceptable agreements and tradeoffs among interests, while acknowledging the fundamental importance of the environment and social goods. We discuss the features of sustainable aggregate resource management.

  3. Important features of Sustainable Aggregate Resource Management

    Science.gov (United States)

    Solar, Slavko V.; Shields, Deborah J.; Langer, William H.

    2004-01-01

    Every society, whether developed, developing or in a phase of renewal following governmental change, requires stable, adequate and secure supplies of natural resources. In the latter case, there could be significant need for construction materials for rebuilding infrastructure, industrial capacity, and housing. It is essential that these large-volume materials be provided in a rational manner that maximizes their societal contribution and minimizes environmental impacts. We describe an approach to resource management based on the principles of sustainable developed. Sustainable Aggregate Resource Management offers a way of addressing the conflicting needs and interests of environmental, economic, and social systems. Sustainability is an ethics based concept that utilizes science and democratic processes to reach acceptable agreements and tradeoffs among interests, while acknowledging the fundamental importance of the environment and social goods. We discuss the features of sustainable aggregate resource management.

  4. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  5. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  6. Statistical mixing and aggregation in Feller diffusion

    International Nuclear Information System (INIS)

    Anteneodo, C; Duarte Queirós, S M

    2009-01-01

    We consider Feller mean-reverting square-root diffusion, which has been applied to model a wide variety of processes with linearly state-dependent diffusion, such as stochastic volatility and interest rates in finance, and neuronal and population dynamics in the natural sciences. We focus on the statistical mixing (or superstatistical) process in which the parameter related to the mean value can fluctuate—a plausible mechanism for the emergence of heavy-tailed distributions. We obtain analytical results for the associated probability density function (both stationary and time-dependent), its correlation structure and aggregation properties. Our results are applied to explain the statistics of stock traded volume at different aggregation scales

  7. Denitrification in Soil Aggregate Analogues-Effect of Aggregate Size and Oxygen Diffusion

    Directory of Open Access Journals (Sweden)

    Steffen Schlüter

    2018-04-01

    Full Text Available Soil-borne nitrous oxide (N2O emissions have a high spatial and temporal variability which is commonly attributed to the occurrence of hotspots and hot moments for microbial activity in aggregated soil. Yet there is only limited information about the biophysical processes that regulate the production and consumption of N2O on microscopic scales in undisturbed soil. In this study, we introduce an experimental framework relying on simplified porous media that circumvents some of the complexities occuring in natural soils while fully accounting for physical constraints believed to control microbial activity in general and denitrification in particular. We used this framework to explore the impact of aggregate size and external oxygen concentration on the kinetics of O2 consumption, as well as CO2 and N2O production. Model aggregates of different sizes (3.5 vs. 7 mm diameter composed of porous, sintered glass were saturated with a defined growth medium containing roughly 109 cells ml−1 of the facultative anaerobic, nosZ-deficient denitrifier Agrobacterium tumefaciens with N2O as final denitrification product and incubated at five different oxygen levels (0–13 vol-%. We demonstrate that the onset of denitrification depends on the amount of external oxygen and the size of aggregates. Smaller aggregates were better supplied with oxygen due to a larger surface-to-volume ratio, which resulted in faster growth and an earlier onset of denitrification. In larger aggregates, the onset of denitrification was more gradual, but with comparably higher N2O production rates once the anoxic aggregate centers were fully developed. The normalized electron flow from the reduced carbon substrate to N-oxyanions (edenit-/etotal- ratio could be solely described as a function of initial oxygen concentration in the headspace with a simple, hyperbolic model, for which the two empirical parameters changed with aggregate size in a consistent way. These findings confirm the

  8. Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli and aggregative Citrobacter freundii: a consortium mediated by putative F pili

    Directory of Open Access Journals (Sweden)

    Araújo Ana CG

    2010-02-01

    Full Text Available Abstract Background Enteroaggregative Escherichia coli (EAEC are enteropathogenic strains identified by the aggregative adhesion (AA pattern that share the capability to form biofilms. Citrobacter freundii is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea. Results During an epidemiologic study focusing on infantile diarrhea, aggregative C. freundii (EACF and EAEC strains were concomitantly recovered from a severe case of mucous diarrhea. Thereby, the occurrence of synergic events involving these strains was investigated. Coinfection of HeLa cells with EACF and EAEC strains showed an 8-fold increase in the overall bacterial adhesion compared with single infections (P traA were capable of forming bacterial aggregates only in the presence of EACF. Scanning electronic microscopy analyses revealed that bacterial aggregates as well as enhanced biofilms formed by EACF and traA-positive EAEC were mediated by non-bundle forming, flexible pili. Moreover, mixed biofilms formed by EACF and traA-positive EAEC strains were significantly reduced using nonlethal concentration of zinc, a specific inhibitor of F pili. In addition, EAEC strains isolated from diarrheic children frequently produced single biofilms sensitive to zinc. Conclusions Putative F pili expressed by EAEC strains boosted mixed biofilm formation when in the presence of aggregative C. freundii.

  9. Pore structure of natural and regenerated soil aggregates

    DEFF Research Database (Denmark)

    Naveed, Muhammad; Arthur, Emmanuel; de Jonge, Lis Wollesen

    2014-01-01

    Quantitative characterization of aggregate pore structure can reveal the evolution of aggregates under different land use and management practices and their effects on soil processes and functions. Advances in X-ray Computed Tomography (CT) provide powerful means to conduct such characterization....... This study examined aggregate pore structure of three differently managed same textured Danish soils (mixed forage cropping, MFC; mixed cash cropping, MCC; cereal cash cropping, CCC) for (i) natural aggregates, and (ii) aggregates regenerated after 20 months of incubation. In total, 27 aggregates (8-16 mm...... pore diameter of 200 and 170 Hm, respectively. Pore shape analysis indicated that CCC and MFC aggregates had an abundance of rounded and elongated pores, respectively, and those of MCC were in-between CCC and MFC. Aggregate pore structure development in the lysimeters was nearly similar irrespective...

  10. Evaluation of recycled concrete as aggregate in new concrete pavements.

    Science.gov (United States)

    2014-04-01

    This study evaluated the use of recycled concrete as coarse aggregate in new concrete pavements. : Recycled concrete aggregate (RCA) produced from demolished pavements in three geographically dispersed locations in Washington state were used to perfo...

  11. performance of concrete with partial replacement of fine aggregates

    African Journals Online (AJOL)

    user

    aggregate with waste glass that will result in optimal compressive strength. A total of 36 cubes were ... to achieve the required strength and durability. The fine aggregate is ..... Ceramic Foundation Annual Technical Report, pp. 143-147. 2000.

  12. THE AGGREGATE IMPACT OF ONLINE RETAIL

    OpenAIRE

    Allen Tran

    2014-01-01

    To study the impact of online retail on aggregate welfare, I use a spatial model to calculate a new measure of store level retail productivity and each store's equilibrium response to increased competitive pressure from online retailers. The model is estimated on confidential store-level data spanning the universe of US retail stores, detailed local-level demographic data and shortest-route data between locations. From counterfactual exercises mimicking improvements in shipping and increased ...

  13. The Role of Content Aggregators In GEOValue

    Science.gov (United States)

    Wright, D. J.; Breyer, S.; Hogeweg, M.; Foust, J.; Jordan, L.; Plunkett, G.

    2016-12-01

    Data (aka content) in the form of numbers or layers, and transformed into information by way of maps, images, graphs, charts, tables, even stories, are foundational for a myriad of decision-makers. Recent advances in information technology, as well as civil remote sensing of the Earth, are rapidly allowing us to advance beyond mere static data collection and archiving, further enabling information awareness and understanding, and leading us towards knowledge and better decision making. However, such volumes, velocities, and varieties of data streams also bring with them serious dilemmas with regard to effective organization, cataloging, and easy access. This is where the role of aggregator comes in, with their provision of the necessary sustainability and reliability of information via proven, well-engineered platforms, all with the necessary interoperability and openness as guaranteed through the adoption of established standards. Information technology (IT) giants such as Google, Facebook, IBM and Apple are well known for aggregating just about every aspect of life in modern society, from our music to our mood swings. A use case of the Environmental Systems Research Institute (aka Esri) is presented as a geospatial aggregator. It has over the years, compiled, assembled and produced a carefully curated library of public content into a global "Living Atlas of the World," organized into different themes such as Earth observation, transportation, demographics, natural hazards, ecological land units, elevation, and more. Among a myriad of decision scenarios with this content to be presented is the tracking of sea ice in the Arctic, estimating potential impact to shipping lanes or coastal infrastructure, and forecasting future conditions. Esri as the main aggregator of Living Atlas content continues to welcome not only contributors who will publish new content to be included in this global Atlas, but fellow curators who will assist in reviewing, organizing, and even

  14. Rationality of limited rationality : some aggregate implications

    OpenAIRE

    Uri M. Possen; Mikko Puhakka

    1994-01-01

    In this paper we let economic agents choose whether to become fully rational or stay boundedly rational. Boundedly rational agents are less sophisticated in their information processing abilities. It is costly to acquire information needed to become fully rational, and thus not all agents are willing to incur those costs. We then explore the aggregate effects of endogenizing the decision whether the agent should or should not become fully rational in handling information. Since fully and boun...

  15. Material properties of frc with recycled aggregate

    Czech Academy of Sciences Publication Activity Database

    Trčková, Jiřina; Procházka, P.

