WorldWideScience

Sample records for agonists potential utility

  1. PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

    Directory of Open Access Journals (Sweden)

    Harrihar A. Pershadsingh

    2008-01-01

    Full Text Available The angiogenic, neovascular proliferative retinopathies, proliferative diabetic retinopathy (PDR, and age-dependent macular degeneration (AMD complicated by choroidal neovascularization (CNV, also termed exudative or “wet” AMD, are common causes of blindness. The antidiabetic thiazolidinediones (TZDs, rosiglitazone, and troglitazone are PPAR agonists with demonstrable antiproliferative, and anti-inflammatory effects, in vivo, were shown to ameliorate PDR and CNV in rodent models, implying the potential efficacy of TZDs for treating proliferative retinopathies in humans. Activation of the angiotensin II type 1 receptor (AT1-R propagates proinflammatory and proliferative pathogenic determinants underlying PDR and CNV. The antihypertensive dual AT1-R blocker (ARB, telmisartan, recently was shown to activate PPAR and improve glucose and lipid metabolism and to clinically improve PDR and CNV in rodent models. Therefore, the TZDs and telmisartan, clinically approved antidiabetic and antihypertensive drugs, respectively, may be efficacious for treating and attenuating PDR and CNV humans. Clinical trials are needed to test these possibilities.

  2. Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

    Directory of Open Access Journals (Sweden)

    Paul Fredrickson

    2014-01-01

    Full Text Available Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13 analog, blocks behavioral sensitization (an animal model for psychostimulant addiction to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine.

  3. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  4. A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

    Science.gov (United States)

    Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

    1994-02-28

    Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

  5. Potential of beta-adrenergic agonists for increasing protein deposition in ruminants in developing countries

    International Nuclear Information System (INIS)

    Berschauer, F.

    1989-01-01

    Various substituted phenylethanolamines, acting on the sympathetic nervous system, have been shown to increase protein retention (via decreased proteolysis) and reduce fat deposition (via increased lipolysis and reduced lipogenesis) in ruminants and monogastrics. Research with finishing lambs in developed countries show various beta-adrenergic agonists to improve growth rate (by 18%), feed conversion (by 12%) and carcass quality (28% increase in area of longissimus dorsi and 33% reduction in subcutaneous fat). Similar effects of beta-agonists on carcass composition of well fed cattle have been reported. The effects of beta-agonists on livestock in developing countries of the tropics have not yet been investigated, but their effects in increasing metabolic rate suggest that treated ruminants would be more vulnerable to hot environments. Beta-agonists appear to improve nitrogen retention to a greater extent in breeds with a lower potential for muscle growth. In view of this, they might be particularly effective in improving nitrogen retention in tropical breeds which have a low growth potential. This aspect, together with the response of undernourished animals in the developing countries, needs investigation. Beta-adrenergic agonists are not yet registered for use in animal production, but product licenses for some of them are expected to be granted soon. (author). 31 refs, 1 fig., 12 tabs

  6. The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control.

    Science.gov (United States)

    Decker, M W; Meyer, M D; Sullivan, J P

    2001-10-01

    Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

  7. Characterization qualitative and potentialities of utilization of ...

    African Journals Online (AJOL)

    Characterization qualitative and potentialities of utilization of methacomposts of poultry in the nurseries aboveground. ... PROMOTING ACCESS TO AFRICAN RESEARCH. AFRICAN ... Journal of Fundamental and Applied Sciences.

  8. Hydrogen utilization potential in subsurface sediments

    DEFF Research Database (Denmark)

    Adhikari, Rishi Ram; Glombitza, Clemens; Nickel, Julia

    2016-01-01

    Pacific, and Gulf of Mexico) with different predominant electron-acceptors. Hydrogenases constitute a diverse family of enzymes expressed by microorganisms that utilize molecular hydrogen as a metabolic substrate, product, or intermediate. The assay reveals the potential for utilizing molecular hydrogen...

  9. Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

    Directory of Open Access Journals (Sweden)

    Yiyi Sun

    Full Text Available Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (--arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

  10. Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task.

    Science.gov (United States)

    Perez-García, Georgina S; Meneses, A

    2005-08-30

    This work aimed to evaluate further the role of 5-HT7 receptors during memory formation in an autoshaping Pavlovian/instrumental learning task. Post-training administration of the potential 5-HT7 receptor agonist AS 19 or antagonist SB-269970 enhanced memory formation or had no effect, respectively. The AS 19 facilitatory effect was reversed by SB-269970, but not by the selective 5-HT1A antagonist WAY100635. Amnesia induced by scopolamine (cholinergic antagonist) or dizocilpine (NMDA antagonist) was also reversed by AS 19. Certainly, reservations regarding the selectivity of AS 19 for 5-HT7 and other 5-HT receptors in vivo are noteworthy and, therefore, its validity for use in animal models as a pharmacological tool. Having mentioned that, it should be noticed that together these data are providing further support to the notion of the 5-HT7 receptors role in memory formation. Importantly, this 5-HT7 receptor agonist AS 19 appears to represent a step forward respect to the notion that potent and selective 5-HT7 receptor agonists can be useful in the treatment of dysfunctional memory in aged-related decline and Alzheimer's disease.

  11. Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging.

    Science.gov (United States)

    Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai

    2007-11-01

    Administration of an orally active agonist (MK-0677) of the growth hormone secretagogue receptor (GHS-R1a) to elderly subjects restored the amplitude of endogenous episodic growth hormone (GH) release to that of young adults. Functional benefits include increased lean mass and bone density and modest improvements in strength. In old mice, a similar agonist partially restored function to the thymus and reduced tumor cell growth and metastasis. Treatment of old mice with the endogenous GHS-R1a agonist ghrelin restored a young liver phenotype. The mechanism involves inhibition of cyclin D3:cdk4/cdk6 activity and increased protein phosphatase-2A (PP2A) activity in liver nuclei, which stabilizes the dephosphorylated form of the transcription factor C/EBPalpha preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear complex. By inhibiting formation of this complex, repression of E2F target genes is de-repressed and C/EBPalpha regulated expression of Pepck, a regulator of gluconeogenesis, is normalized, thereby restoring a young liver phenotype. In the brain, aging is associated with decline in dopamine function. We investigated the potential neuromodulatory role of GHS-R1a on dopamine action. Neurons were identified in the hippocampus, cortex, substantia nigra, and ventral tegmental areas that coexpressed GHS-R1a and dopamine receptor subtype-1 (D1R). Cell culture studies showed that, in the presence of ghrelin and dopamine, GHS-R and D1R form heterodimers, which modified G-protein signal transduction resulting in amplification of dopamine signaling. We speculate that aging is associated with deficient endogenous ghrelin signaling that can be rescued by intervention with GHS-R1a agonists to improve quality of life and maintain independence.

  12. Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2017-01-01

    Full Text Available Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

  13. Hydrogen utilization potential in subsurface sediments

    Directory of Open Access Journals (Sweden)

    Rishi Ram Adhikari

    2016-01-01

    Full Text Available Subsurface microbial communities undertake many terminal electron-accepting processes, often simultaneously. Using a tritium-based assay, we measured the potential hydrogen oxidation catalyzed by hydrogenase enzymes in several subsurface sedimentary environments (Lake Van, Barents Sea, Equatorial Pacific and Gulf of Mexico with different predominant electron-acceptors. Hydrogenases constitute a diverse family of enzymes expressed by microorganisms that utilize molecular hydrogen as a metabolic substrate, product or intermediate. The assay reveals the potential for utilizing molecular hydrogen and allows qualitative detection of microbial activity irrespective of the predominant electron-accepting process. Because the method only requires samples frozen immediately after recovery, the assay can be used for identifying microbial activity in subsurface ecosystems without the need to preserve live material.We measured potential hydrogen oxidation rates in all samples from multiple depths at several sites that collectively span a wide range of environmental conditions and biogeochemical zones. Potential activity normalized to total cell abundance ranges over five orders of magnitude and varies, dependent upon the predominant terminal electron acceptor. Lowest per-cell potential rates characterize the zone of nitrate reduction and highest per-cell potential rates occur in the methanogenic zone. Possible reasons for this relationship to predominant electron acceptor include (i increasing importance of fermentation in successively deeper biogeochemical zones and (ii adaptation of H2ases to successively higher concentrations of H2 in successively deeper zones.

  14. The 5-HT(1F) receptor agonist lasmiditan as a potential treatment of migraine attacks

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C; Olesen, Jes

    2012-01-01

    Lasmiditan is a novel selective 5-HT(1F) receptor agonist. It is both scientifically and clinically relevant to review whether a 5-HT(1F) receptor agonist is effective in the acute treatment of migraine. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo...

  15. Trialkyltin rexinoid-X receptor agonists selectively potentiate thyroid hormone induced programs of xenopus laevis metamorphosis

    NARCIS (Netherlands)

    Mengeling, Brenda J.; Murk, Albertinka J.; Furlow, J.D.

    2016-01-01

    The trialkyltins tributyltin (TBT) and triphenyltin (TPT) can function as rexinoid-X receptor (RXR) agonists. We recently showed that RXR agonists can alter thyroid hormone (TH) signaling in a mammalian pituitary TH-responsive reporter cell line, GH3.TRE-Luc. The prevalence of TBT and TPT in the

  16. Middle East gas utilization and export potential

    International Nuclear Information System (INIS)

    Cornet-Gandolphe, S.

    1995-01-01

    There is huge gas supply potential in the Middle East, which possesses over one third of the world's natural gas reserves. However, marketed production represents only 6% of the world total, demonstrating that gas resources in the Middle East are under utilized. The value of these resources will be realized only if the gas finds a commercial outlet that guarantees proper return on investments for gas producers and the best possible use of this nonrenewable resource for governments. Apart from the chemical sector, which has provided a good outlet for natural gas, the development of natural gas resources in the region has been very limited historically, inhibited by many factors linked to the resource itself and to the characteristics of the region. However, natural gas in the Middle East is now at a crossroads, facing both major challenges and significant opportunities. The region, which currently plays only a marginal role on the world gas market, has the potential to become a leading world supplier, provided a number of political and economic conditions are fulfilled. This paper discusses some of the challenges that Middle Eastern countries face in trying to develop their natural gas resources. It reviews development potential for Middle Eastern gas reserves, whether for local use and/or exports, and it highlights future opportunities. (Author)

  17. Target based screening of small molecule library identifies pregnelonene, a Nrf2 agonist, as a potential radioprotector in zebrafish

    International Nuclear Information System (INIS)

    Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Shrivastava, Nitisha; Indracanti, Prem Kumar; Ray, Jharna

    2014-01-01

    Reactive oxygen species, cellular oxidative stress, tissue inflammation and cell death are the downstream consequences of radiation exposures which ultimately could lead to organism death. Present study aims at identifying potential targets and screening of small molecule compound library for identifying novel and effective radioprotectors. In-silco analysis of known radioprotectors revealed three main function, antioxidant, anti-inflammation and antiapoptosis. In this study, a collection of small molecules (John Hopkins Clinical Compound Library, JHCCL) were screened for these different functions using the biological activity database of NCBI with the help of in-house developed python script. Further, filtering of the JHCCL was done by searching for molecules which are known to be active against target of radiobiological significance, Nrf-2. Close observation of potential hits identified, pregnenolone, as an Nrf-2 agonist which was further evaluated for radioprotection in zebrafish model. Pregnenolone rendered significant protection (at 40 μM; added 1 hour prior to 20 Gy gamma radiation) in terms of damage manifestations (pericardial edema, microcephaly, micropthalmia, yolk sac resorption, curvature of spine, blood flow, body length, heart-beat, blood clot, roughness of skin) and survival advantage (60%) when compared to irradiated control. Further, the ability of pregnenolone to act as a neuroprotectant was also carried out using in-house developed software for assessing neuromotor functions. In comparison to radiation alone group, pregnenolone was found to possess significant neuroactive functions and diminished radiation induced neuronal impairment. Over all these results suggests that pregnenolone is an effective radioprotector which warrants further investigation for validation of its radioprotective action in higher vertebrates. Apart from that the utility of approach to screen out bioactivity data base of various chemical compound libraries for possible

  18. Functionalized Ergot-alkaloids as potential dopamine D3 receptor agonists for treatment of schizophrenia

    Science.gov (United States)

    Ivanova, Bojidarka; Spiteller, Michael

    2012-12-01

    The relationship between the molecular structure and physical properties of functionalized naturally occurred Ergot-alkaloids as potential dopamine D3 receptor agonists is presented. The molecular modeling of the ergoline-skeleton is based on the comprehensive theoretical study of the binding affinity of the isolated chemicals towards the active sites of the D3 sub-type receptor (D3R) loops. The studied proton accepting ability under physiological conditions allows classifying four types of monocationics, characterizing with the different binding modes to D3R involving selected amino acid residues to the active sites. These results marked the pharmaceutical potential and clinical usage of the reported compounds as antipsychotic drugs for Schizophrenia treatment, since they allowed evaluating the highlights of the different hypothesizes of the biochemical causes the illness. The applied complex approach for theoretical and experimental elucidation, including quantum chemistry method, electrospray ionization (ESI) and matrix assisted laser desorption/ionization (MALDI) mass spectrometric (MS) methods, nuclear magnetic resonance and vibrational IR and Raman spectroscopy on the isolated fifteen novel derivatives (1)-(15) and their different protonated forms (1a)-(15a) evidenced a strong dependence of molecular conformation, physical properties and binding affinity. Thus, the semi-synthetic functionalization of the naturally occurred products (NPs), provided significant possibilities to further molecular drugs-design and development of novel derivatives with wanted biological function, using the established profile of selected classes/families of NPs. The work described chiefly the non-linear (NL) approach for the interpretation of the mass chromatograms on the performed hybrid high performance liquid chromatography (HPLC) tandem MS/MS and MS/MS/MS experiments, discussing the merits and great diversity of instrumentation flexibility, thus achieving fundamental

  19. Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat.

    Directory of Open Access Journals (Sweden)

    Guillaume Lucas

    2010-02-01

    Full Text Available We have recently reported that serotonin(4 (5-HT(4 receptor agonists have a promising potential as fast-acting antidepressants. Here, we assess the extent to which this property may be optimized by the concomitant use of conventional antidepressants.We found that, in acute conditions, the 5-HT(4 agonist prucalopride was able to counteract the inhibitory effect of the selective serotonin reuptake inhibitors (SSRI fluvoxamine and citalopram on 5-HT neuron impulse flow, in Dorsal Raphé Nucleus (DRN cells selected for their high (>1.8 Hz basal discharge. The co-administration of both prucalopride and RS 67333 with citalopram for 3 days elicited an enhancement of DRN 5-HT neuron average firing rate, very similar to what was observed with either 5-HT(4 agonist alone. At the postsynaptic level, this translated into the manifestation of a tonus on hippocampal postsynaptic 5-HT(1A receptors, that was two to three times stronger when the 5-HT(4 agonist was combined with citalopram. Similarly, co-administration of citalopram synergistically potentiated the enhancing effect of RS 67333 on CREB protein phosphorylation within the hippocampus. Finally, in the Forced Swimming Test, the combination of RS 67333 with various SSRIs (fluvoxamine, citalopram and fluoxetine was more effective to reduce time of immobility than the separate administration of each compound.These findings strongly suggest that the adjunction of an SSRI to a 5-HT(4 agonist may help to optimize the fast-acting antidepressant efficacy of the latter.

  20. Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup.

    Science.gov (United States)

    Glossop, Paul A; Lane, Charlotte A L; Price, David A; Bunnage, Mark E; Lewthwaite, Russell A; James, Kim; Brown, Alan D; Yeadon, Michael; Perros-Huguet, Christelle; Trevethick, Michael A; Clarke, Nicholas P; Webster, Robert; Jones, Rhys M; Burrows, Jane L; Feeder, Neil; Taylor, Stefan C J; Spence, Fiona J

    2010-09-23

    A novel series of potent and selective sulfonamide derived β(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.

  1. Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Østergaard, L; Frandsen, Christian S.; Madsbad, S

    2016-01-01

    Over the last decade, the discovery of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has increased the treatment options for patients with type 2 diabetes mellitus (T2DM). GLP-1 RAs mimic the effects of native GLP-1, which increases insulin secretion, inhibits glucagon secretion, increases...... satiety and slows gastric emptying. This review evaluates the phase III trials for all approved GLP-1 RAs and reports that all GLP-1 RAs decrease HbA1c, fasting plasma glucose, and lead to a reduction in body weight in the majority of trials. The most common adverse events are nausea and other...... gastrointestinal discomfort, while hypoglycaemia is rarely reported when GLP-1 RAs not are combined with sulfonylurea or insulin. Treatment options in the near future will include co-formulations of basal insulin and a GLP-1 RA....

  2. Characterization of a Broadly Reactive Anti-CD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant.

    Directory of Open Access Journals (Sweden)

    Cameron Martin

    Full Text Available Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb, designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs from these species relative to cells incubated with an isotype control (p<0.001. In addition, the mAb induced significant nitric oxide (p<0.0001 release by bovine macrophages. Furthermore, the mAb upregulated the expression of MHC-II by PBMCs, and stimulated significant (p<0.0001 IL-1α, IL6, IL-8, and TNF-α expression by PBMCs. These results suggest that the mAb 2E4E4 can target and stimulate cells from multiple livestock species and thus, it is a potential candidate for adjuvant development. This is the first study to report an anti-swine CD40 agonistic mAb that is also broadly reactive against multiple species.

  3. In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists.

    Directory of Open Access Journals (Sweden)

    Yaxin Zheng

    Full Text Available Kadsura longipedunculata (KL has been widely used for the treatment of insomnia in traditional Chinese medicine. The aim of this study was to explore the mechanism of the sedative and hypnotic effects of KL.The content of KL was evaluated by HPLC-TOF-MS, and a potential target was found and used to construct its 3D structure to screen for potential ligands among the compounds in KL by using bioinformatics analysis, including similarity ensemble approach (SEA docking, homology modeling, molecular docking and ligand-based pharmacophore. The PCPA-induced insomnia rat model was then applied to confirm the potential targets related to the sedative effects of KL by performing the forced swimming test (FST, the tail suspension test (TST and the measurement of target-related proteins using western blotting and immunofluorescence.Bioinformatics analysis showed that most of lignan compounds in KL were optimal ligands for the 5-HT1A receptor (5-HT1AR, and they were found to be potential targets related to sedative effects; the main lignan content of KL extracts was characterized by HPLC-TOF-MS, with 7 proposed lignans detected. Administration of KL could significantly reduce FST and TST immobility time in the PCPA-induced 5HT-depleted insomnia rat model. The expressions of proteins related to the 5-HT1AR pathway were regulated by extracts of KL in a concentration-dependent manner, indicating that extracts of KL had 5-HT1AR agonist-like effects.In silico analysis and experimental validation together demonstrated that lignan extracts from KL can target 5-HT1AR in insomniac rats, which could shed light on its use as a potential 5-HT1AR agonist drug.

  4. Group III mGlu receptor agonists potentiate the anticonvulsant effect of AMPA and NMDA receptor block.

    Science.gov (United States)

    De Sarro, Giovambattista; Chimirri, Alba; Meldrum, Brian S

    2002-09-06

    We report the anticonvulsant action in DBA/2 mice of two mGlu Group III receptor agonists: (R,S)-4-phosphonophenylglycine, (R,S)-PPG, a compound with moderate mGlu8 selectivity, and of (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid, ACPT-1, a selective agonist for mGlu4alpha receptors. Both compounds, given intracerebroventricularly at doses which did not show marked anticonvulsant activity, produced a consistent shift to the left of the dose-response curves (i.e. enhanced the anticonvulsant properties) of 1-(4'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one hydrochloride, CFM-2, a noncompetitive AMPA receptor antagonist, and 3-((+/-)-2-carboxypiperazin-4-yl)-1-phosphonic acid, CPPene, a competitive NMDA receptor antagonist, in DBA/2 mice. In addition, (R,S)-PPG and ACPT-1 administered intracerebroventricularly prolonged the time course of the anticonvulsant properties of CFM-2 (33 micromol/kg, i.p.) and CPPene (3.3 micromol/kg, i.p.) administered intraperitoneally. We conclude that modest reduction of synaptic glutamate release by activation of Group III metabotropic receptors potentiates the anticonvulsant effect of AMPA and NMDA receptor blockade. Copyright 2002 Elsevier Science B.V.

  5. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    DEFF Research Database (Denmark)

    Fosgerau, Keld; Weber, Uno J; Gotfredsen, Jacob W

    2010-01-01

    Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feas......Background  The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated...... the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies...... was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining...

  6. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Daniel Todd

    Full Text Available Huntington's disease (HD is a devastating, genetic neurodegenerative disease caused by a tri-nucleotide expansion in exon 1 of the huntingtin gene. HD is clinically characterized by chorea, emotional and psychiatric disturbances and cognitive deficits with later symptoms including rigidity and dementia. Pathologically, the cortico-striatal pathway is severely dysfunctional as reflected by striatal and cortical atrophy in late-stage disease. Brain-derived neurotrophic factor (BDNF is a neuroprotective, secreted protein that binds with high affinity to the extracellular domain of the tropomyosin-receptor kinase B (TrkB receptor promoting neuronal cell survival by activating the receptor and down-stream signaling proteins. Reduced cortical BDNF production and transport to the striatum have been implicated in HD pathogenesis; the ability to enhance TrkB signaling using a BDNF mimetic might be beneficial in disease progression, so we explored this as a therapeutic strategy for HD. Using recombinant and native assay formats, we report here the evaluation of TrkB antibodies and a panel of reported small molecule TrkB agonists, and identify the best candidate, from those tested, for in vivo proof of concept studies in transgenic HD models.

  7. Analysis of Hydropower Potential Utilization of Watercourses in Slovakia

    Science.gov (United States)

    Gejguš, Mirko; Aschbacher, Christine; Sablik, Jozef

    2017-09-01

    This article analyzes the hydropower potential of watercourses in Slovakia, defining water as the most promising and most used renewable energy source. The hydro-energetic potential as a source of energy is determined by the calculation of the technically feasible potential of the watercourses, which is divided into exploited and unused. It also identifies the potential of utilizing the unused technical hydro-energetic potential.

  8. Effects of glutamate receptor agonists on the P13 auditory evoked potential and startle response in the rat

    Directory of Open Access Journals (Sweden)

    Christen eSimon

    2011-01-01

    Full Text Available The P13 potential is the rodent equivalent of the P50 potential, which is an evoked response recorded at the vertex (Vx 50 msec following an auditory stimulus in humans. Both the P13 and P50 potentials are only present during waking and rapid eye movement (REM sleep, and are considered to be measures of level of arousal. The source of the P13 and P50 potentials appears to be the pedunculopontine nucleus (PPN, a brainstem nucleus with indirect ascending projections to the cortex through the intralaminar thalamus (ILT, mediating arousal, and descending inhibitory projections to the caudal pontine reticular formation (CPRF, which mediates the auditory startle response (SR. We tested the hypothesis that intracranial microinjection (ICM of glutamate (GLU or GLU receptor agonists will increase the activity of PPN neurons, resulting in an increased P13 potential response, and decreased SR due to inhibitory projections from the PPN to the CPRF, in freely moving animals. Cannulae were inserted into the PPN to inject neuroactive agents, screws were inserted into the Vx in order to record the P13 potential, and electrodes inserted into the dorsal nuchal muscle to record electromyograms (EMGs and SR amplitude. Our results showed that ICM of GLU into the PPN dose-dependently increased the amplitude of the P13 potential and decreased the amplitude of the SR. Similarly, ICM of NMDA or KA into the PPN increased the amplitude of the P13 potential. These findings indicate that glutamatergic input to the PPN plays a role in arousal control in vivo, and changes in glutamatergic input, or excitability of PPN neurons, could be implicated in a number of neuropsychiatric disorders with the common symptoms of hyperarousal and REM sleep dysregulation.

  9. Environmental toxin acrolein alters levels of endogenous lipids, including TRP agonists: A potential mechanism for headache driven by TRPA1 activation

    Directory of Open Access Journals (Sweden)

    Emma Leishman

    2017-01-01

    Full Text Available Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1, a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1 agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization. Keywords: Lipidomics, Endogenous cannabinoid, TRPA1, TRPV1, Lipoamine, Acrolein, Migraine

  10. Identification and in Vivo Evaluation of Liver X Receptor β-Selective Agonists for the Potential Treatment of Alzheimer’s Disease

    Energy Technology Data Exchange (ETDEWEB)

    Stachel, Shawn J.; Zerbinatti, Celina; Rudd, Michael T.; Cosden, Mali; Suon, Sokreine; Nanda, Kausik K.; Wessner, Keith; DiMuzio, Jillian; Maxwell, Jill; Wu, Zhenhua; Uslaner, Jason M.; Michener, Maria S.; Szczerba, Peter; Brnardic, Edward; Rada, Vanessa; Kim, Yuntae; Meissner, Robert; Wuelfing, Peter; Yuan, Yang; Ballard, Jeanine; Holahan, Marie; Klein, Daniel J.; Lu, Jun; Fradera, Xavier; Parthasarathy, Gopal; Uebele, Victor N.; Chen, Zhongguo; Li, Yingjie; Li, Jian; Cooke, Andrew J.; Bennett, D. Jonathan; Bilodeau, Mark T.; Renger, John (Merck); (WuXi App Tec)

    2016-04-14

    Herein, we describe the development of a functionally selective liver X receptor β (LXRβ) agonist series optimized for Emax selectivity, solubility, and physical properties to allow efficacy and safety studies in vivo. Compound 9 showed central pharmacodynamic effects in rodent models, evidenced by statistically significant increases in apolipoprotein E (apoE) and ATP-binding cassette transporter levels in the brain, along with a greatly improved peripheral lipid safety profile when compared to those of full dual agonists. These findings were replicated by subchronic dosing studies in non-human primates, where cerebrospinal fluid levels of apoE and amyloid-β peptides were increased concomitantly with an improved peripheral lipid profile relative to that of nonselective compounds. These results suggest that optimization of LXR agonists for Emax selectivity may have the potential to circumvent the adverse lipid-related effects of hepatic LXR activity.

  11. In vitro phototoxic potential and photochemical properties of imidazopyridine derivative: a novel 5-HT4 partial agonist.

    Science.gov (United States)

    Onoue, Satomi; Igarashi, Naoko; Yamauchi, Yukinori; Kojima, Takashi; Murase, Noriaki; Zhou, Yu; Yamada, Shizuo; Tsuda, Yoshiko

    2008-10-01

    Drug-induced phototoxic skin responses have been recognized as undesirable side effects, and as we previously proposed the determination of reactive oxygen species (ROS) from photo-irradiated compounds can be effective for the prediction of phototoxic potential. In this investigation, we evaluated the photosensitizing properties of imidazopyridine derivative, a novel 5-HT(4) partial agonist, using ROS assay and several analytical/biochemical techniques. Exposure of the compound to simulated sunlight resulted in the significant production of singlet oxygen, which is indicative of its phototoxic potential. In practice, an imidazopyridine derivative under UVA/B light exposure also showed significant photodegradation and even photobiochemical events; peroxidation of fatty acid and genetic damage after DNA-binding, which are considered as causative agents for phototoxic dermatitis. Interestingly, both photodegradation and lipoperoxidation were dramatically attenuated by the addition of radical scavengers, especially singlet oxygen quenchers, suggesting the possible involvement of ROS generation in the phototoxic pathways. In the 3T3 neutral red uptake phototoxicity test, imidazopyridine derivative also showed the phototoxic effect on 3T3 mouse fibroblast cells. These results suggest the phototoxic risk of newly synthesized imidazopyridine derivative and also verify the usefulness of ROS assay for phototoxicity prediction. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  12. Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

    Science.gov (United States)

    Sarmiento, Viviana; Ramirez-Sanchez, Israel; Moreno-Ulloa, Aldo; Romero-Perez, Diego; Chávez, Daniel; Ortiz, Miguel; Najera, Nayelli; Correa-Basurto, Jose; Villarreal, Francisco; Ceballos, Guillermo

    2018-02-15

    To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Mody-3: novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1 receptor agonist therapy.

    Science.gov (United States)

    Docena, Maricor K; Faiman, Charles; Stanley, Christine M; Pantalone, Kevin M

    2014-02-01

    An estimated 1 to 2% of cases of diabetes mellitus have a monogenic basis; however, delayed diagnosis and misdiagnosis as type 1 and 2 diabetes are common. Correctly identifying the molecular basis of an individual's diabetes may significantly alter the management approach to both the patient and his or her relatives. We describe a case of mature onset diabetes of the young (MODY) with sufficient evidence to support the classification of a novel HNF1A (hepatocyte nuclear factor-1-α) mutation as a cause of MODY-3. A 21-year-old Caucasian female presented to our office with a diagnosis of noninsulin-dependent diabetes mellitus (NIDDM) at age 10; glycemia was initially managed with oral antidiabetic (OAD) agents and insulin detemir. The patient reported a strong family history of early-onset NIDDM in both her mother and maternal grandmother, both of whom eventually required insulin therapy to control glycemia. The patient's medical and family history were highly suggestive of maturity-onset diabetes of the young (MODY), and genetic testing was performed. Genetic screening detected a mutation p. Arg200Trp in the HNF1A gene in the patient, her mother, and maternal grandmother, suggesting a diagnosis of MODY-3. This finding resulted in a change of antidiabetic therapy in all 3 patients, including the addition of once-daily liraglutide therapy, which helped improve their glycemic control. Our case report supports the classification of the p. Arg200Trp mutation as a cause of MODY-3. The findings also suggest that glucagon-like peptide-1 (GLP-1) receptor agonist therapy may be of value in managing glycemia in patients with MODY-3.

  14. The PPARα/γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat

    Directory of Open Access Journals (Sweden)

    Kristina Wallenius

    2013-01-01

    Full Text Available Metabolic flexibility was assessed in male Zucker rats: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR agonist, tesaglitazar, 3 μmol/kg/day for 3 weeks. Whole body glucose disposal rate ( and hepatic glucose output (HGO were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,3H]glucose. Indices of tissue specific glucose utilization ( were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-3H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-13C]glucose, 2-deoxy-D-[U-14C]glucose, [U-14C]palmitate, and [9,10-3H]-(R-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of compared to obese controls. This involved increased insulin stimulation of in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (, and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.

  15. Role of methylglyoxal as a transient receptor potential ankyrin 1 agonist in colon motility disturbances associated with diabetes

    Directory of Open Access Journals (Sweden)

    Abdulmohsen Assiri

    2017-01-01

    Full Text Available Introduction: Evidence has been found to suggest that methylglyoxal (MG plays a mediating role in diabetes-related gastrointestinal conditions, and a possible mechanism relating to these conditions could be revealed by determining MG as a transient receptor potential ankyrin 1 (TRPA1 channel agonist. Methods: Muscle strips from the distal colon of male Wistar rats were used, and organ bath was employed to gain insight into the impact of MG + TRPA1 antagonist (HC-030031. Results: Considerable rise of spontaneous contractions for longitudinal muscle strips subjected to pre-treatment with MG were observed. The potentiation of the contractile response of control longitudinal muscle strips to electric field stimulation (EFS took place as a consequence of pre-treatment with 10 mM MG, and maximum response values displayed a rise from 2.16 g ± 0.323 to 3.64 g ± 0.421. 10 μM HC-030031 was observed to block the improvement of EFS responses by MG, and regarding circular muscle strips, a considerable decline in the maximum relaxation response was facilitated by 10 mM MG. Specifically, this was achieved at 20 Hz from 0.26 g ± 0.036 to 0.055 g ± 0.046. Conclusion: MG has been found to directly contract the distal colons of Wistar rats while enhancing the responses initiated as a result of carbachol and EFS. After blockading the impacts using HC-030031, evidence was found to suggest that the mediation of the impacts takes place through the activation of the TRPA1 channel, which occurs from the excretion of excitatory neurotransmitters. The findings also implicate MG in the blocking of inhibitory neurotransmission.

  16. Salvinorin A, a kappa-opioid receptor (KOP-r agonist hallucinogen: Pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Eduardo eButelman

    2015-09-01

    Full Text Available Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins in higher functions, including cognition, and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A- containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and drug reinforcers (including drugs of abuse. KOPr activation (including by salvinorin A can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike all other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects, with a reduced burden of undesirable effects associated with salvinorin A.

  17. Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans

    DEFF Research Database (Denmark)

    Andersen, Hjalte H.; Melholt, Camilla; Hilborg, Sigurd D.

    2017-01-01

    A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists...... and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value....... (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical “cold-like” counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin...

  18. A snapshot of geothermal energy potential and utilization in Turkey

    International Nuclear Information System (INIS)

    Erdogdu, Erkan

    2009-01-01

    Turkey is one of the countries with significant potential in geothermal energy. It is estimated that if Turkey utilizes all of her geothermal potential, she can meet 14% of her total energy need (heat and electricity) from geothermal sources. Therefore, today geothermal energy is an attractive option in Turkey to replace fossil fuels. Besides, increase in negative effects of fossil fuels on the environment has forced many countries, including Turkey, to use renewable energy sources. Also, Turkey is an energy importing country; more than two-thirds of her energy requirement is supplied by imports. In this context, geothermal energy appears to be one of the most efficient and effective solutions for sustainable energy development and environmental pollution prevention in Turkey. Since geothermal energy will be used more and more in the future, its current potential, usage, and assessment in Turkey is the focus of the present study. The paper not only presents a review of the potential and utilization of the geothermal energy in Turkey but also provides some guidelines for policy makers. (author)

  19. Assessment of Global Wind Energy Resource Utilization Potential

    Science.gov (United States)

    Ma, M.; He, B.; Guan, Y.; Zhang, H.; Song, S.

    2017-09-01

    Development of wind energy resource (WER) is a key to deal with climate change and energy structure adjustment. A crucial issue is to obtain the distribution and variability of WER, and mine the suitable location to exploit it. In this paper, a multicriteria evaluation (MCE) model is constructed by integrating resource richness and stability, utilization value and trend of resource, natural environment with weights. The global resource richness is assessed through wind power density (WPD) and multi-level wind speed. The utilizable value of resource is assessed by the frequency of effective wind. The resource stability is assessed by the coefficient of variation of WPD and the frequency of prevailing wind direction. Regression slope of long time series WPD is used to assess the trend of WER. All of the resource evaluation indicators are derived from the atmospheric reanalysis data ERA-Interim with spatial resolution 0.125°. The natural environment factors mainly refer to slope and land-use suitability, which are derived from multi-resolution terrain elevation data 2010 (GMTED 2010) and GlobalCover2009. Besides, the global WER utilization potential map is produced, which shows most high potential regions are located in north of Africa. Additionally, by verifying that 22.22 % and 48.8 9% operational wind farms fall on medium-high and high potential regions respectively, the result can provide a basis for the macroscopic siting of wind farm.

  20. The μ opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway

    Directory of Open Access Journals (Sweden)

    Roberts-Thomson Sarah J

    2006-07-01

    Full Text Available Abstract Background The vanilloid receptor 1 (TRPV1 is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+ responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.

  1. Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

    Science.gov (United States)

    Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

    2017-12-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50  =   0.16 μM) and rosiglitazone (EC 50  =   0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of

  2. Synthesis, characterization and potential utility of doped ceramics based catalysts

    Science.gov (United States)

    Sharma, Ritika; Yadav, Deepshikha; Singh, G. P.; Vyas, G.; Bhojak, N.

    2018-05-01

    Excessive utilization of petrol, diesel and other fossil fuels, continuous increase in their prices, and the big problem of carbon dioxide mission have encouraged scientists and technologist to find either new sources of energy or to develop technologies for the sustainable utilization of fuel. Biofuels are the only energy technologies that can resolve the problem of carbon dioxide emission in the atmosphere as well as reduce the amount of fossil fuel burned. Bio ethanol and biodiesel are the most common types of biofuel which are being used at present. Biodiesel has become more interesting for all the researchers in present scenario. Various feedstock viz. edible, nonedible oils, waste cooking oil, animal fat, algae etc, are using for the production of biodiesel worldwide according to their availability. Selection of efficient heterogeneous catalysts for biodiesel preparation still needs more attention of researchers. The present investigation deals with determination of synthesis, characterization and applications of doped ceramic based materials in different medium. Two of doped ceramic based catalysts which has been potentially used for the production of biodiesel. The Engine performance of biodiesel samples, made from industrial waste oils and ceramic based catalyst, have also been investigated and found up to satisfactory levels.

  3. Space Resource Utilization: Technologies and Potential Synergism with Terrestrial Mining

    Science.gov (United States)

    Sanders, Gerald B.

    2015-01-01

    Space Resources and Their Uses: The idea of using resources in space to support human exploration and settlement or for economic development and profit beyond the surface of Earth has been proposed and discussed for decades. Work on developing a method to extract oxygen from lunar regolith started even before humans set foot on the Moon for the first time. The use of space resources, commonly referred to as In Situ Resource Utilization (ISRU), involves the processes and operations to harness and utilize resources in space (both natural and discarded) to create products for subsequent use. Potential space resources include water, solar wind implanted volatiles (hydrogen, helium, carbon, nitrogen, etc.), vast quantities of metals and minerals in extraterrestrial soils, atmospheric constituents, unlimited solar energy, regions of permanent light and darkness, the vacuum and zero-gravity of space itself, trash and waste from human crew activities, and discarded hardware that has completed its primary purpose. ISRU covers a wide variety of concepts, technical disciplines, technologies, and processes. When considering all aspects of ISRU, there are 5 main areas that are relevant to human space exploration and the commercialization of space: 1. Resource Characterization and Mapping, 2. In Situ Consumables Production, 3. Civil Engineering and Construction, 4. In Situ Energy Production and Storage, and 5. In Situ Manufacturing.

  4. Studies To Examine Potential Tolerability Differences between the 5-HT2C Receptor Selective Agonists Lorcaserin and CP-809101.

    Science.gov (United States)

    Higgins, Guy A; Silenieks, Leonardo B; Patrick, Amy; De Lannoy, Ines A M; Fletcher, Paul J; Parker, Linda A; MacLusky, Neil J; Sullivan, Laura C; Chavera, Teresa A; Berg, Kelly A

    2017-05-17

    Lorcaserin (LOR) is a selective 5-HT 2C receptor agonist that has been FDA approved as a treatment for obesity. The most frequently reported side-effects of LOR include nausea and headache, which can be dose limiting. We have previously reported that in the rat, while LOR produced unconditioned signs characteristic of nausea/malaise, the highly selective 5-HT 2C agonist CP-809101 (CP) produced fewer equivalent signs. Because this may indicate a subclass of 5-HT 2C agonists having better tolerability, the present studies were designed to further investigate this apparent difference. In a conditioned gaping model, a rodent test of nausea, LOR produced significantly higher gapes compared to CP consistent with it having higher emetogenic properties. Subsequent studies were designed to identify features of each drug that may account for such differences. In rats trained to discriminate CP-809101 from saline, both CP and LOR produced full generalization suggesting a similar interoceptive cue. In vitro tests of functional selectivity designed to examine signaling pathways activated by both drugs in CHO (Chinese hamster ovary) cells expressing h5-HT 2C receptors failed to identify evidence for biased signaling differences between LOR and CP. Thus, both drugs showed similar profiles across PLC, PLA 2 , and ERK signaling pathways. In studies designed to examine pharmacokinetic differences between LOR and CP, while drug plasma levels correlated with increasing dose, CSF levels did not. CSF levels of LOR increased proportionally with dose; however CSF levels of CP plateaued from 6 to 12 mg/kg. Thus, the apparently improved tolerability of CP likely reflects a limit to CNS levels attained at relatively high doses.

  5. Survey of renewable energy utilization and development potential in Oceania

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    This paper reports fiscal 2000 survey of renewable energy utilization and development potential in Oceania. In Australia and New Zealand, renewable energy has already fairly been used. In Australia, it is promoted on the government policy level, with cost reduction and improved reliability in progress. The growth of 2% is set as a target in the year 2010. Promising are biomass and wind, while contributory in the long run are photovoltaic energies. New installations of hydraulic power generation are few, but potential is high for mini hydraulic power generation. Social interest is also comparatively high in renewable energies and greenhouse effect gas. However, further technological development is necessary for a full-scale contribution to global environmental problems. The situation in other south Pacific nations depends on their policy, economic condition and level of industrialization; each country heavily imports diesel oil for power generation, is under-developed industry-wise, and is a low income nation. The countries are desperately in need of foreign investment for the purpose of solving these problems. (NEDO)

  6. Geothermal source potential and utilization for alcohol production

    Energy Technology Data Exchange (ETDEWEB)

    Austin, J.C.

    1981-11-01

    A study was conducted to assess the technical and economic feasibility of using a potential geothermal source to drive a fuel grade alcohol plant. Test data from the well at the site indicated that the water temperature at approximately 8500 feet should approach 275/sup 0/F. However, no flow data was available, and so the volume of hot water that can be expected from a well at this site is unknown. Using the available data, numerous fuel alcohol production processes and various heat utilization schemes were investigated to determine the most cost effective system for using the geothermal resource. The study found the direct application of hot water for alcohol production based on atmospheric processes using low pressure steam to be most cost effective. The geothermal flow rates were determined for various sizes of alcohol production facility using 275/sup 0/F water, 235/sup 0/F maximum processing temperature, 31,000 and 53,000 Btu per gallon energy requirements, and appropriate process approach temperatures. It was determined that a 3 million gpy alcohol plant is the largest facility that can practically be powered by the flow from one large geothermal well. An order-of-magnitude cost estimate was prepared, operating costs were calculated, the economic feasibility of the propsed project was examined, and a sensitivity analysis was performed.

  7. Potential and utilization of thermophiles and thermostable enzymes in biorefining

    Directory of Open Access Journals (Sweden)

    Karlsson Eva

    2007-03-01

    Full Text Available Abstract In today's world, there is an increasing trend towards the use of renewable, cheap and readily available biomass in the production of a wide variety of fine and bulk chemicals in different biorefineries. Biorefineries utilize the activities of microbial cells and their enzymes to convert biomass into target products. Many of these processes require enzymes which are operationally stable at high temperature thus allowing e.g. easy mixing, better substrate solubility, high mass transfer rate, and lowered risk of contamination. Thermophiles have often been proposed as sources of industrially relevant thermostable enzymes. Here we discuss existing and potential applications of thermophiles and thermostable enzymes with focus on conversion of carbohydrate containing raw materials. Their importance in biorefineries is explained using examples of lignocellulose and starch conversions to desired products. Strategies that enhance thermostablity of enzymes both in vivo and in vitro are also assessed. Moreover, this review deals with efforts made on developing vectors for expressing recombinant enzymes in thermophilic hosts.

  8. SOCIAL MEDIA IN POLAND – GREAT POTENTIAL UTILIZED BY FEW

    Directory of Open Access Journals (Sweden)

    Michael SEDKOWSKI

    2016-02-01

    Full Text Available Social media are very popular around the world. More and more people adopt this method of communication, as it brings instant and effective ways to stay in touch with ones relatives, coworkers, brands and products. Poland is no exception, as all major brands of the social sphere have decided to prepare localized versions of their product for the Polish market. One could say that Poland is following the global trends very accurately as Facebook has dominated the market and pushed out the indigenous services Brands and corporation utilize the medium to get in touch with their consumers. On the other side, there are public institutions like universities, local governments , that should be interested in getting in touch with people, as reaching out to one’s potential customers has never been easier. This is happening, but on a very small scale and many attempts fail. In this paper, Author explores the possible reasons behind the situation and attempts to form a prognosis for the market of social media in Poland.

  9. Evaluating Utility Gloves as a Potential Reservoir for Pathogenic Bacteria.

    Science.gov (United States)

    Grant, Kathy L; Naber, E Donald; Halteman, William A

    2015-08-01

    This pilot study sought to determine the rate and degree to which gram-negative Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa and gram-positive Staphylococcus aureus occurred on the inside of utility gloves used at University of Maine at Augusta, Dental Health Programs' dental hygiene clinic. Five steam autoclave utility gloves were randomly selected to serve as control and a convenience sample of 10 used utility gloves were selected from the sterilization area. A sample was collected from a predetermined surface area from the inside of each steam autoclave utility glove and used utility glove. Each sample was used to inoculate a Petri plate containing 2 types of culture media. Samples were incubated at 37° C for 30 to 36 hours in aerobic conditions. Colony forming units (CFU) were counted. Confidence intervals (CI) estimated the rate of contamination with gram-negative K. pneumoniae, E. coli and P. aeruginosa on the inside of steam autoclave utility gloves to be n=33 95% CL [0.000, 0.049], used utility gloves to be n=70, 95% CL [0.000, 0.0303]. Data estimated the rate of contamination with gram-positive S. aureus on the inside of steam autoclave utility gloves to be n=35, 95% CL [0.233, 0.530], used utility gloves to be n=70, 95% CL [0.2730, 0.4975]. Culture media expressed a wide range of CFU from 0 to over 200. The risk of utility glove contamination with gram-negative bacteria is likely low. The expressed growth of S. aureus from steam autoclave utility gloves controls raises questions about the effectiveness and safety of generally accepted sterilization standards for the governmentally mandated use of utility gloves. Copyright © 2015 The American Dental Hygienists’ Association.

  10. Antipruritic Effect of Cold-induced and Transient Receptor Potential-agonist-induced Counter-irritation on Histaminergic Itch in Humans.

    Science.gov (United States)

    Andersen, Hjalte H; Melholt, Camilla; Hilborg, Sigurd D; Jerwiarz, Anne; Randers, Amalie; Simoni, Amalie; Elberling, Jesper; Arendt-Nielsen, Lars

    2017-01-04

    A frequent empirical observation is that cold-induced counter-irritation may attenuate itch. The aim of this randomized, single-blinded, exploratory study was to evaluate the counter-irritation effects of cold-stimulation and topical application of transient receptor potential TRPA1/M8-agonists (trans-cinnamaldehyde/L-menthol, respectively), on histamine-induced itch, wheals and neurogenic inflammation in 13 healthy volunteers. Histamine 1% was applied to the volar forearms using skin prick-test lancets. Recorded outcome-parameters were itch intensity, wheal reactions, and neurogenic inflammation (measured by laser-speckle perfusion-imaging). Homotopic thermal counter-irritation was performed with 6 temperatures, ranging from 4°C to 37°C, using a 3 × 3-cm thermal stimulator. Chemical "cold-like" counter-irritation was conducted with 40% L-menthol and 10% trans-cinnamaldehyde, while 5% doxepin was used as a positive antipruritic control/comparator. Cold counter-irritation stimuli from 4°C to 22°C inhibited itch in a stimulus-intensity-dependent manner (p cold-like" counter-irritation with both L-menthol and trans-cinnamaldehyde had antipruritic efficacy similar to doxepin (p Cold-induced counter-irritation had an inhibitory effect on histaminergic itch, suggesting that agonists of cold transduction receptors could be of potential antipruritic value.

  11. Utilization Patterns of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus in Italy: A Retrospective Cohort Study.

    Science.gov (United States)

    Federici, Marco Orsini; McQuillan, Janette; Biricolti, Giovanni; Losi, Serena; Lebrec, Jeremie; Richards, Catrina; Miglio, Cristiana; Norrbacka, Kirsi

    2018-04-01

    Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day. This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated

  12. The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Casadesus, Gemma; Garrett, Matthew R; Webber, Kate M; Hartzler, Anthony W; Atwood, Craig S; Perry, George; Bowen, Richard L; Smith, Mark A

    2006-01-01

    Estrogen and other sex hormones have received a great deal of attention for their speculative role in Alzheimer's disease (AD), but at present a direct connection between estrogen and the pathogenesis of AD remains elusive and somewhat contradictory. For example, on one hand there is a large body of evidence suggesting that estrogen is neuroprotective and improves cognition, and that hormone replacement therapy (HRT) at the onset of menopause reduces the risk of developing AD decades later. However, on the other hand, studies such as the Women's Health Initiative demonstrate that HRT initiated in elderly women increases the risk of dementia. While estrogen continues to be investigated, the disparity of findings involving HRT has led many researchers to examine other hormones of the hypothalamic-pituitary-gonadal axis such as luteinising hormone (LH) and follicle-stimulating hormone. In this review, we propose that LH, rather than estrogen, is the paramount player in the pathogenesis of AD. Notably, both men and women experience a 3- to 4-fold increase in LH with aging, and LH receptors are found throughout the brain following a regional pattern remarkably similar to those neuron populations affected in AD. With respect to disease, serum LH level is increased in women with AD relative to non-diseased controls, and levels of LH in the brain are also elevated in AD. Mechanistically, we propose that elevated levels of LH may be a fundamental instigator responsible for the aberrant reactivation of the cell cycle that is seen in AD. Based on these aforementioned aspects, clinical trials underway with leuprolide acetate, a gonadotropin-releasing hormone agonist that ablates serum LH levels, hold great promise as a ready means of treatment in individuals afflicted with AD.

  13. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Prickaerts, Jos; van Goethem, Nick P; Chesworth, Richard; Shapiro, Gideon; Boess, Frank G; Methfessel, Christoph; Reneerkens, Olga A H; Flood, Dorothy G; Hilt, Dana; Gawryl, Maria; Bertrand, Sonia; Bertrand, Daniel; König, Gerhard

    2012-02-01

    EVP-6124, (R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, is a novel partial agonist of α7 neuronal nicotinic acetylcholine receptors (nAChRs) that was evaluated here in vitro and in vivo. In binding and functional experiments, EVP-6124 showed selectivity for α7 nAChRs and did not activate or inhibit heteromeric α4β2 nAChRs. EVP-6124 had good brain penetration and an adequate exposure time. EVP-6124 (0.3 mg/kg, p.o.) significantly restored memory function in scopolamine-treated rats (0.1 mg/kg, i.p.) in an object recognition task (ORT). Although donepezil at 0.1 mg/kg, p.o. or EVP-6124 at 0.03 mg/kg, p.o. did not improve memory in this task, co-administration of these sub-efficacious doses fully restored memory. In a natural forgetting test, an ORT with a 24 h retention time, EVP-6124 improved memory at 0.3 mg/kg, p.o. This improvement was blocked by the selective α7 nAChR antagonist methyllycaconitine (0.3 mg/kg, i.p. or 10 μg, i.c.v.). In co-application experiments of EVP-6124 with acetylcholine, sustained exposure to EVP-6124 in functional investigations in oocytes caused desensitization at concentrations greater than 3 nM, while lower concentrations (0.3-1 nM) caused an increase in the acetylcholine-evoked response. These actions were interpreted as representing a co-agonist activity of EVP-6124 with acetylcholine on α7 nAChRs. The concentrations of EVP-6124 that resulted in physiological potentiation were consistent with the free drug concentrations in brain that improved memory performance in the ORT. These data suggest that the selective partial agonist EVP-6124 improves memory performance by potentiating the acetylcholine response of α7 nAChRs and support new therapeutic strategies for the treatment of cognitive impairment. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The Potential Utility of Pharmacogenetic Testing in Psychiatry

    Directory of Open Access Journals (Sweden)

    Kathryn R. Gardner

    2014-01-01

    Full Text Available Over the last decade, pharmacogenetics has become increasingly significant to clinical practice. Psychiatric patients, in particular, may benefit from pharmacogenetic testing as many of the psychotropic medications prescribed in practice lead to varied response rates and a wide range of side effects. The use of pharmacogenetic testing can help tailor psychotropic treatment and inform personalized treatment plans with the highest likelihood of success. Recently, many studies have been published demonstrating improved patient outcomes and decreased healthcare costs for psychiatric patients who utilize genetic testing. This review will describe evidence supporting the clinical utility of genetic testing in psychiatry, present several case studies to demonstrate use in everyday practice, and explore current patient and clinician opinions of genetic testing.

  15. Market potential of heat utilization of modular HTR in Japan

    International Nuclear Information System (INIS)

    Ide, Akira; Tasaka, Kanji.

    1993-01-01

    HTR is considered to be the most suitable reactor type to use in the field other than power generation. So it is useful to know market potential of this type of reactor in Japan to justify its development. This potential was estimated to be about 400 200MWt modular HTR reactors. This number will be double if the market of hydrogen is developed. (J.P.N.)

  16. Utility Potential of Parthenium hysterophorus for Its Strategic Management

    Directory of Open Access Journals (Sweden)

    Anita Saini

    2014-01-01

    Full Text Available Parthenium hysterophorus, one of the world’s most dangerous weeds, is responsible for huge losses to the biodiversity, agriculture, economy, and health of livestock and human beings. High competitive success rate and adaptability of the species enable it to dominate diverse types of habitats. Various weed control strategies are being used globally to reduce its population to manageable levels. But owing to many limitations associated with the conventional methods, management of Parthenium still remains a challenge. Recently large scale utilization has been taken up as a holistic approach for the control of weeds. Parthenium hysterophorus can be managed by exploiting this weed in diverse fields. In agriculture, it can be used either as green manure or after composting. Industrially it can be used for producing various value added products. The weed also exhibits many environmental applications. Chemical constituents of Parthenium show extensive range of pharmacological activities suggesting its role as a chemotherapeutic agent. This review briefly discusses the problem of Parthenium and enlists its possible utilities which can open new avenues for effective management of this violent weed.

  17. Measuring the potential utility of seasonal climate predictions

    Science.gov (United States)

    Tippett, Michael K.; Kleeman, Richard; Tang, Youmin

    2004-11-01

    Variation of sea surface temperature (SST) on seasonal-to-interannual time-scales leads to changes in seasonal weather statistics and seasonal climate anomalies. Relative entropy, an information theory measure of utility, is used to quantify the impact of SST variations on seasonal precipitation compared to natural variability. An ensemble of general circulation model (GCM) simulations is used to estimate this quantity in three regions where tropical SST has a large impact on precipitation: South Florida, the Nordeste of Brazil and Kenya. We find the yearly variation of relative entropy is strongly correlated with shifts in ensemble mean precipitation and weakly correlated with ensemble variance. Relative entropy is also found to be related to measures of the ability of the GCM to reproduce observations.

  18. Potential utility of the thematic mapper for surface mine monitoring

    International Nuclear Information System (INIS)

    Irons, J.R.; Lachowski, H.M.

    1981-01-01

    One of many potential applications of the thematic mapper (TM) is surface mine monitoring. To assess this potential, data acquired by an aircraft multispectral scanner over Pennsylvania surface mines were preprocessed to simulate the anticipated spectral, spatial, and radiometric characteristics of TM data. False color imagery and thematic maps were derived from the simulated data and compared to imagery and maps derived from LANDSAT multispectral scanner subsystems data. On the basis of this comparison, TM data should definitely increase the detail and accuracy of remotely acquired surface mine information and may enable the remote determination of compliance with reclamation regulations

  19. Utilization of leaf litter as a potential feed source

    Science.gov (United States)

    Proximate analysis and In-situ nylon bag ruminal dry matter degradation of fall dropped Liriodendron tulipifera (tulip poplar) and Quercus alba (white oak) leaves were used to determine their potential use as a feed source for ruminant livestock animals. Ash content was 8.24 and 4.69 ...

  20. Energy Saving Potential by Utilizing Natural Ventilation under Warm Conditions

    DEFF Research Database (Denmark)

    Oropeza-Perez, Ivan; Østergaard, Poul Alberg

    2014-01-01

    The objective of this article is to show the potential of natural ventilation as a passive cooling method within the residential sector of countries which are located in warm conditions using Mexico as a case study. The method is proposed as performing, with a simplified ventilation model, thermal......–airflow simulations of 27 common cases of dwellings (considered as one thermal zone) based on the combination of specific features of the building design, occupancy and climate conditions. The energy saving potential is assessed then by the use of a new assessment method suitable for large-scale scenarios using...... the actual number of air-conditioned dwellings distributed among the 27 cases. Thereby, the energy saving is presented as the difference in the cooling demand of the dwelling during one year without and with natural ventilation, respectively. Results indicate that for hot-dry conditions, buildings with high...

  1. Environmental characteristics and utilization potential of metallurgical slag: Chapter 19

    Science.gov (United States)

    Piatak, Nadine; De Vivo, Benedetto; Belkin, Harvey E.; Lima, Annamaria

    2018-01-01

    Slag, an abundant byproduct from the pyrometallurgical processing of ores, can be an environmental liability or a valuable resource. The most common environmental impact of slag is from the leaching of potentially toxic elements, acidity, or alkalinity that may impact nearby soils and surface water and groundwater. Factors that influence its environmental behavior include physical characteristics, such as grain size and porosity, chemical composition with some slag being enriched in certain elements, the mineralogy and partitioning of elements in more or less reactive phases, water-slag interactions, and site conditions. Many of these same factors also influence its resource potential. For example, crystalline ferrous slag is most commonly used as construction aggregate, whereas glassy (i.e., granulated) slag is used in cement. Also, the calcium minerals found in ferrous slag result in useful applications in water treatment. In contrast, the high trace-element content of some base-metal slags makes the slags economically attractive for extraction of residual elements. An evaluation tool is used to help categorize a particular slag as an environmental hazard or valuable byproduct. Results for one type of slag, legacy steelmaking slag from the Chicago area in the USA, suggest the material has potential to be used for treating phosphate-rich or acidic waters; however, the pH and trace-element content of resulting solutions may warrant further examination.

  2. Lignocellulosic bioethanol potential utilizing subproducts from the biodiesel production process

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Evan Michael; Oliveira Filho, Delly; Toledo, Olga Moraes [Universidade Federal de Vicosa (DEA/UFV), MG (Brazil). Dept. de Engenharia Agricola

    2008-07-01

    Cellulosic ethanol production is one of the most researched fields in today's biofuels industry, and one of the major problems facing the commercial production of cellulosic ethanol is the challenge of collecting biomass. Oil extraction for biodiesel production yields large amounts of cellulose rich biomass sub-products, which in many cases can produce enough ethanol to meet the alcohol demands of transesterification. Soybean, castor bean, Jatropha Curcas, palm kernel, sunflower seed, rapeseed and cottonseed were studied to determine ethanol production potential from their oil extraction co-products and also the capacity to meet transesterification alcohol demands. Nearly all crops studied were capable of producing enough ethanol for biodiesel production and, in the case of palm kernels, 383% of the transesterification demands could be met with cellulosic ethanol production of the proper sub-products. Based on Brazilian yields, Palm kernels have a production potential of 6725 L ha{sup -1} of ethanol followed by Jatropha curcas with 695 L ha{sup -1}. (author)

  3. Worldwide variance in the potential utilization of Gamma Knife radiosurgery.

    Science.gov (United States)

    Hamilton, Travis; Dade Lunsford, L

    2016-12-01

    OBJECTIVE The role of Gamma Knife radiosurgery (GKRS) has expanded worldwide during the past 3 decades. The authors sought to evaluate whether experienced users vary in their estimate of its potential use. METHODS Sixty-six current Gamma Knife users from 24 countries responded to an electronic survey. They estimated the potential role of GKRS for benign and malignant tumors, vascular malformations, and functional disorders. These estimates were compared with published disease epidemiological statistics and the 2014 use reports provided by the Leksell Gamma Knife Society (16,750 cases). RESULTS Respondents reported no significant variation in the estimated use in many conditions for which GKRS is performed: meningiomas, vestibular schwannomas, and arteriovenous malformations. Significant variance in the estimated use of GKRS was noted for pituitary tumors, craniopharyngiomas, and cavernous malformations. For many current indications, the authors found significant variance in GKRS users based in the Americas, Europe, and Asia. Experts estimated that GKRS was used in only 8.5% of the 196,000 eligible cases in 2014. CONCLUSIONS Although there was a general worldwide consensus regarding many major indications for GKRS, significant variability was noted for several more controversial roles. This expert opinion survey also suggested that GKRS is significantly underutilized for many current diagnoses, especially in the Americas. Future studies should be conducted to investigate health care barriers to GKRS for many patients.

  4. Theoretical potential and utilization of renewable energy in Afghanistan

    Directory of Open Access Journals (Sweden)

    Gul Ahmad Ludin

    2016-12-01

    Full Text Available Nowadays, renewable energy is gaining more attention than other resources for electricity generation in the world. For Afghanistan that has limited domestic production of electric power and is more dependent on the unstable imported power from neighboring countries which pave the way to raise the cost of energy and increased different technical and economic problems. The employment of renewable energy would not only contribute to the independence of energy supply but also can achieve the socio-economic benefits for the country which is trying to rebuild its energy sector with a focus on sustainable energy for its population. From a theoretical point of view, there is a considerable potential of renewable energies such as solar energy, wind power, hydropower, biomass and geothermal energy available in the country. However, despite the presence of widespread non-agricultural and non-residential lands, these resources have not been deployed efficiently. This paper assesses the theoretical potential of the aforementioned types of renewable energies in the country. The study indicates that deployment of renewable energies can not only supplement the power demand but also will create other opportunities and will enable a sustainable energy base in Afghanistan.

  5. Behavioral Effects of a Novel Benzofuranyl-Piperazine Serotonin-2C Receptor Agonist Suggest a Potential Therapeutic Application in the Treatment of Obsessive–Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    Michelle M. Rodriguez

    2017-05-01

    Full Text Available Selective serotonin reuptake inhibitors (SSRIs are the only effective pharmacological treatments for obsessive–compulsive disorder (OCD. Nonetheless, their generally limited efficacy, side-effects, and delayed onset of action require improved medications for this highly prevalent disorder. Preclinical and clinical findings have suggested serotonin2C (5-HT2C receptors as a potential drug target. Data in rats and mice are presented here on the effects of a novel 5-HT2C receptor agonist ((3S-3-Methyl-1-[4-(trifluoromethyl-7-benzofuranyl]-piperazine (CPD 1 with high potency and full efficacy at 5-HT2C receptors and less potency and partial agonism at 5-HT2A and 5-HT2B receptors. Effects of CPD 1 on consummatory (schedule-induced polydipsia in rats and non-consummatory behaviors (marble-burying and nestlet-shredding in mice that are repetitive and non-habituating were studied. We also evaluated the effects of CPD 1 in rats with isoproterenol- and deprivation-induced drinking in rats to compare with the polydipsia studies. The SSRIs, fluoxetine, and chlomipramine decreased the high rates of drinking in rats engendered by a schedule of intermittent food delivery (schedule-induced polydipsia. The effects of fluoxetine, but not of d-amphetamine, were prevented by the selective 5-HT2C receptor antagonist SB242084. The 5-HT2C receptor agonists Ro 60-0175 and CPD 1 also decreased drinking, but unlike the SSRIs and Ro 60-0175, CPD 1 dose-dependently decreased excessive drinking without affecting lever press responses that produced food. The effects of CPD 1 were prevented by SB242084. CPD 1 also suppressed drinking induced by isoproterenol and by water deprivation without affecting normative drinking behavior. CPD 1, like fluoxetine, also suppressed marble-burying and nestlet-shredding in mice at doses that did not affect rotarod performance or locomotor activity. The behavioral specificity of effects of CPD 1 against repetitive and excessive behaviors

  6. Waste utilization strategies and markets in Europe, the export potential

    International Nuclear Information System (INIS)

    Vaeisaenen, P.

    2001-01-01

    advantages and disadvantages. Collection energy waste requires one container more and the recovery is not well. On the other hand the quality is reasonably good and the manufacture of REF can be simple. An exception for the need of an additional container can be found in Kymenlaakson Jaete Oy, there the energy fraction is collected in orange plastic bag in the same waste container as the dry residues. The orange energy waste bags are separated from dry waste by optical separator, which requires extra investments for the waste separation plant. The quality of dry waste can occasionally be poor so the manufacturing process of REF has to tolerate impurities. The yield, on the other hand, is good and the national waste utilization targets can be met

  7. Potential Utility of Non-Cognitive Constructs in Graduate Admissions

    Science.gov (United States)

    Miller, Casey

    2015-03-01

    It is becoming clear that the methods employed by many graduate admissions committees need updating. Regarding outcomes, we cannot select students that will actually graduate much better than would a coin toss. Further, the GRE is often misused. For example, the most recent GRE general test data (2006-2007) shows that for US citizens in the physical sciences, a cut-off score of ~64th percentile (700/155 on old/new test) would eliminate from eligibility: 63% of women vs 42% of men; 76% of all under-represented minorities vs 38% of Asian and 47% of White applicants. Fortunately, Organizational Psychologists have identified and validated several ``non-cognitive constructs'' for admissions: aspects of personality (conscientiousness); and self-management factors. Some intriguing facts about these parameters: they are measurable with the help of social scientists; they do not show race/ethnicity/gender performance differences; they are orthogonal to cognitive metrics measured by GPA and tests scores. These are proven to enhance both validity and diversity in admissions. My goals for this talk are to overview the non-cognitive constructs with the most potential for being used in physics graduate admissions, and to suggest example admissions protocols. Supported by the National Science Foundation.

  8. New Insights into the Potential Roles of 3-Iodothyronamine (T1AM and Newly Developed Thyronamine-Like TAAR1 Agonists in Neuroprotection

    Directory of Open Access Journals (Sweden)

    Lorenza Bellusci

    2017-12-01

    Full Text Available 3-Iodothyronamine (T1AM is an endogenous high-affinity ligand of the trace amine-associated receptor 1 (TAAR1, detected in mammals in many organs, including the brain. Recent evidence indicates that pharmacological TAAR1 activation may offer a novel therapeutic option for the treatment of a wide range of neuropsychiatric and metabolic disorders. To assess potential neuroprotection by TAAR1 agonists, in the present work, we initially investigated whether T1AM and its corresponding 3-methylbiaryl-methane analog SG-2 can improve learning and memory when systemically administered to mice at submicromolar doses, and whether these effects are modified under conditions of MAO inhibition by clorgyline. Our results revealed that when i.p. injected to mice, both T1AM and SG-2 produced memory-enhancing and hyperalgesic effects, while increasing ERK1/2 phosphorylation and expression of transcription factor c-fos. Notably, both compounds appeared to rely on the action of ubiquitous enzymes MAO to produce the corresponding oxidative metabolites that were then able to activate the histaminergic system. Since autophagy is key for neuronal plasticity, in a second line of experiments we explored whether T1AM and synthetic TAAR1 agonists SG1 and SG2 were able to induce autophagy in human glioblastoma cell lines (U-87MG. After treatment of U-87MG cells with 1 μM T1AM, SG-1, SG-2 transmission electron microscopy (TEM and immunofluorescence (IF showed a significant time-dependent increase of autophagy vacuoles and microtubule-associated protein 1 light chain 3 (LC3. Consistently, Western blot analysis revealed a significant increase of the LC3II/LC3I ratio, with T1AM and SG-1 being the most effective agents. A decreased level of the p62 protein was also observed after treatment with T1AM and SG-1, which confirms the efficacy of these compounds as autophagy inducers in U-87MG cells. In the process to dissect which pathway induces ATG, the effects of these compounds

  9. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  10. Study on the Potential Development of Rainwater Utilization in the Hilly City of Southern China

    Science.gov (United States)

    Fu, Xiaoran; Liu, Jiahong; Shao, Weiwei; Zhang, Haixing

    2017-12-01

    Aimed at the current flood problems and the contradiction between supply and demand of water resources in the southern cities of China, the comprehensive utilization of Urban Rainwater Resources (URRs) is a significant solution. At present, the research on the comprehensive utilization system of urban rainwater resources in China is still immature, especially the lack of a comprehensive method for the comprehensive utilization of the rainwater and flood resources in the south. Based on the current mode for utilization of URRs at home and abroad, Fenghuang County in Hunan Province was taken as a case of study, which is a typical mountainous city in the southern China. And the potential development of URRs was simulated and evaluated with a comparison of before and after the exploitation and utilization of URRs in this paper. The reduction effect of flood and waterlogging on the ancient city area is analyzed from SWMM. The simulation results show that the potential of exploitation and utilization of URRs in Fenghuang county is remarkable under the mode of exploitation and utilization which is given priority to flood prevention and control, and the annual development potential is 4.865×105 m3. The rainwater utilization measures of flood control effect is obvious with this mode, and the relevant research results can provide theoretical and technical support for enhancing urban water security capability, water conservation capacity, and disaster mitigation of urban flood.

  11. A combined α7 nicotinic acetylcholine receptor agonist and monoamine reuptake inhibitor, NS9775, represents a novel profile with potential benefits in emotional and cognitive disturbances

    DEFF Research Database (Denmark)

    Andreasen, Jesper T; Redrobe, John P; Nielsen, Elsebet Ø

    2013-01-01

    also improve by nicotinic acetylcholine receptor (nAChR) activation. Preclinical studies have corroborated this and also demonstrated a synergistic antidepressant-like action when nAChR agonists and MRIs are combined. Here, we present the in vitro and in vivo profile of NS9775, a combined full α7 n...

  12. Distribution of hydrocarbon-utilizing microorganisms and hydrocarbon biodegradation potentials in Alaskan continental shelf areas

    International Nuclear Information System (INIS)

    Roubal, G.; Atlas, R.M.

    1978-01-01

    Hydrocarbon-utilizing microogranisms were enumerated from Alaskan continental shelf areas by using plate counts and a new most-probable-number procedure based on mineralization of 14 C-labeled hydrocarbons. Hydrocarbon utilizers were ubiquitously distributed, with no significant overall concentration differences between sampling regions or between surface water and sediment samples. There were, however, significant seasonal differences in numbers of hydrocarbon utilizers. Distribution of hydrocarbon utilizers within Cook Inlet was positively correlated with occurrence of hydrocarbons in the environment. Hydrocarbon biodegradation potentials were measured by using 14 C-radiolabeled hydrocarbon-spiked crude oil. There was no significant correlation between numbers of hydrocarbon utilizers and hydrocarbon biodegradation potentials. The biodegradation potentials showed large seasonal variations in the Beaufort Sea, probably due to seasonal depletion of available nutrients. Non-nutrient-limited biodegradation potentials followed the order hexadecane > naphthalene >> pristane > benzanthracene. In Cook Inlet, biodegradation potentials for hexadecane and naphthalene were dependent on availability of inorganic nutrients. Biodegradation potentials for pristane and benzanthracene were restricted, probably by resistance to attack by available enzymes in the indigenous population

  13. Advance reactor and fuel-cycle systems--potentials and limitations for United States utilities

    International Nuclear Information System (INIS)

    Zebroski, E.L.; Williams, R.F.

    1979-01-01

    This paper reviews the potential benefits and limitations of advance reactor and fuel-cycle systems for United States utilities. The results of the review of advanced technologies show that for the near and midterm, the only advance reactor and fuel-cycle system with significant potential for United States utilities is the current LWR, and evolutionary, not revolutionary, enhancements. For the long term, the liquid-metal breeder reactor continues to be the most promising advance nuclear option. The major factors leading to this conclusion are summarized

  14. Synthesis, radiofluorination, and preliminary evaluation of the potential 5-HT2A receptor agonists [18 F]Cimbi-92 and [18 F]Cimbi-150

    DEFF Research Database (Denmark)

    Edgar, Fraser Graeme; Hansen, Hanne D; Leth-Petersen, Sebastian

    2017-01-01

    An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F-labelled ......An agonist PET tracer is of key interest for the imaging of the 5-HT2A receptor, as exemplified by the previously reported success of [11 C]Cimbi-36. Fluorine-18 holds several advantages over carbon-11, making it the radionuclide of choice for clinical purposes. In this respect, an 18 F......-labelled agonist 5-HT2A receptor (5-HT2A R) tracer is highly sought after. Herein, we report a 2-step, 1-pot labelling methodology of 2 tracer candidates. Both ligands display high in vitro affinities for the 5-HT2A R. The compounds were synthesised from easily accessible labelling precursors, and radiolabelled...

  15. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

    Science.gov (United States)

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

    2012-01-01

    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

  16. Synthesis of [{sup 11}C]-S21007 a novel 5HT{sub 3} partial agonist as a potential tracer for PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Guillouet, S.; Barre, L.; Gourand, F. [CEA Centre de Cyceron, 14 -Caen (France); Lasne, M.C. [Centre National de la Recherche Scientifique, 14 - Caen (France); Rault, S. [Caen Univ., 14 (France). Faculte de Pharmacie

    1996-04-01

    5HT{sub 3} receptors have been the focus of much research during the last decade. The presence of these receptors has been demonstrated in many neuronal tissues, both in periphery and in the CNS. The identification of selective agonists and antagonists for this receptor subtype has allowed the discovery of several important new therapeutic applications as the inhibition of pain, migraine, cytotoxic and radiation-induced emesis and treatment of psychoses and anxiety. The first 5HT{sub 3} antagonist labelled with a {beta}+ emitter atom was [{sup 11}C]MDL72222. The PET studies which have been performed with it in the brain of baboon (distribution, kinetics and binding) have established that it was not a good radioligand to detect a specific binding, due to its high lipophilicity. Other radioligands have been developed since, but their affinities for 5HT{sub 3} receptors PET studies have not been demonstrated. Among a series of of tricyclic piperazine derivatives synthesized, S21007 has been described as a novel selective and partial agonist which possesses a good affinity for 5HT{sub 3} receptors (IC{sub 50} = 1nM) versus other 5HT subtypes studied where IC{sub 50} > 1{mu}M. We report here the radiosynthesis of [{sup 11}C]S21007. (author).

  17. Fuel utilization potential in light water reactors with once-through fuel irradiation (AWBA Development Program)

    International Nuclear Information System (INIS)

    Rampolla, D.S.; Conley, G.H.; Candelore, N.R.; Cowell, G.K.; Estes, G.P.; Flanery, B.K.; Duncombe, E.; Dunyak, J.; Satterwhite, D.G.

    1979-07-01

    Current commercial light water reactor cores operate without recylce of fuel, on a once-through fuel cycle. To help conserve the limited nuclear fuel resources, there is interest in increasing the energy yield and, hence, fuel utilization from once-through fuel irradiation. This report evaluates the potential increase in fuel utilization of light water reactor cores operating on a once-through cycle assuming 0.2% enrichment plant tails assay. This evaluation is based on a large number of survey calculations using techniques which were verified by more detailed calculations of several core concepts. It is concluded that the maximum fuel utilization which could be achieved by practical once-through pressurized light water reactor cores with either uranium or thorium is about 17 MWYth/ST U 3 O 8 (Megawatt Years Thermal per Short Ton of U 3 O 8 ). This is about 50% higher than that of current commercial light water reactor cores. Achievement of this increased fuel utilization would require average fuel burnup beyond 50,000 MWD/MT and incorporation of the following design features to reduce parasitic losses of neutrons: reflector blankets to utilize neutrons that would otherwise leak out of the core; fuel management practices in which a smaller fraction of the core is replaced at each refueling; and neutron economic reactivity control, such as movable fuel control rather than soluble boron control. For a hypothetical situation in which all neutron leakage and parasitic losses are eliminated and fuel depletion is not limited by design considerations, a maximum fuel utilization of about 20 MWYth/ST U 3 O 8 is calculated for either uranium or thorium. It is concluded that fuel utilization for comparable reactor designs is better with uranium fuel than with thorium fuel for average fuel depletions of 30,000 to 35,000 MWD/MT which are characteristic of present light water reactor cores

  18. Market potential and growth areas of public utilities. Electromobility; Marktpotenzial und Wachstumsfeld fuer Energieversorger. Elektromobilitaet

    Energy Technology Data Exchange (ETDEWEB)

    Lueers, Thomas [Homburg und Partner, Mannheim (Germany). Kompetenzzentrum Energy/Utilities; Hanitsch, Kai [Homburg und Partner, Mannheim (Germany)

    2010-11-15

    The automobile industry is in full transition. All manufacturers are working on new drive concepts that meet the increasingly rigid emission specifications. Electric power is favoured as an energy source for the future, which gets public utilities interested in teh attractivity of this growing market. Accurate knowledge of the market potential generated by electromobility provides a basis for a targeted and successful marketing strategy. (orig.)

  19. Evaluation of partial beta-adrenoceptor agonist activity.

    Science.gov (United States)

    Lipworth, B J; Grove, A

    1997-01-01

    A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

  20. Potential for increased wind-generated electricity utilization using heat pumps in urban areas

    International Nuclear Information System (INIS)

    Waite, Michael; Modi, Vijay

    2014-01-01

    Highlights: • Large-scale wind power and increased electric heat pumps were evaluated. • A deterministic model of wind power and electricity demand was developed. • Sub-models for space heating and domestic hot water demand were developed. • Increased use of heat pumps can improve the viability of large-scale wind power. • Larger wind power capacity can meet a target utilization rate with more heat pumps. - Abstract: The U.S. has substantial wind power potential, but given wind’s intermittent availability and misalignment with electricity demand profiles, large-scale deployment of wind turbines could result in high electricity costs due to energy storage requirements or low utilization rates. While fuel switching and heat pumps have been proposed as greenhouse gas (GHG) emissions and energy reduction strategies at the building scale, this paper shows that heat pump adoption could have additional system-wide benefits by increasing the utilization of wind-generated electricity. A model was developed to evaluate the effects of coupling large-scale wind power installations in New York State with increased use of electric heat pumps to meet a portion of space heating and domestic hot water (DHW) demands in New York City. The analysis showed significant increases in wind-generated electricity utilization with increased use of heat pumps, allowing for higher installed capacity of wind power. One scenario indicates that 78.5% annual wind-generated electricity utilization can be achieved with 3 GW of installed wind power capacity generated electricity equal to 20% of existing NYC annual electricity demand; if 20% of space heating and DHW demands are provided by heat pumps, the 78.5% utilization rate can be achieved with an increase of total wind power capacity to 5 GW. Therefore, this integrated supply–demand approach could provide additional system-wide emissions reductions

  1. Resource potential of bamboo, challenges and future directions towards sustainable management and utilization in Ethiopia

    Directory of Open Access Journals (Sweden)

    Getachew Desalegn

    2014-08-01

    Full Text Available Aim of study: Bamboo, the fastest growing and high yielding perennial plant of the world has more than 1500 species and 1500 versatile socio-economic uses and ecological services. Ethiopia has two indigenous bamboo species namely Yushania alpina and Oxytenantheria abyssinica, covering about one million ha with a wide distribution. The objective of this paper is to highlight the potential of bamboo resources, challenges including biodeterioration damage, opportunities and future research directions towards its sustainable management and rational utilization.Area of study: Bamboo resources of EthiopiaMaterial and Methods: Reconnaissance survey was done to some parts of the bamboo growing potential areas in Ethiopia besides the literature review. Main results: The bamboo resource, despite its socio-economic and environmental benefits, currently, in most areas has been under high pressure due to land use changes, bamboo mass- flowering, poor processing with low value addition, and damage by biodeteriorating agents (termites, beetles and fungi. The preservative tests on Ethiopian bamboos revealed low natural durability and highlighted the paramount importance of appropriate protection measures such as Tanalith and vehicles used motor oil to increase durability, service life and rational utilization of bamboo-based products and structures as potential alternative construction and furniture material.Research highlights: Therefore, integrated research and development interventions involving different propagation and managements techniques, harvesting season, processing, value addition including proper seasoning and preservation technologies and marketing are recommended to fill the information and technological gaps on sustainable management and rational utilization of this fast growing and multipurpose bamboo resources in Ethiopia.Key words: Bamboo; challenges; management; socio-economic and environmental significance; utilization.