    2011-01-01

    Roč. 8, č. 2 (2011), s. 105-113 ISSN 1214-9705 R&D Projects: GA ČR GA103/08/1197 Institutional research plan: CEZ:AV0Z30460519 Keywords : recycled aggregate * concrete composite * pullout test Subject RIV: JM - Building Engineering Impact factor: 0.530, year: 2011 http://www.irsm.cas.cz/abstracts/AGG/02_11/1_Trckova.pdf

  16. Social Networks: Rational Learning and Information Aggregation

    Science.gov (United States)

    2009-09-01

    predecessor, Gale and Kariv (2003) who generalize the payoff equalization result of Bala and Goyal (1998) in connected social networks (discussed below...requires more notation. Using Bayes’ Rule and the assumption of equal priors on the state θ, we have that the social belief given by observing... Social Networks: Rational Learning and Information Aggregation by Ilan Lobel B.Sc., Pontif́ıcia Universidade Católica do Rio de Janeiro (2004

  17. On Aggregating Human Capital Across Heterogeneous Cohorts

    DEFF Research Database (Denmark)

    Growiec, Jakub; Groth, Christian

    experience. Under the scenarios considered here, the "macro-Mincer" (log-linear) relationship between aggregate human capital and average years of schooling is obtained only in cases which are inconsistent with heterogeneity in years of schooling and based on empirically implausible demographic survival laws....... Our numerical results indicate that the macro-Mincer equation can be a reasonable approximation of the true relationship only if returns to schooling and work experience are roughly constant across countries...

  18. Aggregation Operator Based Fuzzy Pattern Classifier Design

    DEFF Research Database (Denmark)

    Mönks, Uwe; Larsen, Henrik Legind; Lohweg, Volker

    2009-01-01

    This paper presents a novel modular fuzzy pattern classifier design framework for intelligent automation systems, developed on the base of the established Modified Fuzzy Pattern Classifier (MFPC) and allows designing novel classifier models which are hardware-efficiently implementable....... The performances of novel classifiers using substitutes of MFPC's geometric mean aggregator are benchmarked in the scope of an image processing application against the MFPC to reveal classification improvement potentials for obtaining higher classification rates....

  19. Seasonal variability of soil aggregate stability

    Czech Academy of Sciences Publication Activity Database

    Rohošková, M.; Kodešová, R.; Jirků, V.; Žigová, Anna; Kozák, J.

    2009-01-01

    Roč. 11, - (2009), , , EGU2009-6341-3-EGU2009-6341-3 ISSN 1029-7006. [European Geosciences Union General Assembly. 19.04.2009-24.04.2009, Vienna] R&D Projects: GA ČR GA526/08/0434 Institutional research plan: CEZ:AV0Z30130516 Keywords : seasonal variability * soil aggregate stability * soil types Subject RIV: DF - Soil Science

  20. Dynamic Aggregation Protocol for Wireless Sensor Networks

    OpenAIRE

    Mounir Said , Adel; William Ibrahim , Ashraf; Soua , Ahmed; Afifi , Hossam

    2013-01-01

    International audience; Sensor networks suffer from limited capabilities such as bandwidth, low processing power, and memory size. There is therefore a need for protocols that deliver sensor data in an energy-efficient way to the sink. One of those techniques, it gathers sensors' data in a small size packet suitable for transmission. In this paper, we propose a new Effective Data Aggregation Protocol (DAP) to reduce the energy consumption in Wireless Sensor Networks (WSNs), which prolongs the...

  1. Role of Prion Protein Aggregation in Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Tullio Florio

    2012-07-01

    Full Text Available In several neurodegenerative diseases, such as Parkinson, Alzheimer’s, Huntington, and prion diseases, the deposition of aggregated misfolded proteins is believed to be responsible for the neurotoxicity that characterizes these diseases. Prion protein (PrP, the protein responsible of prion diseases, has been deeply studied for the peculiar feature of its misfolded oligomers that are able to propagate within affected brains, inducing the conversion of the natively folded PrP into the pathological conformation. In this review, we summarize the available experimental evidence concerning the relationship between aggregation status of misfolded PrP and neuronal death in the course of prion diseases. In particular, we describe the main findings resulting from the use of different synthetic (mainly PrP106-126 and recombinant PrP-derived peptides, as far as mechanisms of aggregation and amyloid formation, and how these different spatial conformations can affect neuronal death. In particular, most data support the involvement of non-fibrillar oligomers rather than actual amyloid fibers as the determinant of neuronal death.

  2. Disaggregases, molecular chaperones that resolubilize protein aggregates

    Directory of Open Access Journals (Sweden)

    David Z. Mokry

    2015-08-01

    Full Text Available The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

  3. Explaining the length threshold of polyglutamine aggregation

    International Nuclear Information System (INIS)

    De Los Rios, Paolo; Hafner, Marc; Pastore, Annalisa

    2012-01-01

    The existence of a length threshold, of about 35 residues, above which polyglutamine repeats can give rise to aggregation and to pathologies, is one of the hallmarks of polyglutamine neurodegenerative diseases such as Huntington’s disease. The reason why such a minimal length exists at all has remained one of the main open issues in research on the molecular origins of such classes of diseases. Following the seminal proposals of Perutz, most research has focused on the hunt for a special structure, attainable only above the minimal length, able to trigger aggregation. Such a structure has remained elusive and there is growing evidence that it might not exist at all. Here we review some basic polymer and statistical physics facts and show that the existence of a threshold is compatible with the modulation that the repeat length imposes on the association and dissociation rates of polyglutamine polypeptides to and from oligomers. In particular, their dramatically different functional dependence on the length rationalizes the very presence of a threshold and hints at the cellular processes that might be at play, in vivo, to prevent aggregation and the consequent onset of the disease. (paper)

  4. Explaining the length threshold of polyglutamine aggregation

    Science.gov (United States)

    De Los Rios, Paolo; Hafner, Marc; Pastore, Annalisa

    2012-06-01

    The existence of a length threshold, of about 35 residues, above which polyglutamine repeats can give rise to aggregation and to pathologies, is one of the hallmarks of polyglutamine neurodegenerative diseases such as Huntington’s disease. The reason why such a minimal length exists at all has remained one of the main open issues in research on the molecular origins of such classes of diseases. Following the seminal proposals of Perutz, most research has focused on the hunt for a special structure, attainable only above the minimal length, able to trigger aggregation. Such a structure has remained elusive and there is growing evidence that it might not exist at all. Here we review some basic polymer and statistical physics facts and show that the existence of a threshold is compatible with the modulation that the repeat length imposes on the association and dissociation rates of polyglutamine polypeptides to and from oligomers. In particular, their dramatically different functional dependence on the length rationalizes the very presence of a threshold and hints at the cellular processes that might be at play, in vivo, to prevent aggregation and the consequent onset of the disease.

  5. Characterising risk - aggregated metrics: radiation and noise

    International Nuclear Information System (INIS)

    Passchier, W.

    1998-01-01

    The characterisation of risk is an important phase in the risk assessment - risk management process. From the multitude of risk attributes a few have to be selected to obtain a risk characteristic or profile that is useful for risk management decisions and implementation of protective measures. One way to reduce the number of attributes is aggregation. In the field of radiation protection such an aggregated metric is firmly established: effective dose. For protection against environmental noise the Health Council of the Netherlands recently proposed a set of aggregated metrics for noise annoyance and sleep disturbance. The presentation will discuss similarities and differences between these two metrics and practical limitations. The effective dose has proven its usefulness in designing radiation protection measures, which are related to the level of risk associated with the radiation practice in question, given that implicit judgements on radiation induced health effects are accepted. However, as the metric does not take into account the nature of radiation practice, it is less useful in policy discussions on the benefits and harm of radiation practices. With respect to the noise exposure metric, only one effect is targeted (annoyance), and the differences between sources are explicitly taken into account. This should make the metric useful in policy discussions with respect to physical planning and siting problems. The metric proposed has only significance on a population level, and can not be used as a predictor for individual risk. (author)

  6. Understanding sexual harassment using aggregate construct models.

    Science.gov (United States)

    Nye, Christopher D; Brummel, Bradley J; Drasgow, Fritz

    2014-11-01

    Sexual harassment has received a substantial amount of empirical attention over the past few decades, and this research has consistently shown that experiencing these behaviors has a detrimental effect on employees' well-being, job attitudes, and behaviors at work. However, these findings, and the conclusions that are drawn from them, make the implicit assumption that the empirical models used to examine sexual harassment are properly specified. This article presents evidence that properly specified aggregate construct models are more consistent with theoretical structures and definitions of sexual harassment and can result in different conclusions about the nomological network of harassment. Results from 3 large samples, 2 military and 1 from a civilian population, are used to illustrate the differences between aggregate construct and reflective indicator models of sexual harassment. These analyses suggested that the factor structure and the nomological network of sexual harassment differ when modeling harassment as an aggregate construct. The implications of these results for the continued study of sexual harassment are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  7. Energy Efficient Payload Aggregation in WSNs

    Directory of Open Access Journals (Sweden)

    Ákos MILÁNKOVICH

    2015-06-01

    Full Text Available Creating wireless sensor networks requires a different approach than traditional communication networks because energy efficiency plays a key role in sensor networks, which consist of devices without external power. The amount of energy used determines the lifetime of these devices. In most cases data packets are less sensitive to delay, thus can be aggregated, making it possible to gather more useful information reducing the energy required to transmit information. This article discusses the energy efficiency of different Forward Error Correction algorithms and presents a method to calculate the optimal amount of aggregation of the data packets in terms of power consumption, while taking into account the Bit Error Rate characteristics of the wireless channel. The contribution of this paper is a general method to improve the energy efficiency of wireless sensor networks by using the optimal amount of aggregation in case of different Forward Error Correction codes and channel characteristics. The presented results can be applied to any packet-based wireless protocol.

  8. Concrete manufacture with un-graded recycled aggregates

    OpenAIRE

    Richardson, Alan; Coventry, Kathryn; Graham, Sue

    2009-01-01

    Purpose – The purpose of this paper is to investigate whether concrete that includes un-graded recycled aggregates can be manufactured to a comparable strength to concrete manufactured from virgin aggregates. \\ud \\ud Design/methodology/approach – A paired comparison test was used to evaluate the difference between concrete made with virgin aggregates (plain control) and concrete including recycled waste. Un-graded construction demolition waste and un-graded ground glass were used as aggregate...

  9. Implications Of Aggregate Demand Elasticity For The Phillips Curve

    OpenAIRE

    Ben L. Kyer; Gary E. Maggs

    2004-01-01

    While the general relationship between the aggregate supply curve and the Phillips curve is recognized, the importance of aggregate demand and, in particular, aggregate demand elasticity, for the inflation-unemployment relationship has been untreated. We believe, however, that the elasticity of aggregate demand with respect to the general price level does have some significance for the short-run Phillips curve since, on a general level, the economy's equilibrium price level, inflation rate, r...

  10. SHAPE ANALYSIS OF FINE AGGREGATES USED FOR CONCRETE

    OpenAIRE

    HE, Huan; Courard, Luc; Pirard, Eric; Michel, Frédéric

    2016-01-01

    Fine aggregate is one of the essential components in concrete and significantly influences the material properties. As parts of natures, physical characteristics of fine aggregate are highly relevant to its behaviors in concrete. The most of previous studies are mainly focused on the physical properties of coarse aggregate due to the equipment limitations. In this paper, two typical fine aggregates, i.e. river sand and crushed rock, are selected for shape characterization. The new developed d...

  11. Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization.

    Science.gov (United States)

    Chang, M C; Uang, B J; Tsai, C Y; Wu, H L; Lin, B R; Lee, C S; Chen, Y J; Chang, C H; Tsai, Y L; Kao, C J; Jeng, J H

    2007-09-01

    Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect. We tested the effect of HC on platelet aggregation, thromboxane B(2) (TXB(2)) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed. HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB(2) production. HC inhibited the thrombin-induced TXB(2) production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB(2) production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca(2+) mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo. HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB(2) production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions.

  12. Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity.

    Science.gov (United States)

    Yamashita, Arisa; Hiraki, Yuri; Yamazaki, Tetsuo

    2017-06-10

    αB-crystallin (αBC) is a small heat shock protein. Mutations in the αBC gene are linked to α-crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G αBC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant's aggregation in HeLa cells was prevented by enforced expression of αBC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored αBC (TMαBC). The ER transmembrane CLN6 protein was identified as a TMαBC's binder. CLN6 knockdown in HeLa cells attenuated TMαBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMαBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMαBC was not co-expressed. Furthermore, CLN6's antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMαBC, but also serves as a potential target of therapeutic interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Interaction of amyloid inhibitor proteins with amyloid beta peptides: insight from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Payel Das

    Full Text Available Knowledge of the detailed mechanism by which proteins such as human αB- crystallin and human lysozyme inhibit amyloid beta (Aβ peptide aggregation is crucial for designing treatment for Alzheimer's disease. Thus, unconstrained, atomistic molecular dynamics simulations in explicit solvent have been performed to characterize the Aβ17-42 assembly in presence of the αB-crystallin core domain and of lysozyme. Simulations reveal that both inhibitor proteins compete with inter-peptide interaction by binding to the peptides during the early stage of aggregation, which is consistent with their inhibitory action reported in experiments. However, the Aβ binding dynamics appear different for each inhibitor. The binding between crystallin and the peptide monomer, dominated by electrostatics, is relatively weak and transient due to the heterogeneous amino acid distribution of the inhibitor surface. The crystallin-bound Aβ oligomers are relatively long-lived, as they form more extensive contact surface with the inhibitor protein. In contrast, a high local density of arginines from lysozyme allows strong binding with Aβ peptide monomers, resulting in stable complexes. Our findings not only illustrate, in atomic detail, how the amyloid inhibitory mechanism of human αB-crystallin, a natural chaperone, is different from that of human lysozyme, but also may aid de novo design of amyloid inhibitors.

  14. Linkages between aggregate formation, porosity and soil chemical properties

    NARCIS (Netherlands)

    Regelink, I.C.; Stoof, C.R.; Rousseva, S.; Weng, L.; Lair, G.J.; Kram, P.; Nikolaidis, N.P.; Kercheva, M.; Banwart, S.; Comans, R.N.J.

    2015-01-01

    Linkages between soil structure and physical–chemical soil properties are still poorly understood due to the wide size-range at which aggregation occurs and the variety of aggregation factors involved. To improve understanding of these processes, we collected data on aggregate fractions, soil

  15. Performance of Uplink Carrier Aggregation in LTE-Advanced Systems

    DEFF Research Database (Denmark)

    Wang, Hua; Rosa, Claudio; Pedersen, Klaus

    2010-01-01

    Carrier aggregation (CA) has been proposed to aggregate two or more component carriers (CCs) to support a much wider transmission bandwidth for LTE-Advanced systems. With carrier aggregation, it is possible to schedule a user equipment (UE) on multiple component carriers simultaneously. In this p...

  16. Efficient external memory structures for range-aggregate queries

    DEFF Research Database (Denmark)

    Agarwal, P.K.; Yang, J.; Arge, L.

    2013-01-01

    We present external memory data structures for efficiently answering range-aggregate queries. The range-aggregate problem is defined as follows: Given a set of weighted points in Rd, compute the aggregate of the weights of the points that lie inside a d-dimensional orthogonal query rectangle. The...

  17. Procedure for Validation of Aggregators Providing Demand Response

    DEFF Research Database (Denmark)

    Bondy, Daniel Esteban Morales; Gehrke, Oliver; Thavlov, Anders

    2016-01-01

    of small heterogeneous resources that are geographically distributed. Therefore, a new test procedure must be designed for the aggregator validation. This work proposes such a procedure and exemplifies is with a study case. The validation of aggregators is essential if aggregators are to be integrated...... succesfully into the power system....

  18. Environmental suitability of recycled concrete aggregate in highways : [research summary].

    Science.gov (United States)

    2015-01-01

    Natural highway aggregate is a finite resource that with continued use in construction : activities but some good quality aggregates used in existing concrete structures may be : re-used to replace with the natural aggregate. Due to the repair or rep...

  19. Creep and shrinkage behaviour of concrete with mixed recycled aggregates

    NARCIS (Netherlands)

    Hordijk, D.A.; Uijl, J. den

    1999-01-01

    For environmental reasons the interest in possibilities to use recycled aggregates in concrete is strongly increasing. World-wide, most attention with respect to recycled aggregates is paid to the quality of the aggregates. Still only limited information is available for the mechanica! properties of

  20. Aggregate formation in 3D turbulent-like flows

    NARCIS (Netherlands)

    Dominguez, A.; Aartrijk, van M.; Castello, Del L.; Clercx, H.J.H.; Geurts, B.; Clercx, H

    2006-01-01

    Aggregate formation is an important process in industrial and environ mental turbulent flows. Two examples in the environmental area, where turbulent aggregate formation takes place, are raindrop formation in clouds and Marine Snow (aggregate) formation in the upper layer in the oceans. The

  1. Evaluation of Colemanite Waste as Aggregate Hot Mix Asphalt Concrete

    Directory of Open Access Journals (Sweden)

    Nihat MOROVA

    2015-09-01

    Full Text Available In this study usability of waste colemanite which is obtained after cutting block colemanite for giving proper shape to blocks as an aggregate in hot mix asphalt. For this aim asphalt concrete samples were prepared with four different aggregate groups and optimum bitumen content was determined. First of all only limestone was used as an aggregate. After that, only colemanite aggregate was used with same aggregate gradation. Then, the next step of the study, Marshall samples were produced by changing coarse and fine aggregate gradation as limestone and colemanite and Marshall test were conducted. When evaluated the results samples which produced with only limestone aggregate gave the maximum Marshall Stability value. When handled other mixture groups (Only colemanite, colemanite as coarse aggregate-limestone as fine aggregate, colemanite as fine aggregate-limestone as coarse aggregate all groups were verified specification limits. As a result, especially in areas where there is widespread colemanite waste, if transportation costs did not exceed the cost of limestone, colemanite stone waste could be used instead of limestone in asphalt concrete mixtures as fine aggregate

  2. Vocal Fold Mucus Aggregation in Persons with Voice Disorders

    Science.gov (United States)

    Bonilha, Heather Shaw; White, Lisa; Kuckhahn, Kelsey; Gerlach, Terri Treman; Deliyski, Dimitar D.

    2012-01-01

    Mucus aggregation on the vocal folds is a common finding from laryngeal endoscopy. Patients with voice disorders report the presence of mucus aggregation. Patients also report that mucus aggregation causes them to clear their throat, a behavior believed to be harmful to vocal fold mucosa. Even though clinicians and patients report and discuss…

  3. 40 CFR 63.1408 - Aggregate batch vent stream provisions.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 11 2010-07-01 2010-07-01 true Aggregate batch vent stream provisions... § 63.1408 Aggregate batch vent stream provisions. (a) Emission standards. Owners or operators of aggregate batch vent streams at a new or existing affected source shall comply with either paragraph (a)(1...