  2. Implementation of Research and Development Based on Patent Natural Ingredients and Potential Utilization of Tradition Medicine

    Directory of Open Access Journals (Sweden)

    Tommy Hendrix

    2016-12-01

    Full Text Available The results of research and development based on natural ingredients for traditional medicines become an interesting topic to discuss at this point; it’s shown from increasing number in utilization. The use of traditional medicine especially on natural ingredients at this moment becomes effective solution to increase the level of market acceptance in herbal extracts, including an affordable purchase from potential utilization of natural resources which are owned. By using Matheo Patent XE Ver 10.2 as methodology of searching, we can know potentials useful through strategy, research and development, patent analysis and patent collaboration among users in utilization of Natural Ingredient for Traditional Medicine. From the data result shows majority in the field of chemistry for human necessity related to Health; Amusement; Medical or Veterinary Science; Hygiene sectors with total patent 108, family 65. The use of patent analysis is a way to find how the development of technology and products that have been produced and how commercial processes connecting with technology users, especially in traditional medicine. From the data that exist in particular of patents, it is critical to identify the number of patents that has been registered through the innovation process development including technology dissemination is used.

  3. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

  4. Sports doping: emerging designer and therapeutic β2-agonists.

    Science.gov (United States)

    Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

    2013-10-21

    Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future. © 2013.

  5. Technologies for utilization of industrial excess heat: Potentials for energy recovery and CO2 emission reduction

    International Nuclear Information System (INIS)

    Broberg Viklund, Sarah; Johansson, Maria T.

    2014-01-01

    Highlights: • Technologies for recovery and use of industrial excess heat were investigated. • Heat harvesting, heat storage, heat utilization, and heat conversion technologies. • Heat recovery potential for Gävleborg County in Sweden was calculated. • Effects on global CO 2 emissions were calculated for future energy market scenarios. - Abstract: Industrial excess heat is a large untapped resource, for which there is potential for external use, which would create benefits for industry and society. Use of excess heat can provide a way to reduce the use of primary energy and to contribute to global CO 2 mitigation. The aim of this paper is to present different measures for the recovery and utilization of industrial excess heat and to investigate how the development of the future energy market can affect which heat utilization measure would contribute the most to global CO 2 emissions mitigation. Excess heat recovery is put into a context by applying some of the excess heat recovery measures to the untapped excess heat potential in Gävleborg County in Sweden. Two different cases for excess heat recovery are studied: heat delivery to a district heating system and heat-driven electricity generation. To investigate the impact of excess heat recovery on global CO 2 emissions, six consistent future energy market scenarios were used. Approximately 0.8 TWh/year of industrial excess heat in Gävleborg County is not used today. The results show that with the proposed recovery measures approximately 91 GWh/year of district heating, or 25 GWh/year of electricity, could be supplied from this heat. Electricity generation would result in reduced global CO 2 emissions in all of the analyzed scenarios, while heat delivery to a DH system based on combined heat and power production from biomass would result in increased global CO 2 emissions when the CO 2 emission charge is low

  6. An expose of bioenergy and its potential and utilization in Turkey

    International Nuclear Information System (INIS)

    Erdogdu, Erkan

    2008-01-01

    Turkey is heavily dependent on expensive imported energy resources (oil, gas and coal) that place a big burden on the economy. Air pollution is also becoming a great environmental concern in the country. In this regard, renewable energy resources appear to be one of the most efficient and effective solutions for clean and sustainable energy development in Turkey. Turkey's renewable sources are the second largest source for energy production after coal. About two-thirds of the renewable energy produced is obtained from bioenergy, which is used to meet a variety of energy needs, including generating electricity, heating homes, fueling vehicles and providing process heat for industrial facilities. The amount of usable bioenergy potential of Turkey is approximately 17 Mtoe. This article not only presents a review of the potential and utilization of the bioenergy in Turkey but also provides some guidelines for policy makers

  7. Chronic administration of the dopamine D2/3 agonist ropinirole invigorates performance of a rodent slot machine task, potentially indicative of less distractible or compulsive-like gambling behaviour.

    Science.gov (United States)

    Cocker, Paul J; Tremblay, M; Kaur, S; Winstanley, Catharine A

    2017-01-01

    Whilst dopamine agonist therapies can successfully manage the symptoms of diseases such as Parkinson's disease (PD), fibromyalgia and restless leg syndrome, they can also cause impulse control and addiction disorders such as gambling disorder (GD). These compulsive behaviours seriously undermine the utility of such treatments. The objective of the study was to model this phenomenon using a rodent slot machine task (rSMT) in order to investigate the neurobiological basis underlying such behavioural changes. Male Long Evans rats were trained to perform the rSMT. The D 2 -like agonist ropinirole, or saline, was then delivered continuously for 28 days via osmotic mini-pump. The effects of ropinirole on baseline rSMT performance, as well as extinction and reinstatement sessions, were determined during this time. Brain samples from key frontostriatal regions implicated in GD and PD were then harvested immediately or after a 4-week washout period during which behaviour returned to pre-drug baseline. Ropinirole invigorated task performance, in that drug treatment resulted in a robust and sustained increase in the number of trials completed. Ex vivo analyses revealed that chronic ropinirole treatment led to a pattern of changes indicative of upregulation within the β-arrestin-AKT-GSK3β intracellular cascade, recently theorised to dominate D 2 -mediated signalling under hyperdopaminergic conditions, in the dorsal striatum, rather than the canonical PKA-dependent signalling pathway associated with D 2 receptor activation. Such findings provide novel insight into the role of dopamine signalling in mediating compulsive-like gambling behaviour and may inform more directed pharmacotherapies for the treatment of both idiopathic and iatrogenic GD.

  8. Quantitative appraisal and potential analysis for primary biomass resources for energy utilization in China

    Energy Technology Data Exchange (ETDEWEB)

    Yanli, Yang; Peidong, Zhang; Yonghong, Zheng; Lisheng, Wang [Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of science, Qingdao 266101 (China); Wenlong, Zhang; Yongsheng, Tian [Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of science, Qingdao 266101 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China)

    2010-12-15

    As the largest agricultural country, China has abundant biomass resources, but the distribution is scattered and difficult to collect. It is essential to estimate the biomass resource and its potential for bioenergy utilization in China. In this study, the amount of main biomass resources for possible energy use and their energy utilization potential in China are analyzed based on statistical data. The results showed that the biomass resource for possible energy use amounted to 8.87 x 10{sup 8} tce in 2007 of which the crops straw is 1.42 x 10{sup 8} tce, the forest biomass is 2.85 x 10{sup 8} tce, the poultry and livestock manure is 4.40 x 10{sup 7} tce, the municipal solid waste is 1.35 x 10{sup 6} tce, and the organic waste water is 6.46 x 10{sup 6} tce. Through the information by thematic map, it is indicated that, except arctic-alpine areas and deserts, the biomass resource for possible energy use was presented a relatively average distribution in China, but large gap was existed in different regions in the concentration of biomass resources, with the characteristics of East dense and West sparse. It is indicated that the energy transformation efficiency of biomass compressing and shaping, biomass anaerobic fermentation and biomass gasification for heating have higher conversion efficiency. If all of the biomass resources for possible energy use are utilized by these three forms respectively, 7.66 x 10{sup 12} t of biomass briquettes fuel, 1.98 x 10{sup 12} m{sup 3} of low calorific value gas and 3.84 x 10{sup 11} m{sup 3} of biogas could be produced, 3.65 x 10{sup 8} t to 4.90 x 10{sup 8} t of coal consumption could be substituted, and 6.12 x 10{sup 8} t to 7.53 x 10{sup 8} t of CO{sub 2} emissions could be reduced. With the enormous energy utilization potential of biomass resources and the prominent benefit of energy saving and emission reduction, it proves an effective way to adjust the energy consumption structure, to alleviate the energy crisis, to ensure

  9. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources.

    Science.gov (United States)

    Luthfi, Abdullah Amru Indera; Manaf, Shareena Fairuz Abdul; Illias, Rosli Md; Harun, Shuhaida; Mohammad, Abdul Wahab; Jahim, Jamaliah Md

    2017-04-01

    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

  10. Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders.

    Science.gov (United States)

    McLean, Samantha L; Grayson, Ben; Marsh, Samuel; Zarroug, Samah H O; Harte, Michael K; Neill, Jo C

    2016-04-01

    Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer's disease and has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders, including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several attempts to develop new therapies, these remain an unmet clinical need. In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7 and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task following a 6h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar object in the retention trial following a 6h ITI. Although a narrow dose range of PNU-282987 and RJR-2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987 (10mg/kg) and the lowest dose of RJR-2403 (0.1mg/kg), indicative of enhanced cognitive performance. Interestingly, these compounds were also efficacious when administered either before the acquisition or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the formation and retrieval of recognition memory. Copyright © 2016. Published by Elsevier B.V.

  11. Potential utility of MRI in the evaluation of children at risk of renal scarring

    International Nuclear Information System (INIS)

    Chan Yuleung; Chan Kamwing; Roebuck, D.J.; Chu, W.C.W.; Metreweli, C.; Yeung Chungkwong; Lee Kimhung

    1999-01-01

    Background. Gadolinium-enhanced MRI has recently been employed in the diagnosis of acute pyelonephritis. Its potential utility in the diagnosis of renal scars in children is unknown. Objective. To evaluate the potential utility of MRI using fat-saturated T1-weighted (T1-W) and post-gadolinium, short-tau inversion-recovery (STIR) sequences in detecting renal scarring by comparison with technetium dimercaptosuccinic acid ( 99 m Tc-DMSA) renal scintigraphy in children at risk of renal scarring. Materials and methods. A group of 24 children with spina bifida and neurogenic bladder or anorectal anomaly was studied. No patient had a history of acute pyelonephritis. Documented urinary tract infection (UTI) was present in 10 children (42 %). The remaining 14 (58 %) children had a history of asymptomatic bacteriuria. None had clinical signs or symptoms of acute UTI at the time of the study. 99 m Tc-DMSA and MRI were performed to detect renal scarring. 99 m Tc-DMSA scans were supplemented with pinhole imaging. MRI of the kidneys employed a fat-saturated T1-W sequence and a post-gadolinium STIR sequence employing a short echo time. Results. Of the kidneys studied, 33 % (n = 16) had evidence of a renal parenchymal defect suggestive of scarring on 99 m Tc-DMSA. The concordance in the detection of a scarred kidney by post-gadolinium STIR sequence and 99 m Tc-DMSA is 94 %; that by fat-saturated T1-W sequence and 99 m Tc-DMSA is 82 %; that by both sequences (positive result on either sequence) and 99 m Tc-DMSA is 100 %. Using 99 m Tc-DMSA as the gold standard, MRI had a sensitivity of 100 % and a specificity of 78 % in the diagnosis of a scarred kidney. The concordance in the detection of a scarred zone by post-gadolinium STIR sequence and 99 m Tc-DMSA is 68 %; that by fat-saturated T1-W sequence and DMSA is 44 %; that by both sequences (positive result on either sequence) and 99 m Tc-DMSA is 84 %. MRI had a sensitivity of 84 % and a specificity of 86 % in the diagnosis of a

  12. The Era of International Space Station Utilization Begins: Research Strategy, International Collaboration, and Realized Potential

    Science.gov (United States)

    Thumm, Tracy; Robinson, Julie A.; Ruttley, Tara; Johnson-Green, Perry; Karabadzhak, George; Nakamura, Tai; Sorokin, Igor V.; Zell, Martin; Jean, Sabbagh

    2010-01-01

    With the assembly of the International Space Station (ISS) nearing completion and the support of a full-time crew of six, a new era of utilization for research is beginning. For more than 15 years, the ISS international partnership has weathered financial, technical and political challenges proving that nations can work together to complete assembly of the largest space vehicle in history. And while the ISS partners can be proud of having completed one of the most ambitious engineering projects ever conceived, the challenge of successfully using the platform remains. During the ISS assembly phase, the potential benefits of space-based research and development were demonstrated; including the advancement of scientific knowledge based on experiments conducted in space, development and testing of new technologies, and derivation of Earth applications from new understanding. The configurability and human-tended capabilities of the ISS provide a unique platform. The international utilization strategy is based on research ranging from physical sciences, biology, medicine, psychology, to Earth observation, human exploration preparation and technology demonstration. The ability to complete follow-on investigations in a period of months allows researchers to make rapid advances based on new knowledge gained from ISS activities. During the utilization phase, the ISS partners are working together to track the objectives, accomplishments, and the applications of the new knowledge gained. This presentation will summarize the consolidated international results of these tracking activities and approaches. Areas of current research on ISS with strong international cooperation will be highlighted including cardiovascular studies, cell and plant biology studies, radiation, physics of matter, and advanced alloys. Scientific knowledge and new technologies derived from research on the ISS will be realized through improving quality of life on Earth and future spaceflight endeavours

  13. A potential of utilizing renewable energy sources and the state support in Slovakia

    Directory of Open Access Journals (Sweden)

    Lívia Bodonská

    2007-04-01

    Full Text Available The renewable energy sources are domestic sources of energy that help to enhance the safety of energy supplies and the diversification of energy sources. The utilization of such sources complies with the environmental acceptability requirement and leads to a reduction in greenhouse gas emissions. The renewable energy is proved to be commercially viable for a growing list of consumers and uses. The renewable energy technologies provide many benefits that go well beyond the energy alone. More and more, the renewable energies contribute to the three pillars of the sustainable development in the economy, environment and the society.Several renewable energy technologies are established in world markets, building global industries and infrastructures. Other renewables become competitive in growing markets, and some are widely recognised as the lowest cost option for stand-alone and offgrid applications. An increased utilization of renewable energy sources in the heat and electricity generation is one of priority tasks of the Slovak Republic to boost the use of domestic energy potential and thus to decrease the Slovakia’s dependence on imported fossil fuels.

  14. The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Luis F Razgado-Hernandez

    Full Text Available The progressive degeneration of the dopamine neurons of the pars compacta of substantia nigra and the consequent loss of the dopamine innervation of the striatum leads to the impairment of motor behavior in Parkinson's disease. Accordingly, an efficient therapy of the disease should protect and regenerate the dopamine neurons of the substantia nigra and the dopamine innervation of the striatum. Nigral neurons express Brain Derived Neurotropic Factor (BDNF and dopamine D3 receptors, both of which protect the dopamine neurons. The chronic activation of dopamine D3 receptors by their agonists, in addition, restores, in part, the dopamine innervation of the striatum. Here we explored whether the over-expression of BDNF by dopamine neurons potentiates the effect of the activation of D3 receptors restoring nigrostriatal innervation. Twelve-month old Wistar rats were unilaterally injected with 6-hydroxydopamine into the striatum. Five months later, rats were treated with the D3 agonist 7-hydroxy-N,N-di-n-propy1-2-aminotetralin (7-OH-DPAT administered i.p. during 4½ months via osmotic pumps and the BDNF gene transfection into nigral cells using the neurotensin-polyplex nanovector (a non-viral transfection that selectively transfect the dopamine neurons via the high-affinity neurotensin receptor expressed by these neurons. Two months after the withdrawal of 7-OH-DPAT when rats were aged (24 months old, immunohistochemistry assays were made. The over-expression of BDNF in rats receiving the D3 agonist normalized gait and motor coordination; in addition, it eliminated the muscle rigidity produced by the loss of dopamine. The recovery of motor behavior was associated with the recovery of the nigral neurons, the dopamine innervation of the striatum and of the number of dendritic spines of the striatal neurons. Thus, the over-expression of BDNF in dopamine neurons associated with the chronic activation of the D3 receptors appears to be a promising strategy

  15. Extracellular vesicles from parasitic helminths and their potential utility as vaccines.

    Science.gov (United States)

    Mekonnen, Gebeyaw Getnet; Pearson, Mark; Loukas, Alex; Sotillo, Javier

    2018-03-01

    Helminths are multicellular parasites affecting nearly three billion people worldwide. To orchestrate a parasitic existence, helminths secrete different molecules, either in soluble form or contained within extracellular vesicles (EVs). EVs are secreted by most cell types and organisms, and have varied roles in intercellular communication, including immune modulation and pathogenesis. Areas covered: In this review, we describe the nucleic acid and proteomic composition of EVs from helminths, with a focus on the protein vaccine candidates present on the EV surface membrane, and discuss the potential utility of helminth EVs and their constituent proteins in the fight against helminth infections. Expert commentary: A significant number of proteins present in helminth-secreted EVs are known vaccine candidates. The characterization of helminth EV proteomes will shed light on host-pathogen interactions, facilitate the discovery of new diagnostic biomarkers, and provide a novel approach for the development of new control measures against helminth infections.

  16. Diffusion and Perfusion MR Imaging in Acute Stroke: Clinical Utility and Potential Limitations for Treatment Selection

    DEFF Research Database (Denmark)

    Bateman, Mathew; Slater, Lee-Anne; Leslie-Mazwi, Thabele M

    2017-01-01

    Magnetic resonance (MR) diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) offer unique insight into acute ischemic stroke pathophysiology. These techniques may offer the ability to apply pathophysiology to accurately individualize acute stroke reperfusion treatment, including ...... to be investigated in ongoing randomized controlled trials, and continued research into these techniques will help achieve the goal of tissue-based decision making and individualized acute stroke treatment....... extending the opportunity of reperfusion treatment to well beyond the current time-based treatment windows. This review examines the use of DWI and PWI in the major stroke trials, their current clinical utility, and potential limitations for reperfusion treatment selection. DWI and PWI continue...

  17. Use of Pregabalin - A Nationwide Pharmacoepidemiological Drug Utilization Study with Focus on Abuse Potential

    DEFF Research Database (Denmark)

    Schjerning, O; Pottegård, A; Damkier, P

    2016-01-01

    INTRODUCTION: Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder and neuropathic pain with a licensed dosage range of 150 mg to 600 mg/day. Growing concern about the abuse potential of pregabalin is partly based on reports of pregabalin being used...... in dosages that exceed the approved therapeutic range. METHODS: To identify predictors of pregabalin use above recommended dosage, we conducted a pharmacoepidemological drug utilization study using the Danish nationwide registers. We deployed 4 measures of abuse: high use (≥600 mg/day) or very high use (≥1...... 200 mg/day) over a 6- or 12-month period, respectively. Multiple logistic regression was used to identify patient and treatment characteristics that were associated with either abuse marker. RESULTS: Out of 42 520 pregabalin users 4 090 (9.6%) were treated with more than 600 mg/day for 6 months and 2...

  18. The Potential for Electrofuels Production in Sweden Utilizing Fossil and Biogenic CO2 Point Sources

    International Nuclear Information System (INIS)

    Hansson, Julia; Hackl, Roman; Taljegard, Maria; Brynolf, Selma; Grahn, Maria

    2017-01-01

    This paper maps, categorizes, and quantifies all major point sources of carbon dioxide (CO 2 ) emissions from industrial and combustion processes in Sweden. The paper also estimates the Swedish technical potential for electrofuels (power-to-gas/fuels) based on carbon capture and utilization. With our bottom-up approach using European databases, we find that Sweden emits approximately 50 million metric tons of CO 2 per year from different types of point sources, with 65% (or about 32 million tons) from biogenic sources. The major sources are the pulp and paper industry (46%), heat and power production (23%), and waste treatment and incineration (8%). Most of the CO 2 is emitted at low concentrations (<15%) from sources in the southern part of Sweden where power demand generally exceeds in-region supply. The potentially recoverable emissions from all the included point sources amount to 45 million tons. If all the recoverable CO 2 were used to produce electrofuels, the yield would correspond to 2–3 times the current Swedish demand for transportation fuels. The electricity required would correspond to about 3 times the current Swedish electricity supply. The current relatively few emission sources with high concentrations of CO 2 (>90%, biofuel operations) would yield electrofuels corresponding to approximately 2% of the current demand for transportation fuels (corresponding to 1.5–2 TWh/year). In a 2030 scenario with large-scale biofuels operations based on lignocellulosic feedstocks, the potential for electrofuels production from high-concentration sources increases to 8–11 TWh/year. Finally, renewable electricity and production costs, rather than CO 2 supply, limit the potential for production of electrofuels in Sweden.

  19. Improving yield potential in crops under elevated CO(2): Integrating the photosynthetic and nitrogen utilization efficiencies.

    Science.gov (United States)

    Kant, Surya; Seneweera, Saman; Rodin, Joakim; Materne, Michael; Burch, David; Rothstein, Steven J; Spangenberg, German

    2012-01-01

    Increasing crop productivity to meet burgeoning human food demand is challenging under changing environmental conditions. Since industrial revolution atmospheric CO(2) levels have linearly increased. Developing crop varieties with increased utilization of CO(2) for photosynthesis is an urgent requirement to cope with the irreversible rise of atmospheric CO(2) and achieve higher food production. The primary effects of elevated CO(2) levels in most crop plants, particularly C(3) plants, include increased biomass accumulation, although initial stimulation of net photosynthesis rate is only temporal and plants fail to sustain the maximal stimulation, a phenomenon known as photosynthesis acclimation. Despite this acclimation, grain yield is known to marginally increase under elevated CO(2). The yield potential of C(3) crops is limited by their capacity to exploit sufficient carbon. The "C fertilization" through elevated CO(2) levels could potentially be used for substantial yield increase. Rubisco is the rate-limiting enzyme in photosynthesis and its activity is largely affected by atmospheric CO(2) and nitrogen availability. In addition, maintenance of the C/N ratio is pivotal for various growth and development processes in plants governing yield and seed quality. For maximizing the benefits of elevated CO(2), raising plant nitrogen pools will be necessary as part of maintaining an optimal C/N balance. In this review, we discuss potential causes for the stagnation in yield increases under elevated CO(2) levels and explore possibilities to overcome this limitation by improved photosynthetic capacity and enhanced nitrogen use efficiency. Opportunities of engineering nitrogen uptake, assimilatory, and responsive genes are also discussed that could ensure optimal nitrogen allocation toward expanding source and sink tissues. This might avert photosynthetic acclimation partially or completely and drive for improved crop production under elevated CO(2) levels.

  20. Improving yield potential in crops under elevated CO2: Integrating the photosynthetic and nitrogen utilization efficiencies

    Science.gov (United States)

    Kant, Surya; Seneweera, Saman; Rodin, Joakim; Materne, Michael; Burch, David; Rothstein, Steven J.; Spangenberg, German

    2012-01-01

    Increasing crop productivity to meet burgeoning human food demand is challenging under changing environmental conditions. Since industrial revolution atmospheric CO2 levels have linearly increased. Developing crop varieties with increased utilization of CO2 for photosynthesis is an urgent requirement to cope with the irreversible rise of atmospheric CO2 and achieve higher food production. The primary effects of elevated CO2 levels in most crop plants, particularly C3 plants, include increased biomass accumulation, although initial stimulation of net photosynthesis rate is only temporal and plants fail to sustain the maximal stimulation, a phenomenon known as photosynthesis acclimation. Despite this acclimation, grain yield is known to marginally increase under elevated CO2. The yield potential of C3 crops is limited by their capacity to exploit sufficient carbon. The “C fertilization” through elevated CO2 levels could potentially be used for substantial yield increase. Rubisco is the rate-limiting enzyme in photosynthesis and its activity is largely affected by atmospheric CO2 and nitrogen availability. In addition, maintenance of the C/N ratio is pivotal for various growth and development processes in plants governing yield and seed quality. For maximizing the benefits of elevated CO2, raising plant nitrogen pools will be necessary as part of maintaining an optimal C/N balance. In this review, we discuss potential causes for the stagnation in yield increases under elevated CO2 levels and explore possibilities to overcome this limitation by improved photosynthetic capacity and enhanced nitrogen use efficiency. Opportunities of engineering nitrogen uptake, assimilatory, and responsive genes are also discussed that could ensure optimal nitrogen allocation toward expanding source and sink tissues. This might avert photosynthetic acclimation partially or completely and drive for improved crop production under elevated CO2 levels. PMID:22833749

  1. Potential utility of MRI in the evaluation of children at risk of renal scarring

    Energy Technology Data Exchange (ETDEWEB)

    Chan Yuleung; Chan Kamwing; Roebuck, D.J.; Chu, W.C.W.; Metreweli, C. [Dept. of Diagnostic Radiology and Organ Imaging, Chinese Univ. of Hong Kong, Shatin (China); Yeung Chungkwong; Lee Kimhung [Dept. of Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China)

    1999-11-01

    Background. Gadolinium-enhanced MRI has recently been employed in the diagnosis of acute pyelonephritis. Its potential utility in the diagnosis of renal scars in children is unknown. Objective. To evaluate the potential utility of MRI using fat-saturated T1-weighted (T1-W) and post-gadolinium, short-tau inversion-recovery (STIR) sequences in detecting renal scarring by comparison with technetium dimercaptosuccinic acid ({sup 99} {sup m}Tc-DMSA) renal scintigraphy in children at risk of renal scarring. Materials and methods. A group of 24 children with spina bifida and neurogenic bladder or anorectal anomaly was studied. No patient had a history of acute pyelonephritis. Documented urinary tract infection (UTI) was present in 10 children (42 %). The remaining 14 (58 %) children had a history of asymptomatic bacteriuria. None had clinical signs or symptoms of acute UTI at the time of the study. {sup 99} {sup m}Tc-DMSA and MRI were performed to detect renal scarring. {sup 99} {sup m}Tc-DMSA scans were supplemented with pinhole imaging. MRI of the kidneys employed a fat-saturated T1-W sequence and a post-gadolinium STIR sequence employing a short echo time. Results. Of the kidneys studied, 33 % (n = 16) had evidence of a renal parenchymal defect suggestive of scarring on {sup 99} {sup m}Tc-DMSA. The concordance in the detection of a scarred kidney by post-gadolinium STIR sequence and {sup 99} {sup m}Tc-DMSA is 94 %; that by fat-saturated T1-W sequence and {sup 99} {sup m}Tc-DMSA is 82 %; that by both sequences (positive result on either sequence) and {sup 99} {sup m}Tc-DMSA is 100 %. Using {sup 99} {sup m}Tc-DMSA as the gold standard, MRI had a sensitivity of 100 % and a specificity of 78 % in the diagnosis of a scarred kidney. The concordance in the detection of a scarred zone by post-gadolinium STIR sequence and {sup 99} {sup m}Tc-DMSA is 68 %; that by fat-saturated T1-W sequence and DMSA is 44 %; that by both sequences (positive result on either sequence) and {sup 99

  2. Potential utility of precision medicine for older adults with polypharmacy: a case series study

    Directory of Open Access Journals (Sweden)

    Finkelstein J

    2016-04-01

    Full Text Available Joseph Finkelstein,1 Carol Friedman,1 George Hripcsak,1 Manuel Cabrera2 1Department of Biomedical Informatics, 2Department of Medicine, Columbia University, New York, NY, USA Abstract: Pharmacogenomic (PGx testing has been increasingly used to optimize drug regimens; however, its potential in older adults with polypharmacy has not been systematically studied. In this hypothesis-generating study, we employed a case series design to explore potential utility of PGx testing in older adults with polypharmacy and to highlight barriers in implementing this methodology in routine clinical practice. Three patients with concurrent chronic heart and lung disease aged 74, 78, and 83 years and whose medication regimen comprised 26, 17, and 18 drugs, correspondingly, served as cases for this study. PGx testing identified major genetic polymorphisms in the first two cases. The first case was identified as “CYP3A4/CYP3A5 poor metabolizer”, which affected metabolism of eleven prescribed drugs. The second case had “CYP2D6 rapid metabolizer” status affecting three prescribed medications, two of which were key drugs for managing this patient's chronic conditions. Both these patients also had VKORC1 allele *A, resulting in higher sensitivity to warfarin. All cases demonstrated a significant number of potential drug–drug interactions. Both patients with significant drug–gene interactions had a history of frequent hospitalizations (six and 23, respectively, whereas the person without impaired cytochrome P450 enzyme activity had only two acute episodes in the last 5 years, although he was older and had multiple comorbidities. Since all patients received guideline-concordant therapy from the same providers and were adherent to their drug regimen, we hypothesized that genetic polymorphism may represent an additional risk factor for higher hospitalization rates in older adults with polypharmacy. However, evidence to support or reject this hypothesis is yet to

  3. Evaluating Potential Human Health Risks Associated with the Development of Utility-Scale Solar Energy Facilities on Contaminated Sites

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, J. -J. [Argonne National Lab. (ANL), Argonne, IL (United States); Chang, Y. -S. [Argonne National Lab. (ANL), Argonne, IL (United States); Hartmann, H. [Argonne National Lab. (ANL), Argonne, IL (United States); Wescott, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Kygeris, C. [Indiana Univ. of Pennsylvania, PA (United States)

    2013-09-01

    This report presents a general methodology for obtaining preliminary estimates of the potential human health risks associated with developing a utility-scale solar energy facility on a contaminated site, based on potential exposures to contaminants in soils (including transport of those contaminants into the air).

  4. Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists

    Energy Technology Data Exchange (ETDEWEB)

    Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

    2018-04-01

    There is a need to develop novel, high-throughput screening and prioritization methods to identify chemicals with adverse estrogen, androgen, and thyroid activity to protect human health and the environment and is of interest to the Endocrine Disruptor Screening Program. The current aim is to explore the utility of zebrafish as a testing paradigm to classify endocrine activity using phenotypically anchored transcriptome profiling. Transcriptome analysis was conducted on embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at a concentration that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of the animals exposed. Analysis of the top 1000 significant differentially expressed transcripts across all treatments identified a unique transcriptional and phenotypic profile for thyroid hormone receptor agonists, which can be used as a biomarker screen for potential thyroid hormone agonists.

  5. Complex-scaling of screened Coulomb potentials for resonance calculations utilizing the modified Bessel functions

    Science.gov (United States)

    Jiao, Li-Guang; Ho, Yew Kam

    2014-05-01

    The screened Coulomb potential (SCP) has been extensively used in atomic physics, nuclear physics, quantum chemistry and plasma physics. However, an accurate calculation for atomic resonances under SCP is still a challenging task for various methods. Within the complex-scaling computational scheme, we have developed a method utilizing the modified Bessel functions to calculate doubly-excited resonances in two-electron atomic systems with configuration interaction-type basis. To test the validity of our method, we have calculated S- and P-wave resonance states of the helium atom with various screening strengths, and have found good agreement with earlier calculations using different methods. Our present method can be applied to calculate high-lying resonances associated with high excitation thresholds of the He+ ion, and with high-angular-momentum states. The derivation and calculation details of our present investigation together with new results of high-angular-momentum states will be presented at the meeting. Supported by NSC of Taiwan.

  6. Assessing the Potential of Utilization and Storage Strategies for Post-Combustion CO2 Emissions Reduction

    International Nuclear Information System (INIS)

    Armstrong, Katy; Styring, Peter

    2015-01-01

    The emissions reduction potential of three carbon dioxide handling strategies for post-combustion capture is considered. These are carbon capture and sequestration/storage (CCS), enhanced hydrocarbon recovery (EHR), and carbon dioxide utilization (CDU) to produce synthetic oil. This is performed using common and comparable boundary conditions including net CO 2 sequestered based on equivalent boundary conditions. This is achieved using a “cradle to grave approach” where the final destination and fate of any product is considered. The input boundary is pure CO 2 that has been produced using a post-combustion capture process as this is common between all processes. The output boundary is the emissions resulting from any product produced with the assumption that the majority of the oil will go to combustion processes. We also consider the “cradle to gate” approach where the ultimate fate of the oil is not considered as this is a boundary condition often applied to EHR processes. Results show that while CCS can make an impact on CO 2 emissions, CDU will have a comparable effect whilst generating income while EHR will ultimately increase net emissions. The global capacity for CDU is also compared against CCS using data based on current and planned CCS projects. Analysis shows that current CDU represent a greater volume of capture than CCS processes and that this gap is likely to remain well beyond 2020 which is the limit of the CCS projects in the database.

  7. Economic problems of utilization of hydroenergetic potential of the Slovak Republic and possibilities for their solution

    Energy Technology Data Exchange (ETDEWEB)

    Dusicka, M [Slovenske elektrarne, a.s., Vodne elektrarne Trencin, o.z. (Slovakia)

    1997-12-01

    The aim of this paper is to clarify basic inputs into economic calculations of hydro power projects which then can drastically affect efficiency of these projects in different ways as there are no distinct economic and legal regulations in the Slovak Republic as the hydroelectric potential (HEP utilization is concerned. In 1995, the share of individual resources of electrical system (ES) in production in the Slovak Republic was as follows: nuclear plants - 41.86%, steam power plants - 24,93%, hydroelectrical power plants (HPP) - 18.93%, factory power plants - 9.09%, and import - 5.19%. However, in the same year, the individual resources of ES in the Slovak Republic shared in a balance of installed capacity - 7.114 MW as follows: nuclear power plants - 24.7%, steam power plants - 32.0%, HPP -33.4%, and factory power plants - 10.9%. Financing of the building of HPP -power engineering and water management ones (the Ministry of National Economy and the Ministry of Agriculture at present) is discussed. 1 ref.

  8. Potential utility of combination therapy with nateglinide and telmisartan for metabolic derangements in Zucker Fatty rats.

    Science.gov (United States)

    Kajioka, T; Miura, K; Kitahara, Y; Yamagishi, S

    2007-12-01

    The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular disease. Insulin resistance and/or impaired early-phase insulin secretion are major determinants of postprandial hyperglycemia. In this study, we investigated the potential utility of combination therapy with telmisartan, an angiotensin II receptor blocker and nateglinide, a rapid-onset/short-duration insulinotropic agent, for the treatment of postprandial hyperglycemia and metabolic derangements in Zucker Fatty (ZF) rats. ZF rats fed twice daily were given vehicle, 50 mg/kg of nateglinide, 5 mg/kg of telmisartan, or both for 6 weeks. Combination therapy with nateglinide and telmisartan for 2 weeks ameliorated postprandial hyperglycemia in ZF rats fed twice daily. Furthermore, 6-week treatment with nateglinide and telmisartan not only decreased fasting plasma insulin, triglycerides, and free fatty acid levels, but also improved the responses of blood glucose to insulin and subsequently reduced the decremental glucose areas under the curve in the ZF rats. Combination therapy also restored the decrease of plasma adiponectin levels in the ZF rats. Monotherapy with nateglinide or telmisartan alone didnot significantly improve these metabolic parameters. These observations demonstrate that combination therapy with nateglinide and telmisartan may improve the metabolic derangements by ameliorating early phase of insulin secretion as well as insulin resistance in ZF rats fed twice daily. Our present findings suggest that the combination therapy with nateglinide and telmisartan could be a promising therapeutic strategy for the treatment of the metabolic syndrome.

  9. Evaluation of Universitas Indonesia’s Recharge Pond Performance and Potential Utilization for Raw Water Source

    Directory of Open Access Journals (Sweden)

    Nyoman Suwartha

    2012-05-01

    Full Text Available The UI recharge pond has been constructed 5 years ago. However, monitoring and evaluation activities on its performances are very lack. Aims of this study are to understand the recharge rate, and to evaluate existing quantity and water quality of the pond during dry and rainy season. Measurement of water depth, rainfall intensity, and evaporation is conducted to determine water availability, recharge rate, and water balance of the recharge pond. Amount of surface water is collected from recharge pond and river at three sampling point to determine existing water quality of the pond. The results showed that recharge rate of the pond between dry season (3.2 mm/day and wet season (6.1 mm/day are considered as insignificant different. The water balance of the recharge pond shows an excessive rate. Various physics and chemical parameters (turbidity, color, TDS, pH, and  Cl are found to have concentration lower than the water quality standard. The results suggest that the pond surface water is remain suitable to be recharged into aquifer zone so that sustaining ground water conservation campaign, and it is potential to be utilized as an additional  raw water source for domestic water demand of UI Campus Depok.

  10. Potential harmful effects on agricultural environments of sewage sludge utilization as a fertilizer

    International Nuclear Information System (INIS)

    Suess, A.

    1997-01-01

    There can be harmful effects of sewage-sludge utilization in agriculture. However, these can be overcome by treatment of the sludge and by appropriate farm-management practices. Sewage sludge is of increasing potential importance to farmers because of its value as a fertilizer. But some compounds in sludge can be harmful for plants, animals and man. Heavy metals may be taken up by plants, and the higher the content in the soil, the greater the uptake. There are substantial differences in heavy-metal accumulation and tolerance among plant species. With respect to pathogens (for example Salmonella) in sludge, recent developments in decontamination processes can provide greater guarantee of preservation of the environment. Gamma-radiation treatment at a dose of 3 kGy has been proven effective. The use of sewage sludge in agriculture is attractive from the economical and environmental points of view. It is therefore important that farmers are provided not only with more information about the nutrient effects, but also about risks, if any, of leaching of heavy metals and microbial condition to groundwater. To achieve this, there must be close co-operation between farmers and the authorities responsible for disposal of sewage sludge. (author)

  11. Economic problems of utilization of hydroenergetic potential of the Slovak Republic and possibilities for their solution

    International Nuclear Information System (INIS)

    Dusicka, M.

    1997-01-01

    The aim of this paper is to clarify basic inputs into economic calculations of hydro power projects which then can drastically affect efficiency of these projects in different ways as there are no distinct economic and legal regulations in the Slovak Republic as the hydroelectric potential (HEP utilization is concerned. In 1995, the share of individual resources of electrical system (ES) in production in the Slovak Republic was as follows: nuclear plants - 41.86%, steam power plants - 24,93%, hydroelectrical power plants (HPP) - 18.93%, factory power plants - 9.09%, and import - 5.19%. However, in the same year, the individual resources of ES in the Slovak Republic shared in a balance of installed capacity - 7.114 MW as follows: nuclear power plants - 24.7%, steam power plants - 32.0%, HPP -33.4%, and factory power plants - 10.9%. Financing of the building of HPP -power engineering and water management ones (the Ministry of National Economy and the Ministry of Agriculture at present) is discussed. 1 ref

  12. Characterization and utilization potential of basalt rock from East-Lampung district

    Science.gov (United States)

    Isnugroho, K.; Hendronursito, Y.; Birawidha, D. C.

    2018-01-01

    The aim of this research was to study the petrography and chemical properties of basalt rock from East Lampung district, Lampung province. Petrography analysis was performed using a polarization microscope, and analysis of chemical composition using X-RF method. From the analysis of basalt rock samples, the mineral composition consists of pyroxene, plagioclase, olivine, and opaque minerals. Basic mass of basalt rock samples is, composed of plagioclase and pyroxene with subhedral-anhedral shape, forming intergranular texture, and uniform distribution. Mineral plagioclase is colorless and blade shape, transformed into opaque minerals with a size of basalt rock samples, consisting of 37.76-59.64 SiO2; 10.10-20.93 Fe2O3; 11.77-14.32 Al2O3; 5.57-14.75 CaO; 5.37-9.15 MgO; 1.40-3.34 Na2O. From the calculation, obtained the value of acidity ratio (Ma) = 3.81. With these values, indicate that the basalt rock from East Lampung district has the potential to be utilized as stone wool fiber.

  13. Dopaminergic agonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

  14. The most important structures utilizing primary and secondary hydroenergetic potential for electric energy production

    International Nuclear Information System (INIS)

    Zacharovsky, M.