  4. 21 CFR 1303.13 - Adjustments of aggregate production quotas.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Adjustments of aggregate production quotas. 1303.13 Section 1303.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE QUOTAS Aggregate Production and Procurement Quotas § 1303.13 Adjustments of aggregate production quotas. (a) The...

  5. 21 CFR 1303.11 - Aggregate production quotas.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Aggregate production quotas. 1303.11 Section 1303.11 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE QUOTAS Aggregate Production and Procurement Quotas § 1303.11 Aggregate production quotas. (a) The Administrator shall determine...

  6. Cigarette smoking increases white blood cell aggregation in whole blood.

    OpenAIRE

    Bridges, A B; Hill, A; Belch, J J

    1993-01-01

    We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.

  7. Effect of natural antioxidants on the aggregation and disaggregation ...

    African Journals Online (AJOL)

    Conclusion: High antioxidant activities were positively correlated with the inhibition of Aβ aggregation, although not with the disaggregation of pre-formed Aβ aggregates. Nevertheless, potent antioxidants may be helpful in treating Alzheimer's disease. Keywords: Alzheimer's disease, β-Amyloid, Aggregation, Disaggregation ...

  8. Aggregated nanoplatelets: optical properties and optically induced deaggregation

    International Nuclear Information System (INIS)

    Jayabalan, J; Singh, Asha; Chari, Rama; Srivastava, Himanshu; Srivastava, A K; Mukhopadhyay, P K; Oak, S M

    2008-01-01

    A study of aggregation and laser-induced deaggregation of silver nanospheres and nanoplatelets in colloidal form is presented. Changes in the extinction spectrum caused by aggregation are explained using a two-particle approximation. In the case of platelets, controlled laser irradiation is shown to reverse the aggregation process.

  9. Aggregated nanoplatelets: optical properties and optically induced deaggregation

    Energy Technology Data Exchange (ETDEWEB)

    Jayabalan, J; Singh, Asha; Chari, Rama [Laser Physics Application Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Srivastava, Himanshu; Srivastava, A K [Indus Synchrotrons Utilization Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India); Mukhopadhyay, P K; Oak, S M [Solid State Laser Division, Raja Ramanna Centre for Advanced Technology, Indore 452013 (India)], E-mail: jjaya@cat.ernet.in

    2008-11-05

    A study of aggregation and laser-induced deaggregation of silver nanospheres and nanoplatelets in colloidal form is presented. Changes in the extinction spectrum caused by aggregation are explained using a two-particle approximation. In the case of platelets, controlled laser irradiation is shown to reverse the aggregation process.

  10. Aggregate formation in 3D turbulent-like flows

    NARCIS (Netherlands)

    Dominguez, A.; Clercx, H.J.H.

    2006-01-01

    Aggregate formation is an important process in industrial and environmental turbulent flows. In oceans turbulence play an important role on Marine Snow (aggregate) formation. For a proper description, the study of aggregate formation in turbulent flows requires a particle based model i.e. following

  11. Retiring the Short-Run Aggregate Supply Curve

    Science.gov (United States)

    Elwood, S. Kirk

    2010-01-01

    The author argues that the aggregate demand/aggregate supply (AD/AS) model is significantly improved--although certainly not perfected--by trimming it of the short-run aggregate supply (SRAS) curve. Problems with the SRAS curve are shown first for the AD/AS model that casts the AD curve as identifying the equilibrium level of output associated…

  12. Biological abatement of cellulase inhibitors

    Science.gov (United States)

    Bio-abatement uses a fungus to metabolize and remove fermentation inhibitors. To determine whether bio-abatement could alleviate enzyme inhibitor effects observed in biomass liquors after pretreatment, corn stover at 10% (w/v) solids was pretreated with either dilute acid or liquid hot water. The ...

  13. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

    2004-01-01

    -amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

  14. Corrosion inhibitors. Manufacture and technology

    International Nuclear Information System (INIS)

    Ranney, M.W.

    1976-01-01

    Detailed information is presented relating to corrosion inhibitors. Areas covered include: cooling water, boilers and water supply plants; oil well and refinery operations; fuel and lubricant additives for automotive use; hydraulic fluids and machine tool lubes; grease compositions; metal surface treatments and coatings; and general processes for corrosion inhibitors

  15. Cell Surface Binding and Internalization of Aβ Modulated by Degree of Aggregation

    Directory of Open Access Journals (Sweden)

    David A. Bateman

    2011-01-01

    Full Text Available The amyloid peptides, Aβ40 and Aβ42, are generated through endoproteolytic cleavage of the amyloid precursor protein. Here we have developed a model to investigate the interaction of living cells with various forms of aggregated Aβ40/42. After incubation at endosomal pH 6, we observed a variety of Aβ conformations after 3 (Aβ3, 24 (Aβ24, and 90 hours (Aβ90. Both Aβ4224 and Aβ4024 were observed to rapidly bind and internalize into differentiated PC12 cells, leading to accumulation in the lysosome. In contrast, Aβ40/4290 were both found to only weakly associate with cells, but were observed as the most aggregated using dynamic light scattering and thioflavin-T. Internalization of Aβ40/4224 was inhibited with treatment of monodansylcadaverine, an endocytosis inhibitor. These studies indicate that the ability of Aβ40/42 to bind and internalize into living cells increases with degree of aggregation until it reaches a maximum beyond which its ability to interact with cells diminishes drastically.

  16. β-Amyloid-derived pentapeptide RIIGLa inhibits Aβ1-42 aggregation and toxicity

    International Nuclear Information System (INIS)

    Fueloep, Livia; Zarandi, Marta; Datki, Zsolt; Soos, Katalin; Penke, Botond

    2004-01-01

    Pr-IIGL a , a derivative of the tetrapeptide β-amyloid 31-34 (Aβ 31-34 ), exerts controversial effects: it is toxic in a neuroblastoma culture, but it protects glial cells from the cytotoxic action of Aβ 1-42 . For an understanding of this phenomenon, a new pentapeptide, RIIGL a was synthetized, and both compounds were studied by different physicochemical and biological methods. Transmission electron microscopic (TEM) studies revealed that Pr-IIGL a forms fibrillar aggregates, whereas RIIGL a does not form fibrils. Congo red binding studies furnished the same results. Aggregated Pr-IIGL a acts as a cytotoxic agent in neuroblastoma cultures, but RIIGL a does not display inherent toxicity. RIIGL a co-incubated with Aβ 1-42 inhibits the formation of mature amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar Aβ 1-42 . These results indicate that RIIGL a is an effective inhibitor of both the aggregation and the toxic effects of Aβ 1-42 and can serve as a lead compound for the design of novel neuroprotective peptidomimetics

  17. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry

    Directory of Open Access Journals (Sweden)

    Irina V. Gorudko

    2013-07-01

    Myeloperoxidase (MPO is a heme-containing enzyme released from activated leukocytes into the extracellular space during inflammation. Its main function is the production of hypohalous acids that are potent oxidants. MPO can also modulate cell signaling and inflammatory responses independently of its enzymatic activity. Because MPO is regarded as an important risk factor for cardiovascular diseases associated with increased platelet activity, we studied the effects of MPO on human platelet functional properties. Laser scanning confocal microscopy was used to reveal carbohydrate-independent MPO binding to human platelet membrane. Adding MPO to platelets did not activate their aggregation under basal conditions (without agonist. In contrast, MPO augmented agonist-induced platelet aggregation, which was not prevented by MPO enzymatic activity inhibitors. It was found that exposure of platelets to MPO leads to actin cytoskeleton reorganization and an increase in their elasticity. Furthermore, MPO evoked a rise in cytosolic Ca2+ through enhancement of store-operated Ca2+ entry (SOCE. Together, these findings indicate that MPO is not a direct agonist but rather a mediator that binds to human platelets, induces actin cytoskeleton reorganization and affects the mechanical stiffness of human platelets, resulting in potentiating SOCE and agonist-induced human platelet aggregation. Therefore, an increased activity of platelets in vascular disease can, at least partly, be provided by MPO elevated concentrations.

  18. Mechanical properties of recycled concrete with demolished waste concrete aggregate and clay brick aggregate

    Science.gov (United States)

    Zheng, Chaocan; Lou, Cong; Du, Geng; Li, Xiaozhen; Liu, Zhiwu; Li, Liqin

    2018-06-01

    This paper presents an experimental investigation on the effect of the replacement of natural coarse aggregate (NCA) with either recycled concrete aggregate (RCA) or recycled clay brick aggregate (RBA) on the compressive strengths of the hardened concrete. Two grades (C25 and C50) of concrete were investigated, which were achieved by using different water-to-cement ratios. In each grade concrete five different replacement rates, 0%, 25%, 50%, 75% and 100% were considered. In order to improve the performance of the recycled aggregates in the concrete mixes, the RCA and RBA were carefully sieved by using the optimal degradation. In this way the largest reduction in the 28-day compressive strength was found to be only 7.2% and 9.6% for C25 and C50 recycled concrete when the NCA was replaced 100% by RCA, and 11% and 13% for C25 and C50 recycled concrete when the NCA was replaced 100% by RBA. In general, the concrete with RCA has better performance than the concrete with RBA. The comparison of the present experimental results with those reported in literature for hardened concrete with either RCA or RBA demonstrates the effectiveness in improving the compressive strength by using the optimal gradation of recycled aggregates.

  19. Sustainable normal and high strength recycled aggregate concretes using crushed tested cylinders as coarse aggregates

    Directory of Open Access Journals (Sweden)

    Bilal S. Hamad

    2017-12-01

    Full Text Available The paper reports on a research program that was designed at the American University of Beirut (AUB to investigate the fresh and hardened mechanical properties of a high performance concrete mix produced with partial or full substitution of crushed natural lime-stone aggregates with recycled aggregates from crushed tested cylinders in batching plants. Choosing crushed cylinders as source of recycling would result in reusing portion of the waste products of the concrete production industry. An extensive concrete batching and testing program was conducted to achieve two optimum normal and high strength concrete mixes. The variables were the nominal concrete strength (28 or 60 MPa and the percentage replacement of natural coarse aggregates with recycled aggregates from crushed tested cylinders (0, 20, 40, 60, 80, or 100%. Normal strength tested cylinders were used as source of the recycled aggregates for the normal strength concrete (NSC mix and high strength tested cylinders were used for the high strength concrete (HSC mix. Tests on the trial batches included plastic state slump and hardened state mechanical properties including cylinder compressive strength, cylinder splitting tensile strength, modulus of elasticity, and standard beams flexural strength. The results indicated no significant effect on the slump and around 10% average reduction in the hardened mechanical properties for both investigated levels of concrete compressive strength.

  20. Sand Cement Brick Containing Recycled Concrete Aggregate as Fine-Aggregate Replacement

    Directory of Open Access Journals (Sweden)

    Sheikh Khalid Faisal

    2017-01-01

    Full Text Available Nowadays, the usage amount of the concrete is increasing drastically. The construction industry is a huge consumer of natural consumer. It is also producing the huge wastage products. The usage of concrete has been charged to be not environmentally friendly due to depletion of reserve natural resources, high energy consumption and disposal issues. The conservation of natural resources and reduction of disposal site by reuse and recycling waste material was interest possibilites. The aim of this study is to determine the physical and mechanical properties of sand cement brick containing recycled concrete aggregate and to determine the optimum mix ratio containing recycled concrete aggregate. An experiment done by comparing the result of control specimen using 100% natural sand with recycled concrete aggregate replacement specimen by weight for 55%, 65%, and 75%. The sample was tested under density, compressive strength, flexural strength and water absorption to study the effect of using recycled concrete aggregate on the physical and mechanical properties of bricks. The result shows that the replacement of natural sand by recycled concrete aggregate at the level of 55% provide the highest compressive and flexural strength compared to other percentage and control specimen. However, if the replacement higher than 55%, the strength of brick was decreased for compressive and flexural strength, respectively. The relationship of compressive-flexural strength is determined from statistical analysis and the predicted result can be obtained by using equation ff,RCA = 0.5375 (fc0.3272.

  1. Hybrid electric vehicles TOPTEC

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-06-21

    This one-day TOPTEC session began with an overview of hybrid electric vehicle technology. Updates were given on alternative types of energy storage, APU control for low emissions, simulation programs, and industry and government activities. The keynote speech was about battery technology, a key element to the success of hybrids. The TOPEC concluded with a panel discussion on the mission of hybrid electric vehicles, with a perspective from industry and government experts from United States and Canada on their view of the role of this technology.

  2. Hybrid systems with constraints

    CERN Document Server

    Daafouz, Jamal; Sigalotti, Mario

    2013-01-01

    Control theory is the main subject of this title, in particular analysis and control design for hybrid dynamic systems.The notion of hybrid systems offers a strong theoretical and unified framework to cope with the modeling, analysis and control design of systems where both continuous and discrete dynamics interact. The theory of hybrid systems has been the subject of intensive research over the last decade and a large number of diverse and challenging problems have been investigated. Nevertheless, many important mathematical problems remain open.This book is dedicated mainly to

  3. Towers of hybrid mesons

    International Nuclear Information System (INIS)

    Semay, Claude; Buisseret, Fabien; Silvestre-Brac, Bernard

    2009-01-01

    A hybrid meson is a quark-antiquark pair in which, contrary to ordinary mesons, the gluon field is in an excited state. In the framework of constituent models, the interaction potential is assumed to be the energy of an excited string. An approximate, but accurate, analytical solution of the Schroedinger equation with such a potential is presented. When applied to hybrid charmonia and bottomonia, towers of states are predicted in which the masses are a linear function of a harmonic oscillator band number for the quark-antiquark pair. Such a formula could be a reliable guide for the experimental detection of heavy hybrid mesons.

  4. Hybrid Bloch brane

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D.; Lima, Elisama E.M.; Losano, L. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, PB (Brazil)

    2017-02-15

    This work reports on models described by two real scalar fields coupled with gravity in the five-dimensional spacetime, with a warped geometry involving one infinite extra dimension. Through a mechanism that smoothly changes a thick brane into a hybrid brane, one investigates the appearance of hybrid branes hosting internal structure, characterized by the splitting on the energy density and the volcano potential, induced by the parameter which controls interactions between the two scalar fields. In particular, we investigate distinct symmetric and asymmetric hybrid brane scenarios. (orig.)

  5. Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

    Directory of Open Access Journals (Sweden)

    Kurokawa Y

    2017-05-01

    Full Text Available Yoshika Kurokawa,1 Hideko Sone,1 Tin-Tin Win-Shwe,1 Yang Zeng,1 Hiroyuki Kimura,2 Yosuke Koyama,1 Yusuke Yagi,2 Yasuto Matsui,3 Masashi Yamazaki,4 Seishiro Hirano1 1Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki, 2Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 3Department of Environmental Engineering, Kyoto University Graduate School of Engineering, Kyoto, 4TIA Center Office, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan Abstract: Dendrimers have been expected as excellent nanodevices for brain medication. An amine-terminated polyamidoamine dendrimer (PD, an unmodified plain type of PD, has the obvious disadvantage of cytotoxicity, but still serves as an attractive molecule because it easily adheres to the cell surface, facilitating easy cellular uptake. Single-photon emission computed tomographic imaging of a mouse following intravenous injection of a radiolabeled PD failed to reveal any signal in the intracranial region. Furthermore, examination of the permeability of PD particles across the blood–brain barrier (BBB in vitro using a commercially available kit revealed poor permeability of the nanoparticles, which was suppressed by an inhibitor of caveolae-mediated endocytosis, but not by an inhibitor of macropinocytosis. Physicochemical analysis of the PD revealed that cationic PDs are likely to aggregate promptly upon mixing with body fluids and that this prompt aggregation is probably driven by non-Derjaguin–Landau–Verwey–Overbeek attractive forces originating from the surrounding divalent ions. Atomic force microscopy observation of a freshly cleaved mica plate soaked in dendrimer suspension (culture media confirmed prompt aggregation. Our study revealed poor transfer of intravenously administered cationic PDs into the intracranial nervous tissue, and the results of our analysis

  6. Rosuvastatin ameliorates cognitive impairment in rats fed with high-salt and cholesterol diet via inhibiting acetylcholinesterase activity and amyloid beta peptide aggregation.

    Science.gov (United States)

    Husain, I; Akhtar, M; Abdin, M Zainul; Islamuddin, M; Shaharyar, M; Najmi, A K

    2018-04-01

    Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ 1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ 1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aβ 1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aβ 1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.

  7. Hybrid thin films derived from UV-curable acrylate-modified waterborne polyurethane and monodispersed colloidal silica

    Directory of Open Access Journals (Sweden)

    C. H. Yang

    2012-01-01

    Full Text Available Hybrid thin films containing nano-sized inorganic domains were synthesized from UV-curable acrylate-modified waterborne polyurethane (WPU-AC and monodispersed colloidal silica with coupling agent. The coupling agent, 3-(trimethoxysilylpropyl methacrylate (MSMA, was bonded onto colloidal silica first, and then mixed with WPU-AC to form a precursor solution. This precursor was spin coated, dried and UV-cured to generate the hybrid films. The silica content in the hybrid thin films was varied from 0 to 30 wt%. Experimental results showed the aggregation of silica particles in the hybrid films. Thus, the silica domain in the hybrid films was varied from 30 to 50 nm by the different ratios of MSMAsilica to WPU-AC. The prepared hybrid films from the crosslinked WPU-AC/MSMA-silica showed much better thermal stability and mechanical properties than pure WPU-AC.

  8. Formula hybrid SAE.

    Science.gov (United States)

    2013-09-01

    User-friendly tools are needed for undergraduates to learn about component sizing, powertrain integration, and control : strategies for student competitions involving hybrid vehicles. A TK Solver tool was developed at the University of Idaho for : th...

  9. Hybrid adsorptive membrane reactor

    Science.gov (United States)

    Tsotsis, Theodore T [Huntington Beach, CA; Sahimi, Muhammad [Altadena, CA; Fayyaz-Najafi, Babak [Richmond, CA; Harale, Aadesh [Los Angeles, CA; Park, Byoung-Gi [Yeosu, KR; Liu, Paul K. T. [Lafayette Hill, PA

    2011-03-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  10. Hybrid plasmachemical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Lelevkin, V. M., E-mail: lelevkin44@mail.ru; Smirnova, Yu. G.; Tokarev, A. V. [Kyrgyz-Russian Slavic University (Kyrgyzstan)

    2015-04-15

    A hybrid plasmachemical reactor on the basis of a dielectric barrier discharge in a transformer is developed. The characteristics of the reactor as functions of the dielectric barrier discharge parameters are determined.