    1997-01-01

    In this paper the construction, technological parameters and operation of Gabcikovo (primary hydro energy power) and Cierny Vah (secondary hydro energy power) are described. Construction of the hydroelectric power plant (HPP) Gabcikovo started in 1978 as a part of a system of hydro power projects Gabcikovo-Nagymaros. Basic technical data are: installed capacity 8 x 90 MW, production in an average aqueous year 2.650 GWh, number of hydroelectric generating sets (HGS) 8, turbine flow 8 x 413-636 m 3 /s, head 12.9-24 m.The Gabcikovo plant produced 9.163 GWh of electricity from the beginning of its operation till the end of 1966. The construction of the pumped storage plant (PSP) Cierny Vah started in 1976 and it was put into operation at the end of 1980. The main goal of the PSP Cierny Vah is to meet the control functions of an electrification system of the Slovak Republic, a substitute function in the cases of unexpected power outages and a planned electricity production from re-pumping. Technological parts are: six re-pumping vertical HGS in a three machine arrangement - a motor-generator, a turbine, a pump - are located in three double-blocks. Basic technical data: installed capacity 6 x 122.4 MW + 0.768 MW, yearly production 1,281 GWh, number of HGS 6, number of domestic hydroelectric generating sets 1, turbine flow 3 x 30 m / s, pump flow 6 x 22 m 3 /s, upper reservoir volume 3.7 mil. m 3 , max. head 434 m, peak time 5.71 hour, pumping time 7.78 hour, re-pumping cycle efficiency 74.36%. From putting the PSP into operation till the end of 1996, the HGS in operation 145,269 hours in total, including 53,332 hours in a turbine mode of operation, 70,293 hours in a pumping mode operation and 21,644 hours in a compensation mode operation. Whereas they supplied 5,346 GWh in the mains and the consumed 6,933 GWh of electricity for pumping. Hydroenergetic potential is a primary source of energy which is recyclable, i.e. unexhaustible and also ecologically the most tolerable

  15. Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

    Science.gov (United States)

    Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

    2016-01-01

    Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

  16. Gonadotropin releasing hormone agonists: Expanding vistas

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Gonadotropin-releasing hormone (GnRH agonists are derived from native GnRH by amino acid substitution which yields the agonist resistant to degradation and increases its half-life. The hypogonadotropic hypogonadal state produced by GnRH agonists has been often dubbed as "pseudomenopause" or "medical oophorectomy," which are both misnomers. GnRH analogues (GnRH-a work by temporarily "switching off" the ovaries. Ovaries can be "switched off" for the therapy and therapeutic trial of many conditions which include but are not limited to subfertility, endometriosis, adenomyosis, uterine leiomyomas, precocious puberty, premenstrual dysphoric disorder, chronic pelvic pain, or the prevention of menstrual bleeding in special clinical situations. Rapidly expanding vistas of usage of GnRH agonists encompass use in sex reassignment of male to female transsexuals, management of final height in cases of congenital adrenal hyperplasia, and preserving ovarian function in women undergoing cytotoxic chemotherapy. Hypogonadic side effects caused by the use of GnRH agonists can be tackled with use of "add-back" therapy. Goserelin, leuprolide, and nafarelin are commonly used in clinical practice. GnRH-a have provided us a powerful therapeutic approach to the treatment of numerous conditions in reproductive medicine. Recent synthesis of GnRH antagonists with a better tolerability profile may open new avenues for both research and clinical applications. All stakeholders who are partners in women′s healthcare need to join hands to spread awareness so that these drugs can be used to realize their full potential.

  17. Utilization potentiality of coal as a reductant for the production of sponge iron. [5 refs

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, H P

    1976-10-01

    With the ambitious plan of the Government of India to produce about 70 million tonnes of steel per annum towards the end of the century, the requirement of coal would be enormous. This calls for judicious planning and conservation of coal. Modern trend in steel plant practice is to use blast furnaces of capacity 10,000 to 12,000 t/day requiring superior quality coke of low ash content which will become scarce. Concerted efforts should be made to by-pass blast furnace technique by adopting direct reduction for the production of metallized iron ore, that is sponge iron, and using this as feed stock in electric furnaces. Experience has shown that the use of sponge iron as feed stock for electric arc furnaces instead of the scrap available from various fabrication and steel works results in better production of alloy steels. The use of non-coking coal as reductant for production of sponge iron will help conserve coking coal for bigger steel plants. In the solid state reduction process the technological design of the sponge iron plant has to be tailored to the type of feed stock to be used, particularly iron ore and coal. In India, non-coking coal is available at close proximity to the iron ore mines containing high grade iron ore. Planning for sponge iron, utilizing large reserves of non-coking coal as feed stock therefore has considerable potentiality. India has vast reserves of high grade iron ore and comparatively meager amount of coking coal. This calls for planning for sponge iron using non-coking coal as feed stock.

  18. Antioxidant and Antibacterial Potential of Silver Nanoparticles: Biogenic Synthesis Utilizing Apple Extract

    Directory of Open Access Journals (Sweden)

    Upendra Nagaich

    2016-01-01

    Full Text Available The advancement of the biological production of nanoparticles using herbal extracts performs a significant role in nanotechnology discipline as it is green and does not engage harsh chemicals. The objective of the present investigation was to extract flavonoids in the mode of apple extract and synthesize its silver nanoparticles and ultimately nanoparticles loading into hydrogels. The presence of flavonoids in apple extract was characterized by preliminary testing like dil. ammonia test and confirmatory test by magnesium ribbon test. The synthesized silver nanoparticles were characterized using UV spectroscopy, particle size and surface morphology, and zeta potential. Silver nanoparticles loaded hydrogels were evaluated for physical appearance, pH, viscosity, spreadability, porosity, in vitro release, ex vivo permeation, and antibacterial (E. coli and S. aureus and antioxidant studies (DPPH radical scavenging assay. Well dispersed silver nanoparticles below were observed in scanning electron microscope image. Hydrogels displayed in vitro release of 98.01%  ±  0.37% up to 24 h and ex vivo permeation of 98.81  ±  0.24% up to 24 h. Hydrogel effectively inhibited the growth of both microorganism indicating good antibacterial properties. The value of percent radical inhibition was 75.16%  ±  0.04 revealing its high antioxidant properties. As an outcome, it can be concluded that antioxidant and antiageing traits of flavonoids in apple extract plus biocidal feature of silver nanoparticles can be synergistically and successfully utilized in the form of hydrogel.

  19. Estimating potential stranded commitments for U.S. investor-owned electric utilities

    International Nuclear Information System (INIS)

    Baxter, L.; Hirst, E.

    1995-01-01

    New technologies, low natural gas prices, and federal and state utility regions are restructuring the electricity industry. Yesterday's vertically integrated utility with a retail monopoly franchise may be a very different organization in a few years. Conferences, regulatory-commission hearings, and other industry fora are dominated by debates over the extent and form of utility deintegration, wholesale competition, and retail wheeling. A key obstacle to restructuring the electricity industry is stranded commitments. Past investments, power-purchase contracts, and public-policy-driven programs that made sense in an era of cost-of-service regulation may not be cost-effective in a competitive power market. Regulators, utilities, and other parties face tough decisions concerning the mitigation and allocation of these stranded commitments. The authors developed and applied a simple method to calculate the amount of stranded commitments facing US investor-owned electric utilities. The results obtained with this method depend strongly on a few key assumptions: (1) the fraction of utility sales that is at risk with respect to competition, (2) the market price of electric generation, and (3) the number of years during which the utility would lose money because of differences between its embedded cost of production and the market price

  20. Utilization of Used Nuclear Fuel in a Potential Future US Fuel Cycle Scenario - 13499

    Energy Technology Data Exchange (ETDEWEB)

    Worrall, Andrew [Oak Ridge National Laboratory, P.O. BOX 2008 MS6172, Oak Ridge, TN, 37831-6172 (United States)

    2013-07-01

    from the FRs due to time in the core, cooling time, reprocessing, and re-fabrication time is built into the analysis, along with impacts in delays and other key assumptions and sensitivities have been investigated. The results of this assessment highlight how the UNF from future reactors (LWRs and FRs) and the resulting fissile materials (U and Pu) from reprocessing can be effectively utilized, and show that the timings of future nuclear programs are key considerations (both for reactors and fuel cycle facilities). The analysis also highlights how the timings are relevant to managing the UNF and how such an analysis can therefore assist in informing the potential future R and D strategy and needs of the US fuel cycle programs and reactor technology. (authors)

  1. Utilization of Used Nuclear Fuel in a Potential Future US Fuel Cycle Scenario - 13499

    International Nuclear Information System (INIS)

    Worrall, Andrew

    2013-01-01

    from the FRs due to time in the core, cooling time, reprocessing, and re-fabrication time is built into the analysis, along with impacts in delays and other key assumptions and sensitivities have been investigated. The results of this assessment highlight how the UNF from future reactors (LWRs and FRs) and the resulting fissile materials (U and Pu) from reprocessing can be effectively utilized, and show that the timings of future nuclear programs are key considerations (both for reactors and fuel cycle facilities). The analysis also highlights how the timings are relevant to managing the UNF and how such an analysis can therefore assist in informing the potential future R and D strategy and needs of the US fuel cycle programs and reactor technology. (authors)

  2. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

    2016-08-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  3. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.; Chernov, V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Stasyuk, E.; Rogov, A.; Il’ina, E.; Larionova, L.; Skuridin, V. [Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  4. Enhancement of the potential to utilize octopine in the nonfluorescent Pseudomonas sp. strain 92

    International Nuclear Information System (INIS)

    Gill, S.S.; Boivin, R.; Dion, P.

    1991-01-01

    The nonfluorescent Pseudomonas sp. strain 92 requires the presence of a supplementary carbon source for growth on octopine, whereas the spontaneous mutant RB100 has acquired the capacity to utilize this opine as the sole carbon and nitrogen source. Insertional mutagenesis of RB100 with transposon Tn5 generated mutants which were unable to grow on octopine and others which grew slowly on this substrate. Both types of mutants yielded revertants that had regained the ability to utilize octopine. Some of the revertants had lost the transposon, whereas in others the transposon was retained but with rearrangements of the insertion site. Genes of octopine catabolism from strain 92 were cloned on a cosmid vector to generate pK3. The clone pK3 conferred the ability to utilize octopine as the sole carbon and nitrogen source on the host Pseudomonas putida KT2440. Although they conferred an equivalent growth phenotype, the mutant genes carried by RB100 and the cloned genes on pK3 differed in their regulation. Utilization of [ 14 C]octopine was inducible by octopine in RB100 and was constitutive in KT2440(pK3)

  5. Benchmarking to Identify Practice Variation in Test Ordering: A Potential Tool for Utilization Management.

    Science.gov (United States)

    Signorelli, Heather; Straseski, Joely A; Genzen, Jonathan R; Walker, Brandon S; Jackson, Brian R; Schmidt, Robert L

    2015-01-01

    Appropriate test utilization is usually evaluated by adherence to published guidelines. In many cases, medical guidelines are not available. Benchmarking has been proposed as a method to identify practice variations that may represent inappropriate testing. This study investigated the use of benchmarking to identify sites with inappropriate utilization of testing for a particular analyte. We used a Web-based survey to compare 2 measures of vitamin D utilization: overall testing intensity (ratio of total vitamin D orders to blood-count orders) and relative testing intensity (ratio of 1,25(OH)2D to 25(OH)D test orders). A total of 81 facilities contributed data. The average overall testing intensity index was 0.165, or approximately 1 vitamin D test for every 6 blood-count tests. The average relative testing intensity index was 0.055, or one 1,25(OH)2D test for every 18 of the 25(OH)D tests. Both indexes varied considerably. Benchmarking can be used as a screening tool to identify outliers that may be associated with inappropriate test utilization. Copyright© by the American Society for Clinical Pathology (ASCP).

  6. Possibilities of further utilization of hydroenergetic potential of the Slovak Republic

    Energy Technology Data Exchange (ETDEWEB)

    Tarbajovsky, L

    1997-12-01

    This entry deals with a description of possibilities of energetic utilization of so far not used sections of main streams, it does not cover possibilities of construction of hydroelectric power plans on border streams (rivers Vah, Hron, and Orava) and less important streams in the eastern part of the Slovak Republic.

  7. Possibilities of further utilization of hydroenergetic potential of the Slovak Republic

    International Nuclear Information System (INIS)

    Tarbajovsky, L.

    1997-01-01

    This entry deals with a description of possibilities of energetic utilization of so far not used sections of main streams, it does not cover possibilities of construction of hydroelectric power plans on border streams (rivers Vah, Hron, and Orava) and less important streams in the eastern part of the Slovak Republic

  8. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  9. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  10. Agribusiness geothermal energy utilization potential of Klamath and Western Snake River Basins, Oregon. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lienau, P.J.

    1978-03-01

    Resource assessment and methods of direct utilization for existing and prospective food processing plants have been determined in two geothermal resource areas in Oregon. Ore-Ida Foods, Inc. and Amalgamated Sugar Company in the Snake River Basin; Western Polymer Corporation (potato starch extraction) and three prospective industries--vegetable dehydration, alfalfa drying and greenhouses--in the Klamath Basin have been analyzed for direct utilization of geothermal fluids. Existing geologic knowledge has been integrated to indicate locations, depth, quality, and estimated productivity of the geothermal reservoirs. Energy-economic needs and balances, along with cost and energy savings associated with field development, delivery systems, in-plant applications and fluid disposal have been calculated for interested industrial representatives.

  11. Biostimulants and Its Potential Utilization in Functional Water-soluble Fertilizers

    Directory of Open Access Journals (Sweden)

    ZHANG Qiang

    2018-02-01

    Full Text Available Biostimulants are becoming widely applied and extended in the fertilizer industry, because of their effects on soil improvement, anti-stress ability enhancement and root growth promotion, which can increase efficient uptake and utilization of soil nutrients, crop yield and quality.This review introduced the concepts of biostimulants, and summarized the functions and related mechanisms of commonly-applied biostimulants in the market, i.e.humic acid, amino acid, seaweed extracts and plant-growth-promoting bacteria(PGPR. The properties and applied characteristics of different organic wastes containing some biostimulating compounds as the main material of functional water soluble fertilizers (WSFin the industry were presented. The technical keys to compound these organic wastes with some bio-active substances to produce the functional WSF were explored, with the aims to support the value -added utilization of organic wastes, reduce the use of fertilizers, and promote crops忆 quality and quantity.

  12. Design fractures and commercial potential of superconducting magnetic energy storage for electric utility application

    International Nuclear Information System (INIS)

    Lloyd, R.J.; Schoenung, S.

    1986-01-01

    Historically, energy storage in the United States has been provided by a few pumped hydroelectric plants, but siting constraints and high cost severely limit the use of this option. Two other options which will soon be in use are batteries and compressed air energy storage. A fourth option, currently being developed for load leveling is Superconducting Magnetic Energy Storage (SMES). This paper reports the design features and estimated costs of utility scale SMES plants. For moderate discharge duration, SMES is projected to have substantially lower revenue requirements and better availability than other load leveling options. The Electric Power Research Institute has prepared a plan for commercialization which could, if aggressively pursued, lead to a demonstrated SMES technology that is available for utility commitment by the late 1990's

  13. Enhancing effects of picocyanobacteria on growth and hydrocarbon consumption potential of the associated oil-utilizing bacteria

    International Nuclear Information System (INIS)

    Radwan, S.S.; Al-Hasan, R.H.; Salamah, S.

    2004-01-01

    Marine surface waters around the world are rich in unicellular cyanobacteria or picocyanobacteria. This paper presents the results of a study which focused on the interaction of microorganisms in naturally occurring marine consortium active in hydrocarbon attenuation. Picocyanobacteria are minute phototrophs which accumulate hydrocarbons from water without any potential for oxidizing these compounds. This study demonstrates that the picocyanobacteria are part of a microbial consortia floating on the water surface of the Arabian Gulf. The consortia are include a rich population of oil-utilizing true bacteria whose growth and activities are improved in the presence of cyanobacterial partners. Each gram of picocyanobacterial biomass was associated with 10 8 - 10 12 cells of oil-utilizing bacteria. Studies have shown that oil-utilizing bacteria grow better in the presence of their partner picocyanobacteria. In addition, the oil-utilizing bacteria resulted in more powerful hydrocarbon attenuation in the presence of picocyanobacteria. Picocyanobacterial cells accumulate hydrocarbon from water without biodegrading it. The oil-utilizing bacteria grew on hydrocarbons for a source of carbon and energy. It was concluded that the oil-polluted environment of the Arabian Gulf can be cleaned effectively by the cooperative activities of this oil consuming group of bacteria composed of symbiotic microorganisms floating in the Gulf waters. 17 refs., 1 tab., 6 figs

  14. Simulation Suggests that medical group mergers won't undermine the potential utility of health information exchanges.

    Science.gov (United States)

    Rudin, Robert S; Schneider, Eric C; Volk, Lynn A; Szolovits, Peter; Salzberg, Claudia A; Simon, Steven R; Bates, David W

    2012-03-01

    Federal and state agencies are investing substantial resources in the creation of community health information exchanges, which are consortia that enable independent health care organizations to exchange clinical data. However, under pressure to form accountable care organizations, medical groups may merge and support private health information exchanges. Such activity could reduce the potential utility of community exchanges-that is, the exchanges' capacity to share patient data across hospitals and physician practices that are independent. Simulations of care transitions based on data from ten Massachusetts communities suggest that there would have to be many such mergers to undermine the potential utility of health information exchanges. At the same time, because hospitals and the largest medical groups account for only 10-20 percent of care transitions in a community, information exchanges will still need to recruit a large proportion of the medical groups in a given community for the exchanges to maintain their usefulness in fostering information exchange across independent providers.

  15. Simulation Suggests That Medical Group Mergers Won’t Undermine The Potential Utility Of Health Information Exchanges

    Science.gov (United States)

    Schneider, Eric C.; Volk, Lynn A.; Szolovits, Peter; Salzberg, Claudia A.; Simon, Steven R.; Bates, David W.

    2013-01-01

    Substantial resources are being invested in health information exchanges (HIE), community-based consortia that enable independent health-care organizations to exchange clinical data. However, under pressure to form accountable care organizations, medical groups may merge and support private HIE, reducing the potential utility of community HIEs. Simulations of “care transitions” based on data from 10 Massachusetts communities suggest that mergers would have to be considerable to substantially reduce the potential utility of an HIE. Nonetheless, simulations also suggest that HIEs will need to recruit a large proportion of the medical groups in a community, as hospitals and the largest groups account for only 10 to 20% of care transitions in communities. PMID:22392665

  16. A study on utilization improvement of cogeneration potential in a complex industrial steam and power plant

    International Nuclear Information System (INIS)

    Mierka, O.; Variny, M.

    2012-01-01

    Efficient cogeneration is widely acknowledged as one of measures reducing primary energy use and emissions of greenhouse gases and other pollutants. This contribution bears on analyses of complex industrial power plants, incorporating the concept of exergetic and exergoecomic balances-a concept that has been rarely utilized in Slovakia up to day. Emphasis is laid on synergic use of marginal and exergoecomic analysis, thus assessing the economics of various complex cogeneration units' operational modes. The whole study, together with resulting recommendations for cogeneration efficiency improvement of the given unit is an excerpt of corresponding author's doctoral thesis. (Authors)

  17. A study on utilization improvement of cogeneration potential in a complex industrial steam and power plant

    International Nuclear Information System (INIS)

    Mierka, O.; Variny, M.

    2012-01-01

    Efficient cogeneration is widely acknowledged as one of measures reducing primary energy use and emissions of greenhouse gases and other pollutants. This contribution bears on analyses of complex industrial power plants, incorporating the concept of exergetic and exergoeconomic balances-a concept that has been rarely utilized in Slovakia up to day. Emphasis is laid on synergic use of marginal and exergoeconomic analysis, thus assessing the economics of various complex cogeneration units' operational modes. The whole study, together with resulting recommendations for cogeneration efficiency improvement of the given unit is an excerpt of corresponding author's doctoral thesis. (Authors)

  18. Trial Watch: Toll-like receptor agonists for cancer therapy.

    Science.gov (United States)

    Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2013-08-01

    Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.

  19. Use of transglutaminases in foods and potential utilization of plants as a transglutaminase source – Review

    Directory of Open Access Journals (Sweden)

    Fernando Bittencourt Luciano

    2012-09-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2012v25n4p1   Transglutaminases (TGases are enzymes able to catalyze acyl-transfer reactions introducing covalent cross-links between proteins, peptides and primary amines. Animal TGases were the first studied and are divided in nine different groups of isoenzymes. They have a wide range of functions in the metabolism of most animal cells, and share the characteristic of being Ca2+-dependent. Microbial and plant TGases were also identified, and there is a vast heterogeneity among their amino acid sequences. Interestingly, it seems that all transglutaminases share a specific amino acid triad of Cys-His-Asp in their catalytic site, which can be found in all tertiary structures of the enzymes yet studied so far. Microbial TGases are the most widely used for food modification due to lower costs and high yields involved with their extraction and purification when compared to mammal sources. TGases are ubiquitously found in a variety of plants, and their utilization for food transformation has been proposed. However, there is only a single attempt using vegetal TGase in food systems, where apple pomace was used to improve the quality of pork meat. The transference of mammalian TGase genes to plants has also been considered and they were found to be successfully expressed in rice and tobacco leaves. These results lead to a new approach, where TGases could be literally farmed for food utilization.

  20. Use of transglutaminases in foods and potential utilization of plants as a transglutaminase source – Review

    Directory of Open Access Journals (Sweden)

    Fernando B. Luciano

    2012-11-01

    Full Text Available Transglutaminases (TGases are enzymes able to catalyze acyl-transfer reactions introducing covalent cross-links between proteins, peptides and primary amines. Animal TGases were the first studied and are divided in nine different groups of isoenzymes. They have a wide range of functions in the metabolism of most animal cells, and share the characteristic of being Ca2+-dependent. Microbial and plant TGases were also identified, and here is a vast heterogeneity among their amino acid sequences. Interestingly, it seems that all transglutaminases share a specific amino acid triad of Cys-His-Asp in their catalytic site, which can be found in all tertiary structures of the enzymes yet studied so far. Microbial TGases are the most widely used for food modification due to lower costs and high yields involved with their extraction and purification when compared to mammal sources. TGases are ubiquitously found in a variety of plants, and their utilization for food transformation has been proposed. However, there is only a single attempt using vegetal TGase in food systems, where apple pomace was used to improve the quality of pork meat. The transference of mammalian TGase genes to plants has also been considered and they were found to be successfully expressed in rice and tobacco leaves. These results lead to a new approach, where TGases could be literally farmed for food utilization.

  1. GLP-1 agonists for type 2 diabetes

    DEFF Research Database (Denmark)

    Jespersen, Maria J; Knop, Filip K; Christensen, Mikkel

    2013-01-01

    and legal documents in the form of assessment reports from the European Medicines Agency and the United States Food and Drug Administration. EXPERT OPINION: GLP-1-based therapy combines several unique mechanisms of action and have the potential to gain widespread use in the fight against diabetes......Within recent years, glucagon-like peptide 1 receptor agonists (GLP-1-RA) have emerged as a new treatment option for type 2 diabetes. The GLP-1-RA are administered subcutaneously and differ substantially in pharmacokinetic profiles. AREAS COVERED: This review describes the pharmacokinetics...

  2. Review of the potential for utilizing washery refuse in N. S. W. and Queensland

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, K M

    1977-06-01

    The growing importance attached to the environment, coupled with the increasing quantities of coal refuse resulting from expanded coal production has highlighted the problem of coal refuse disposal and provided the necessary impetus to find uses for the by-product, which will eventually be regarded as a fuel and engineering material rather than a waste. Potential areas of use will be as a fuel; as a potential fuel replacement and raw material additive for brick manufacture; as a raw material for lightweight aggregate manufacture; as a construction material; for agricultural purposes, or a number of other areas of special use. The successful marketing of coal refuse will depend on an in-depth technical market analysis being carried out, followed by practical research and a comprehensive product examination and identification program being undertaken.

  3. Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

    Science.gov (United States)

    Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

    2016-05-01

    Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Potential utilities of optimal estimation and control in nuclear power plants

    International Nuclear Information System (INIS)

    Tylee, J.L.; Purviance, J.E.

    1983-01-01

    Optimal estimation and control theories offer the potential for more precise control and diagnosis of nuclear power plants. The important element of these theories is that a mathematical plant model is used in conjunction with the actual plant data to optimize some performance criteria. These criteria involve important plant variables and incorporate a sense of the desired plant performance. Several applications of optimal estimation and control to nuclear systems are discussed

  5. Recovery of fission products from waste solutions utilizing controlled cathodic potential electrolysis

    International Nuclear Information System (INIS)

    Carlin, W.W.; Darlington, W.B.

    1975-01-01

    Fission products, e.g., palladium, rhodium and technetium, are recovered from aqueous waste solutions thereof, e.g., aged Purex alkaline waste solutions. The metal values from the waste solutions are extracted by ion exchange techniques. The metals adsorbed by the ion exchange resin are eluted and selectively recovered by controlled cathodic potential electrolysis. The metal values deposited on the cathode are recovered and, if desired, further purified

  6. Achieving the economic potential for industrial cogeneration in Ontario: A financial perspective on electric utility policy

    International Nuclear Information System (INIS)

    Diemer, S.G.; Cain, S.R.

    1993-01-01

    The impact of private vs public ownership regimes on the magnitude of achievable industrial cogeneration capacity in Ontario is assessed. Estimates of technical and economic potential are presented for several industrial subsectors and heat demand categories, showing that nearly all of the technically feasible 7,600 MW is also economically efficient given a value of power of at least 4 cents/kWh in 1991 dollars. Using financial data and investment criteria specific to the two forms of ownership, the project evaluation model points to a significantly larger quantum of financial (achievable) potential with public rather than private development of industrial cogeneration. At avoided costs and associated buyback rates of 4 and 5 cents/kWh, the achievable cogeneration capacities are ca 2,400 and 7,600 MW under public ownership and 132 and 3,000 MW under private ownership. Ratepayer savings are significant: the full economic potential can be achieved through public ownership at a buyback rate of 5 cents/kWh; under private ownership, a comparable capacity requires a 6 cents buyback rate, reflecting additional ratepayer costs of nearly $600 million annually. 1 fig., 4 tabs

  7. Nitrogen Utilization and Environmental Losses from Organic Farming and Biochar's Potential to Improve N Efficiency.

    Science.gov (United States)

    Pereira, E. I.; SIX, J. W. U. A.

    2014-12-01

    The response of plant performance and nitrogen (N) dynamics to biochar amendments were studied across various levels of N input for two growing seasons in mesocosms representing an organic lettuce production systems. A silt loam soil was amended with pine chip (PC) and walnut shell (WS) biochar (10 t ha-1) in combination with five organic N fertilization rates 0%, 25%, 50%, 75%, and 100% of 225 kg N ha-1. N output through harvest, leachate, and nitrous oxide (N2O) emissions were determined to assess N utilization and environmental losses of biochar-amended soils. Analysis of plant performance indicate that PC and WS biochar did not provide any increases in plant biomass in soils that received less than business-as-usual fertilization rates. At 100% N fertilization rate, biochar amendments (both PC and WS) improved lettuce biomass production, which resulted in significant increases in NUE with no effects on N2O emissions. Furthermore, N losses via leaching were decreased by PC biochar at 100% N fertilization rates. Thus, due to increases in plant biomass and decreases in N losses via leachate, PC biochar significantly decreased the ratio of N lost over N exported in biomass. Findings from this study suggest that biochar can provide some beneficial effects to organic farming systems, however, not in all circumstances, given the effects seem to vary with biochar type and fertilization level.

  8. Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for Broccoli By-Product Utilization.

    Science.gov (United States)

    Liu, Mengpei; Zhang, Lihua; Ser, Suk Lan; Cumming, Jonathan R; Ku, Kang-Mo

    2018-04-13

    The phytonutrient concentrations of broccoli ( Brassica oleracea var. italica) florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids, chlorophylls, vitamins E and K, essential mineral elements, total phenolic content, antioxidant activity, and expression of glucosinolate biosynthesis and hydrolysis genes were quantified from the different broccoli tissues. Broccoli florets had higher concentrations of amino acids, glucoraphanin, and neoglucobrassicin compared to other tissues, whereas leaves were higher in carotenoids, chlorophylls, vitamins E and K, total phenolic content, and antioxidant activity. Leaves were also good sources of calcium and manganese compared to other tissues. Stems had the lowest nitrile formation from glucosinolate. Each tissue exhibited specific core gene expression profiles supporting glucosinolate metabolism, with different gene homologs expressed in florets, stems, and leaves, which suggests that tissue-specific pathways function to support primary and secondary metabolic pathways in broccoli. This comprehensive nutrient and bioactive compound profile represents a useful resource for the evaluation of broccoli by-product utilization in the human diet, and as feedstocks for bioactive compounds for industry.

  9. Utilization of rice husk ash to enhance radon resistant potential of concrete

    International Nuclear Information System (INIS)

    Jain, Ravinder; Kant, Krishan; Yadav, Mani Kant; Chauhan, R.P.

    2013-01-01

    The radiological and health implication posed by radon and their decay products are well known. The soil containing varying amount of radionuclides is the primary source of indoor radon. The indoor radon level depends upon its entrance through the pores of the ground and floor. Thus it is necessary to restrict the radon from soil to enter indoors by application of materials with low radon diffusion coefficient. The method used for radon shielding purpose in present study utilizes the rice husk ash for substitution with cement to achieve low diffusion coefficient. The study describes the method to optimize the condition of preparation of rice husk ash using X-ray diffraction and fluorescence spectroscopy techniques. The rice husk substitution with cement was optimized by compressive and porosity test of concrete cubes. The diffusion coefficient through concrete modified by rice husk ash was carried out by scintillation radon monitor and specially design radon diffusion chamber. The radon exhalation rates from concrete carried out using active technique decreasing radon emanation from concrete with increase of rice husk ash. The result of present study suggest substitution of 20-30% rice husk ash with cement to achieve lower radon diffusion and exhalation rates with higher compressive strength as compared to control concrete. (author)

  10. A safe potential juice clarifying pectinase from Trichoderma viride EF-8 utilizing Egyptian onion skins

    Directory of Open Access Journals (Sweden)

    Abdel-Mohsen S. Ismail

    2016-06-01

    Full Text Available The production of a notable, safe and highly active pectinase by the local fungal strain Trichoderma viride EF-8 utilizing the abundant pigmented Egyptian onion (Allium cepa L. skins (6.5%, w/v was achieved in 4 days submerged fermentation (SMF cultures, at temperature and pH of 30 °C and 4.0, respectively. The indigenously produced pectinase was partially purified by 50% batch ethanol precipitation and its general properties were studied following the standard procedures. The lyophilized enzyme preparation was free of any ochra or aflatoxins. The optimum conditions for the partially purified enzyme form were 2 mg/mL and 1% (w/v enzyme protein and substrate (citrus pectin concentrations, reaction pH and temperature of 7.0 and 40 °C, respectively. The results presented the low cost onion skins waste as the major substrate for the fungal pectinase production and its subsequent use in perfect fruit (apple, lemon and orange juices clarification with remarkable stability during and after this process, which certainly enhance fruit juices processing in the tropics.

  11. Agricultural utilization of biosolids: A review on potential effects on soil and plant grown.

    Science.gov (United States)

    Sharma, Bhavisha; Sarkar, Abhijit; Singh, Pooja; Singh, Rajeev Pratap

    2017-06-01

    Environmental and economic implications linked with the proper ecofriendly disposal of modern day wastes, has made it essential to come up with alternative waste management practices that reduce the environmental pressures resulting from unwise disposal of such wastes. Urban wastes like biosolids are loaded with essential plant nutrients. In this view, agricultural use of biosolids would enable recycling of these nutrients and could be a sustainable approach towards management of this hugely generated waste. Therefore biosolids i.e. sewage sludge can serve as an important resource for agricultural utilization. Biosolids are characterized by the occurrence of beneficial plant nutrients (essential elements and micro and macronutrients) which can make help them to work as an effective soil amendment, thereby minimizing the reliance on chemical fertilizers. However, biosolids might contain toxic heavy metals that may limit its usage in the cropland. Heavy metals at higher concentration than the permissible limits may lead to food chain contamination and have fatal consequences. Biosolids amendment in soil can improve physical and nutrient property of soil depending on the quantity and portion of the mixture. Hence, biosolids can be a promising soil ameliorating supplement to increase plant productivity, reduce bioavailability of heavy metals and also lead to effective waste management. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Comparative Phytonutrient Analysis of Broccoli By-Products: The Potentials for Broccoli By-Product Utilization

    Directory of Open Access Journals (Sweden)

    Mengpei Liu

    2018-04-01

    Full Text Available The phytonutrient concentrations of broccoli (Brassica oleracea var. italica florets, stems, and leaves were compared to evaluate the value of stem and leaf by-products as a source of valuable nutrients. Primary metabolites, including amino acids, organic acids, and sugars, as well as glucosinolates, carotenoids, chlorophylls, vitamins E and K, essential mineral elements, total phenolic content, antioxidant activity, and expression of glucosinolate biosynthesis and hydrolysis genes were quantified from the different broccoli tissues. Broccoli florets had higher concentrations of amino acids, glucoraphanin, and neoglucobrassicin compared to other tissues, whereas leaves were higher in carotenoids, chlorophylls, vitamins E and K, total phenolic content, and antioxidant activity. Leaves were also good sources of calcium and manganese compared to other tissues. Stems had the lowest nitrile formation from glucosinolate. Each tissue exhibited specific core gene expression profiles supporting glucosinolate metabolism, with different gene homologs expressed in florets, stems, and leaves, which suggests that tissue-specific pathways function to support primary and secondary metabolic pathways in broccoli. This comprehensive nutrient and bioactive compound profile represents a useful resource for the evaluation of broccoli by-product utilization in the human diet, and as feedstocks for bioactive compounds for industry.

  13. Utilization of renewable energy potential in Pakistan - a goal oriented approach through industry-cum-academia linkage

    International Nuclear Information System (INIS)

    Khalil, M.S.

    2011-01-01

    Due to the recent power crisis in Pakistan, it is essential to utilize the god gifted renewable energy potentials in the form of hydro-power, solar, wind etc. With recent developments in emerging technologies globally, it is the basic need for indigenous development of renewable energy resources. It can be done through research and development by bridging the gaps between industries and technical institutions. In the world, this approach is being carried out not only for the development but for sustain ability of the R and D in the field of renewable energies. Local industries can play a vital role in using latest computational techniques in the research and development areas with the utilization of technical and engineering institutions. For sustainable development of renewable energy resources in the country, local industry have to come forward and contribute toward the betterment of the country. (author)

  14. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  15. Utility and potential of rapid epidemic intelligence from internet-based sources.

    Science.gov (United States)

    Yan, S J; Chughtai, A A; Macintyre, C R

    2017-10-01

    Rapid epidemic detection is an important objective of surveillance to enable timely intervention, but traditional validated surveillance data may not be available in the required timeframe for acute epidemic control. Increasing volumes of data on the Internet have prompted interest in methods that could use unstructured sources to enhance traditional disease surveillance and gain rapid epidemic intelligence. We aimed to summarise Internet-based methods that use freely-accessible, unstructured data for epidemic surveillance and explore their timeliness and accuracy outcomes. Steps outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were used to guide a systematic review of research related to the use of informal or unstructured data by Internet-based intelligence methods for surveillance. We identified 84 articles published between 2006-2016 relating to Internet-based public health surveillance methods. Studies used search queries, social media posts and approaches derived from existing Internet-based systems for early epidemic alerts and real-time monitoring. Most studies noted improved timeliness compared to official reporting, such as in the 2014 Ebola epidemic where epidemic alerts were generated first from ProMED-mail. Internet-based methods showed variable correlation strength with official datasets, with some methods showing reasonable accuracy. The proliferation of publicly available information on the Internet provided a new avenue for epidemic intelligence. Methodologies have been developed to collect Internet data and some systems are already used to enhance the timeliness of traditional surveillance systems. To improve the utility of Internet-based systems, the key attributes of timeliness and data accuracy should be included in future evaluations of surveillance systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. The potential of bioash for utilization in road construction in eastern Croatia

    Science.gov (United States)

    Zagvozda, Martina; Dimter, Sanja; Rukavina, Tatjana

    2017-12-01

    In recent years usage of biomass as energy source has intensified in eastern Croatia. Newly built biomass power plants generate great amounts of bioash that is being disposed at landfills. Due to its favorable properties bioashes could be reused as alternative materials in road construction or road fundation. Therefore, research on application of bioashes in construction industry is being conducted at Faculty of Civil Engineering in Osijek. The main motivation behind this research, in a form of biomass and bioash production in eastern Croatia as well as international research on potential application of this types of bioashes, is show in this paper.

  17. Market potential of utility-purpose energy storage in Japan up to the year 2050

    International Nuclear Information System (INIS)

    Tanaka, T.; Kurihara, I.

    1998-01-01

    The market potential of future energy storage in power network systems in Japan is estimated by using the linear programming method under two main scenarios for the years 2030 and 2050. One is a base scenario in which the power demand and associated performances are simply extrapolated from the present to the future year of interest. The other is a modified scenario under which they are influenced by foreseeable changes in social structure and introduction of demand-side energy storage. This estimation indicates that the optimum capacity of energy storage will be about 10 to 15% of the total generation capacity. (author)

  18. Geopressured aquifers - utilization of the energy potential of the Endorf thermal water deposit

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, S; Hantelmann, G v

    1984-01-01

    The Endorf thermal water deposit (Rupel, 4229 to 4264 m) belongs to the type of ''geopressured aquifers''. The overall aim of the project is to exploit the energy stored in the deposit in the form of thermal brine (temperature: 115/sup 0/C) and natural gas (96% methane). In this first report on the project state, an overview on prehistory is followed by a description of the currently implemented test programme and its subsequent evaluation which aim at obtaining more exact knowledge concerning the present deposit conditions and, while doing so, indications of the energy content of the deposit in order to determine the energy potential theoretically exploitable at the well head.

  19. Screw engine used as an expander in ORC for low-potential heat utilization

    Science.gov (United States)

    Richter, Lukáš

    2017-09-01

    This paper deals with a screw motor that is used as an expander in an ORC (Organic Rankin Cycle) system, whose organic working substance allows the transformation of low-potential heat (waste heat, solar and geothermal energy) into electrical energy. The article describes the specific properties of an organic substance and a screw motor that must be considered when designing and assembling a complete power unit. Screw machines are not commonly used as expansion devices, so it is necessary to perform an analysis that makes it possible to adapt the screw machine to the expansion process in terms of profiling and design.

  20. Distribution, utilization structure and potential of biomass resources in rural China: With special references of crop residues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, H [Laboratory of Quantitative Vegetation Ecology, Institute of Botany, Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Jiang, G M [Laboratory of Quantitative Vegetation Ecology, Institute of Botany, Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093 (China); Agronomy Department, Shandong Agricultural University, Tai' an 271018, Shandong Province (China); Zhuang, H Y [National Bio-Energy CO., LTD, No. 26B, Financial Street, Xicheng District, Beijing 100032 (China); Shandong Academy of Sciences, No. 19, Keyuan Road, Ji' nan 250014, Shandong Province (China); Wang, K J [Agronomy Department, Shandong Agricultural University, Tai' an 271018, Shandong Province (China)

    2008-06-15

    As the largest developing country in the world, China is urgently in short of energy and natural resources. However, biological resources such as crop residues are burnt in the field, which cause serious environmental pollution. Still it is not clear how much storage and potential of these huge crop residues are in China. This paper firstly reported the distribution, utilization structure and potential of crop biomass and provided the tangible information of crop residues in rural China through careful collecting and recalculating data. From 1995 to 2005, China produces some 630 million tons of crop residues per year, 50% of which comes from east and central south of China. The amount of crop residues is 1.3 times of the total yield of crops, 2 times of the total fodder of grassland, which covers 41% of China's territory. Crop residues of corn, wheat and rice amounted to 239, 137 and 116 million tons, respectively, accounting for nearly 80% of the total crop residues. Unfortunately, the utilizing structure is seriously improper for such abundant biomass resources. Although 23% of the crop residues are used for forage, 4% for industry materials and 0.5% for biogas, the large parts are used with lower efficiency or wasted, with 37% being directly combusted by farmers, 15% lost during collection and the rest 20.5% discarded or directly burnt in the field. Reasonable adjustment of the utilizing pattern and popularization of the recycling agriculture are essential out-ways for residues, with the development of the forage industry being the breakthrough point. We suggested that utilizing the abandoned 20.5% of the total residues for forage and combining agriculture and stock raising can greatly improve the farm system and cut down fertilizer pollution. Through the development of forage industries, the use efficiency of crop residues could be largely enhanced. Commercializing and popularizing technologies of biomass gasification and liquefaction might be substitute

  1. Potential utilization of biodiesel as alternative fuel for compression ignition engine in Malaysia

    Science.gov (United States)

    Wahab, M. A.; Ma'arof, M. I. N.; Ahmad, I. N.; Husain, H.

    2017-10-01

    Biodiesel is a type of fuel which is derived from various sources of vegetable plants and waste fuels. Today, numerous biodiesels have been engineered to be at par or even better in term of performance in comparison to pure diesel. Therefore, biodiesel has shown a promising sign as one of the best candidate in overcoming total dependency on pure diesel. This paper gives review on various tests and experiments conducted on biodiesel in order to highlight the potentials given by this particular fuel. In addition, providing the supporting evidences to further endorse for a mass usage of biodiesel in Malaysia - simultaneously, driving the country to become a potential global biodiesel producer in the near future. The reviewed studies were obtained mainly via indexed journals and online libraries. Conclusively, every test and study for every blend of biodiesel had shown consistent positive results in regards to performance and in overcoming emission related issues. Thus, providing the evidence that biodiesel is highly reliable. Malaysia as a semi-agricultural nation could take the advantage in becoming one of the leading global biodiesel producers. Nevertheless, this will requires total cooperation of every concerned government bodies and authorities.

  2. Utilization of potentially inappropriate medications in elderly patients in a tertiary care teaching hospital in India

    Directory of Open Access Journals (Sweden)

    Binit N Jhaveri

    2014-01-01

    Full Text Available Aim: To evaluate the use of potentially inappropriate medicines in elderly inpatients in a tertiary care teaching hospital. Materials and Methods: Retrospective analysis was performed for cases of elderly patients admitted between January 2010 and December 2010. Data on age, gender, diagnosis, duration of hospital stay, treatment, and outcome were collected. Prescriptions were assessed for the use of potentially inappropriate medications in geriatric patients by using American Geriatric Society Beer′s criteria (2012 and PRISCUS list (2010. Results: A total of 676 geriatric patients (52.12% females were admitted in the medicine ward. The average age of geriatric patients was 72.69 years. According to Beer′s criteria, at least one inappropriate medicine was prescribed in 590 (87.3% patients. Metoclopramide (54.3%, alprazolam (9%, diazepam (8%, digoxin > 0.125 mg/day (5%, and diclofenac (3.7% were the commonly used inappropriate medications. Use of nonsteroidal anti-inflammatory drugs (NSAIDs in heart and renal failure patients was the commonly identified drug-disease interaction. According to PRISCUS list, at least one inappropriate medication was prescribed in 210 (31.06% patients. Conclusion: Use of inappropriate medicines is highly prevalent in elderly patients.

  3. Microbial Biofilm Community Variation in Flowing Habitats: Potential Utility as Bioindicators of Postmortem Submersion Intervals

    Directory of Open Access Journals (Sweden)

    Jennifer M. Lang

    2016-01-01

    Full Text Available Biofilms are a ubiquitous formation of microbial communities found on surfaces in aqueous environments. These structures have been investigated as biomonitoring indicators for stream heath, and here were used for the potential use in forensic sciences. Biofilm successional development has been proposed as a method to determine the postmortem submersion interval (PMSI of remains because there are no standard methods for estimating the PMSI and biofilms are ubiquitous in aquatic habitats. We sought to compare the development of epinecrotic (biofilms on Sus scrofa domesticus carcasses and epilithic (biofilms on unglazed ceramic tiles communities in two small streams using bacterial automated ribosomal intergenic spacer analysis. Epinecrotic communities were significantly different from epilithic communities even though environmental factors associated with each stream location also had a significant influence on biofilm structure. All communities at both locations exhibited significant succession suggesting that changing communities throughout time is a general characteristic of stream biofilm communities. The implications resulting from this work are that epinecrotic communities have distinctive shifts at the first and second weeks, and therefore the potential to be used in forensic applications by associating successional changes with submersion time to estimate a PMSI. The influence of environmental factors, however, indicates the lack of a successional pattern with the same organisms and a focus on functional diversity may be more applicable in a forensic context.

  4. Utilization of grasses for potential biofuel production and phytoremediation of heavy metal contaminated soils.

    Science.gov (United States)

    Balsamo, Ronald A; Kelly, William J; Satrio, Justinus A; Ruiz-Felix, M Nydia; Fetterman, Marisa; Wynn, Rodd; Hagel, Kristen

    2015-01-01

    This research focuses on investigating the use of common biofuel grasses to assess their potential as agents of long-term remediation of contaminated soils using lead as a model heavy metal ion. We present evidence demonstrating that switch grass and Timothy grass may be potentially useful for long-term phytoremediation of heavy metal contaminated soils and describe novel techniques to track and remove contaminants from inception to useful product. Enzymatic digestion and thermochemical approaches are being used to convert this lignocellulosic feedstock into useful product (sugars, ethanol, biocrude oil+biochar). Preliminary studies on enzymatic hydrolysis and fast pyrolysis of the Switchgrass materials that were grown in heavy metal contaminated soil and non-contaminated soils show that the presence of lead in the Switchgrass material feedstock does not adversely affect the outcomes of the conversion processes. These results indicate that the modest levels of contaminant uptake allow these grass species to serve as phytoremediation agents as well as feedstocks for biofuel production in areas degraded by industrial pollution.

  5. Solar energy potential in Macedonia, experience of utilization and possibility for development

    International Nuclear Information System (INIS)

    Markovska, Natasha

    2004-01-01

    In the paper, a correlation between solar energy and sustain development has been considered, based on the concept of negentropy. Namely, the introduction of solar energy and renewable s in general corresponds to the proposed negentropic extension of the standard pathways in world metabolism, including science and technology as a supplementary negentropic resource. In addition the solar global irradiation in R. Macedonia is estimated and some favorable fields for photovoltaic application are emphasized. Recently, the interest in building integrated photovoltaic installations has started to increase within governmental and municipality authorities, as well as some industrial companies. To serve a national public awareness program of solar electricity promotion and education, the indigenous solar energy potential, optimization of possible PV installation, and three test cases of building-integrated grid-connected experimental facilities have been studied. The results showed the feasibility and performance of the proposed concepts

  6. Potential utilization of algal protein concentrate as a food ingredient in space habitats

    Science.gov (United States)

    Nakhost, Z.; Karel, M.

    1989-01-01

    Green alga Scenedesmus obliquus was studied as one of the potential sources of macronutrients in a space habitat. Algal protein concentrate (70.5% protein) was incorporated into a variety of food products such as bran muffins, fettuccine (spinach noodle imitation) and chocolate chip cookies. Food products containing 20 to 40% of incorporated algal proteins were considered. In the sensory analysis the greenish color of the bran muffins and cookies was not found to be objectional. The mild spinachy flavor (algae flavor) was less detectable in chocolate chip cookies than in bran muffins. The color and taste of the algae noodles were found to be pleasant and compared well with commercially available spinach noodles. Commercially available spray-dried Spirulina algae was also incorporated so the products can be compared with those containing Scenedesmus obliquus concentrate. Food products containing commercial algae had a dark green color and a "burnt after taste" and were less acceptable to the panelists.

  7. A GIS based national assessment of algal bio-oil production potential through flue gas and wastewater co-utilization

    International Nuclear Information System (INIS)

    Orfield, Nolan D.; Keoleian, Gregory A.; Love, Nancy G.

    2014-01-01

    The high theoretical productivity of microalgae makes it a promising energy crop, but economically viable large-scale production facilities have yet to emerge. Coupling algae cultivation ponds with flue gas emissions from power utilities to provide carbon dioxide and municipal wastewater to provide nutrients has been recommended as a solution. This flue gas and wastewater co-utilization (FWC) strategy not only reduces the upstream impacts and costs associated with providing inputs, but also provides a credit for wastewater treatment, a service currently required to reduce production costs to a viable level. This study provides the first national assessment of the potential for producing algal bio-oil in the United States using FWC. Spatial-temporal algae growth was simulated using solar radiation and temperature data to calculate the average annual algae yield for any location, which significantly impacts feasibility. The results of this model were integrated into a geospatial analysis which establishes the economically viable bio-oil production potential of FWC by accounting for the relative abundance of the input resources and their proximity. At most, 1.7 billion liters of bio-oil could be produced annually in a manner economically competitive with crude oil prices of $80 per barrel. The amount of nutrients in wastewater limits yields to 20.5 L of bio-oil per capita annually, and climatic constraints further reduce this potential by nearly 60%. Carbon dioxide constraints play a negligible role. Although the bio-oil production potential of FWC is relatively small, it does provide an opportunity to increase national biofuel output while providing a needed service. - Highlights: • Spatial-temporal algae growth was simulated using historical climate data. • A geospatial overlay analysis was used to assess national production potential. • Nutrient availability in wastewater is most limiting. • At most, 1.7 billion liters of algal biofuel per year could be

  8. Chinese perceptions of the utility of nuclear weapons. Prospects and potential problems in disarmament

    Energy Technology Data Exchange (ETDEWEB)

    Jing-dong, Yuan

    2010-07-01

    deployment of the long-anticipated DF- 31 and DF-31A long-range ballistic missiles and the Jin-class ballistic missile submarines. In addition, China is also developing anti-space weapons and missile defense, as well as cruise missile capabilities. The qualitative as well as quantitative improvements of the Chinese nuclear arsenal raise important questions for the global nuclear balance in 2025 as the United States and Russia implement their nuclear disarmament commitments, further cutting down their nuclear arsenals. But the more critical question to ask is how Beijing views the utility of nuclear weapons and how and to what extent such perspectives influence China's attitudes toward and participation in multilateral nuclear disarmament. This paper begins with a detailed analysis of Chinese positions on the role of nuclear weapons and of its arms control and disarmament policies. This is followed by a preliminary discussion of Chinese responses to the nuclear-free world initiative. Finally, the paper concludes by offering some recommendations on what needs to take place to remove the obstacles and concerns that may prohibit Beijing from endorsing and participating in efforts toward eliminating nuclear weapons. (author)

  9. Chinese perceptions of the utility of nuclear weapons. Prospects and potential problems in disarmament

    International Nuclear Information System (INIS)

    Jing-dong, Yuan

    2010-01-01

    -anticipated DF- 31 and DF-31A long-range ballistic missiles and the Jin-class ballistic missile submarines. In addition, China is also developing anti-space weapons and missile defense, as well as cruise missile capabilities. The qualitative as well as quantitative improvements of the Chinese nuclear arsenal raise important questions for the global nuclear balance in 2025 as the United States and Russia implement their nuclear disarmament commitments, further cutting down their nuclear arsenals. But the more critical question to ask is how Beijing views the utility of nuclear weapons and how and to what extent such perspectives influence China's attitudes toward and participation in multilateral nuclear disarmament. This paper begins with a detailed analysis of Chinese positions on the role of nuclear weapons and of its arms control and disarmament policies. This is followed by a preliminary discussion of Chinese responses to the nuclear-free world initiative. Finally, the paper concludes by offering some recommendations on what needs to take place to remove the obstacles and concerns that may prohibit Beijing from endorsing and participating in efforts toward eliminating nuclear weapons. (author)

  10. Evaluation of Fertilizer Potential of Different K Compounds Prepared Utilizing Sea Bittern as Feed Stock

    Directory of Open Access Journals (Sweden)

    Khanjan Trivedi

    2017-09-01

    Full Text Available Aim: Many countries import potassic fertilizers due to dearth of K-mineral deposits. Therefore processes to obtain K-nutrient sources from sea bittern were developed by our Institute. The present investigation evaluated the fertilizer potential of three different sea bittern-derived (SBD potassium forms developed viz., potassium schoenite, potassium nitrate and potassium ammonium sulfate on maize productivity in two cropping seasons.Methods: The pot and field experiments consisted of four treatments, wherein the three K forms were applied at the recommended rate of 40 kg K2O ha−1 and were compared with commercially used sulfate of potash. The effect of these fertilizers on different parameters of plant and soil were evaluated.Results: The application of SBD-potassic fertilizers led to enhancement in growth, productivity and quality of maize which related well with higher photosynthesis, nutrient uptake and soil quality parameters. On an average all the three forms of sea bittern-derived potash enhanced yield of maize over control by 22.3 and 23.8%, respectively, in pot and field trials. The best performance was under SBD-KNO3, which also recorded the highest benefit: cost ratio of 1.76.Conclusion: The K-fertilizers derived from sea-bittern—a waste product of salt industry—can thus be economically used to improve crop production sustainably.

  11. Toward brain-computer interface based wheelchair control utilizing tactually-evoked event-related potentials

    Science.gov (United States)

    2014-01-01

    Background People with severe disabilities, e.g. due to neurodegenerative disease, depend on technology that allows for accurate wheelchair control. For those who cannot operate a wheelchair with a joystick, brain-computer interfaces (BCI) may offer a valuable option. Technology depending on visual or auditory input may not be feasible as these modalities are dedicated to processing of environmental stimuli (e.g. recognition of obstacles, ambient noise). Herein we thus validated the feasibility of a BCI based on tactually-evoked event-related potentials (ERP) for wheelchair control. Furthermore, we investigated use of a dynamic stopping method to improve speed of the tactile BCI system. Methods Positions of four tactile stimulators represented navigation directions (left thigh: move left; right thigh: move right; abdomen: move forward; lower neck: move backward) and N = 15 participants delivered navigation commands by focusing their attention on the desired tactile stimulus in an oddball-paradigm. Results Participants navigated a virtual wheelchair through a building and eleven participants successfully completed the task of reaching 4 checkpoints in the building. The virtual wheelchair was equipped with simulated shared-control sensors (collision avoidance), yet these sensors were rarely needed. Conclusion We conclude that most participants achieved tactile ERP-BCI control sufficient to reliably operate a wheelchair and dynamic stopping was of high value for tactile ERP classification. Finally, this paper discusses feasibility of tactile ERPs for BCI based wheelchair control. PMID:24428900

  12. Potential utilization of Citrullus lanatus var. Colocynthoides waste as a novel source of pectin.

    Science.gov (United States)

    Korish, Mohamed

    2015-04-01

    The Citrullus lanatus var. Colocynthoides is an ancestor type of watermelon. It was investigated as a new source of pectin. It was cultivated in Egypt for seeds only, while the remaining fruits are discarded as waste. Effect of different extraction conditions such as pH, solid: liquid ratio, temperature and extraction time on pectin yield of Citrullus lanatus var. Colocynthoides waste was investigated in the present study. The highest yield (19.75 % w/w) was achieved at pH 2, solid: liquid ratio1:15 and 85 °C, for 60 min. Methylation degree and galacturonic acid content of extracted pectin were 55.25 %, w/w and 76.84 %, w/w. The main neutral sugars were galactose followed by arabinose and rhamnose. In addition, glucose, xylose and mannose existed as constituents in the pectin hydrolysate. The results indicated that Citrullus lanatus var. Colocynthoide waste is a potential new source of pectin.

  13. Utilization potential of wood clones of Eucalyptus urophylla in the production of wood-cement panels

    Directory of Open Access Journals (Sweden)

    Lourival Marin Mendes

    2011-03-01

    Full Text Available The objective of this study was to evaluate the potential of using clones of Eucalyptus urophylla in the production of wood-cement panels. The study used six clones of Eucalyptus urophylla with 8 years of age, from the Companhia Mineira de Metais, located in Paracatu - MG. For the formation of the panels it was used Portland cement CP V - ARI / Plus, possessing high initial resistance to mineral binder and calcium chloride (CaCl2 as accelerator for the cement curing. The panels were produced with the following parameters: dimensions of 49.5 x 49.5 x 1.5 cm, nominal density of 1.2 g/cm ³, relation wood: cement (1:2.5 and relation water: cement (1:1.5. The results can showed that: (1 for thickness swelling in two and twenty-four hours, only clones 19.28 and 58 attended the specifications, (2 for water absorption, clone 62 showed the best results, (3 to internal bond, only clone 58 didn`t attend specifications, (4 for the compression, clones 19.36 and 58 showed the best results, (5 for MOE and MOR, none of the clones presented values compatible to the bison process. It is suggested the continuation of this line of research, including the manipulation of variables of production, so that all properties be compatible to the minimum required standards.

  14. Potential lignocellulose resources and their utilization by ruminants in tropical regions

    International Nuclear Information System (INIS)

    Sansoucy, R.; Mahadevan, P.

    1983-01-01

    The nature and estimated quantities of potential lignocellulose resources in tropical regions are described. The most abundant sources of these materials are the natural grasslands, crop residues and by-products, e.g. sugar cane, cereals and fruits, and, to a limited extent, cultivated grasses, e.g. guinea and elephant grass. The availability of these resources to livestock is limited by a variety of environmental and logistic factors, e.g. seasonality of production and problems of collection and transport. Additionally, the nutritive value of pastures and fodders in the tropics is relatively lower than in temperate regions owing to their higher fibre and lower N and P content, with consequent lowering of intake and digestibility. Crop residues also have low N and high lignin contents and are generally deficient in fermentable energy, fermentable N, protein and micronutrients. The possibilities for improving the nutritive value of tropical feeds are discussed; these include supplementation with urea, molasses and minerals, good quality forage, and/or ''by-pass'' nutrients, e.g. oil cakes, and treatment by various physical, chemical or biological methods. (author)

  15. Potential to cofire high-sulfur coal and MSW/RDF in Illinois utility boilers: A survey and analysis

    International Nuclear Information System (INIS)

    South, D.W.

    1993-01-01

    The disposal of refuse is of ever-increasing concern for municipalities and other organizations and agencies throughout the United States. Disposal in landfills is becoming more costly, and new landfills are more difficult to site because of stricter environmental regulations. Mass burning incinerators for municipal solid wastes (MSW) have also met with increased public resistance due to excessive emissions. Nevertheless, increased awareness of the need for alternative disposal techniques has led to a new interest in cofiring MSW with coal. In addition to solid waste concerns, the requirements to reduce SO 2 and NO x emissions from coal-fired utility boilers in the Clean Air Act Amendments of 1990, present an opportunity to cofire MSW/RDF with coal as an emission control measure. These issues were the impetus for a 1992 study (conducted by ANL for the Illinois Clean Coal Institute) to examine the potential to cofire coal with MSW/RDF in Illinois utility boilers. This paper will provide a synopsis of the ANL/ICCI report. It will summarize (1) the combustibility and emission characteristics of high-sulfur coal and MSW/RDF; (2) the facilities firing RDF and/or producing/selling RDF, together with their combustion and emissions experience; (3) the applicable emissions regulations in Illinois; and (4) the analysis of candidate utility boilers in Illinois capable of cofiring, together with the effect on coal consumption and SO 2 and NO x emissions that would result from 20% cofiring with RDF/MSW

  16. An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

    Science.gov (United States)

    Zhou, Ping; Zev Rymer, William

    2004-12-01

    The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

  17. The most important structures utilizing primary and secondary hydroenergetic potential for electric energy production

    Energy Technology Data Exchange (ETDEWEB)

    Zacharovsky, M [Slovenske elektrarne, a.s., Vodne elektrarne Trencin (Slovakia)

    1997-12-01

    In this paper the construction, technological parameters and operation of Gabcikovo (primary hydro energy power) and Cierny Vah (secondary hydro energy power) are described. Construction of the hydroelectric power plant (HPP) Gabcikovo started in 1978 as a part of a system of hydro power projects Gabcikovo-Nagymaros. Basic technical data are: installed capacity 8 x 90 MW, production in an average aqueous year 2.650 GWh, number of hydroelectric generating sets (HGS) 8, turbine flow 8 x 413-636 m{sup 3}/s, head 12.9-24 m.The Gabcikovo plant produced 9.163 GWh of electricity from the beginning of its operation till the end of 1966. The construction of the pumped storage plant (PSP) Cierny Vah started in 1976 and it was put into operation at the end of 1980. The main goal of the PSP Cierny Vah is to meet the control functions of an electrification system of the Slovak Republic, a substitute function in the cases of unexpected power outages and a planned electricity production from re-pumping. Technological parts are: six re-pumping vertical HGS in a three machine arrangement - a motor-generator, a turbine, a pump - are located in three double-blocks. Basic technical data: installed capacity 6 x 122.4 MW + 0.768 MW, yearly production 1,281 GWh, number of HGS 6, number of domestic hydroelectric generating sets 1, turbine flow 3 x 30 m{sup /}s, pump flow 6 x 22 m{sup 3}/s, upper reservoir volume 3.7 mil. m{sup 3}, max. head 434 m, peak time 5.71 hour, pumping time 7.78 hour, re-pumping cycle efficiency 74.36%. From putting the PSP into operation till the end of 1996, the HGS in operation 145,269 hours in total, including 53,332 hours in a turbine mode of operation, 70,293 hours in a pumping mode operation and 21,644 hours in a compensation mode operation. Whereas they supplied 5,346 GWh in the mains and the consumed 6,933 GWh of electricity for pumping. Hydroenergetic potential is a primary source of energy which is recyclable, i.e. unexhaustible and also ecologically the

  18. Workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. Part II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-01

    The publication has been set up as proceedings of the workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. The proceedings consist of the following chapters: (1) Use of a part and a secondary hydroenergetic potential of the Slovak Republic for electric energy production and its impact on the environment; (2) Economic problems of utilization of hydroenergetic potential of the Slovak Republic and possibilities for their solution; (3) Modernization of control systems of primary and secondary hydro energetic sources of electricity from the point of view of their fulfillment of important functions in operation of a power engineering system in the Slovak Republic; (4) The most important structures utilizing primary and secondary hydroenergetic potential for electric energy production; (5) Progressive technologies, modernization of hydro power projects aimed at rationalization in a use of hydroenergetic potential and environment protection; (6) Possibilities of further utilization of hydroenergetic potential of the Slovak Republic.

  19. Workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. Part II

    International Nuclear Information System (INIS)

    1997-01-01

    The publication has been set up as proceedings of the workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. The proceedings consist of the following chapters: (1) Use of a part and a secondary hydroenergetic potential of the Slovak Republic for electric energy production and its impact on the environment; (2) Economic problems of utilization of hydroenergetic potential of the Slovak Republic and possibilities for their solution; (3) Modernization of control systems of primary and secondary hydro energetic sources of electricity from the point of view of their fulfillment of important functions in operation of a power engineering system in the Slovak Republic; (4) The most important structures utilizing primary and secondary hydroenergetic potential for electric energy production; (5) Progressive technologies, modernization of hydro power projects aimed at rationalization in a use of hydroenergetic potential and environment protection; (6) Possibilities of further utilization of hydroenergetic potential of the Slovak Republic

  20. The Potential and Utilization of Unused Energy Sources for Large-Scale Horticulture Facility Applications under Korean Climatic Conditions

    Directory of Open Access Journals (Sweden)

    In Tak Hyun

    2014-07-01

    Full Text Available As the use of fossil fuel has increased, not only in construction, but also in agriculture due to the drastic industrial development in recent times, the problems of heating costs and global warming are getting worse. Therefore, introduction of more reliable and environmentally-friendly alternative energy sources has become urgent and the same trend is found in large-scale horticulture facilities. In this study, among many alternative energy sources, we investigated the reserves and the potential of various different unused energy sources which have infinite potential, but are nowadays wasted due to limitations in their utilization. In addition, we utilized available unused energy as a heat source for a heat pump in a large-scale horticulture facility and analyzed its feasibility through EnergyPlus simulation modeling. Accordingly, the discharge flow rate from the Fan Coil Unit (FCU in the horticulture facility, the discharge air temperature, and the return temperature were analyzed. The performance and heat consumption of each heat source were compared with those of conventional boilers. The result showed that the power load of the heat pump was decreased and thus the heat efficiency was increased as the temperature of the heat source was increased. Among the analyzed heat sources, power plant waste heat which had the highest heat source temperature consumed the least electric energy and showed the highest efficiency.

  1. Potential utility of environmental DNA for early detection of Eurasian watermilfoil (Myriophyllum spicatum)

    Science.gov (United States)

    Newton, Jeremy; Sepulveda, Adam; Sylvester, K; Thum, Ryan

    2016-01-01

    EWM invasions have negative impacts on native biodiversity, recreational boating, fishing, and other types of aquatic tourism (e.g., Eiswerth et al. 2000). On a broader scale, EWM can also be harmful to man-made aquatic infrastructure, such as hydroelectric dams. If an EWM invasion can be detected in an early stage where eradication is still a possibility, many of these negative consequences can be limited or prevented altogether (e.g., Madsen et al. 2002). The purpose of this research was to develop and validate a traditional polymerase chain reaction (PCR) assay for the detection of pure and hybridized EWM DNA using both laboratory and field experiments. We performed a pilot experiment in outdoor tanks to determine the basic functionality and sensitivity of the assay. Following this initial test, we collected field samples from Michigan and Montana lakes with and without known EWM populations. Taken together, our findings suggest that eDNA techniques have potential to be a useful strategy for the early detection of EWM.

  2. Biomaterials Approaches for Utilizing the Regenerative Potential of the Peripheral Nerve Injury Microenvironment

    Science.gov (United States)

    Wrobel, Melissa Renee

    following classical activation (M1/pro-inflammatory) with lipopolysaccharide (LPS; 1microg/mL) and would accelerate the transformation of Schwann cells from an immature state fol-lowing injury to a mature/pro-myelinating one. Cell phenotypes were functionally assessed using quantified reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, and sandwich-ELISA based antibody arrays to measure changes in mRNA expression, mor-phology, and cytokine release, respectively. Macrophages cultured with the SCM and HA fibers had significantly reduced M1 gene expression, released lower levels of M1 cytokines (IL-1a, RANTES and TFN-a) and assumed an elongated morphology indicative of M2. These cues also induced changes in the Schwann cells including significantly reduced area, increased elongation, decreased expression of immature genes (GFAP) and increased expression of mature genes (Krox20 and Oct6). These results suggest that the SCM and HA nanofibers could trigger non-neuronal cells towards regenerative programs more quickly than traditional PNI interventions. Changes induced by biomaterials have distinct benefits over the use of immunomodulatory cy-tokines and would be a novel approach to direct repair. Our collective studies offer improved in-sight into the endogenous potential of the injured peripheral nerve and offer ways to incorporate intrinsic repair cues into a biomaterial system for treating large gaps.

  3. Long-acting β2-agonists in asthma

    DEFF Research Database (Denmark)

    Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten

    2018-01-01

    Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without...... and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from...... mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue....

  4. Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan.

    Science.gov (United States)

    Inoue, Daisuke; Nakama, Koki; Sawada, Kazuko; Watanabe, Taro; Takagi, Mai; Sei, Kazunari; Yang, Min; Hirotsuji, Junji; Hu, Jianying; Nishikawa, Jun-ichi; Nakanishi, Tsuyoshi; Ike, Michihiko

    2010-04-01

    This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) alpha in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan. To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARalpha agonist contamination in the river basins. RARalpha agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6 ng-atRA/L and 23.5 ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARalpha agonists are always present and widespread in the rivers. Comparative investigation of RARalpha and estrogen receptor alpha agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARalpha agonist contamination was entirely different from that of the estrogenic compound contamination. This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARalpha agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARalpha agonists in the rivers. Although a trial conducted to identify RARalpha agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARalpha agonistic activity were not RAs (natural RAR ligands) and 4-oxo-RAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China. These findings suggest that there are unknown RARalpha agonists with high

  5. Capacity and levels of utilization of tourism potentials of Yankari and Cross River National Parks – implications for optimistic ecotourism development in Nigeria

    Directory of Open Access Journals (Sweden)

    PC Ngoka

    2013-01-01

    Full Text Available Development of sustainable tourism constitutes an essential component of Nigeria’s agenda for attaining sustainable development by the year 2020. The level of utilization of existing tourism capacities of national parks can affect the attainment of this goal. The present study examined capacity and levels of utilization of tourism potentials of Yankari National Park (YNP and Cross River National Park (CRNP. Mean visitor holding capacity (MVHC of each park over the period 2002 – 2006 was determined. Further, mean visitation of the parks during the study period was obtained from records of tourism visitation of the parks. From these, capacity utilizations were determined. Cross sectional survey of levels of utilization of attractions in each park was conducted using questionnaire. YNP recorded 49.3% capacity utilization; while CRNP had 3.5%. Both parks witnessed varying levels of utilization of their existing potentials. In YNP, game viewing and warm spring bathing had high levels of utilization (91% and 64% respectively. Old iron smelting sites and Dukkey Wells recorded low levels of utilization (1.0% each. In CRNP, rainforest experience and cave adventure had high utilization levels (93.3% and 68.3% respectively. Neither park had optimum use of its potentials. Updating of parks’ tourism infrastructure and creation of better awareness of the parks as tourist destinations were recommended for beefing up capacity and levels of utilization of the parks.

  6. Utilization of agrarian potentials'. Challenges for agriculturists and society; Agrar-Potenziale nutzen.. Herausforderung fuer Landwirte und Gesellschaft

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    Within the scope of the meeting 'Utilization of agrarian potentials' held by Deutsche Landwirtschaftliche Gesellschaft e.V. at 8th to 10th January, 2008, in Muenster (Federal Republic of Germany) the following lectures were held: (a) The world markets move - challenges for production (Joachim von Braun); (b) Global markets - future terms of references for the agriculture: guidelines for future strategies under new objectives (Juergen Zeddies); (c) Structural change and globalization - challenges for cooperative societies as market partners of the agriculture (Andreas Schueren, Dieter Hake); (d) More efficient utilization of scarce resources - we need changed thought patterns and decision patterns (Carl-Albrecht Bartmer); (e) Optimal intensities in the agriculture - the requirement of the hour: Adjustment of production at optimal intensity (Theo Jachmann); (f) Growth potentials of selected locations for the agriculture - area productivity in the international comparison (Klaus Nehring); (g) Optimization of the intensities in the crop farming - new challenges, possible adjustments (Hubertus Paetow); (h) Considering inventory management? The fertilization of tomorrow (Klaus Muenchhoff); (i) Value added chain of grain - quality requirements from the view of the traceability: The test system grain (Petra Melisch); (j) Young farmers full of optimism - current results of interview for the estimation of the situation and future and to efficiency potentials (Marika Prasser-Strith); (k) The responsibility for the soil - challenges at technology for cultivation and tillage (Franz-Georg von Busse); (l) The sustainable use of the plough land is an obligation - plough land is precious. (Lothar Hoevelmann); (m) Development of milk cattle companies till 2015 - strategic future planning now necessarily (Johannes Thomsen); (n) The ethical responsibility for a sustainable and global development - agriculture and nutrition (Beatrice van Saan-Klein, Markus Vogt); (o) Ethical

  7. Not Utilized Learning Potentials

    DEFF Research Database (Denmark)

    Kragelund, Linda

    2007-01-01

      When the Danish Nursing Education in 2002 became a Bachelor Degree the clinical part of the education was reduced. Therefore, it was necessary to optimize learning in practice.       I made a qualitative investigation to describe student nurses' learning processes in non-routine situations where...... they interact with psychiatric patients. The theoretical framework includes primarily P. Jarvis' concept disjuncture and A. Heller's theory about everyday life. The empirical part of the study is primarily based on qualitative semi-structured interviews with, observations of and obser-views with a volunteer......-conscious disjuncture, in development of the concept pseudo-everyday life activities and in a categorizing mo­del for and a theory about student nurses' learning processes. The theory includes relations between 4 types of  disjuncture, 3 types of content in the learning processes, and factors that provoke...

  8. Potential Effect and Analysis of High Residential Solar Photovoltaic (PV Systems Penetration to an Electric Distribution Utility (DU

    Directory of Open Access Journals (Sweden)

    Jeffrey Tamba Dellosa

    2016-11-01

    Full Text Available The Renewable Energy Act of 2008 in the Philippines provided an impetus for residential owners to explore solar PV installations at their own rooftops through the Net-Metering policy. The Net-Metering implementation through the law however presented some concerns with inexperienced electric DU on the potential effect of high residential solar PV system installations. It was not known how a high degree of solar integration to the grid can possibly affect the operations of the electric DU in terms of energy load management. The primary objective of this study was to help the local electric DU in the analysis of the potential effect of high residential solar PV system penetration to the supply and demand load profile in an electric distribution utility (DU grid in the province of Agusan del Norte, Philippines. The energy consumption profiles in the year 2015 were obtained from the electric DU operating in the area. An average daily energy demand load profile was obtained from 0-hr to the 24th hour of the day based from the figures provided by the electric DU. The assessment part of the potential effect of high solar PV system integration assumed four potential total capacities from 10 Mega Watts (MW to 40 MW generated by all subscribers in the area under study at a 10 MW interval. The effect of these capacities were measured and analyzed with respect to the average daily load profile of the DU. Results of this study showed that a combined installations beyond 20 MWp coming from all subscribers is not viable for the local electric DU based on their current energy demand or load profile. Based from the results obtained, the electric DU can make better decisions in the management of high capacity penetration of solar PV systems in the future, including investment in storage systems when extra capacities are generated. Article History: Received July 15th 2016; Received in revised form Sept 23rd 2016; Accepted Oct 1st 2016; Available online How to Cite

  9. An Estimation of the Potential Utilization in Iranian Pharmaceutical Industry Involved in the Stock Exchange, 2008-2012

    Science.gov (United States)

    Annabi, Majid; Kebriaeezadeh, Abbas; Mohammadi, Timor; Marashi Shoshtari, Seyed Nasrolah; Abedin Dorkoosh, Farid; Pourreza, Abolghasem; Heydari, Hassan

    2017-01-01

    The aim of this study was to measure the potential of production and the capacity used in the pharmaceutical industry. Capacity use is the actual production rate to the potential output, which reflects the gap between actual production and production capacity. Through econometric methods, translog cost function in the short run along with functions of share cost of production factors is estimated through seemingly unrelated repeated regression (SURE) as a multivariate regression analysis provided by zeller. During the study the capacity used is decreasing. The capacity used, which calculated by weighted average, also decreased and the amount during the study period is much less than the simple average of the industry. Average capacity utilization in the industry over five years of study is equal to 57% while the average capacity used calculated by the weighted of industry average is 37%. To enhance the economic potential requires a proper use of resources, creation of favorable economic structure and productivity of the industry. Due to the large amount of unused capacity in the pharmaceutical industry there is no need to invest anymore unless in new grounds and it is obvious that more investment will change using capacity. PMID:29552074

  10. An Estimation of the Potential Utilization in Iranian Pharmaceutical Industry Involved in the Stock Exchange, 2008-2012.

    Science.gov (United States)

    Annabi, Majid; Kebriaeezadeh, Abbas; Mohammadi, Timor; Marashi Shoshtari, Seyed Nasrolah; Abedin Dorkoosh, Farid; Pourreza, Abolghasem; Heydari, Hassan

    2017-01-01

    The aim of this study was to measure the potential of production and the capacity used in the pharmaceutical industry. Capacity use is the actual production rate to the potential output, which reflects the gap between actual production and production capacity . Through econometric methods, translog cost function in the short run along with functions of share cost of production factors is estimated through seemingly unrelated repeated regression (SURE) as a multivariate regression analysis provided by zeller. During the study the capacity used is decreasing. The capacity used, which calculated by weighted average, also decreased and the amount during the study period is much less than the simple average of the industry. Average capacity utilization in the industry over five years of study is equal to 57% while the average capacity used calculated by the weighted of industry average is 37%. To enhance the economic potential requires a proper use of resources, creation of favorable economic structure and productivity of the industry. Due to the large amount of unused capacity in the pharmaceutical industry there is no need to invest anymore unless in new grounds and it is obvious that more investment will change using capacity.

  11. The Potential for Electrofuels Production in Sweden Utilizing Fossil and Biogenic CO{sub 2} Point Sources

    Energy Technology Data Exchange (ETDEWEB)

    Hansson, Julia, E-mail: julia.hansson@ivl.se [Climate and Sustainable Cities, IVL Swedish Environmental Research Institute, Stockholm (Sweden); Division of Physical Resource Theory, Department of Energy and Environment, Chalmers University of Technology, Göteborg (Sweden); Hackl, Roman [Climate and Sustainable Cities, IVL Swedish Environmental Research Institute, Stockholm (Sweden); Taljegard, Maria [Division of Energy Technology, Department of Energy and Environment, Chalmers University of Technology, Göteborg (Sweden); Brynolf, Selma; Grahn, Maria [Division of Physical Resource Theory, Department of Energy and Environment, Chalmers University of Technology, Göteborg (Sweden)

    2017-03-13

    This paper maps, categorizes, and quantifies all major point sources of carbon dioxide (CO{sub 2}) emissions from industrial and combustion processes in Sweden. The paper also estimates the Swedish technical potential for electrofuels (power-to-gas/fuels) based on carbon capture and utilization. With our bottom-up approach using European databases, we find that Sweden emits approximately 50 million metric tons of CO{sub 2} per year from different types of point sources, with 65% (or about 32 million tons) from biogenic sources. The major sources are the pulp and paper industry (46%), heat and power production (23%), and waste treatment and incineration (8%). Most of the CO{sub 2} is emitted at low concentrations (<15%) from sources in the southern part of Sweden where power demand generally exceeds in-region supply. The potentially recoverable emissions from all the included point sources amount to 45 million tons. If all the recoverable CO{sub 2} were used to produce electrofuels, the yield would correspond to 2–3 times the current Swedish demand for transportation fuels. The electricity required would correspond to about 3 times the current Swedish electricity supply. The current relatively few emission sources with high concentrations of CO{sub 2} (>90%, biofuel operations) would yield electrofuels corresponding to approximately 2% of the current demand for transportation fuels (corresponding to 1.5–2 TWh/year). In a 2030 scenario with large-scale biofuels operations based on lignocellulosic feedstocks, the potential for electrofuels production from high-concentration sources increases to 8–11 TWh/year. Finally, renewable electricity and production costs, rather than CO{sub 2} supply, limit the potential for production of electrofuels in Sweden.

  12. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  13. Emerging GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2011-01-01

    and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds. Expert opinion: An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven...... development may improve the effects of GLP-1 even further with optimized pharmacokinetic profiles resulting in fewer side effects. Meta-analyses have shown promising effects on cardiovascular disease and data from ongoing multicenter trials with cardiovascular endpoints are expected in 2015....

  14. The epileptogenic spectrum of opiate agonists.

    Science.gov (United States)

    Snead, O C; Bearden, L J

    1982-11-01

    The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

  15. Improving Fructose Utilization and Butanol Production by Clostridium acetobutylicum via Extracellular Redox Potential Regulation and Intracellular Metabolite Analysis.

    Science.gov (United States)

    Chen, Li-Jie; Wu, You-Duo; Xue, Chuang; Bai, Feng-Wu

    2017-10-01

    Jerusalem artichoke (JA) can grow well in marginal lands with high biomass yield, and thus is a potential energy crop for biorefinery. The major biomass of JA is from tubers, which contain inulin that can be easily hydrolyzed into a mixture of fructose and glucose, but fructose utilization for producing butanol as an advanced biofuel is poor compared to glucose-based ABE fermentation by Clostridium acetobutylicum. In this article, the impact of extracellular redox potential (ORP) on the process is studied using a mixture of fructose and glucose to simulate the hydrolysate of JA tubers. When the extracellular ORP is controlled above -460 mV, 13.2 g L -1 butanol is produced from 51.0 g L -1 total sugars (40.1 g L -1 fructose and 10.9 g L -1 glucose), leading to dramatically increased butanol yield and butanol/ABE ratio of 0.26 g g -1 and 0.67, respectively. Intracellular metabolite and q-PCR analysis further indicate that intracellular ATP and NADH availabilities are significantly improved together with the fructose-specific PTS expression at the lag phase, which consequently facilitate fructose transport, metabolic shift toward solventogenesis and carbon flux redistribution for butanol biosynthesis. Therefore, the extracellular ORP control can be an effective strategy to improve butanol production from fructose-based feedstock. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.