  11. Marine Fish Hybridization

    KAUST Repository

    He, Song

    2017-01-01

    for each hybrid offspring in each case, haploweb analysis on diagnostic markers (nuclear and/or mitochondrial) and the DAPC/PCA analysis on microsatellite data were used. By combining the genetic evidences, morphological traits, and ecological observations

  12. Perspectives in the development of hybrid bifunctional antitumour agents.

    Science.gov (United States)

    Musso, Loana; Dallavalle, Sabrina; Zunino, Franco

    2015-08-15

    In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents. Copyright © 2015. Published by Elsevier Inc.

  13. Aggregation of flexible polyelectrolytes: Phase diagram and dynamics.

    Science.gov (United States)

    Tom, Anvy Moly; Rajesh, R; Vemparala, Satyavani

    2017-10-14

    Similarly charged polymers in solution, known as polyelectrolytes, are known to form aggregated structures in the presence of oppositely charged counterions. Understanding the dependence of the equilibrium phases and the dynamics of the process of aggregation on parameters such as backbone flexibility and charge density of such polymers is crucial for insights into various biological processes which involve biological polyelectrolytes such as protein, DNA, etc. Here, we use large-scale coarse-grained molecular dynamics simulations to obtain the phase diagram of the aggregated structures of flexible charged polymers and characterize the morphology of the aggregates as well as the aggregation dynamics, in the presence of trivalent counterions. Three different phases are observed depending on the charge density: no aggregation, a finite bundle phase where multiple small aggregates coexist with a large aggregate and a fully phase separated phase. We show that the flexibility of the polymer backbone causes strong entanglement between charged polymers leading to additional time scales in the aggregation process. Such slowing down of the aggregation dynamics results in the exponent, characterizing the power law decay of the number of aggregates with time, to be dependent on the charge density of the polymers. These results are contrary to those obtained for rigid polyelectrolytes, emphasizing the role of backbone flexibility.

  14. Recycled aggregates in concrete production: engineering properties and environmental impact

    Directory of Open Access Journals (Sweden)

    Seddik Meddah Mohammed

    2017-01-01

    Full Text Available Recycled concrete aggregate is considered as the most abundant and used secondary aggregate in concrete production, other types of solid waste are also being used in concrete for specific purposes and to achieve some desired properties. Recycled aggregates and particularly, recycled concrete aggregate substantially affect the properties and mix design of concrete both at fresh and hardened states since it is known by high porosity due to the adhered layer of old mortar on the aggregate which results in a high water absorption of the recycled secondary aggregate. This leads to lower density and strength, and other durability related properties. The use of most recycled aggregate in concrete structures is still limited to low strength and non-structural applications due to important drop in strength and durability performances generated. Embedding recycled aggregates in concrete is now a current practice in many countries to enhance sustainability of concrete industry and reduce its environmental impacts. The present paper discusses the various possible recycled aggregates used in concrete production, their effect on both fresh and hardened properties as well as durability performances. The economic and environmental impacts of partially or fully substituting natural aggregates by secondary recycled aggregates are also discussed.

  15. Partitioning of red blood cell aggregates in bifurcating microscale flows

    Science.gov (United States)

    Kaliviotis, E.; Sherwood, J. M.; Balabani, S.

    2017-03-01

    Microvascular flows are often considered to be free of red blood cell aggregates, however, recent studies have demonstrated that aggregates are present throughout the microvasculature, affecting cell distribution and blood perfusion. This work reports on the spatial distribution of red blood cell aggregates in a T-shaped bifurcation on the scale of a large microvessel. Non-aggregating and aggregating human red blood cell suspensions were studied for a range of flow splits in the daughter branches of the bifurcation. Aggregate sizes were determined using image processing. The mean aggregate size was marginally increased in the daughter branches for a range of flow rates, mainly due to the lower shear conditions and the close cell and aggregate proximity therein. A counterintuitive decrease in the mean aggregate size was apparent in the lower flow rate branches. This was attributed to the existence of regions depleted by aggregates of certain sizes in the parent branch, and to the change in the exact flow split location in the T-junction with flow ratio. The findings of the present investigation may have significant implications for microvascular flows and may help explain why the effects of physiological RBC aggregation are not deleterious in terms of in vivo vascular resistance.

  16. Mechanical Dissociation of Platelet Aggregates in Blood Stream

    Science.gov (United States)

    Hoore, Masoud; Fedosov, Dmitry A.; Gompper, Gerhard; Complex; Biological Fluids Group Team

    2017-11-01

    von Willebrand factor (VWF) and platelet aggregation is a key phenomenon in blood clotting. These aggregates form critically in high shear rates and dissolve reversibly in low shear rates. The emergence of a critical shear rate, beyond which aggregates form and below which they dissolve, has an interesting impact on aggregation in blood flow. As red blood cells (RBCs) migrate to the center of the vessel in blood flow, a RBC free layer (RBC-FL) is left close to the walls into which the platelets and VWFs are pushed back from the bulk flow. This margination process provides maximal VWF-platelet aggregation probability in the RBC-FL. Using mesoscale hydrodynamic simulations of aggregate dynamics in blood flow, it is shown that the aggregates form and grow in RBC-FL wherein shear rate is high for VWF stretching. By growing, the aggregates penetrate to the bulk flow and get under order of magnitude lower shear rates. Consequently, they dissolve and get back into the RBC-FL. This mechanical limitation for aggregates prohibits undesired thrombosis and vessel blockage by aggregates, while letting the VWFs and platelets to aggregate close to the walls where they are actually needed. The support by the DFG Research Unit FOR 1543 SHENC and CPU time Grant by the Julich Supercomputing Center are acknowledged.

  17. Measurement of platelet aggregation, independently of patient platelet count

    DEFF Research Database (Denmark)

    Vinholt, P J; Frederiksen, H; Hvas, A-M

    2017-01-01

    with collagen-related peptide). Platelet aggregation had a negative predictive value of 100% for a bleeding tendency among patients. Conclusion The established platelet aggregation assay was applicable for thrombocytopenic patients, and improved the identification of bleeding risk.......Essentials •Platelet function may influence bleeding risk in thrombocytopenia, but useful tests are needed. •A flow cytometric platelet aggregation test independent of the patient platelet count was made. •Platelet aggregation was reduced in thrombocytopenic patients with hematological cancer....... •High platelet aggregation ruled out bleeding tendency in thrombocytopenic patients. Summary Background Methods for testing platelet aggregation in thrombocytopenia are lacking. Objective To establish a flow-cytometric test of in vitro platelet aggregation independently of the patient's platelet count...

  18. Strength of masonry blocks made with recycled concrete aggregates

    Science.gov (United States)

    Matar, Pierre; Dalati, Rouba El

    The idea of recycling concrete of demolished buildings aims at preserving the environment. Indeed, the reuse of concrete as aggregate in new concrete mixes helped to reduce the expenses related to construction and demolition (C&D) waste management and, especially, to protect the environment by reducing the development rate of new quarries. This paper presents the results of an experimental study conducted on masonry blocks containing aggregates resulting from concrete recycling. The purpose of this study is to investigate the effect of recycled aggregates on compressive strength of concrete blocks. Tests were performed on series of concrete blocks: five series each made of different proportions of recycled aggregates, and one series of reference blocks exclusively composed of natural aggregates. Tests showed that using recycled aggregates with addition of cement allows the production of concrete blocks with compressive strengths comparable to those obtained on concrete blocks made exclusively of natural aggregates.

  19. Piecewise Polynomial Aggregation as Preprocessing for Data Numerical Modeling

    Science.gov (United States)

    Dobronets, B. S.; Popova, O. A.

    2018-05-01

    Data aggregation issues for numerical modeling are reviewed in the present study. The authors discuss data aggregation procedures as preprocessing for subsequent numerical modeling. To calculate the data aggregation, the authors propose using numerical probabilistic analysis (NPA). An important feature of this study is how the authors represent the aggregated data. The study shows that the offered approach to data aggregation can be interpreted as the frequency distribution of a variable. To study its properties, the density function is used. For this purpose, the authors propose using the piecewise polynomial models. A suitable example of such approach is the spline. The authors show that their approach to data aggregation allows reducing the level of data uncertainty and significantly increasing the efficiency of numerical calculations. To demonstrate the degree of the correspondence of the proposed methods to reality, the authors developed a theoretical framework and considered numerical examples devoted to time series aggregation.

  20. Logic-based aggregation methods for ranking student applicants

    Directory of Open Access Journals (Sweden)

    Milošević Pavle

    2017-01-01

    Full Text Available In this paper, we present logic-based aggregation models used for ranking student applicants and we compare them with a number of existing aggregation methods, each more complex than the previous one. The proposed models aim to include depen- dencies in the data using Logical aggregation (LA. LA is a aggregation method based on interpolative Boolean algebra (IBA, a consistent multi-valued realization of Boolean algebra. This technique is used for a Boolean consistent aggregation of attributes that are logically dependent. The comparison is performed in the case of student applicants for master programs at the University of Belgrade. We have shown that LA has some advantages over other presented aggregation methods. The software realization of all applied aggregation methods is also provided. This paper may be of interest not only for student ranking, but also for similar problems of ranking people e.g. employees, team members, etc.

  1. Automatic analysis of microscopic images of red blood cell aggregates

    Science.gov (United States)

    Menichini, Pablo A.; Larese, Mónica G.; Riquelme, Bibiana D.

    2015-06-01

    Red blood cell aggregation is one of the most important factors in blood viscosity at stasis or at very low rates of flow. The basic structure of aggregates is a linear array of cell commonly termed as rouleaux. Enhanced or abnormal aggregation is seen in clinical conditions, such as diabetes and hypertension, producing alterations in the microcirculation, some of which can be analyzed through the characterization of aggregated cells. Frequently, image processing and analysis for the characterization of RBC aggregation were done manually or semi-automatically using interactive tools. We propose a system that processes images of RBC aggregation and automatically obtains the characterization and quantification of the different types of RBC aggregates. Present technique could be interesting to perform the adaptation as a routine used in hemorheological and Clinical Biochemistry Laboratories because this automatic method is rapid, efficient and economical, and at the same time independent of the user performing the analysis (repeatability of the analysis).