    Science.gov (United States)

    Chen, Wen-Lian; Wang, Yue-Ying; Zhao, Aihua; Xia, Li; Xie, Guoxiang; Su, Mingming; Zhao, Linjing; Liu, Jiajian; Qu, Chun; Wei, Runmin; Rajani, Cynthia; Ni, Yan; Cheng, Zhen; Chen, Zhu; Chen, Sai-Juan; Jia, Wei

    2016-11-14

    Rapidly proliferating leukemic progenitor cells consume substantial glucose, which may lead to glucose insufficiency in bone marrow. We show that acute myeloid leukemia (AML) cells are prone to fructose utilization with an upregulated fructose transporter GLUT5, which compensates for glucose deficiency. Notably, AML patients with upregulated transcription of the GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of the antileukemic agent, Ara-C. In conclusion, this study highlights enhanced fructose utilization as a metabolic feature of AML and a potential therapeutic target. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Metabolic effects of beta2-agonists in relation to exercise performance

    DEFF Research Database (Denmark)

    Kalsen, Anders

    2015-01-01

    athletes. The present PhD thesis is based on four manuscripts in which the acute effects of beta2-agonists on exercise performance were investigated. The aims were 1) to investigate whether supratherapeutic inhalation of beta2-agonists enhances muscle strength, anaerobic performance and aerobic performance......, 2) to uncover the mechanisms behind potential beta2-adrenergic improvements in anaerobic performance, 3) to investigate whether inhalation of beta2-agonists is ergogenic in elite athletes with or without airway hyperresponsiveness (AHR). Results from the studies of the thesis show...... administration of a certain dose, but a further increase in dose does not seem to elicit a greater performance-enhancing effect. Moreover, the effects of beta2-agonists on performance are unaffected by training status and AHR, but athletes with AHR who regularly use beta2-agonists get a reduced ergogenic...

  18. AGONISTIC BEHAVIOR OF LABORATORY MICE

    Directory of Open Access Journals (Sweden)

    D. Cinghiţă

    2005-01-01

    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  19. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Science.gov (United States)

    Zhou, Wei; Zhang, Xuan; Zhu, Cai-Lian; He, Zhi-Yan; Liang, Jing-Ping; Song, Zhong-Chen

    2016-01-01

    "Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation. Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA). Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgpA, rgpB, hag

  20. Melatonin Receptor Agonists as the "Perioceutics" Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response.

    Directory of Open Access Journals (Sweden)

    Wei Zhou

    Full Text Available "Perioceutics" including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential "perioceutics" treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS-induced inflammation.Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM. The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8 was measured by enzyme-linked immunosorbent assay (ELISA.Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence factors (kgp, rgp

  1. Features of undiagnosed breast cancers at screening breast MR imaging and potential utility of computer-aided evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Mirinae; Cho, Nariya; Bea, Min Sun; Koo, Hye Ryoung; Kim, Won Hwa; Lee, Su Hyun; Chu, A Jung [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-02-15

    To retrospectively evaluate the features of undiagnosed breast cancers on prior screening breast magnetic resonance (MR) images in patients who were subsequently diagnosed with breast cancer, as well as the potential utility of MR-computer-aided evaluation (CAE). Between March 2004 and May 2013, of the 72 consecutive pairs of prior negative MR images and subsequent MR images with diagnosed cancers (median interval, 32.8 months; range, 5.4-104.6 months), 36 (50%) had visible findings (mean size, 1.0 cm; range, 0.3-5.2 cm). The visible findings were divided into either actionable or under threshold groups by the blinded review by 5 radiologists. MR imaging features, reasons for missed cancer, and MR-CAE features according to actionability were evaluated. Of the 36 visible findings on prior MR images, 33.3% (12 of 36) of the lesions were determined to be actionable and 66.7% (24 of 36) were underthreshold; 85.7% (6 of 7) of masses and 31.6% (6 of 19) of non-mass enhancements were classified as actionable lesions. Mimicking physiologic enhancements (27.8%, 10 of 36) and small lesion size (27.8%, 10 of 36) were the most common reasons for missed cancer. Actionable findings tended to show more washout or plateau kinetic patterns on MR-CAE than underthreshold findings, as the 100% of actionable findings and 46.7% of underthreshold findings showed washout or plateau (p = 0.008). MR-CAE has the potential for reducing the number of undiagnosed breast cancers on screening breast MR images, the majority of which are caused by mimicking physiologic enhancements or small lesion size.

  2. Phosphorus(V)-corrole: synthesis, spectroscopic properties, theoretical calculations, and potential utility for in vivo applications in living cells.

    Science.gov (United States)

    Liang, Xu; Mack, John; Zheng, Li-Min; Shen, Zhen; Kobayashi, Nagao

    2014-03-17

    The synthesis and properties of phosphorus(V) 5,10,15-tris(4-methoxycarbonylphenyl)corrole (1) have been investigated, and its potential utility for bioimaging applications in living cells has been explored. As would normally be anticipated for corrole complexes, the intensity of the Q(0,0) bands of 1 is greater than those of comparable phosphorus(V) tetraphenylporphyrins, but the ΦF values (0.25 for 1) are found to be comparable. A detailed analysis of the electronic structure of the complex was carried out by comparing electronic absorption and MCD spectral data to the results of TD-DFT calculations. The meso-aryl substituents, which enhance the lipophilicity of 1 and hence result in its localization in intracellular membranes during HeLa cell experiments, are predicted to result in a narrowing of the HOMO-LUMO gap and hence a red shift of the Q(0,0) bands toward the optical window in biological tissues.

  3. Assessing the Potential of Utilization and Storage Strategies for Post-Combustion CO{sub 2} Emissions Reduction

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Katy; Styring, Peter, E-mail: p.styring@sheffield.ac.uk [UK Centre for Carbon Dioxide Utilization, Department of Chemical and Biological Engineering, The University of Sheffield, Sheffield (United Kingdom)

    2015-03-03

    The emissions reduction potential of three carbon dioxide handling strategies for post-combustion capture is considered. These are carbon capture and sequestration/storage (CCS), enhanced hydrocarbon recovery (EHR), and carbon dioxide utilization (CDU) to produce synthetic oil. This is performed using common and comparable boundary conditions including net CO{sub 2} sequestered based on equivalent boundary conditions. This is achieved using a “cradle to grave approach” where the final destination and fate of any product is considered. The input boundary is pure CO{sub 2} that has been produced using a post-combustion capture process as this is common between all processes. The output boundary is the emissions resulting from any product produced with the assumption that the majority of the oil will go to combustion processes. We also consider the “cradle to gate” approach where the ultimate fate of the oil is not considered as this is a boundary condition often applied to EHR processes. Results show that while CCS can make an impact on CO{sub 2} emissions, CDU will have a comparable effect whilst generating income while EHR will ultimately increase net emissions. The global capacity for CDU is also compared against CCS using data based on current and planned CCS projects. Analysis shows that current CDU represent a greater volume of capture than CCS processes and that this gap is likely to remain well beyond 2020 which is the limit of the CCS projects in the database.

  4. Beta-agonists and animal welfare

    Science.gov (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  5. Small molecule fluoride toxicity agonists.

    Science.gov (United States)

    Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

    2015-04-23

    Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Estimation of low-potential heat recuperation efficiency of smoke fumes in a condensation heat utilizer under various operation conditions of a boiler and a heating system

    Science.gov (United States)

    Ionkin, I. L.; Ragutkin, A. V.; Luning, B.; Zaichenko, M. N.

    2016-06-01

    For enhancement of the natural gas utilization efficiency in boilers, condensation heat utilizers of low-potential heat, which are constructed based on a contact heat exchanger, can be applied. A schematic of the contact heat exchanger with a humidifier for preheating and humidifying of air supplied in the boiler for combustion is given. Additional low-potential heat in this scheme is utilized for heating of the return delivery water supplied from a heating system. Preheating and humidifying of air supplied for combustion make it possible to use the condensation utilizer for heating of a heat-transfer agent to temperature exceeding the dewpoint temperature of water vapors contained in combustion products. The decision to mount the condensation heat utilizer on the boiler was taken based on the preliminary estimation of the additionally obtained heat. The operation efficiency of the condensation heat utilizer is determined by its structure and operation conditions of the boiler and the heating system. The software was developed for the thermal design of the condensation heat utilizer equipped by the humidifier. Computation investigations of its operation are carried out as a function of various operation parameters of the boiler and the heating system (temperature of the return delivery water and smoke fumes, air excess, air temperature at the inlet and outlet of the condensation heat utilizer, heating and humidifying of air in the humidifier, and portion of the circulating water). The heat recuperation efficiency is estimated for various operation conditions of the boiler and the condensation heat utilizer. Recommendations on the most effective application of the condensation heat utilizer are developed.

  7. Quantitative protein and fat metabolism in bull calves treated with beta-adrenergic agonist

    DEFF Research Database (Denmark)

    Chwalibog, André; Jensen, K; Thorbek, G

    1996-01-01

    Protein and energy utilization and quantitative retention of protein, fat and energy was investigated with 12 Red Danish bulls during two subsequent 6 weeks trials (Sections A and B) at a mean live weight of 195 and 335 kg respectively. Treatments were control (Group 1) and beta-agonist (L-644...... matter, metabolizable energy and digestible protein was of the same magnitude for all groups. The beta-agonist had no significant effect on protein digestibility and metabolizability of energy, but daily live weight gain was significantly higher in the treated bulls. The utilization of digested protein...

  8. Dopamine agonists and risk: impulse control disorders in Parkinson's disease.

    Science.gov (United States)

    Voon, Valerie; Gao, Jennifer; Brezing, Christina; Symmonds, Mkael; Ekanayake, Vindhya; Fernandez, Hubert; Dolan, Raymond J; Hallett, Mark

    2011-05-01

    Impulse control disorders are common in Parkinson's disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a 'Sure' choice and a 'Gamble' choice of moderate risk. To commence each trial, in the 'Gain' condition, individuals started at $0 and in the 'Loss' condition individuals started at -$50 below the 'Sure' amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk ('Gamble Risk'). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the 'Gain' relative to the 'Loss' condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.

  9. Cultivation of energy crops. Environmental impacts, competitive utilization and potentials; Anbau von Energiepflanzen. Umweltauswirkungen, Nutzungskonkurrenzen und Potenziale

    Energy Technology Data Exchange (ETDEWEB)

    Muehlenhoff, Joerg

    2013-04-15

    This background paper under consideration reports on the utilization of energy crops with regard to energy supply and climate change. Energy crops are renewable plants which are grown only for energy utilization. The harvested biomass is prepared for the power supply, heat supply and fuel supply by means of different usage paths.

  10. Feasibility and potential utility of multicomponent exhaled breath analysis for predicting development of radiation pneumonitis after stereotactic ablative radiotherapy.

    Science.gov (United States)

    Moré, Jayaji M; Eclov, Neville C W; Chung, Melody P; Wynne, Jacob F; Shorter, Joanne H; Nelson, David D; Hanlon, Alexandra L; Burmeister, Robert; Banos, Peter; Maxim, Peter G; Loo, Billy W; Diehn, Maximilian

    2014-07-01

    In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors. Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters. Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development. The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.

  11. ADN-1184 a monoaminergic ligand with 5-HT(6/7) receptor antagonist activity: pharmacological profile and potential therapeutic utility.

    Science.gov (United States)

    Kołaczkowski, M; Mierzejewski, P; Bieńkowski, P; Wesołowska, A; Newman-Tancredi, A

    2014-02-01

    Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side effects, which are problematic in elderly patients. A need therefore exists for drugs that are better suited for the treatment of BPSD. We used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. ADN-1184 exhibits substantial 5-HT6 /5-HT7 /5-HT2A /D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies and inhibited conditioned avoidance response (MED = 3 mg·kg(-1) i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg·kg(-1) i.p.; higher doses were not significantly active). Notably, up to 30 mg·kg(-1) ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg·kg(-1) i.p.). ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is better than that of commonly used atypical antipsychotics tested under the same conditions and suggests that it is feasible to identify drugs that improve BPSD, without exacerbating cognitive deficit or movement impairment, which are of particular concern in patients with dementia. © 2013 The British Pharmacological Society.

  12. ADN-1184 a monoaminergic ligand with 5-HT6/7 receptor antagonist activity: pharmacological profile and potential therapeutic utility

    Science.gov (United States)

    Kołaczkowski, M; Mierzejewski, P; Bieńkowski, P; Wesołowska, A; Newman-Tancredi, A

    2014-01-01

    Background and Purpose Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side effects, which are problematic in elderly patients. A need therefore exists for drugs that are better suited for the treatment of BPSD. Experimental Approach We used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. Key Results ADN-1184 exhibits substantial 5-HT6/5-HT7/5-HT2A/D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies and inhibited conditioned avoidance response (MED = 3 mg·kg−1 i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg·kg−1 i.p.; higher doses were not significantly active). Notably, up to 30 mg·kg−1 ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg·kg−1 i.p.). Conclusions and Implications ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is better than that of commonly used atypical antipsychotics tested under the same conditions and suggests that it is feasible to identify drugs that improve BPSD, without exacerbating cognitive deficit or movement impairment, which are of particular concern in patients with dementia. PMID:24199650

  13. Aquatic insects of New York salt marsh associated with mosquito larval habitat and their potential utility as bioindicators.

    Science.gov (United States)

    Rochlin, Ilia; Dempsey, Mary E; Iwanejko, Tom; Ninivaggi, Dominick V

    2011-01-01

    The aquatic insect fauna of salt marshes is poorly characterized, with the possible exception of biting Diptera. Aquatic insects play a vital role in salt marsh ecology, and have great potential importance as biological indicators for assessing marsh health. In addition, they may be impacted by measures to control mosquitoes such as changes to the marsh habitat, altered hydrology, or the application of pesticides. Given these concerns, the goals of this study were to conduct the first taxonomic survey of salt marsh aquatic insects on Long Island, New York, USA and to evaluate their utility for non-target pesticide impacts and environmental biomonitoring. A total of 18 species from 11 families and five orders were collected repeatedly during the five month study period. Diptera was the most diverse order with nine species from four families, followed by Coleoptera with four species from two families, Heteroptera with three species from three families, then Odonata and the hexapod Collembola with one species each. Water boatmen, Trichocorixa verticalis Fieber (Heteroptera: Corixidae) and a shore fly, Ephydra subopaca Loew (Diptera: Ephydridae), were the two most commonly encountered species. An additional six species; Anurida maritima Guérin-Méneville (Collembola: Neanuridae), Mesovelia mulsanti White (Heteroptera: Mesovelidae), Enochrus hamiltoni Horn (Coleoptera: Hydrophilidae), Tropisternus quadristriatus Horn (Coleoptera: Hydrophilidae), Dasyhelea pseudocincta Waugh and Wirth (Diptera: Ceratopogonidae), and Brachydeutera argentata Walker (Diptera: Ephydridae), were found regularly. Together with the less common Erythrodiplax berenice Drury (Odonata: Libellulidae), these nine species were identified as the most suitable candidates for pesticide and environmental impact monitoring due to abundance, position in the food chain, and extended seasonal occurrence. This study represents a first step towards developing an insect-based index of biological integrity for

  14. Utilization of non-conventional systems for conversion of biomass to food components: Potential for utilization of algae in engineered foods

    Science.gov (United States)

    Karel, M.; Kamarei, A. R.; Nakhost, Z.

    1985-01-01

    The major nutritional components of the green algae (Scenedesmus obliquus) grown in a Constant Cell density Apparatus were determined. Suitable methodology to prepare proteins from which three major undesirable components of these cells (i.e., cell walls, nucleic acids, and pigments) were either removed or substantially reduced was developed. Results showed that processing of green algae to protein isolate enhances its potential nutritional and organoleptic acceptability as a diet component in a Controlled Ecological Life Support System.

  15. Using virtual reality to provide health care information to people with intellectual disabilities: acceptability, usability, and potential utility.

    Science.gov (United States)

    Hall, Valerie; Conboy-Hill, Suzanne; Taylor, Dave

    2011-11-14

    People with intellectual disabilities have poor access to health care, which may be further compromised by a lack of accessible health information. To be effective, health information must be easily understood and remembered. People with intellectual disabilities learn better from multimodal information sources, and virtual reality offers a 3-dimensional (3D) computer-generated environment that can be used for providing information and learning. To date, research into virtual reality experiences for people with intellectual disabilities has been limited to skill-based training and leisure opportunities within the young to mid age ranges. This study assessed the acceptability, usability, and potential utility of a virtual reality experience as a means of providing health care-related information to people with intellectual disabilities. We designed a prototype multimodal experience based on a hospital scenario and situated on an island in the Second Life 3D virtual world. We wanted to know how people of different ages and with varying levels of cognitive function would participate in the customized virtual environment, what they understood from being there, and what they remembered a week later. The study drew on qualitative data. We used a participatory research approach that involved working alongside people with intellectual disabilities and their supporters in a community setting. Cognitive function was assessed, using the Matrix Analogies Test and the British Picture Vocabulary Scale, to describe the sample. Participants, supported by facilitators, were video recorded accessing and engaging with the virtual environment. We assessed recall 1 week later, using a specialized interview technique. Data were downloaded into NVivo 8 and analyzed using the framework analysis technique. Study participants were 20 people aged between 20 and 80 years with mild to severe intellectual disabilities. All participants were able to access the environment and voluntarily stayed

  16. Using Virtual Reality to Provide Health Care Information to People With Intellectual Disabilities: Acceptability, Usability, and Potential Utility

    Science.gov (United States)

    Conboy-Hill, Suzanne; Taylor, Dave

    2011-01-01

    Background People with intellectual disabilities have poor access to health care, which may be further compromised by a lack of accessible health information. To be effective, health information must be easily understood and remembered. People with intellectual disabilities learn better from multimodal information sources, and virtual reality offers a 3-dimensional (3D) computer-generated environment that can be used for providing information and learning. To date, research into virtual reality experiences for people with intellectual disabilities has been limited to skill-based training and leisure opportunities within the young to mid age ranges. Objective This study assessed the acceptability, usability, and potential utility of a virtual reality experience as a means of providing health care-related information to people with intellectual disabilities. We designed a prototype multimodal experience based on a hospital scenario and situated on an island in the Second Life 3D virtual world. We wanted to know how people of different ages and with varying levels of cognitive function would participate in the customized virtual environment, what they understood from being there, and what they remembered a week later. Methods The study drew on qualitative data. We used a participatory research approach that involved working alongside people with intellectual disabilities and their supporters in a community setting. Cognitive function was assessed, using the Matrix Analogies Test and the British Picture Vocabulary Scale, to describe the sample. Participants, supported by facilitators, were video recorded accessing and engaging with the virtual environment. We assessed recall 1 week later, using a specialized interview technique. Data were downloaded into NVivo 8 and analyzed using the framework analysis technique. Results Study participants were 20 people aged between 20 and 80 years with mild to severe intellectual disabilities. All participants were able to access

  17. The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome.

    Science.gov (United States)

    Dang, Dien; Cunnington, David; Swieca, John

    2011-01-01

    The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs. A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated. Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures. This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

  18. Airway Peroxidases Catalyze Nitration of the β2-Agonist Salbutamol and Decrease Its Pharmacological Activity

    OpenAIRE

    Reszka, Krzysztof J.; Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.

    2011-01-01

    β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hy...

  19. Dopamine Agonists and Pathologic Behaviors

    Directory of Open Access Journals (Sweden)

    Brendan J. Kelley

    2012-01-01

    Full Text Available The dopamine agonists ropinirole and pramipexole exhibit highly specific affinity for the cerebral dopamine D3 receptor. Use of these medications in Parkinson’s disease has been complicated by the emergence of pathologic behavioral patterns such as hypersexuality, pathologic gambling, excessive hobbying, and other circumscribed obsessive-compulsive disorders of impulse control in people having no history of such disorders. These behavioral changes typically remit following discontinuation of the medication, further demonstrating a causal relationship. Expression of the D3 receptor is particularly rich within the limbic system, where it plays an important role in modulating the physiologic and emotional experience of novelty, reward, and risk assessment. Converging neuroanatomical, physiological, and behavioral science data suggest the high D3 affinity of these medications as the basis for these behavioral changes. These observations suggest the D3 receptor as a therapeutic target for obsessive-compulsive disorder and substance abuse, and improved understanding of D3 receptor function may aid drug design of future atypical antipsychotics.

  20. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg

    2007-01-01

    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  1. [Comparison of potential yield and resource utilization efficiency of main food crops in three provinces of Northeast China under climate change].

    Science.gov (United States)

    Wang, Xiao-yu; Yang, Xiao-guang; Sun, Shuang; Xie, Wen-juan

    2015-10-01

    Based on the daily data of 65 meteorological stations from 1961 to 2010 and the crop phenology data in the potential cultivation zones of thermophilic and chimonophilous crops in Northeast China, the crop potential yields were calculated through step-by-step correction method. The spatio-temporal distribution of the crop potential yields at different levels was analyzed. And then we quantified the limitations of temperature and precipitation on the crop potential yields and compared the differences in the climatic resource utilization efficiency. The results showed that the thermal potential yields of six crops (including maize, rice, spring wheat, sorghum, millet and soybean) during the period 1961-2010 deceased from west to east. The climatic potential yields of the five crops (spring wheat not included) were higher in the south than in the north. The potential yield loss rate due to temperature limitations of the six crops presented a spatial distribution pattern and was higher in the east than in the west. Among the six main crops, the yield potential loss rate due to temperature limitation of the soybean was the highest (51%), and those of the other crops fluctuated within the range of 33%-41%. The potential yield loss rate due to water limitation had an obvious regional difference, and was high in Songnen Plain and Changbai Mountains. The potential yield loss rate of spring wheat was the highest (50%), and those of the other four rainfed crops fluctuated within the range of 8%-10%. The solar energy utilization efficiency of the six main crops ranged from 0.9% to 2.7%, in the order of maize> sorghum>rice>millet>spring wheat>soybean. The precipitation utilization efficiency of the maize, sorghum, spring wheat, millet and soybean under rainfed conditions ranged from 8 to 35 kg . hm-2 . mm-1, in the order of maize>sorghum>spring wheat>millet>soybean. In those areas with lower efficiency of solar energy utilization and precipitation utilization, such as Changbai

  2. Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

    Science.gov (United States)

    Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

    2015-11-18

    Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

  3. Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

    Science.gov (United States)

    Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

    2011-03-01

    Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  4. Progress in the development of histamine H3 receptor antagonists/inverse agonists: a patent review (2013-2017).

    Science.gov (United States)

    Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

    2018-03-01

    Since years, ligands blocking histamine H 3 receptor (H 3 R) activity (antagonists/inverse agonists) are interesting targets in the search for new cures for CNS disorders. Intensive works done by academic and pharmaceutical company researchers have led to many potent and selective H 3 R antagonists/inverse agonists. Some of them have reached to clinical trials. Areas covered: Patent applications from January 2013 to September 2017 and the most important topics connected with H 3 R field are analysed. Espacenet, Patentscope, Pubmed, GoogleScholar or Cochrane Library online databases were principially used to collect all the materials. Expert opinion: The research interest in histamine H 3 R field is still high although the number of patent applications has decreased during the past 4 years (around 20 publications). Complexity of histamine H 3 R biology e.g. many isoforms, constitutive activity, heteromerization with other receptors (dopamine D 2 , D 1 , adenosine A 2A ) and pharmacology make not easy realization and evaluation of therapeutic potential of anti-H 3 R ligands. First results from clinical trials have verified potential utility of histamine H 3 R antagonist/inverse agonists in some diseases. However, more studies are necessary for better understanding of an involvement of the histaminergic system in CNS-related disorders and helping more ligands approach to clinical trials and the market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor; hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase; MAO - monoamine oxidase.

  5. Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

    Science.gov (United States)

    Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

    2009-06-01

    In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

  6. Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

    DEFF Research Database (Denmark)

    Goncalves de Azavedo, Carlos M. B. P.; Watterson, Kenneth R; Wargent, Ed T

    2016-01-01

    The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure......-activity relationship studies of a previously disclosed non-acidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although...... a significant fraction of these non-carboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice...

  7. Potentialities of biotechnology for the reduction and utilization for energy purposes of wastes generated by food industry

    Energy Technology Data Exchange (ETDEWEB)

    1982-10-19

    The study dealt with the present trends in biotechnology related to the methods for the reduction and utilization, for energy purposes, of wastes generated by food industry and to the methods for controlling the emission of pollutants from industrial plants with emphasis on meat industry, dairy industry, food-packing trade, sugar industry, vinification, fatty foods, fish meal, beverage industry.

  8. Case Studies of Potential Facility-Scale and Utility-Scale Non-Hydro Renewable Energy Projects across Reclamation

    Energy Technology Data Exchange (ETDEWEB)

    Haase, S.; Burman, K.; Dahle, D.; Heimiller, D.; Jimenez, A.; Melius, J.; Stoltenberg, B.; VanGeet, O.

    2013-05-01

    This report summarizes the results of an assessment and analysis of renewable energy opportunities conducted for the U.S. Department of the Interior, Bureau of Reclamation by the National Renewable Energy Laboratory. Tasks included assessing the suitability for wind and solar on both a utility and facility scale.

  9. Nest-building behavior of Monk Parakeets and insights into potential mechanisms for reducing damage to utility poles

    Directory of Open Access Journals (Sweden)

    Kevin R. Burgio

    2014-09-01

    Full Text Available The Monk Parakeet (Myiopsitta monachus commonly uses utility poles as a substrate for building large, bulky nests. These nests often cause fires and electric power outages, creating public safety risks and increasing liability and maintenance costs for electric companies. Previous research has focused on lethal methods and chemical contraception to prevent nesting on utility poles and electrical substations. However, implementation of lethal methods has led to public protests and lawsuits, while chemical contraception may affect other than the targeted species, and must be continually reapplied for effectiveness. One non-lethal alternative, nest removal, is costly and may not be a sustainable measure if Monk Parakeet populations continue to grow. In order to identify cost-effective non-lethal solutions to problems caused by Monk Parakeet nesting, we studied their behavior as they built nests on utility poles. Monk Parakeets initiate nests by attaching sticks at the intersection of the pole and electric lines. We found that parakeets use the electric lines exclusively to gain access to the intersection of lines and pole during nest initiation, and continue to use the lines intensively throughout construction. Monk Parakeets also have more difficulty attaching sticks during the early stages of nest construction than when the nest is nearing completion. These findings suggest that intervention during the earlier stages of nest building, by excluding Monk Parakeets from electric lines adjacent to poles, may be an effective, non-lethal method of reducing or eliminating parakeets nesting on, and damaging, utility poles.

  10. PPAR Agonists and Metabolic Syndrome: An Established Role?

    Directory of Open Access Journals (Sweden)

    Margherita Botta

    2018-04-01

    Full Text Available Therapeutic approaches to metabolic syndrome (MetS are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs, blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C. PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug–drug interactions (i.e., gemfibrozil and myopathy should also be acknowledged.

  11. Development of specific dopamine D-1 agonists and antagonists

    International Nuclear Information System (INIS)

    Sakolchai, S.

    1987-01-01

    To develop potentially selective dopamine D-1 agonists and to investigate on the structural requirement for D-1 activity, the derivatives of dibenzocycloheptadiene are synthesized and pharmacologically evaluated. The target compounds are 5-aminomethyl-10,11-dihydro-1,2-dihydroxy-5H-dibenzo[a,d]cycloheptene hydrobromide 10 and 9,10-dihydroxy-1,2,3,7,8,12b-hexahydrobenzo[1,2]cyclohepta[3,4,5d,e]isoquinoline hydrobromide 11. In a dopamine-sensitive rat retinal adenylate cyclase assay, a model for D-1 activity, compound 10 is essentially inert for both agonist and antagonist activity. In contrast, compound 11 is approximately equipotent to dopamine in activation of the D-1 receptor. Based on radioligand and binding data, IC 50 of compound 11 for displacement of 3 H-SCH 23390, a D-1 ligand, is about 7 fold less than that for displacement of 3 H-spiperone, a D-2 ligand. These data indicate that compound 11 is a potent selective dopamine D-1 agonist. This study provides a new structural class of dopamine D-1 acting agent: dihydroxy-benzocycloheptadiene analog which can serve as a lead compound for further drug development and as a probe for investigation on the nature of dopamine D-1 receptor

  12. Complete genome sequence of Burkholderia sp. strain PAMC28687, a potential octopine-utilizing bacterium isolated from Antarctica lichen.

    Science.gov (United States)

    Han, So-Ra; Yu, Sang-Cheol; Ahn, Do-Hwan; Park, Hyun; Oh, Tae-Jin

    2016-05-20

    We report the complete genome sequence of Burkholderia sp. PAMC28687, which was isolated from the Antarctica lichen Useea sp., for better understanding of its catabolic traits in utilizing octopine as a source of carbon/nitrogen between Burkholderia and lichen. The genome consists of three circular chromosomes with five circular plasmids for the total 6,881,273bp sized genome with a G+C content of 58.14%. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A snapshot into the uptake and utilization of potential oligosaccharide prebiotics by probiotic lactobacilli and bifidobacteria as accessed by transcriptomics, functional genomics, and recombinant protein characterization

    DEFF Research Database (Denmark)

    Andersen, Joakim Mark

    and lifestyle diseases are currently well documented. Selective utilization, of primarily non-digestible carbohydrates, termed prebiotics, by probiotics has been identified as an attribute of probiotic action, however the molecular mechanisms of prebiotics utilization and in particular the specificities...... of carbohydrate transporters and glycoside hydrolases that confer this remain largely unknown, limiting a robust understanding for the basis of selective utilization of known prebiotics and the discovery and documentation of novel prebiotics. The aim of this Ph.D. thesis was to identify the genes involved...... with uptake and catabolism of potential prebiotics by the probiotics Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bl-04 as model organisms, using DNA whole genome microarrays and by in silico pathway re-construction to identify key genes for further functional analysis by gene...

  14. Investigations of potential microbial methanogenic and carbon monoxide utilization pathways in ultra-basic reducing springs associated with present-day continental serpentinization: the Tablelands, NL, CAN

    Directory of Open Access Journals (Sweden)

    Penny Lea Morrill

    2014-11-01

    Full Text Available Ultra-basic reducing springs at continental sites of serpentinization act as portals into the biogeochemistry of a subsurface environment with H2 and CH4 present. Very little, however, is known about the carbon substrate utilization, energy sources, and metabolic pathways of the microorganisms that live in this ultra-basic environment. The potential for microbial methanogenesis with bicarbonate, formate, acetate, and propionate precursors and carbon monoxide (CO utilization pathways were tested in laboratory experiments by adding substrates to water and sediment from the Tablelands, NL, CAD, a site of present-day continental serpentinization. Microbial methanogenesis was not observed after bicarbonate, formate, acetate, or propionate addition. CO was consumed in the live experiments but not in the killed controls and the residual CO in the live experiments became enriched in 13 C. The average isotopic enrichment factor resulting from this microbial utilization of CO was estimated to be 11.2 ± 0.2‰. Phospholipid fatty acid concentrations and δ13C values suggest limited incorporation of carbon from CO into microbial lipids. This indicates that in our experiments, CO was used primarily as an energy source, but not for biomass growth. Environmental DNA sequencing of spring fluids collected at the same time as the addition experiments yielded a large proportion of Hydrogenophaga-related sequences, which is consistent with previous metagenomic data indicating the potential for these taxa to utilize CO.

  15. Investigations of potential microbial methanogenic and carbon monoxide utilization pathways in ultra-basic reducing springs associated with present-day continental serpentinization: the Tablelands, NL, CAN.

    Science.gov (United States)

    Morrill, Penny L; Brazelton, William J; Kohl, Lukas; Rietze, Amanda; Miles, Sarah M; Kavanagh, Heidi; Schrenk, Matthew O; Ziegler, Susan E; Lang, Susan Q

    2014-01-01

    Ultra-basic reducing springs at continental sites of serpentinization act as portals into the biogeochemistry of a subsurface environment with H2 and CH4 present. Very little, however, is known about the carbon substrate utilization, energy sources, and metabolic pathways of the microorganisms that live in this ultra-basic environment. The potential for microbial methanogenesis with bicarbonate, formate, acetate, and propionate precursors and carbon monoxide (CO) utilization pathways were tested in laboratory experiments by adding substrates to water and sediment from the Tablelands, NL, CAD, a site of present-day continental serpentinization. Microbial methanogenesis was not observed after bicarbonate, formate, acetate, or propionate addition. CO was consumed in the live experiments but not in the killed controls and the residual CO in the live experiments became enriched in (13)C. The average isotopic enrichment factor resulting from this microbial utilization of CO was estimated to be 11.2 ± 0.2‰. Phospholipid fatty acid concentrations and δ(13)C values suggest limited incorporation of carbon from CO into microbial lipids. This indicates that in our experiments, CO was used primarily as an energy source, but not for biomass growth. Environmental DNA sequencing of spring fluids collected at the same time as the addition experiments yielded a large proportion of Hydrogenophaga-related sequences, which is consistent with previous metagenomic data indicating the potential for these taxa to utilize CO.

  16. The Potential to Forgo Social Welfare Gains through Over reliance on Cost Effectiveness/Cost Utility Analyses in the Evidence Base for Public Health

    International Nuclear Information System (INIS)

    Cohen, D.R.; Patel, N.

    2010-01-01

    Economic evaluations of clinical treatments most commonly take the form of cost effectiveness or cost utility analyses. This is appropriate since the main sometimes the only benefit of such interventions is increased health. The majority of economic evaluations in public health, however, have also been assessed using these techniques when arguably cost benefit analyses would in many cases have been more appropriate, given its ability to take account of non health benefits as well. An examination of the non health benefits from a sample of studies featured in a recent review of economic evaluations in public health illustrates how over focusing on cost effectiveness/cost utility analyses may lead to forgoing potential social welfare gains from programmes in public health. Prior to evaluation, programmes should be considered in terms of the potential importance of non health benefits and where these are considerable would be better evaluated by more inclusive economic evaluation techniques.

  17. Scaffold-based pan-agonist design for the PPARα, PPARβ and PPARγ receptors.

    Directory of Open Access Journals (Sweden)

    Li-Song Zhang

    Full Text Available As important members of nuclear receptor superfamily, Peroxisome proliferator-activated receptors (PPAR play essential roles in regulating cellular differentiation, development, metabolism, and tumorigenesis of higher organisms. The PPAR receptors have 3 identified subtypes: PPARα, PPARβ and PPARγ, all of which have been treated as attractive targets for developing drugs to treat type 2 diabetes. Due to the undesirable side-effects, many PPAR agonists including PPARα/γ and PPARβ/γ dual agonists are stopped by US FDA in the clinical trials. An alternative strategy is to design novel pan-agonist that can simultaneously activate PPARα, PPARβ and PPARγ. Under such an idea, in the current study we adopted the core hopping algorithm and glide docking procedure to generate 7 novel compounds based on a typical PPAR pan-agonist LY465608. It was observed by the docking procedures and molecular dynamics simulations that the compounds generated by the core hopping and glide docking not only possessed the similar functions as the original LY465608 compound to activate PPARα, PPARβ and PPARγ receptors, but also had more favorable conformation for binding to the PPAR receptors. The additional absorption, distribution, metabolism and excretion (ADME predictions showed that the 7 compounds (especially Cpd#1 hold high potential to be novel lead compounds for the PPAR pan-agonist. Our findings can provide a new strategy or useful insights for designing the effective pan-agonists against the type 2 diabetes.

  18. Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant—Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation

    Directory of Open Access Journals (Sweden)

    Bélin Poletto Mezzomo

    2015-12-01

    Full Text Available In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o. or with a single intraperitoneal (i.p. injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed. This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling.

  19. Potential of utilizing asphalt dust waste as filler material in the production of sustainable self compacting concrete (SCC)

    Science.gov (United States)

    Ismail, Isham; Shahidan, Shahiron; Bahari, Nur Amira Afiza Saiful

    2017-12-01

    Waste materials from many industries are widely used in the production of sustainable green concrete. Utilizing asphalt dust waste (ADW) as a filler material in the development of self-compacting concrete (SCC) is one of the alternative solutions for reducing environmental waste. SCC is an innovative concrete that does not require vibration for placing and compaction. However, there is limited information on the effects of utilizing ADW in the development of SCC. Therefore, this research study examines the effects of various w/b ratios (0.2, 0.3 and 0.4) and differing amounts of ADW (0% to 50%) on the rheological properties of fresh state concrete. The compressive strength of the SCC was tested only for 7 and 28 days as preliminary studies. The results revealed that mixtures MD730, MD740 and MD750 showed satisfactory results for the slump flow, J-Ring, L-Box and V-Funnel test during the fresh state. The compressive strength values obtained after 28 days for MD730, MD740 and MD750 were 35.1 MPa, 36.8 MPa and 29.4 MPa respectively. In conclusion, the distribution of materials in mixtures has significant effect in achieving rheological properties and compressive strength of SCC.

  20. Melatonin Receptor Agonists as the “Perioceutics” Agents for Periodontal Disease through Modulation of Porphyromonas gingivalis Virulence and Inflammatory Response

    Science.gov (United States)

    Zhu, Cai-Lian; He, Zhi-Yan; Liang, Jing-Ping; Song, Zhong-Chen

    2016-01-01

    Aim “Perioceutics” including antimicrobial therapy and host modulatory therapy has emerged as a vital adjunctive treatment of periodontal disease. Melatonin level was significantly reduced in patients with periodontal diseases suggesting melatonin could be applied as a potential “perioceutics” treatment of periodontal diseases. This study aims to investigate the effects of melatonin receptor agonists (melatonin and ramelteon) on Porphyromonas gingivalis virulence and Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced inflammation. Methods Effects of melatonin receptor agonists on Porphyromonas gingivalis planktonic cultures were determined by microplate dilution assays. Formation, reduction, and viability of Porphyromonas gingivalis biofilms were detected by crystal violet staining and MTT assays, respectively. Meanwhile, biofilms formation was also observed by confocal laser scanning microscopy (CLSM). The effects on gingipains and hemolytic activities of Porphyromonas gingivalis were evaluated using chromogenic peptides and sheep erythrocytes. The mRNA expression of virulence and iron/heme utilization was assessed using RT-PCR. In addition, cell viability of melatonin receptor agonists on human gingival fibroblasts (HGFs) was evaluated by MTT assays. After pretreatment of melatonin receptor agonists, HGFs were stimulated with Pg-LPS and then release of cytokines (IL-6 and lL-8) was measured by enzyme-linked immunosorbent assay (ELISA). Results Melatonin and ramelteon did exhibit antimicrobial effects against planktonic culture. Importantly, they inhibited biofilm formation, reduced the established biofilms, and decreased biofilm viability of Porphyromonas gingivalis. Furthermore, they at sub-minimum inhibitory concentration (sub-MIC) concentrations markedly inhibited the proteinase activities of gingipains and hemolysis in a dose-dependent manner. They at sub-MIC concentrations significantly inhibited the mRNA expression of virulence

  1. Small-molecule AT2 receptor agonists

    DEFF Research Database (Denmark)

    Hallberg, Mathias; Sumners, Colin; Steckelings, U Muscha

    2018-01-01

    The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist...... with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8......, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also...

  2. Protective effects of the angiotensin II ATreceptor agonist compound 21 in ischemic stroke

    DEFF Research Database (Denmark)

    Bennion, Douglas M; Jones, Chad H; Dang, Alex N

    2018-01-01

    ) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2receptor agonists are blood-brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver...... in certain human central nervous system diseases, the N2B application of AT2receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.......-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective...

  3. Utilization of by-products from the tequila industry. Part 2: Potential value of Agave tequilana Weber azul leaves.

    Science.gov (United States)

    Iñiguez-Covarrubias, G; Díaz-Teres, R; Sanjuan-Dueñas, R; Anzaldo-Hernández, J; Rowell, R M

    2001-04-01

    The leaves of the agave plant are left in the field after harvesting the heads for tequila production. Different types of agave leaves were isolated, classified, and their content in the total plant determined. The usable fractions were collected and their properties determined. Of the total wet weight of the agave plant, 54% corresponds to the agave head, 32% corresponds to materials which could be usable for sugar and fiber production which leaves 14% of the wet plant without apparent utility. The fractions with higher total reducing sugars (TRS) content were the fresh fraction of partially dry leaves stuck to the head and the leaf bases with a TRS content of 16.1% and 13.1%, respectively. The highest TRS concentration (16-28%) is in the agave head which is used for tequila production. The leaves are 90-120 cm long and 8-12 cm wide and contain fiber bundles that are 23-52 cm long and 0.6-13 mm wide. The ultimate fiber length is approximately 1.6 mm with an average width of 25 microns. There are several types of leaf fibers that can be utilized depending on what part of the plant they come from and what product is desired. Agave leaf fibers were pulped using a soda pulping process and the pulp was hand formed into test sheets. Test sheets made from pulped agave leaf fibers had a breaking length comparable to paper made from both pine and eucalyptus fibers, but the tear index and burst index were lower than the other two papers.

  4. Growth patterns reflect response to antiretroviral therapy in HIV-positive infants: potential utility in resource-poor settings.

    Science.gov (United States)

    Benjamin, D K; Miller, W C; Ryder, R W; Weber, D J; Walter, E; McKinney, R E

    2004-01-01

    Laboratory monitoring of HIV-infected children is the current standard of care in the United States to guide the appropriate use of antiretroviral therapy (ART). Although ART is becoming a reality in some developing countries, laboratory monitoring of ART is costly, necessitating creative approaches to monitoring. As an initial step to guide monitoring of HIV progression in low resource settings, we assessed the utility of the physical examination to predict clinical progression of HIV. We conducted a retrospective cohort study of HIV-infected children using data from Pediatric AIDS Clinical Trials Group Protocol 300. We developed a clinical predictive model, and compared the utility of the clinical model to the change in HIV RNA viral load as diagnostic tests of ART failure. The clinical model incorporated treatment regimen, age, and height velocity: a three-level clinical predictive model provided likelihood ratios of 0.3, 3.9, and 14. For decline in RNA the likelihood ratios were 0.2 (> 1 log decline), 1.4, and 3.5 (> log increase). We developed a simple clinical predictive model that was able to predict clinical progression of HIV after initiation of new ART. The clinical model performed similarly to using changes in HIV RNA viral load. These data should be validated internationally and prospectively, because the test subjects were from a resource rich environment and growth patterns in undernourished children may be impacted differently by HIV and its treatment. The model was most pertinent to children 36 months of age or younger, and was conducted in children receiving monotherapy and dual therapy.

  5. Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

    Science.gov (United States)

    Williams, W C; Copeland, C; Boykin, E; Quell, S J; Lehmann, D M

    2015-01-01

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [(3) H]methyl thymidine. A more recent non-isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation in vivo. To further improve the utility of this assay, we developed an ex vivo BrdU labeling procedure eliminating the need for in vivo injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non-sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the in vivo LLNA:BrdU-enzyme-linked immunosorbent assay labeling procedure. We also used the ex vivo BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and cis-diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC2 values. We conclude that this ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  6. Discovery of a potent and selective GPR120 agonist

    DEFF Research Database (Denmark)

    Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel

    2012-01-01

    GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation...... is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist....

  7. Energy supply and demand in Uruguay River basin and the potential impact of its utilization over hydric resources

    International Nuclear Information System (INIS)

    Lanna, Antonio Eduardo

    1992-01-01

    This paper focuses the Brazilian piece of Rio Uruguay emphasizing its great energy potential for hydroelectric power generation. In order to solve problems with energy demand, another sources of energy are suggested for composing together hydroelectric power the energy matrix. The environmental aspects are also considered. 2 refs., 9 tabs

  8. The Relationship between Weather and Lunar Changes on Student Achievement and Measures School Districts Utilize to Combat Potential Impact

    Science.gov (United States)

    Stuart, Kendra

    2013-01-01

    Classroom disruptions present an obstacle to raising student achievement for teachers and school administrators. This study was designed to investigate potential relationships between weather, specifically barometric pressure, or the lunar cycle, and whether either had a direct correlation with student discipline referrals. The intent was to…

  9. Potentials for the production of industrial basic material from native tuber crops and perspectives for their utilization

    Energy Technology Data Exchange (ETDEWEB)

    Schittenhelm, S.; Dambroth, M.

    1984-01-01

    In the present paper the potentials of native tuber crops for the production of raw material for the industry are discussed and the first results presented. The following points are especially important: Based on their high yield potential the potato and the Jerusalem artichoke are especially valuable as industrial crops. First breeding results with potato show that improvements in tuber yield, which are necessary for a better competitive ability are possible. To what extent hybrids between our cultivated potato and different primitive forms can be used as industrial potatoes has to be tested. In order to reduce production input the resistance against nematodes and lade blight is most important for the production of basic populations of potatoes for industrial purposes. The succes of breeding Jerusalem artichoke depends on solving the problems of bad seed set.

  10. Potential of energetic utilization of grains residual biomass; Potencial de utilizacao energetica de biomassa residual de graos

    Energy Technology Data Exchange (ETDEWEB)

    Mourad, Anna L. [Instituto de Tecnologia de Alimentos (ITAL), Campinas, SP (Brazil). Centro de Tecnologia de Embalagem], e-mail: anna@ital.sp.gov.br; Ambrogi, Vinicius S.; Guerra, Sinclair M.G. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Engenharia Mecanica], e-mail: ambrogi@fem.unicamp.br, e-mail: sguerra@fem.unicamp.br

    2004-07-01

    The biomass resulting from the rejected parts of grains, as straw and peel of rice, corn, wheat, soy, all great cultivations in the country, has potential to be takes advantage as energy. It was considered that the contribution of this residual biomass is near of 167,8 million GJ/year, value that could be added to the use already established of the cane bagasse for energy purpose (658 million GJ, in 2001). This energy can be used for drying of these same grains (energy expense estimate of 67 million GJ), currently obtained from oil. It can also substitute the fuel oil used in the agricultural section, in the industries of food and beverage, ceramic and textile (sections that consumed 67.822 GJ in 2001). In Sao Paulo state the regions with greater potential to install biomass plants are located in Assis, Avare and Itapeva EDR (regional development office). (author)

  11. Cold suppresses agonist-induced activation of TRPV1.

    Science.gov (United States)

    Chung, M-K; Wang, S

    2011-09-01

    Cold therapy is frequently used to reduce pain and edema following acute injury or surgery such as tooth extraction. However, the neurobiological mechanisms of cold therapy are not completely understood. Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and pathological pain under conditions of inflammation or injury. Although capsaicin-induced nociception, neuropeptide release, and ionic currents are suppressed by cold, it is not known if cold suppresses agonist-induced activation of recombinant TRPV1. We demonstrate that cold strongly suppressed the activation of recombinant TRPV1 by multiple agonists and capsaicin-evoked currents in trigeminal ganglia neurons under normal and phosphorylated conditions. Cold-induced suppression was partially impaired in a TRPV1 mutant that lacked heat-mediated activation and potentiation. These results suggest that cold-induced suppression of TRPV1 may share a common molecular basis with heat-induced potentiation, and that allosteric inhibition may contribute, in part, to the cold-induced suppression. We also show that combination of cold and a specific antagonist of TRPV1 can produce an additive suppression. Our results provide a mechanistic basis for cold therapy and may enhance anti-nociceptive approaches that target TRPV1 for managing pain under inflammation and tissue injury, including that from tooth extraction.

  12. Aquatic Insects of New York Salt Marsh Associated with Mosquito Larval Habitat and their Potential Utility as Bioindicators

    OpenAIRE

    Rochlin, Ilia; Dempsey, Mary E.; Iwanejko, Tom; Ninivaggi, Dominick V.

    2011-01-01

    The aquatic insect fauna of salt marshes is poorly characterized, with the possible exception of biting Diptera. Aquatic insects play a vital role in salt marsh ecology, and have great potential importance as biological indicators for assessing marsh health. In addition, they may be impacted by measures to control mosquitoes such as changes to the marsh habitat, altered hydrology, or the application of pesticides. Given these concerns, the goals of this study were to conduct the first taxonom...

  13. Promotion Effect of Asian Dust on Phytoplankton Growth and Potential Dissolved Organic Phosphorus Utilization in the South China Sea

    Science.gov (United States)

    Chu, Qiang; Liu, Ying; Shi, Jie; Zhang, Chao; Gong, Xiang; Yao, Xiaohong; Guo, Xinyu; Gao, Huiwang

    2018-03-01

    Dust deposition is an important nutrient source to the South China Sea (SCS), but few in situ experiments were conducted on phytoplankton response to the deposition. We conducted onboard incubation experiments at three stations near Luzon Strait in the SCS, with addition of multiple dissolved inorganic nutrients, Asian dust, and rainwater. From our results, nitrogen and phosphorus were both urgently needed for phytoplankton growth in the SCS, indicated by the evident Chl a response to the addition of nitrogen and phosphorus together. Almost no evident response was observed by adding phosphorus or iron alone to incubation waters, although a delayed response of Chl a in mass concentration was observed by adding nitrogen alone. The latter implied a possible utilization of dissolved organic phosphorus because of insufficient dissolved inorganic phosphorus in incubation waters. Under such nutrient condition, Asian dust showed an apparent promotion effect on phytoplankton growth by providing sufficient amounts of nitrogen but low phosphorus. Meanwhile, it was found that large sized (> 5 μm) phytoplankton community showed different responses to dust addition at different stations. At stations A3 and A6, Chaetoceros spp. became the dominant species during the bloom period, while at station WG2, Nitzschia spp. became dominant. In combination with different initial nutrients and Chl a levels at the three stations, the different phytoplankton community evolution implied the response difference to external inputs between oligotrophic (stations A3 and A6) and ultraoligotrophic (station WG2) conditions in the SCS.

  14. Reciprocity of agonistic support in ravens.

    Science.gov (United States)

    Fraser, Orlaith N; Bugnyar, Thomas

    2012-01-01

    Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals.

  15. Endophytic Bacteria Associated with Hieracium piloselloides: Their Potential for Hydrocarbon-Utilizing and Plant Growth-Promotion.

    Science.gov (United States)

    Pawlik, Małgorzata; Piotrowska-Seget, Zofia

    2015-01-01

    The aim of this study was to assess the potential of 18 crude-oil-degrading endophytic bacteria for removal of hydrocarbons and promotion of plant growth. Strains were isolated from Hieracium piloselloides (tall hawkweed), which grows in soil heavily polluted with petroleum hydrocarbons. Bacteria from the genus Pseudomonas were abundant among the isolates. The potential for hydrocarbon degradation was evaluated by polymerase chain reaction (PCR) analyses of the genes alkB, alkH, C23O, P450, and pah. It was found that 88.89% of the endophytic bacteria contained gene-encoding polycyclic aromatic hydrocarbon (PAH) initial dioxygenase, 61% possessed the 2,3-catechol dioxygenase gene, and 39% of strains that were tested had the cytochrome P-450 hydroxylase gene. All isolates were capable of producing indole-3-acetic acid (1.8-76.4 μg/ml). Only 17% of them were able to produce siderophores, excrete cellulase, and solubilize phosphate. Hydrogen cyanide synthesis occurred in 33% of endophytic bacteria. The 1-aminocyclopropane-1-carboxylate deaminase activity in isolates that were screened was in the range of 2.6 to 74.1 μmol α-ketobutyrate/mg/h. This feature of the bacteria indicated that isolates may enhance the phytoremediation process. Data suggest that crude-oil-degrading endophytic bacteria possess potential to be promising candidates for enhancement of phytoremediation of hydrocarbon-contaminated soil. Further evaluation of these bacteria is needed in order to assess the role played in the degradation of petroleum hydrocarbons.

  16. Theoretical potential for low energy consumption phase change memory utilizing electrostatically-induced structural phase transitions in 2D materials

    Science.gov (United States)

    Rehn, Daniel A.; Li, Yao; Pop, Eric; Reed, Evan J.

    2018-01-01

    Structural phase-change materials are of great importance for applications in information storage devices. Thermally driven structural phase transitions are employed in phase-change memory to achieve lower programming voltages and potentially lower energy consumption than mainstream nonvolatile memory technologies. However, the waste heat generated by such thermal mechanisms is often not optimized, and could present a limiting factor to widespread use. The potential for electrostatically driven structural phase transitions has recently been predicted and subsequently reported in some two-dimensional materials, providing an athermal mechanism to dynamically control properties of these materials in a nonvolatile fashion while achieving potentially lower energy consumption. In this work, we employ DFT-based calculations to make theoretical comparisons of the energy required to drive electrostatically-induced and thermally-induced phase transitions. Determining theoretical limits in monolayer MoTe2 and thin films of Ge2Sb2Te5, we find that the energy consumption per unit volume of the electrostatically driven phase transition in monolayer MoTe2 at room temperature is 9% of the adiabatic lower limit of the thermally driven phase transition in Ge2Sb2Te5. Furthermore, experimentally reported phase change energy consumption of Ge2Sb2Te5 is 100-10,000 times larger than the adiabatic lower limit due to waste heat flow out of the material, leaving the possibility for energy consumption in monolayer MoTe2-based devices to be orders of magnitude smaller than Ge2Sb2Te5-based devices.

  17. Genome and metagenome enabled analyses reveal new insight into the global biogeography and potential urea utilization in marine Thaumarchaeota.

    Science.gov (United States)

    Ahlgren, N.; Parada, A. E.; Fuhrman, J. A.

    2016-02-01

    Marine Thaumarchaea are an abundant, important group of marine microbial communities as they fix carbon, oxidize ammonium, and thus contribute to key N and C cycles in the oceans. From an enrichment culture, we have sequenced the complete genome of a new Thaumarchaeota strain, SPOT01. Analysis of this genome and other Thaumarchaeal genomes contributes new insight into its role in N cycling and clarifies the broader biogeography of marine Thaumarchaeal genera. Phylogenomics of Thaumarchaeota genomes reveal coherent separation into clusters roughly equivalent to the genus level, and SPOT01 represents a new genus of marine Thaumarchaea. Competitive fragment recruitment of globally distributed metagenomes from TARA, Ocean Sampling Day, and those generated from a station off California shows that the SPOT01 genus is often the most abundant genus, especially where total Thaumarchaea are most abundant in the overall community. The SPOT01 genome contains urease genes allowing it to use an alternative form of N. Genomic and metagenomic analysis also reveal that among planktonic genomes and populations, the urease genes in general are more frequently found in members of the SPOT01 genus and another genus dominant in deep waters, thus we predict these two genera contribute most significantly to urea utilization among marine Thaumarchaea. Recruitment also revealed broader biogeographic and ecological patterns of the putative genera. The SPOT01 genus was most abundant at colder temperatures (45 degrees). The genus containing Nitrosopumilus maritimus had the highest temperature range, and the genus containing Candidatus Nitrosopelagicus brevis was typically most abundant at intermediate temperatures and intermediate latitudes ( 35-45 degrees). Together these genome and metagenome enabled analyses provide significant new insight into the ecology and biogeochemical contributions of marine archaea.

  18. Utilization of controllable load for system operations services - Potential in the power system; Utnyttjande av styrbara laster foer systemdrifttjaenster - Potential i kraftsystemet

    Energy Technology Data Exchange (ETDEWEB)

    Bojrup, Martin; Petersson, Andreas; Agneholm, Evert

    2013-04-15

    The frequency quality in the synchronized Nordic power system has decreased significantly during the last years. At the same time the procurement costs for frequency control services from the producers has increased dramatically. The decreased frequency quality has also resulted in an increased wear on production units taking part in frequency control. The large scale integration of renewable s, such as wind power, will probably result in a need for more frequency control resources. In order to increase the frequency control resources in the power system and find more cost efficient solutions this project suggests a development of a method for load control based on grid frequency. The suggested load control is applicable on loads fed by a variable-speed drive (VSD) and the purpose is to use energy loads, i.e. loads that not necessary need a constant power. By using the control capacity in these loads the power consumption from these loads can be controlled without causing any notable inconveniences for the customers. In the report the future potential is estimated for different ancillary services. As the installation of new VSDs and exchange of existing VSDs are performed to a large extent every year it is possible, already some years after implementation, to see an impact in the power system.

  19. FXR agonist activity of conformationally constrained analogs of GW 4064.

    Science.gov (United States)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

    2009-08-15

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  20. Pediatric Predispositional Genetic Risk Communication: Potential Utility for Prevention and Control of Melanoma Risk as an Exemplar.

    Science.gov (United States)

    Wu, Yelena P; Mays, Darren; Kohlmann, Wendy; Tercyak, Kenneth P

    2017-10-01

    Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life. We draw from the adult melanoma genetic risk communication and pediatric health behavior change literatures to suggest ways in which genetic test reporting and complementary education could be delivered to children who carry a hereditary risk for melanoma and their families in order to foster children's engagement in melanoma preventive behaviors. Genetic discoveries will continue to yield new opportunities to provide predispositional genetic risk information to unaffected individuals, including children, and could be delivered within programs that provide personalized and translational approaches to cancer prevention.

  1. Physicochemical Properties of Sea Water and Bittern in Indonesia: Quality Improvement and Potential Resources Utilization for Marine Environmental Sustainability

    Directory of Open Access Journals (Sweden)

    Mirna Apriani

    2018-05-01

    Full Text Available The traditional salt production in Indonesia was investigated to report the preparation and processing of salt, determine the characteristics of sea water and bittern as well as explore the potential of bittern management with appropriate technology. Field study and comprehensive analysis were performed so as to better understand the salt making, providing valuable information for the proposal of targeted management strategies in salt quality improvement and wastewater recovery. The results show that Na^+,Cl^- and Ca^(2+ in East Java Province bittern were found greater than the majority of values found in the literature. The highest concentrations of Na^+,Cl^- and Ca^(2+ were measured in Camplong-Sampang District. The highest concentrations of Mg^(2+and trace metals were recorded in Panceng-Gresik District. The trace metals found in sea water and bittern need particular concern to be removed without disposing of sea water minerals. The potential number of bittern in Indonesia promoted the development of the bittern management for magnesium recovery and achieving marine environment sustainability. High purified material recovery can be achieved by using crystallization technology.

  2. Expected utility without utility

    OpenAIRE

    Castagnoli, E.; Licalzi, M.

    1996-01-01

    This paper advances an interpretation of Von Neumann–Morgenstern’s expected utility model for preferences over lotteries which does not require the notion of a cardinal utility over prizes and can be phrased entirely in the language of probability. According to it, the expected utility of a lottery can be read as the probability that this lottery outperforms another given independent lottery. The implications of this interpretation for some topics and models in decision theory are considered....

  3. Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2012-01-01

    Incretin-based therapies, which include the GLP-1 receptor agonists and DPP-4 inhibitors, use the antidiabetic properties of potentiating the GLP-1 receptor signalling via the regulation of insulin and glucagon secretion, inhibition of gastric emptying and suppression of appetite. Most physicians...... will start antidiabetic treatment with metformin, but adding a GLP-1 receptor agonist as the second drug seems to be optimal since more patients will reach an HbA1c below 7% than with a DPP-4 inhibitor or another oral antidiabetic agents and with minimal risk of hypoglycaemia. The GLP-1 receptor agonists...

  4. Direct assessment of cumulative aryl hydrocarbon receptor agonist activity in sera from experimentally exposed mice and environmentally exposed humans

    DEFF Research Database (Denmark)

    Schlezinger, Jennifer J; Bernard, Pamela L; Haas, Amelia

    2010-01-01

    (PCB)-exposed Faroe Islanders using an AhR-driven reporter cell line. To validate relationships between serum AhR agonist levels and biological outcomes, AhR agonist activity in mouse sera correlated with toxic end points. AhR agonist activity in unmanipulated ("neat") human sera was compared......, was associated with the frequency of recent pilot whale dinners, but did not correlate with levels of PCBs quantified by GC/MS. Surprisingly, significant "baseline" AhR activity was found in commercial human sera. CONCLUSIONS: An AhR reporter assay revealed cumulative levels of AhR activation potential in neat...

  5. Using program impact pathways to understand and improve program delivery, utilization, and potential for impact of Helen Keller International's homestead food production program in Cambodia.

    Science.gov (United States)

    Olney, Deanna K; Vicheka, Sao; Kro, Meng; Chakriya, Chhom; Kroeun, Hou; Hoing, Ly Sok; Talukder, Aminzzaman; Quinn, Victoria; Iannotti, Lora; Becker, Elisabeth; Roopnaraine, Terry

    2013-06-01

    Evidence of the impact of homestead food production programs on nutrition outcomes such as anemia and growth is scant. In the absence of information on program impact pathways, it is difficult to understand why these programs, which have been successful in increasing intake of micronutrient-rich foods, have had such limited documented impact on nutrition outcomes. To conduct a process evaluation of Helen Keller International's (HKI's) homestead food production program in Cambodia to assess whether the program was operating as planned (in terms of design, delivery, and utilization) and to identify ways in which the program might need to be strengthened in order to increase its potential for impact. A program theory framework, which laid out the primary components along the hypothesized program impact pathways, was developed in collaboration with HKI and used to design the research. Semistructured interviews and focus group discussions with program beneficiaries (n = 36 and 12, respectively), nonbeneficiaries (n = 12), and program implementers (n = 17 and 2, respectively) and observations of key program delivery points, including health and nutrition training sessions (n = 6), village model farms (n = 6), and household gardens of beneficiaries (n = 36) and nonbeneficiaries (n = 12), were conducted to assess the delivery and utilization of the primary program components along the impact pathways. The majority of program components were being delivered and utilized as planned. However, challenges with some of the key components posited to improve outcomes such as anemia and growth were noted. Among these were a gap in the expected pathway from poultry production to increased intake of eggs and poultry meat, and some weaknesses in the delivery of the health and nutrition training sessions and related improvements in knowledge among the village health volunteers and beneficiaries. Although the program has been successful in delivering the majority of the program

  6. Effects of protein-coated nanofibers on conformation of gingival fibroblast spheroids: potential utility for connective tissues regeneration.

    Science.gov (United States)

    Kaufman, Gili; Whitescarver, Ryan; Nunes, Laiz; Palmer, Xavier-Lewis; Skrtic, Drago; Tutak, Wojtek

    2017-10-09

    Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust healing of connective tissues. We propose utilizing gas-brushed nanofibers coated with collagen and fibrin for that purpose. Our hypotheses are that protein-coated nanofibers will: (i) attract and mobilize cells in various spatial orientations, and (ii) regulate the expression levels of specific extracellular matrix (ECM)-associated proteins, determining the initial conformational nature of dense and soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co-glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell attraction and rearrangement was followed by F-actin staining and confocal microscopy. Thicknesses of the cell layers, developed within the nanofibers, were quantified by imageJ software. The expression of collagen1α1 chain (Col1α1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was determined by quantitative reverse transcription analysis. Collagen- and fibrin- coated nanofibers induced cell migration toward fibers and supported cellular growth within the scaffolds. Both proteins affected the spatial rearrangement of fibroblasts by favoring packed cell clusters or intermittent cell spreading. These cell arrangements resembled the structural characteristic of dense and soft connective tissues, respectively. Within 3 days of incubation, fibroblast spheroids interacted with the fibers and grew robustly by increasing their thickness compared to monolayers. While the ECM key components, such as fibronectin and MMP2 encoding genes, were expressed in both protein groups, Col1α1 was predominantly expressed in bundled fibroblasts grown on collagen fibers. This enhanced expression of collagen1 is typical for dense connective tissue. Based on results of this study, our gas-blown, collagen- and fibrin-coated PLGA nanofibers are viable candidates for

  7. Effects of protein-coated nanofibers on conformation of gingival fibroblast spheroids: potential utility for connective tissue regeneration.

    Science.gov (United States)

    Kaufman, Gili; Whitescarver, Ryan A; Nunes, Laiz; Palmer, Xavier-Lewis; Skrtic, Drago; Tutak, Wojtek

    2018-01-24

    Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust healing of connective tissues. We propose utilizing gas-brushed nanofibers coated with collagen and fibrin for that purpose. Our hypotheses are that protein-coated nanofibers will: (i) attract and mobilize cells in various spatial orientations, and (ii) regulate the expression levels of specific extracellular matrix (ECM)-associated proteins, determining the initial conformational nature of dense and soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co-glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell attraction and rearrangement was followed by F-actin staining and confocal microscopy. Thicknesses of the cell layers, developed within the nanofibers, were quantified by ImageJ software. The expression of collagen1α1 chain (Col1α1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was determined by quantitative reverse transcription analysis. Collagen- and fibrin- coated nanofibers induced cell migration toward fibers and supported cellular growth within the scaffolds. Both proteins affected the spatial rearrangement of fibroblasts by favoring packed cell clusters or intermittent cell spreading. These cell arrangements resembled the structural characteristic of dense and soft connective tissues, respectively. Within three days of incubation, fibroblast spheroids interacted with the fibers, and grew robustly by increasing their thickness compared to monolayers. While the ECM key components, such as fibronectin and MMP2 encoding genes, were expressed in both protein groups, Col1α1 was predominantly expressed in bundled fibroblasts grown on collagen fibers. This enhanced expression of collagen1 is typical for dense connective tissue. Based on results of this study, our gas-blown, collagen- and fibrin-coated PLGA nanofibers are viable candidates for

  8. The environmental impact and cost efficiency of combustible waste utilization - the potential and impact of ongoing technology developments

    Energy Technology Data Exchange (ETDEWEB)

    Zevenhoven, M.; Hupa, M.

    2008-08-15

    power/utility boilers. Gasification will become more important as source of syngas production. Co-firing/gas firing in gas turbines of syngas after RDF gasification and gas cleanup has already been proven to be possible. Production of liquid-fuels from syngas after gasification and gas cleanup is more in a development stage but may help solving the shortage of new fuels to be used in traffic. Pyrolysis applications are still in the development stage either demonstrated (PVC treatment) or applied on a small scale and not proven to be economic feasible on larger scale (Plasma conversion). Here market forces will determine whether new technology will be developed further. (orig.)

  9. Spectral Doppler Waveforms for Diagnosis of Appendicitis: Potential Utility of Point Peak Systolic Velocity and Resistive Index Values.

    Science.gov (United States)

    Shin, Lewis K; Jeffrey, R Brooke; Berry, Gerald J; Olcott, Eric W

    2017-12-01

    Purpose To test the hypothesis that appendiceal spectral Doppler waveforms can distinguish patients with and patients without appendicitis. Materials and Methods In this retrospective study, Doppler waveforms were obtained from intramural appendiceal arteries identified with color Doppler imaging in 60% (93 of 155) of consecutive patients whose appendices were visualized at graded compression ultrasonography (US) performed for suspected appendicitis (53 male and 40 female; age, 1-56 years; mean, 14.5 years) over the 5-month period from November 2015 through March 2016. Point, non-angle-corrected peak systolic velocity (PSV) and resistive index (RI) values were compared between patients with and patients without appendicitis by utilizing histopathologically proven appendicitis and 6-week clinical follow-up as diagnostic reference standards. Data were assessed by using the Student t test, exact binomial distribution, two-sample test of proportions, and receiver operating characteristic analysis. Results Among the 93 patients, 36 (38.7%) had proven appendicitis (mean PSV, 19.7 cm/sec; mean RI, 0.69) and 57 patients (61.2%) did not (mean PSV, 7.1 cm/sec, P appendicitis was 0.97 (95% confidence interval [CI]: 0.95, 1.00) for PSV and 0.86 (95% CI: 0.78, 0.95; P = .011) for RI. Chosen discriminatory criteria of PSV greater than 10 cm/sec and RI greater than 0.65 yielded specificity for appendicitis of 94.7% and 96.5% with sensitivity of 88.9% and 63.9% (P = .013) and negative predictive value of 93.1% and 80.9% (P = .045), respectively. Original clinical graded compression US interpretations based on established US findings demonstrated specificity of 96.2% and sensitivity of 100.0%. Considering the subset of 20 patients whose maximum outer diameter measured 6-8 mm, the discriminatory criteria of PSV greater than 10 cm/sec and RI greater than 0.65 yielded specificity for appendicitis of 88.9% each, with sensitivity of 100.0% and 63.6% and negative predictive value of 100

  10. Phrenic nerve neurotization utilizing the spinal accessory nerve: technical note with potential application in patients with high cervical quadriplegia.

    Science.gov (United States)

    Tubbs, R Shane; Pearson, Blake; Loukas, Marios; Shokouhi, Ghaffar; Shoja, Mohammadali M; Oakes, W Jerry

    2008-11-01

    High cervical quadriplegia is associated with high morbidity and mortality. Artificial respiration in these patients carries significant long-term risks such as infection, atelectasis, and respiratory failure. As phrenic nerve pacing has been proven to free many of these patients from ventilatory dependency, we hypothesized that neurotization of the phrenic nerve with the spinal accessory nerve (SAN) may offer one potential alternative to phrenic nerve stimulation via pacing and may be more efficacious and longer lasting without the complications of an implantable device. Ten cadavers (20 sides) underwent exposure of the cervical phrenic nerve and the SAN in the posterior cervical triangle. The SAN was split into anterior and posterior halves and the anterior half transposed to the ipsilateral phrenic nerve as it crossed the anterior scalene muscle. The mean distance between the cervical phrenic nerve and the SAN in the posterior cervical triangle was 2.5 cm proximally, 4 cm at a midpoint, and 6 cm distally. The range for these measurements was 2 to 4 cm, 3.5 to 5 cm, and 4 to 8.5 cm, respectively. The mean excess length of SAN available after transposition to the more anteromedially placed phrenic nerve was 5 cm (range 4 to 6.5 cm). The mean diameter of these regional parts of the spinal accessory and phrenic nerves was 2 and 2.5 mm, respectively. No statistically significant difference was found for measurements between sides. To our knowledge, using the SAN for neurotization to the phrenic nerve for potential use in patients with spinal cord injury has not been previously explored. Following clinical trials, these data may provide a mechanism for self stimulation of the diaphragm and obviate phrenic nerve pacing in patients with high cervical quadriplegia. Our study found that such a maneuver is technically feasible in the cadaver.

  11. Sports doping: Emerging designer and therapeutic B2-agonists

    NARCIS (Netherlands)

    Fragkaki, A.G.; Georgakopoulos, C.; Sterk, S.S.; Nielen, M.W.F.

    2013-01-01

    Beta2-adrenergic agonists, or ß2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of ß2-agonists is prohibited in sports by the World Anti-Doping

  12. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Utility of whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs).

    Science.gov (United States)

    Hoffman, David H; Ream, Justin M; Hajdu, Christina H; Rosenkrantz, Andrew B

    2017-04-01

    To evaluate whole-lesion ADC histogram metrics for assessing the malignant potential of pancreatic intraductal papillary mucinous neoplasms (IPMNs), including in comparison with conventional MRI features. Eighteen branch-duct IPMNs underwent MRI with DWI prior to resection (n = 16) or FNA (n = 2). A blinded radiologist placed 3D volumes-of-interest on the entire IPMN on the ADC map, from which whole-lesion histogram metrics were generated. The reader also assessed IPMN size, mural nodularity, and adjacent main-duct dilation. Benign (low-to-intermediate grade dysplasia; n = 10) and malignant (high-grade dysplasia or invasive adenocarcinoma; n = 8) IPMNs were compared. Whole-lesion ADC histogram metrics demonstrating significant differences between benign and malignant IPMNs were: entropy (5.1 ± 0.2 vs. 5.4 ± 0.2; p = 0.01, AUC = 86%); mean of the bottom 10th percentile (2.2 ± 0.4 vs. 1.6 ± 0.7; p = 0.03; AUC = 81%); and mean of the 10-25th percentile (2.8 ± 0.4 vs. 2.3 ± 0.6; p = 0.04; AUC = 79%). The overall mean ADC, skewness, and kurtosis were not significantly different between groups (p ≥ 0.06; AUC = 50-78%). For entropy (highest performing histogram metric), an optimal threshold of >5.3 achieved a sensitivity of 100%, a specificity of 70%, and an accuracy of 83% for predicting malignancy. No significant difference (p = 0.18-0.64) was observed between benign and malignant IPMNs for cyst size ≥3 cm, adjacent main-duct dilatation, or mural nodule. At multivariable analysis of entropy in combination with all other ADC histogram and conventional MRI features, entropy was the only significant independent predictor of malignancy (p = 0.004). Although requiring larger studies, ADC entropy obtained from 3D whole-lesion histogram analysis may serve as a biomarker for identifying the malignant potential of IPMNs, independent of conventional MRI features.

  14. Environmental and technical assessments of the potential utilization of sewage sludge ashes (SSAs) as secondary raw materials in construction.

    Science.gov (United States)

    Chen, Maozhe; Blanc, Denise; Gautier, Mathieu; Mehu, Jacques; Gourdon, Rémy

    2013-05-01

    Ashes produced by thermal treatments of sewage sludge exhibit common properties with cement. For example, major elements present in SSA are the same of major elements of cement. Hydraulic properties of SSA are quite the same of cement ones. They may therefore be used to substitute part of cement in concrete or other cementitious materials, provided that technical prescriptions are satisfied and that environmental risks are not significantly increased. The objective of the present study was to determine the appropriate substitution ratios to satisfy both technical and environmental criteria. In a first step, the elemental composition and particle size distribution of the ashes were measured. Then the ashes were used along with Portland cement and sand at different ratios of substitution to produce mortar and concrete which were cured for up to 90 days into parallelepipedic or cylindrical monoliths. The mechanical properties of the monoliths were measured using standard procedures for flexural and compressive strengths, and compared to blanks containing no ashes. The environmental criteria were assessed using leaching tests conducted according to standard protocols both on the ashes and the monoliths, and compared to the blanks. Results showed that the characteristics of the ashes ranged between those of cement and sand because of their larger particle size and higher content in SiO2 as compared to cement. The monoliths made with the highest substitution ratios exhibited a significant decrease in flexural and compressive strengths. However, when the ashes were used in partial substitution of cement at appropriate ratios, the concrete monoliths exhibited similar compressive strengths as the blank samples. The most appropriate ratios were found to be 10% substitution of cement and 2% substitution of sand. The leaching tests conducted on the ashes in their powdery form revealed that amongst the potential contaminants analyzed only Mo and Se were leached at

  15. Utilizing potential field data to support delineation of groundwater aquifers in the southern Red Sea coast, Saudi Arabia

    International Nuclear Information System (INIS)

    Elawadi, Eslam; Mogren, Saad; Ibrahim, Elkhedr; Batayneh, Awni; Al-Bassam, Abdulaziz

    2012-01-01

    In this paper potential field data are interpreted to map the undulation of the basement surface, which represents the bottom of the water bearing zones, and to delineate the tectonic framework that controls the groundwater flow and accumulation in the southern Red Sea coastal area of Saudi Arabia. The interpretation reveals that the dominant structural trend is a NW (Red Sea) trend that resulted in a series of faulted tilted blocks. These tilted blocks are dissected by another cross-cut NE trend which shapes and forms a series of fault-bounded small basins. These basins and the bounded structural trends control and shape the flow direction of the groundwater in the study area, i.e. they act as groundwater conduits. Furthermore, the present results indicate that volcanic intrusions are present as subsurface flows, which hinder the groundwater exploration and drilling activities in most of the area; in some localities these volcanic flows crop out at the surface and cover the groundwater bearing formations. Furthermore, the gravity and magnetic data interpretation indicates the possible existence of a large structural basin occupying the southeastern side of the study area. This basin is bounded with NW and NE trending faults and is expected to be a good host for groundwater aquifers; thus it is a promising site for hydrogeological investigation. (paper)

  16. Novel kinin B1 receptor agonists with improved pharmacological profiles.

    Science.gov (United States)

    Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

    2009-04-01

    There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

  17. Concrete-polymer composite materials and their potential for construction, urban waste utilization, and nuclear waste storage

    International Nuclear Information System (INIS)

    Fowler, E.E.; Steinberg, Meyer.

    1974-01-01

    A wide range of concrete-polymer composites have been investigated by Brookhaven National Laboratory. Polymer impregnated concrete (PIC) is basically formed by drying cured conventional concrete, displacing the air from open cell void volume, diffusing low viscosity monomer (less than 10 cps) through the open cell structure, saturating the concrete with the monomer and in-situ polymerizing the monomer to polymer by most convenient means. Mainly free-radical vinyl type monomers are used. For increased thermal stability, crosslinking agents and thermosetting monomers such as styrene-trimethylol propane trimethacrylate (TMPTMA) and polyester-styrene are used. Much informations on the formation, structural properties and durability of PIC have been accumulated over past five years. U.S. Patent 3,567,496 has been issued on the production of PIC. Compressive strength can be increased from 352 kg/cm 2 of conventional concrete to 1,410 kg/cm 2 . Water absorption is reduced by 99% and the freeze-thaw resistance is remarkably improved. With high silica cement, strong basaltic aggregate, and high temperature steam curing, strength increase from 845 to over 2,630 kg/cm 2 can be obtained. A maximum of 238 kg/cm 2 tensile strength has been obtained with the steam-cured concrete. In the steam- cured concrete, polymer loading roughly around 8% by weight is obtained. Aggregates can include the urban solid waste discarded by man. Sewage and solid waste refuse-polymer concrete has been produced by using garbage as aggregate and sewage as the hydrating media for cement. The potentially important application of hydrauric cement concrete, in combination with the polymers in PIC and PC, is the storage of long-living radioactive wastes from nuclear industry. (Iwakiri, K.)

  18. Evaluation of the Green Microalga Monoraphidium sp. Dek19 Growth Utilizing Ethanol Plant Side Streams and Potential for Biofuel Production

    Science.gov (United States)

    Colson, David Michael

    This research was conducted to evaluate the potential for growth of Monoraphidium sp. Dek19 using side streams from an ethanol plant for culture medium. Additionally, the potential of using enzymes to break down the cell wall material to release fermentable sugars and oil was examined. The ethanol streams selected were methanator influent, methanator effluent, and thin stillage. This species of microalgae has been previously studied and found to have the ability to grow in and remediate the effluent water from the DeKalb Sanitary District (DSD). The Monoraphidium sp. Dek19 was grown in various concentrations of the ethanol plant side streams concurrently with algae cultures grown in the DSD effluent. The algae cultures were grown in 250ml flasks to determine the optimal concentrations of the ethanol streams. The concentrations with the growth rate and cell counts closest to or higher than the DSD effluents were selected for further examination. These concentrations were repeated to evaluate the most optimal growth conditions using the ethanol streams in comparison to the DSD effluent grown algae. The selected growth condition for the ethanol streams was determined to be using the methanator effluent as the base water component with the thin stillage added to a 2% concentration. The 2% concentration showed an average increase in cell count to be 8.49% higher than the control cell count. The methanator influent was discarded as a base water component, as the growth of the algae was 40.18% less than that of the control. Other concentrations considered resulted in a decrease in cell. count ranging from 9.20-48.97%. The three closest growth results of the concentration of thin stillage and methanator effluent (1%, 2%, and 4%) were scaled up to 2L flasks to confirm the results on a larger scale. The results showed a greater reduction in the cell count of the 1% and 4% concentrations, 23.52% and 16.31% reduction in cell count respectively. The 2% concentration showed a

  19. Workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. Part I

    International Nuclear Information System (INIS)

    1997-01-01

    The publication has been set up as proceedings of the workshop on the role of enhancement of utilization of primary and secondary hydro potential in the context of environmental protection. The proceedings consist of the following chapters: (1) BOT schemes as financial model of hydro power projects; (2) Application of pumped storage plants in the control of the Slovak power system and the possibility of pumped storage plant Ipel exploitation towards the year 2010; (3) Use of hydro energetic potential of streams from the aspects of nature conservation on the example of north Slovakia; (4) Ecological aspects of the hydro power industry and possible means to improve ecological conditions of water reservoirs; (5) Preparation and realization of HPP Zilina; (6) Freudenau HPP. ecological measures and groundwater management; (7) Present state of hydro power development in Austria

  20. The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, M B; Fuxe, K; Werge, T

    2002-01-01

    The adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism...... showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles....