  2. Feasibility Study on Manufacturing Lightweight Aggregates from Water Purification Sludge

    Science.gov (United States)

    Peng, Ching-Fang; Chen, How-Ji

    2018-02-01

    This study mainly discussed the feasibility of manufacturing lightweight aggregates from water purification sludge in Taiwan. They were analysed for the physical and chemical composition before the sintering test for lightweight aggregates in a laboratory. Then the physical and mechanical properties of the synthesized aggregates were assessed. The result showed that the chemical composition of sludge in the water purification plants was within the appropriate range for manufacturing lightweight aggregate as proposed in the literature. The sintering test demonstrated that the particle density of aggregates from the ten types of water purification sludge were mostly less than 1.8 g/cm3. In addition, the dry unit weight, the organic impurity, the ignition loss, and other characteristics of synthesized aggregates met the requirement of CNS standards, while its water absorption and crushing strength also fulfilled the general commercial specifications. Therefore, reclamation of water purification sludge for production of lightweight aggregate is indeed feasible.

  3. Hybrid vertical cavity laser

    DEFF Research Database (Denmark)

    Chung, Il-Sug; Mørk, Jesper

    2010-01-01

    A new hybrid vertical cavity laser structure for silicon photonics is suggested and numerically investigated. It incorporates a silicon subwavelength grating as a mirror and a lateral output coupler to a silicon ridge waveguide.......A new hybrid vertical cavity laser structure for silicon photonics is suggested and numerically investigated. It incorporates a silicon subwavelength grating as a mirror and a lateral output coupler to a silicon ridge waveguide....

  4. Aggregation, sedimentation, dissolution and bioavailability of ...

    Science.gov (United States)

    To understand their fate and transport in estuarine systems, the aggregation, sedimentation, and dissolution of CdSe quantum dots (QDs) in seawater were investigated. Hydrodynamic size increased from 40 to 60 nm to >1 mm within 1 h in seawater, and the aggregates were highly polydispersed. Their sedimentation rates in seawater were measured to be 4–10 mm/day. Humic acid (HA), further increased their size and polydispersity, and slowed sedimentation. Light increased their dissolution and release of dissolved Cd. The ZnS shell also slowed release of Cd ions. With sufficient light, HA increased the dissolution of QDs, while with low light, HA alone did not change their dissolution. The benthic zone in estuarine systems is the most probable long-term destination of QDs due to aggregation and sedimentation. The bioavailability of was evaluated using the mysid Americamysis bahia. The 7-day LC50s of particulate and dissolved QDs were 290 and 23 μg (total Cd)/L, respectively. For mysids, the acute toxicity appears to be from Cd ions; however, research on the effects of QDs should be conducted with other organisms where QDs may be lodged in critical tissues such as gills or filtering apparatus and Cd ions may be released and delivered directly to those tissues. Because of their increasing use and value to society, cadmium-based quantum dots (QDs) will inevitably find their way into marine systems. In an effort to understand the fate and transport of CdSe QDs in estuar

  5. Study on Quality Aggregate Construction Powder

    International Nuclear Information System (INIS)

    Myat Ko; Kyaw Naing; Thazin Lwin; Khin Mar Tun

    2008-03-01

    This research work deals with a view to promote cement replacement materials i-e aggregate construction powder, also known as building powder or construction powder . It has been used as lime substituent in construction work in Myanmar since 1990's. It is mixed with other construction materials such as cement, sand, etc. and used in plastering, tiling, arranging bricks and smoothing the face of the buildings.This work also deals with some aspects in physical properties of four different aggregate construction powder samples such as Moe Hein, Man Thiri, Shwe Taung and Kyauk Sue. In addition, these four different samples were characterized by using spectroscopic methods such as ED-XRF, AAS, FT-IR and XRD. In support of the finding by the analytical assays of Moe Hein aggregate construction powder, it indicated the percent composition of the presence of SiO2 12.13%, Al2O3 7.40%, Fe2O3 0.94%, CaO 41.00%,MgO 1.50% total sulphur 1.15%, chloride 1.49%, carbonate 43.63% and sulphate 3.44%. The analytical assays of Sin Min cement, Kyant cement, brick powder and pozzolan were also carried out in this research work. The mixing between various ratios of Moe Hein and Kyant cement as well as Sin Min II cement were done and their mechanical strengths such as setting time, tensile strength and compressive strength of each sample were studied. The quality of mixing ratio 50:50 of Moe Hein and Kyant cement was found to be comparable to the ASTM standard type II Protland cement which is for general use.

  6. Family aggregation of cardiovascular disease mortality

    DEFF Research Database (Denmark)

    Silventoinen, Karri; Hjelmborg, Jacob; Möller, Sören

    2017-01-01

    Background: Familial factors play an important role in the variation of risk factors of cardiovascular diseases (CVD), but less is known about how they affect the risk of death from CVD. We estimated familial aggregation of CVD mortality for twins offering the maximum level of risk due to genetic...... and other familial factors. Methods: Altogether, 132 771 twin individuals, including 65 196 complete pairs from Denmark, Finland and Sweden born in 1958 or earlier, participated in this study. During the register-based follow-up, 11 641 deaths occurred from coronary heart disease (CHD), including 6280...

  7. Software for the grouped optimal aggregation technique

    Science.gov (United States)

    Brown, P. M.; Shaw, G. W. (Principal Investigator)

    1982-01-01

    The grouped optimal aggregation technique produces minimum variance, unbiased estimates of acreage and production for countries, zones (states), or any designated collection of acreage strata. It uses yield predictions, historical acreage information, and direct acreage estimate from satellite data. The acreage strata are grouped in such a way that the ratio model over historical acreage provides a smaller variance than if the model were applied to each individual stratum. An optimal weighting matrix based on historical acreages, provides the link between incomplete direct acreage estimates and the total, current acreage estimate.

  8. Aggregated Control of Domestic Heat Pumps

    DEFF Research Database (Denmark)

    Nielsen, Kirsten M.; Andersen, Palle; Pedersen, Tom S.

    2013-01-01

    A challenge in Denmark in the near future is to balance the electrical grid due to a large increase in the renewable energy production mainly from wind turbines. In this work an aggregated control system using heat pumps in single family houses to help balancing the grid is investigated....... The control system is able to adjust the consumptions of the heat pump without affecting the comfort in the houses and uses this ability to shift the total consumption to hours with high wind energy production....

  9. An Aß concatemer with altered aggregation propensities

    DEFF Research Database (Denmark)

    Giehm, L; Dal Degan, F; Fraser, P

    2010-01-01

    We present an analysis of the conformational and aggregative properties of an A beta concatemer (Con-Alz) of interest for vaccine development against Alzheimer's disease. Con-Alz consists of 3 copies of the 43 residues of the A beta peptide separated by the P2 and P30 T-cell epitopes from...... stage in the fibrillation process. Physically linking multiple copies of the A beta-peptide may thus sterically restrict Con-Alz against forming cytotoxic oligomers, forcing it instead to adopt a less well-organized assembly of intermeshed polypeptide chains. (C) 2010 Elsevier B.V. All rights reserved....

  10. Familial aggregation and heritability of pyloric stenosis

    DEFF Research Database (Denmark)

    Krogh, Camilla; Fischer, Thea K; Skotte, Line

    2010-01-01

    stenosis from monozygotic twins to fourth-generation relatives according to sex and maternal and paternal contributions and to estimate disease heritability. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of 1,999,738 children born in Denmark between 1977 and 2008 and followed up.......51-4.99) for half-cousins. We found no difference in rate ratios for maternal and paternal relatives of children with pyloric stenosis and no difference according to sex of cohort member or sex of relative. The heritability of pyloric stenosis was 87%. CONCLUSION: Pyloric stenosis in Danish children shows strong...... familial aggregation and heritability....

  11. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    OpenAIRE

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0??M) and collagen- (2.0??g/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H2O), Amomyrtus l...

  12. High-throughput screening assay of hepatitis C virus helicase inhibitors using fluorescence-quenching phenomenon

    International Nuclear Information System (INIS)

    Tani, Hidenori; Akimitsu, Nobuyoshi; Fujita, Osamu; Matsuda, Yasuyoshi; Miyata, Ryo; Tsuneda, Satoshi; Igarashi, Masayuki; Sekiguchi, Yuji; Noda, Naohiro

    2009-01-01

    We have developed a novel high-throughput screening assay of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase inhibitors using the fluorescence-quenching phenomenon via photoinduced electron transfer between fluorescent dyes and guanine bases. We prepared double-stranded DNA (dsDNA) with a 5'-fluorescent-dye (BODIPY FL)-labeled strand hybridized with a complementary strand, the 3'-end of which has guanine bases. When dsDNA is unwound by helicase, the dye emits fluorescence owing to its release from the guanine bases. Our results demonstrate that this assay is suitable for quantitative assay of HCV NS3 helicase activity and useful for high-throughput screening for inhibitors. Furthermore, we applied this assay to the screening for NS3 helicase inhibitors from cell extracts of microorganisms, and found several cell extracts containing potential inhibitors.

  13. Human hybrid hybridoma

    Energy Technology Data Exchange (ETDEWEB)

    Tiebout, R.F.; van Boxtel-Oosterhof, F.; Stricker, E.A.M.; Zeijlemaker, W.P.

    1987-11-15

    Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. The authors have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. They fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1kappa antibody directed against tetanus toxiod and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassay. The results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies. Bispecific antibodies activity was measured by means of two radioimmunoassays.

  14. Systems for hybrid cars

    Science.gov (United States)

    Bitsche, Otmar; Gutmann, Guenter

    Not only sharp competition but also legislation are pushing development of hybrid drive trains. Based on conventional internal combustion engine (ICE) vehicles, these drive trains offer a wide range of benefits from reduced fuel consumption and emission to multifaceted performance improvements. Hybrid electric drive trains may also facilitate the introduction of fuel cells (FC). The battery is the key component for all hybrid drive trains, as it dominates cost and performance issues. The selection of the right battery technology for the specific automotive application is an important task with an impact on costs of development and use. Safety, power, and high cycle life are a must for all hybrid applications. The greatest pressure to reduce cost is in soft hybrids, where lead-acid embedded in a considerate management presents the cheapest solution, with a considerable improvement in performance needed. From mild to full hybridization, an improvement in specific power makes higher costs more acceptable, provided that the battery's service life is equivalent to the vehicle's lifetime. Today, this is proven for the nickel-metal hydride system. Lithium ion batteries, which make use of a multiple safety concept, and with some development anticipated, provide even better prospects in terms of performance and costs. Also, their scalability permits their application in battery electric vehicles—the basis for better performance and enhanced user acceptance. Development targets for the batteries are discussed with a focus on system aspects such as electrical and thermal management and safety.

  15. Iron-reducing bacteria accumulate ferric oxyhydroxide nanoparticle aggregates that may support planktonic growth.

    Science.gov (United States)

    Luef, Birgit; Fakra, Sirine C; Csencsits, Roseann; Wrighton, Kelly C; Williams, Kenneth H; Wilkins, Michael J; Downing, Kenneth H; Long, Philip E; Comolli, Luis R; Banfield, Jillian F

    2013-02-01

    Iron-reducing bacteria (FeRB) play key roles in anaerobic metal and carbon cycling and carry out biogeochemical transformations that can be harnessed for environmental bioremediation. A subset of FeRB require direct contact with Fe(III)-bearing minerals for dissimilatory growth, yet these bacteria must move between mineral particles. Furthermore, they proliferate in planktonic consortia during biostimulation experiments. Thus, a key question is how such organisms can sustain growth under these conditions. Here we characterized planktonic microbial communities sampled from an aquifer in Rifle, Colorado, USA, close to the peak of iron reduction following in situ acetate amendment. Samples were cryo-plunged on site and subsequently examined using correlated two- and three-dimensional cryogenic transmission electron microscopy (cryo-TEM) and scanning transmission X-ray microscopy (STXM). The outer membranes of most cells were decorated with aggregates up to 150 nm in diameter composed of ∼3 nm wide amorphous, Fe-rich nanoparticles. Fluorescent in situ hybridization of lineage-specific probes applied to rRNA of cells subsequently imaged via cryo-TEM identified Geobacter spp., a well-studied group of FeRB. STXM results at the Fe L(2,3) absorption edges indicate that nanoparticle aggregates contain a variable mixture of Fe(II)-Fe(III), and are generally enriched in Fe(III). Geobacter bemidjiensis cultivated anaerobically in the laboratory on acetate and hydrous ferric oxyhydroxides also accumulated mixed-valence nanoparticle aggregates. In field-collected samples, FeRB with a wide variety of morphologies were associated with nano-aggregates, indicating that cell surface Fe(III) accumulation may be a general mechanism by which FeRB can grow while in planktonic suspension.

  16. Self-Assembled CNT-Polymer Hybrids in Single-Walled Carbon Nanotubes Dispersed Aqueous Triblock Copolymer Solutions

    Science.gov (United States)

    Vijayaraghavan, D.; Manjunatha, A. S.; Poojitha, C. G.

    2018-04-01

    We have carried out scanning electron microscopy (SEM), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), electrical conductivity, and 1H NMR studies as a function of temperature on single-walled carbon nanotubes (SWCNTs) dispersed aqueous triblock copolymer (P123) solutions. The single-walled carbon nanotubes in this system aggregate to form bundles, and the bundles aggregate to form net-like structures. Depending on the temperature and phases of the polymer, this system exhibits three different self-assembled CNT-polymer hybrids. We find CNT-unimer hybrid at low temperatures, CNT-micelle hybrid at intermediate temperatures wherein the polymer micelles are adsorbed in the pores of the CNT nets, and another type of CNT-micelle hybrid at high temperatures wherein the polymer micelles are adsorbed on the surface of the CNT bundles. Our DSC thermogram showed two peaks related to these structural changes in the CNT-polymer hybrids. Temperature dependence of the 1H NMR chemical shifts of the molecular groups of the polymer and the AC electrical conductivity of the composite also showed discontinuous changes at the temperatures at which the CNT-polymer hybrid's structural changes are seen. Interestingly, for a higher CNT concentration (0.5 wt.%) in the system, the aggregated polymer micelles adsorbed on the CNTs exhibit cone-like and cube-like morphologies at the intermediate and at high temperatures respectively.

  17. Photo-induced reorganization of molecular packing of amphi-PIC J-aggregates (single J-aggregate spectroscopy)

    International Nuclear Information System (INIS)

    Malyukin, Yu.V.; Sorokin, A.V.; Yefimova, S.L.; Lebedenko, A.N.

    2005-01-01

    Confocal luminescence microscopy has been used to excite and collect luminescence from single amphi-PIC J-aggregate. Two types of J-aggregates have been revealed in the luminescence image: bead-like J-aggregates, which diameter is less than 1 μm and rod-like ones, which length is about 3 μm and diameter is less than 1 μm. It has been found that single rod-like and bead-like J-aggregates exhibit different luminescence bands with different decay parameters. At the off-resonance blue tail excitation, the J-aggregate exciton luminescence disappeared within a certain time period and a new band appeared, which cannot be attributed to the monomer emission. The luminescence image shows that the J-aggregate is not destroyed. However, J-aggregate storage in darkness does not recover its exciton luminescence

  18. Semiworks source aggregate area management study report

    International Nuclear Information System (INIS)

    1993-05-01

    This report presents the results of an aggregate area management study (AAMS) for the Semi-Works Aggregate Area in the 200 Areas of the US Department of Energy (DOE) . Hanford Site in Washington State. This scoping level study provides the basis for initiating Remedial Investigation/Feasibility Study (RI/FS) activities under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) or Resource Conservation and Recovery Act (RCRA) Facility Investigations WD and Corrective Measures Studies (CMS) under RCRA. This report also integrates select RCRA treatment storage, or disposal (TSD) closure activities with CERCLA and RCRA past-practice investigations. This approach is described and justified in The Hanford Federal Facility Agreement and Consent Order Change Package. This strategy provides new concepts for: accelerating decision-malting by maximizing the use of existing data consistent with data quality objectives (DQOs); and undertaking expedited response actions (ERAS) and/or interim remedial measures (IRMs), as appropriate, to either remove threats to human health and welfare and the environment, or to reduce risk by reducing toxicity, mobility, or volume of contaminants

  19. Active motility in bimodular bacterial aggregates

    Science.gov (United States)

    Zeng, Yu; Liu, Bin

    2017-11-01

    Dispersal capability is essential for microorganisms to achieve long-distance translocation, thus crucial for their abundance in various environments. In general, active dispersals are attributed to the movements of self-powered planktonic cells, while sessile cells that live a colonial life often disperse passively through flow entrainments. Here, we report another means of active dispersal employed by aggregates of sessile cells. The spherical rosette colonies of the bacterium Caulobacter crescentus are aggregates of sessile stalked cells, of which a small proportion undergo cell division, grow active flagella and effect whole-rosette motility. We show that these rosettes actively disperse both in bulk water and near the solid-liquid interface. In particular, the proximity of a self-powered rosette to the solid surface promotes a rolling movement, leading to its persistent transportation along the solid boundary. The active dispersal of these rosettes demonstrated a novel mode of colonial transportation that is based on the division of labor between sessile and motile cells. The authors thank the support of National Science Foundation CREST: Center for Cellular and Biomolecular Machines at UC Merced (NSF-HRD-1547848).

  20. Passive RFID Rotation Dimension Reduction via Aggregation

    Science.gov (United States)

    Matthews, Eric

    Radio Frequency IDentification (RFID) has applications in object identification, position, and orientation tracking. RFID technology can be applied in hospitals for patient and equipment tracking, stores and warehouses for product tracking, robots for self-localisation, tracking hazardous materials, or locating any other desired object. Efficient and accurate algorithms that perform localisation are required to extract meaningful data beyond simple identification. A Received Signal Strength Indicator (RSSI) is the strength of a received radio frequency signal used to localise passive and active RFID tags. Many factors affect RSSI such as reflections, tag rotation in 3D space, and obstacles blocking line-of-sight. LANDMARC is a statistical method for estimating tag location based on a target tag's similarity to surrounding reference tags. LANDMARC does not take into account the rotation of the target tag. By either aggregating multiple reference tag positions at various rotations, or by determining a rotation value for a newly read tag, we can perform an expected value calculation based on a comparison to the k-most similar training samples via an algorithm called K-Nearest Neighbours (KNN) more accurately. By choosing the average as the aggregation function, we improve the relative accuracy of single-rotation LANDMARC localisation by 10%, and any-rotation localisation by 20%.