  1. Exploring the Potential Competitiveness of Utility-Scale Photovoltaics plus Batteries with Concentrating Solar Power, 2015–2030

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, David [National Renewable Energy Lab. (NREL), Golden, CO (United States); Margolis, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Denholm, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Stekli, Joseph [Dept. of Energy (DOE), Washington DC (United States). Office of Solar Energy Technologies Program

    2016-08-01

    ancillary services and the ability to store off-peak grid energy. Alternatively, direct thermal energy storage allows a greater capture of solar energy, reducing the potential for curtailments in very high solar scenarios. So while this analysis evaluates a key performance metric (cost per unit of generation) under a range of cost projections, additional analysis of the value per unit of generation will be needed to comprehensively assess the relative competitiveness of solar energy systems deployed with energy storage.

  2. Drug-induced Hypothermia by 5HT1A Agonists Provide Neuroprotection in Experimental Stroke

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Hasseldam, Henrik; Nybro Smith, Matthias

    2014-01-01

    BACKGROUND: Drug-induced hypothermia reduces brain damage in animal stroke models and is an undiscovered potential in human stroke treatment. We studied hypothermia induced by the serotonergic agonists S14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine) and ipsapirone in a rat...... therapeutic hypothermia....

  3. The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat

    DEFF Research Database (Denmark)

    Schilperoort, Maaike; van Dam, Andrea D; Hoeke, Geerte

    2018-01-01

    the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content...

  4. Major drawbacks and additional benefits of agonist trigger--not ovarian hyperstimulation syndrome related

    DEFF Research Database (Denmark)

    Shapiro, Bruce S; Andersen, Claus Yding

    2015-01-01

    optimal luteal support. The agonist trigger option also allows continued stimulation and subsequent trigger of high responders with reasonable safety, potentially leading to retrievals of larger cohorts of mature oocytes. It may also reduce the number of retrievals needed to achieve a large family...

  5. Subtype selective kainic acid receptor agonists

    DEFF Research Database (Denmark)

    Bunch, Lennart; Krogsgaard-Larsen, Povl

    2009-01-01

    (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

  6. Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia

    OpenAIRE

    Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M.; McCullough, Louise; Andreasson, Katrin

    2008-01-01

    Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE2 receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE2 EP2, EP3, and EP4 receptors, would reduce brain injury in the murine m...

  7. NKT-cell glycolipid agonist as adjuvant in synthetic vaccine.

    Science.gov (United States)

    Liu, Zheng; Guo, Jun

    2017-11-27

    NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering "danger signal" and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Trial Watch: Toll-like receptor agonists in oncological indications.

    Science.gov (United States)

    Aranda, Fernando; Vacchelli, Erika; Obrist, Florine; Eggermont, Alexander; Galon, Jérôme; Sautès-Fridman, Catherine; Cremer, Isabelle; Henrik Ter Meulen, Jan; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

    2014-01-01

    Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic.

  9. Maximum utilization of women's potentials.

    Science.gov (United States)

    1998-01-01

    Balayan's Municipal Center for Women was created to recognize women's role in the family and community in nation-building; to support the dignity and integrity of all people, especially women, and fight against rape, incest, wife beating, sexual harassment, and sexual discrimination; to empower women through education; to use women as equal partners in achieving progress; to end gender bias and discrimination, and improve women's status; and to enact progressive legal and moral change in favor of women and women's rights. The organization's functions in the following areas are described: education and information dissemination, community organizing, the provision of economic and livelihood assistance, women's counseling, health assistance, legislative advocacy and research, legal assistance, women's networking, and monitoring and evaluation.

  10. PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings.

    Directory of Open Access Journals (Sweden)

    Monica Puligheddu

    Full Text Available Nicotinic acetylcholine receptors (nAChRs are involved in seizure mechanisms. Hence, nocturnal frontal lobe epilepsy was the first idiopathic epilepsy linked with specific mutations in α4 or β2 nAChR subunit genes. These mutations confer gain of function to nAChRs by increasing sensitivity toward acetylcholine. Consistently, nicotine elicits seizures through nAChRs and mimics the excessive nAChR activation observed in animal models of the disease. Treatments aimed at reducing nicotinic inputs are sought as therapies for epilepsies where these receptors contribute to neuronal excitation and synchronization. Previous studies demonstrated that peroxisome proliferator-activated receptors-α (PPARα, nuclear receptor transcription factors, suppress nicotine-induced behavioral and electrophysiological effects by modulating nAChRs containing β2 subunits. On these bases, we tested whether PPARα agonists were protective against nicotine-induced seizures. To this aim we utilized behavioral and electroencephalographic (EEG experiments in C57BL/J6 mice and in vitro patch clamp recordings from mice and rats. Convulsive doses of nicotine evoked severe seizures and bursts of spike-waves discharges in ∼100% of mice. A single dose of the synthetic PPARα agonist WY14643 (WY, 80 mg/kg, i.p. or chronic administration of fenofibrate, clinically available for lipid metabolism disorders, in the diet (0.2% for 14 days significantly reduced or abolished behavioral and EEG expressions of nicotine-induced seizures. Acute WY effects were reverted by the PPARα antagonist MK886 (3 mg/kg, i.p.. Since neocortical networks are crucial in the generation of ictal activity and synchrony, we performed patch clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs from frontal cortex layer II/III pyramidal neurons. We found that both acute and chronic treatment with PPARα agonists abolished nicotine-induced sIPSC increases. PPARα within the CNS are key

  11. Examining the potential of natural gas demand-side measures to benefit customers, the distribution utility, and the environment: two case studies from Europe

    International Nuclear Information System (INIS)

    Almeida, A.T. de; Carvalho, A.; Mariano, J.; Broege, M.

    2004-01-01

    The aim of this paper is to demonstrate how integrated resource planning (IRP) oriented to the gas sector can be applied both in new networks and in mature networks, and to present the advantages of its application. One case study is described, in the western central region of Portugal, to illustrate the results of a pilot project on natural gas IRP implementation in a new network in the European Union (EU). The city of Burg, Germany, with a mature gas network with district heating was also analysed in terms of IRP potential. The most important phases of the integrated resource plan definition and implementation (especially those oriented to the demand-side) are presented, namely, the definition of the most efficient technologies (including solar energy), fuel-switching possibilities, a detailed study of the impacts in the economy, environment and society, and the policy incentives necessary to motivate the gas utility companies to perform IRP. In the main case study, the suggested implementation plan would lead to a reduction of around 4.7% in natural gas consumption. Additionally, 13.3% of cost-effective fuel switching from other competing forms of energy to natural gas can be achieved. A proposed EU energy services directive on mandatory energy-efficiency activities for gas and electricity distribution utilities in the EU, will promote the large-scale implementation of the proposed approach in Europe. (author)

  12. Effects of potential once-through improvements on the uranium utilization in the closed LWR cycle assuming self generated recycling of uranium and plutonium

    International Nuclear Information System (INIS)

    1979-06-01

    This paper is concerned with potential improvements to the resource utilization of current generation light water reactors operating on a closed U/Pu fuel cycle. Only those modifications to existing systems layout and fuel cycle practise are discussed that have been considered in Working Group 8 A for the once-through cycle. The objective is to give an impression how much the difference in resource utilization between the once-through and the closed U/Pu cycle were changed if both cycles were reoptimized independantly from each other with respect to uranium consumption. No commercial recycling of U/Pu has been taken place to date in 1300 MWe light water reactors. The feasibility of thermal recycling has been demonstrated however on an industrial scale in reactors of the 300 MWe class. (Obrigheim, Gundremmingen). From this experience and from extensive design calculations it has been concluded that for Pu bearing fuel assemblies of 1300 MWe plants it would be favorable to use the same structural layout and similar fuel management procedures as for uranium assemblies. This would result in plant life-time averaged uranium savings on the order of 35 - 40 % relative to the once-through cycle in case of the Self Generated Recycling Mode

  13. A technical analysis for cogeneration systems with potential applications in twelve California industrial plants. [energy saving heat-electricity utility systems

    Science.gov (United States)

    Moretti, V. C.; Davis, H. S.; Slonski, M. L.

    1978-01-01

    In a study sponsored by the State of California Energy Resources Conservation and Development Commission, 12 industrial plants in five utility districts were surveyed to assess the potential applications of the cogeneration of heat and electricity in California industry. Thermodynamic calculations were made for each plant in determining the energy required to meet the existing electrical and steam demands. The present systems were then compared to conceptual cogeneration systems specified for each plant. Overall energy savings were determined for the cogeneration applications. Steam and gas turbine topping cycle systems were considered as well as bottoming cycle systems. Types of industries studied were: pulp and paper, timber, cement, petroleum refining, enhanced oil recovery, foods processing, steel and glass

  14. Switch from antagonist to agonist after addition of a DOTA chelator to a somatostatin analog

    International Nuclear Information System (INIS)

    Reubi, Jean Claude; Cescato, Renzo; Waser, Beatrice; Erchegyi, Judit; Rivier, Jean E.

    2010-01-01

    Peptide receptor targeting has become an increasingly attractive method to target tumors diagnostically and radiotherapeutically. Peptides linked to a variety of chelators have been developed for this purpose. They have, however, rarely been tested for their agonistic or antagonistic properties. We report here on a somatostatin antagonist that switched to an agonist upon coupling to a DOTA chelator. Two novel somatostatin analogs, 406-040-15 and its DOTA-coupled counterpart 406-051-20, with and without cold Indium labeling, were tested for their somatostatin receptor subtypes 1-5 (sst 1 -sst 5 ) binding affinity using receptor autoradiography. Moreover, they were tested functionally for their ability to affect sst 2 and sst 3 internalization in vitro in HEK293 cells stably expressing the human sst 2 or sst 3 receptor, using an immunofluorescence microscopy-based internalization assay. All three compounds were characterized as pan-somatostatin analogs having a high affinity for all five sst. In the sst 2 internalization assay, all three compounds showed an identical behavior, namely, a weak agonistic effect complemented by a weak antagonistic effect, compatible with the behavior of a partial agonist. Conversely, in the sst 3 internalization assay, 406-040-15 was a full antagonist whereas its DOTA-coupled counterpart, 406-051-20, with and without Indium labeling, switched to a full agonist. Adding the DOTA chelator to the somatostatin analog 406-040-15 triggers a switch at sst 3 receptor from an antagonist to an agonist. This indicates that potential radioligands for tumor targeting should always be tested functionally before further development, in particular if a chelator is added. (orig.)

  15. The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

    2003-01-01

    The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu......The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic...... interneurons, were examined in hippocampal slice cultures exposed to N-methyl-D-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100-1000 microM) was neuroprotective in slice cultures co-exposed to NMDA (10 microM) for 48 h......, while muscimol (100-1000 microM) and ATPA (1-3 microM) were without effect. The results demonstrate that direct GABA(A) agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo....

  16. Sulfoximines as potent RORγ inverse agonists.

    Science.gov (United States)

    Ouvry, Gilles; Bihl, Franck; Bouix-Peter, Claire; Christin, Olivier; Defoin-Platel, Claire; Deret, Sophie; Feret, Christophe; Froude, David; Hacini-Rachinel, Feriel; Harris, Craig S; Hervouet, Catherine; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Parnet, Veronique; Pascau, Coralie; Pascau, Jonathan; Pierre, Romain; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent F

    2018-05-01

    Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. [Safety and tolerability of GLP-1 receptor agonists].

    Science.gov (United States)

    Soldevila, Berta; Puig-Domingo, Manel

    2014-09-01

    Glucagon-like peptide-1 receptor agonists (GLP-1ra) are a new group of drugs with a glucose-lowering action due to their incretin effect. The GLP-1 receptor is expressed in various human tissues, which could be related to the pleiotropic effects of human GLP-1, as well as to the adverse effects described in patients treated with GLP-1ra. The risk of hypoglycaemia is low, which is one of the main considerations in the safety of this family of compounds and is also important to patients with diabetes. The most frequent adverse effect is nausea, which usually occurs at the start of treatment and is transient in 20-60% of affected patients. This article also reviews the information available on antibody formation, the potential effect on the thyroid gland, and the controversial association between this group of drugs with pancreatitis and cancer. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Simultaneous determination of 11 β-agonists in human urine using high-performance liquid chromatography/tandem mass spectrometry with isotope dilution.

    Science.gov (United States)

    Wang, Xiaoli; Guo, Tao; Wang, Shanshan; Yuan, Jinpeng; Zhao, Rusong

    2015-04-01

    The misuse of β-agonists constitutes a potential risk to public health and has been forbidden in many countries. In this study, we describe a method for specific, sensitive and rapid detection of β-agonists in human urine. Urine samples were extracted with ethyl acetate, without any additional purification step, and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) with Clenbuterol-D9 and Salbuterol-D3 as internal standards. The intra- and interday precision values of the method were all application of UPLC-MS-MS method in β-agonists detection of human urine will be helpful in veterinary control of β-agonists and for studying the effect of β-agonists on human health. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Effect of Delta-tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans

    NARCIS (Netherlands)

    Beaumont, H.; Jensen, J.; Carlsson, A.; Ruth, M.; Lehmann, A.; Boeckxstaens, G. E.

    2009-01-01

    Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB(1)/CB(2) receptor agonist Delta(9)-tetrahydrocannabinol

  20. Electrophysiological actions of GABAB agonists and antagonists in rat dorso-lateral septal neurones in vitro.

    Science.gov (United States)

    Bon, C; Galvan, M

    1996-06-01

    1. The actions of GABAB-receptor agonists and antagonists on rat dorso-lateral septal neurones in vitro were recorded with intracellular microelectrodes. 2. In the presence of 1 microM tetrodotoxin to prevent indirect neuronal effects caused by action potential-dependent neurotransmitter release, bath application of baclofen (0.1-30 microM) or SK&F 97541 (0.01-3 microM) evoked concentration-dependent hyperpolarizations which reversed close to the potassium equilibrium potential; the EC50S were 0.55 and 0.05 microM, respectively. No significant desensitization was observed during prolonged agonist exposure (dorso-lateral septal nucleus express conventional GABAB receptors, which are involved in the generation of slow inhibitory postsynaptic potentials. CGP 55845A is the most potent GABAB receptor antagonist described in this brain area.

  1. Repeated 7-Day Treatment with the 5-HT2C Agonist Lorcaserin or the 5-HT2A Antagonist Pimavanserin Alone or in Combination Fails to Reduce Cocaine vs Food Choice in Male Rhesus Monkeys.

    Science.gov (United States)

    Banks, Matthew L; Negus, S Stevens

    2017-04-01

    Cocaine use disorder is a global public health problem for which there are no Food and Drug Administration-approved pharmacotherapies. Emerging preclinical evidence has implicated both serotonin (5-HT) 2C and 2A receptors as potential mechanisms for mediating serotonergic attenuation of cocaine abuse-related neurochemical and behavioral effects. Therefore, the present study aim was to determine whether repeated 7-day treatment with the 5-HT 2C agonist lorcaserin (0.1-1.0 mg/kg per day, intramuscular; 0.032-0.1 mg/kg/h, intravenous) or the 5-HT 2A inverse agonist/antagonist pimavanserin (0.32-10 mg/kg per day, intramuscular) attenuated cocaine reinforcement under a concurrent 'choice' schedule of cocaine and food availability in rhesus monkeys. During saline treatment, cocaine maintained a dose-dependent increase in cocaine vs food choice. Repeated pimavanserin (3.2 mg/kg per day) treatments significantly increased small unit cocaine dose choice. Larger lorcaserin (1.0 mg/kg per day and 0.1 mg/kg/h) and pimavanserin (10 mg/kg per day) doses primarily decreased rates of operant behavior. Coadministration of ineffective lorcaserin (0.1 mg/kg per day) and pimavanserin (0.32 mg/kg per day) doses also failed to significantly alter cocaine choice. These results suggest that neither 5-HT 2C receptor activation nor 5-HT 2A receptor blockade are sufficient to produce a therapeutic-like decrease in cocaine choice and a complementary increase in food choice. Overall, these results do not support the clinical utility of 5-HT 2C agonists and 5-HT 2A inverse agonists/antagonists alone or in combination as candidate anti-cocaine use disorder pharmacotherapies.

  2. A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

    Directory of Open Access Journals (Sweden)

    Daniel M Appledorn

    2010-03-01

    Full Text Available Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

  3. Heterologous Expression in Remodeled C. elegans: A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening.

    Science.gov (United States)

    Law, Wenjing; Wuescher, Leah M; Ortega, Amanda; Hapiak, Vera M; Komuniecki, Patricia R; Komuniecki, Richard

    2015-04-01

    Monoamines, such as 5-HT and tyramine (TA), paralyze both free-living and parasitic nematodes when applied exogenously and serotonergic agonists have been used to clear Haemonchus contortus infections in vivo. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists. Key receptors were expressed heterologously in chimeric, genetically-engineered Caenorhabditis elegans, at sites likely to yield robust phenotypes upon agonist stimulation. This approach potentially preserves the unique pharmacologies of the receptors, while including nematode-specific accessory proteins and the nematode cuticle. Importantly, the sensitivity of monoamine-dependent paralysis could be increased dramatically by hypotonic incubation or the use of bus mutants with increased cuticular permeabilities. We have demonstrated that the monoamine-dependent inhibition of key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. Specifically, 5-HT paralyzed C. elegans 5-HT receptor null animals expressing either nematode, insect or human orthologues of a key Gαo-coupled 5-HT1-like receptor in the cholinergic motor neurons. Importantly, 8-OH-DPAT and PAPP, 5-HT receptor agonists, differentially paralyzed the transgenic animals, with 8-OH-DPAT paralyzing mutant animals expressing the human receptor at concentrations well below those affecting its C. elegans or insect orthologues. Similarly, 5-HT and TA paralyzed C. elegans 5-HT or TA receptor null animals, respectively, expressing either C. elegans or H. contortus 5-HT or TA-gated Cl- channels in either C. elegans cholinergic motor neurons or body wall muscles. Together, these data suggest that this heterologous, ectopic expression screening approach will be useful for the identification of agonists for key monoamine receptors from parasites and could have broad application for the identification

  4. Heterologous Expression in Remodeled C. elegans: A Platform for Monoaminergic Agonist Identification and Anthelmintic Screening.

    Directory of Open Access Journals (Sweden)

    Wenjing Law

    2015-04-01

    Full Text Available Monoamines, such as 5-HT and tyramine (TA, paralyze both free-living and parasitic nematodes when applied exogenously and serotonergic agonists have been used to clear Haemonchus contortus infections in vivo. Since nematode cell lines are not available and animal screening options are limited, we have developed a screening platform to identify monoamine receptor agonists. Key receptors were expressed heterologously in chimeric, genetically-engineered Caenorhabditis elegans, at sites likely to yield robust phenotypes upon agonist stimulation. This approach potentially preserves the unique pharmacologies of the receptors, while including nematode-specific accessory proteins and the nematode cuticle. Importantly, the sensitivity of monoamine-dependent paralysis could be increased dramatically by hypotonic incubation or the use of bus mutants with increased cuticular permeabilities. We have demonstrated that the monoamine-dependent inhibition of key interneurons, cholinergic motor neurons or body wall muscle inhibited locomotion and caused paralysis. Specifically, 5-HT paralyzed C. elegans 5-HT receptor null animals expressing either nematode, insect or human orthologues of a key Gαo-coupled 5-HT1-like receptor in the cholinergic motor neurons. Importantly, 8-OH-DPAT and PAPP, 5-HT receptor agonists, differentially paralyzed the transgenic animals, with 8-OH-DPAT paralyzing mutant animals expressing the human receptor at concentrations well below those affecting its C. elegans or insect orthologues. Similarly, 5-HT and TA paralyzed C. elegans 5-HT or TA receptor null animals, respectively, expressing either C. elegans or H. contortus 5-HT or TA-gated Cl- channels in either C. elegans cholinergic motor neurons or body wall muscles. Together, these data suggest that this heterologous, ectopic expression screening approach will be useful for the identification of agonists for key monoamine receptors from parasites and could have broad application for

  5. Pareto utility

    NARCIS (Netherlands)

    Ikefuji, M.; Laeven, R.J.A.; Magnus, J.R.; Muris, C.H.M.

    2013-01-01

    In searching for an appropriate utility function in the expected utility framework, we formulate four properties that we want the utility function to satisfy. We conduct a search for such a function, and we identify Pareto utility as a function satisfying all four desired properties. Pareto utility

  6. Biliary anatomy in potential right hepatic lobe living donor liver transplantation (LDLT): The utility of CT cholangiography in the setting of inconclusive MRCP

    International Nuclear Information System (INIS)

    McSweeney, Sean E.; Kim, Tae Kyoung; Jang, Hyun-Jung; Khalili, Korosh

    2012-01-01

    Objective: To determine the utility of CT cholangiography (CT-Ch) in preoperative evaluation of the biliary anatomy of living-donor liver transplantation (LDLT) donors when magnetic resonance cholangiopancreatography (MRCP) is inconclusive. Materials and methods: Over a 2-year period, 22 potential living liver donors underwent contrast-enhanced CT-Ch for preoperative evaluating biliary anatomy due to inconclusive results on MRCP and subsequently donated their right hepatic lobe. Nineteen of them underwent intraoperative cholangiography and were included in this study. Two radiologists retrospectively reviewed both MRCP and CT-Ch with 1-month interval and documented the types of bile duct branching patterns and visualization score of intrahepatic bile ducts (4-point scale). Results: There were no complications associated with CT-Ch examinations. CT-Ch was concordant with the reference standard in 18/19 (95%) including 7/8 typical branching type and 11/11 anomalous branching types. MRCP was concordant with the reference standard in 14/19 (74%) including 4/8 typical branching types and 10/11 anomalous branching types. The discordant case by CT-Ch was the identification of a tiny accessory right intrahepatic duct joining the common bile duct which was not visualized on intraoperative cholangiography. CT-Ch showed higher visualization score (mean, 3.9) than MRCP (mean, 2.6) (P < .001). Conclusion: CT-Ch can be effectively used for the depiction of the branching pattern of the bile duct at the hepatic hilum when MRCP is inconclusive.

  7. Principles of agonist recognition in Cys-loop receptors

    DEFF Research Database (Denmark)

    Lynagh, Timothy Peter; Pless, Stephan Alexander

    2014-01-01

    , functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically...

  8. Combining GLP-1 receptor agonists with insulin

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Vilsbøll, T

    2013-01-01

    Due to the increasing prevalence of type 2 diabetes mellitus (T2DM), the emergent trend towards diagnosis in younger patients and the progressive nature of this disease, many more patients than before now require insulin to maintain glycaemic control. However, there is a degree of inertia among...... physicians and patients regarding the initiation and intensification of insulin therapy, in part due to concerns about the associated weight gain and increased risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase insulin release and suppress glucagon secretion in a glucose......, compared with insulin, the antihyperglycaemic efficacy of GLP-1RAs is limited. The combination of a GLP-1RA and insulin might thus be highly effective for optimal glucose control, ameliorating the adverse effects typically associated with insulin. Data from clinical studies support the therapeutic...

  9. CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction

    Science.gov (United States)

    Xi, Zheng-Xiong; Song, Rui; Li, Xia; Lu, Guan-Yi; Peng, Xiao-Qing; He, Yi; Bi, Guo-Hua; Sheng, Siyuan Peter; Yang, Hong-Ju; Zhang, Haiying; Li, Jin; Froimowitz, Mark; Gardner, Eliot L

    2017-01-01

    Agonist-replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32476, that may have translational potential for treating cocaine addiction. In vitro ligand-binding assays suggest that CTDP-32476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT. Systemic administration of CTDP-32476 alone produced a slow-onset, long-lasting increase in extracellular nucleus accumbens DA, locomotion, and brain-stimulation reward. Drug-naive rats did not self-administer CTDP-32476. In a substitution test, cocaine self-administration rats displayed a progressive reduction in CTDP-32476 self-administration with an extinction pattern of drug-taking behavior, suggesting significantly lower addictive potential than cocaine. Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaine-associated cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbens. These findings suggest that CTDP-32476 is a unique DAT inhibitor that not only could satisfy ‘drug hunger' through its slow-onset long-lasting DAT inhibitor action, but also render subsequent administration of cocaine ineffectual—thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction. PMID:27534265

  10. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

    Directory of Open Access Journals (Sweden)

    Schmidt M

    2014-05-01

    Full Text Available Morten Schmidt,1 Jesper Hallas,2 Søren Friis1,31Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Pharmacology, University of Southern Denmark, Odense, Denmark; 3Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, DenmarkBackground: Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID use can be obtained from prescription registries.Objectives: To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify the proportion of total sales that was sold on prescription.Method: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription.Results: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence of prescribed low-dose aspirin increased throughout the study period, notably among men. Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs decreased moderately after 2004, but substantial variation according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92% for low-dose aspirin, 66% for ibuprofen, and 100% for all other NSAIDs.Conclusion: The potential for identifying NSAID use from prescription

  11. [Cancer screening service utilization and willingness-to-pay of urban populations in China: a cross-sectional survey from potential service demander's perspective].

    Science.gov (United States)

    Dong, P; Qiu, W Q; Shi, J F; Mao, A Y; Huang, H Y; Sun, Z X; Huang, J W; Liao, X Z; Liu, G X; Wang, D B; Bai, Y N; Sun, X J; Ren, J S; Guo, L W; Lan, L; Liu, Y Q; Gong, J Y; Yang, L; Xing, X J; Song, B B; Zhou, Q; Mai, L; Zhu, L; Du, L B; Zhang, Y Z; Zhou, J Y; Qin, M F; Wu, S L; Qi, X; Sun, X H; Lou, P A; Cai, B; Zhang, K; He, J; Dai, M

    2018-02-10

    Objective: To explore the sustainability of cancer screening strategy from potential demander's perspective in Chinese country, we conducted a study on the use of cancer screening services and willingness-to-pay among the urban community residents. All the participants of this study had not been on the Cancer Screening Program in Urban China (CanSPUC) or any other national level cancer screening projects. Methods: Target communities and populations were selected from the 16 project provinces in China which were on the program between 2014 and 2015, by using the multi-center cross-sectional convenience sampling method. Chi-square was used to compare the rates on the utilization of service and willingness-to-pay across the different subgroups. Logistic progression was conducted to examine factors that associated with the service utilization and willingness-to-pay. Results: A total of 16 394 participants were included in this study. Among them, 12.1% (1 984/16 394) had ever been on a cancer screening program. Populations with following characteristics as: being elderly (60-69 years, OR =1.27, 95% CI : 1.13-1.43), female (male, OR = 0.56, 95% CI : 0.50-0.62), having had higher education (high school/specialized secondary school, OR = 1.51, 95% CI : 1.35-1.70; college or over, OR =2.10, 95% CI : 1.36-3.25), working for public ( OR =2.85, 95% CI : 2.26-3.59), enterprises or self-employed agencies ( OR =1.32, 95% CI : 1.06-1.64), having higher income (60 000-150 000 Chinese Yuan, OR =1.55, 95% CI : 1.39-1.73; ≥150 000 Chinese Yuan, OR =2.57, 95% CI : 2.09-3.15), under basic medical insurance programs for urban employees/for government servants'( OR =1.15, 95% CI : 1.01-1.32), on basic medical insurance set for urban residents'/on commercial medical insurance programs etc . ( OR =1.01, 95% CI : 0.84-1.22), were in favor of the services. When neglecting the fee for charge, 65.8% (10 795/16 394) of the participants said that they could accept the cancer screening program

  12. Starch films: production, properties and potential of utilization / Filmes de amido: produção, propriedades e potencial de utilização

    Directory of Open Access Journals (Sweden)

    Fábio Yamashita

    2010-04-01

    Full Text Available There is an increasing interest in the utilization of renewable resources for the production of food packaging. Among the biopolymers, starches from several sources have been considered as one of the most promising material for this purpose, and the reasons for this are that starches are biodegradable, are inexpensive and available in the worldwide. This work presents a bibliography review about biodegradable starch films characterization and potential of utilization. Discusses the starch films mechanical and barrier properties, the cristallinity and the effects of the use of plasticizers over these properties. The discussed informations indicate that exist great possibilities for these materials in food packaging, which depend on the production of more stable materials and the development of production technology in industrial scale.O interesse no emprego de matérias-primas provenientes de recursos renováveis para a produção de embalagens de alimentos vem crescendo. Dentre os biopolímeros mais promissores para este fim estão os amidos de diversas fontes botânicas, que são biodegradáveis, têm custo baixo e estão disponíveis em todo o mundo. Diante disto, este trabalho apresenta uma revisão bibliográfica sobre a caracterização e o potencial de utilização de filmes biodegradáveis a base de amido. Discute as propriedades mecânicas, de barreira e a cristalinidade dos filmes de amido e o efeito do uso de plastificantes sobre estas propriedades. As informações disponibilizadas mostram que existem grandes possibilidades de utilização destes materiais como embalagens de alimentos que, no entanto, dependem da produção de materiais mais estáveis às condições de armazenamento e do desenvolvimento de tecnologia de produção em escala industrial.

  13. Efficacy and Safety of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus Treatment: Systematic Review

    Directory of Open Access Journals (Sweden)

    Ana Paula Martins

    2016-04-01

    Full Text Available Introduction: Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes mellitus that mimic the endogenous hormone glucagon-like peptide 1. Glucagon-like peptide 1 regulates glucose levels by stimulating glucose-dependent insulin secretion, suppressing glucagon secretion, delayed gastric emptying and promoting satiety. The individualized treatment of type 2 diabetes mellitus, using various glucagon--like peptide receptor agonists, has recently been described and the interest related to these drugs continues to grow. Objectives: To review the efficacy and safety of glucagon-like peptide 1 agonists in patients with inadequately controlled type 2 diabetes mellitus on metformin alone, highlighting their added value in therapeutic use comparatively to second line oral therapies used in type 2 diabetes mellitus. Methods: Studies were obtained from electronic searches of The Cochrane Library and PubMed. Randomized controlled trials were selected if they were at least 8 weeks in duration; compared a glucagon-like peptide 1 analogue with an oral anti-diabetic agent in patients experiencing inadequate glycemic control with metformin monotherapy; and reported hemoglobin A1c data in non-pregnant adults with type 2 diabetes mellitus. Results: Of 72 potentially relevant articles identified, 23 were retrieved for detailed evaluation and 10 met the inclusion criteria. The majority of glucagon-like peptide 1 agonists showed equivalent or superior efficacy than most active comparators for reducing hemoglobin A1c, with a greater proportion of patients achieving hemoglobin A1c <7%. Glucagon-like peptide 1 agonists also showed extra-glycemic effects such as weight loss and the reduction of important cardiovascular parameters. Side effects included gastrointestinal complications, mainly nausea, vomiting and diarrhea. The incidence of hypoglycemia was less common for this class of agents. Conclusion: Glucagon-like peptide 1

  14. Modeling of Dust Levels Associated with Potential Utility-Scale Solar Development in the San Luis Valley-Taos Plateau Study Area

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y. -S. [Argonne National Lab. (ANL), Argonne, IL (United States); Kotamarthi, R. [Argonne National Lab. (ANL), Argonne, IL (United States); Hartmann, H. M. [Argonne National Lab. (ANL), Argonne, IL (United States); Patton, T. [Argonne National Lab. (ANL), Argonne, IL (United States); Finster, M. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-07-01

    The San Luis Valley (SLV)–Taos Plateau study area in south-central Colorado and north-central New Mexico is a large alpine valley surrounded by mountains with an area of approximately 6,263,000 acres (25,345 km2) (Figure ES.1-1). This area receives ample sunshine throughout the year, making it an ideal location for solar energy generation, and there are currently five photovoltaic facilities operating on private lands in the SLV, ranging in capacity from 1 to 30 megawatt (MW). In 2012 the Bureau of Land Management (BLM) launched its Solar Energy Program, which included the identification of four solar energy zones (SEZs) in the SLV totaling 16,308 acres (66 km2), as well as over 50,000 (202 km2) acres of other BLM-administered lands potentially available for application for solar development. The SEZ areas, named Antonito Southeast, De Tilla Gulch, Fourmile East, and Los Mogotes East, were defined by the BLM as areas well-suited for utility-scale (i.e., larger than 20 MW) production of solar energy where solar energy development would be prioritized (BLM 2012). Nonetheless, it was recognized that solar development in the SEZs would result in some unavoidable adverse impacts, and so the BLM initiated a solar regional mitigation strategy (SRMS) study for three of the SEZs (BLM and Argonne 2016). The SRMS is designed to identify residual impacts of solar development in the SEZs (that is, those that cannot be avoided or minimized onsite), identify those residual impacts that warrant compensatory mitigation when considering the regional status and trends of the resources, identify appropriate regional compensatory mitigation locations and actions to address those residual impacts, and recommend appropriate fees to implement those compensatory mitigation measures.

  15. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

  16. Effects of the PPARγ agonist troglitazone on endothelial cells in vivo and in vitro: Differences between human and mouse

    International Nuclear Information System (INIS)

    Kakiuchi-Kiyota, Satoko; Vetro, Joseph A.; Suzuki, Shugo; Varney, Michelle L.; Han, Huai-Yun; Nascimento, Merielen; Pennington, Karen L.; Arnold, Lora L.; Singh, Rakesh K.; Cohen, Samuel M.

    2009-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists have been or are being developed for clinical use in the treatment of type 2 diabetes mellitus and hyperlipidemias. A common tumor finding in rodent carcinogenicity studies for these agonists is hemangioma/hemangiosarcoma in mice but not in rats. We hypothesized that increased endothelial cell proliferation may be involved in the mechanism of PPAR agonist-induced vascular tumors in mice, and we investigated the effects on endothelial cells utilizing troglitazone, the first clinically used PPARγ agonist, in vivo and in vitro. Troglitazone (400 and 800 mg/kg/day) induced hemangiosarcomas in mice in a 2-year bioassay. We showed that troglitazone increased endothelial cell proliferation in brown and white adipose tissue and liver in mice at sarcomagenic doses after 4 weeks of treatment. Troglitazone was cytotoxic both to human dermal microvascular endothelial cells (HMEC1) and mouse mammary fat pad microvascular endothelial cells (MFP MVEC) at high concentrations. However, MFP MVEC were more resistant to the cytotoxic effects of troglitazone based on the much lower LC 50 in HMEC1 (17.4 μM) compared to MFP MVEC (92.2 μM). Troglitazone increased the proliferation and survival of MFP MVEC but not HMEC1 in growth factor reduced conditions. Our data demonstrate that troglitazone may induce hemangiosarcomas in mice, at least in part, through enhancement of survival and proliferation of microvascular endothelial cells. Such an effect does not occur with human cells, suggesting that human may react differently to exposure to PPAR agonists compared with mice.

  17. Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare -up protocol in poor responders: a preliminary study.

    Science.gov (United States)

    Berker, Bülent; Duvan, Candan İltemir; Kaya, Cemil; Aytaç, Ruşen; Satıroğlu, Hakan

    2010-01-01

    To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI.

  18. (S-5-ethynyl-anabasine, a novel compound, is a more potent agonist than other nicotine alkaloids on the nematode Asu-ACR-16 receptor

    Directory of Open Access Journals (Sweden)

    Fudan Zheng

    2017-04-01

    Here, we describe the synthesis of a novel agonist, (S-5-ethynyl-anabasine, and show that it is more potent (EC50 0.14 ± 0.01 μM than other nicotine alkaloids on Asu-ACR-16. Agonists acting on ACR-16 receptors have the potential to circumvent drug resistance to anthelmintics, like levamisole, that do not act on the ACR-16 receptors.

  19. Agonistic anti-TIGIT treatment inhibits T cell responses in LDLr deficient mice without affecting atherosclerotic lesion development.

    Directory of Open Access Journals (Sweden)

    Amanda C Foks

    Full Text Available OBJECTIVE: Co-stimulatory and co-inhibitory molecules are mainly expressed on T cells and antigen presenting cells and strongly orchestrate adaptive immune responses. Whereas co-stimulatory molecules enhance immune responses, signaling via co-inhibitory molecules dampens the immune system, thereby showing great therapeutic potential to prevent cardiovascular diseases. Signaling via co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT directly inhibits T cell activation and proliferation, and therefore represents a novel therapeutic candidate to specifically dampen pro-atherogenic T cell reactivity. In the present study, we used an agonistic anti-TIGIT antibody to determine the effect of excessive TIGIT-signaling on atherosclerosis. METHODS AND RESULTS: TIGIT was upregulated on CD4(+ T cells isolated from mice fed a Western-type diet in comparison with mice fed a chow diet. Agonistic anti-TIGIT suppressed T cell activation and proliferation both in vitro and in vivo. However, agonistic anti-TIGIT treatment of LDLr(-/- mice fed a Western-type diet for 4 or 8 weeks did not affect atherosclerotic lesion development in comparison with PBS and Armenian Hamster IgG treatment. Furthermore, elevated percentages of dendritic cells were observed in the blood and spleen of agonistic anti-TIGIT-treated mice. Additionally, these cells showed an increased activation status but decreased IL-10 production. CONCLUSIONS: Despite the inhibition of splenic T cell responses, agonistic anti-TIGIT treatment does not affect initial atherosclerosis development, possibly due to increased activity of dendritic cells.

  20. Nicotine receptor partial agonists for smoking cessation

    Directory of Open Access Journals (Sweden)

    Kate Cahill

    Full Text Available BACKGROUND: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist and reducing smoking satisfaction (acting as an antagonist. OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist' in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialized register was in December 2011. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs, using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two recent cytisine trials (937 people

  1. Nicotine receptor partial agonists for smoking cessation.

    Science.gov (United States)

    Cahill, Kate; Stead, Lindsay F; Lancaster, Tim

    2012-04-18

    Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including cytisine, dianicline and varenicline for smoking cessation. We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, PsycINFO and Web of Science using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in December 2011. We also searched online clinical trials registers. We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. Two recent cytisine trials (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled RR of

  2. Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats

    DEFF Research Database (Denmark)

    Castoldi, Giovanna; di Gioia, Cira Rt; Bombardi, Camila

    2014-01-01

    Aim of the study was to evaluate the effect of compound 21 (C21), selective AT2 receptor agonist, in diabetic nephropathy and the potential additive effect of C21, when associated to losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The ...

  3. Oil drilling rig diesel power-plant fuel efficiency improvement potentials through rule-based generator scheduling and utilization of battery energy storage system

    International Nuclear Information System (INIS)

    Pavković, Danijel; Sedić, Almir; Guzović, Zvonimir

    2016-01-01

    Highlights: • Isolated oil drilling rig microgrid power flows are analyzed over 30 days. • Rule-based diesel generator scheduling is proposed to reduce fuel consumption. • A battery energy storage is parameterized and used for peak load leveling. • The effectiveness of proposed hybrid microgrid is verified by simulations. • Return-of-investment might be expected within 20% of battery system lifetime. - Abstract: This paper presents the development of a rule-based energy management control strategy suitable for isolated diesel power-plants equipped with a battery energy storage system for peak load shaving. The proposed control strategy includes the generator scheduling strategy and peak load leveling scheme based on current microgrid active and reactive power requirements. In order to investigate the potentials for fuel expenditure reduction, 30 days-worth of microgrid power flow data has been collected on an isolated land-based oil drilling rig powered by a diesel generator power-plant, characterized by highly-variable active and reactive load profiles due to intermittent engagements and disengagements of high-power electric machinery such as top-drive, draw-works and mud-pump motors. The analysis has indicated that by avoiding the low-power operation of individual generators and by providing the peak power requirements (peak shaving) from a dedicated energy storage system, the power-plant fuel efficiency may be notably improved. An averaged power flow simulation model has been built, comprising the proposed rule-based power flow control strategy and the averaged model of a suitably sized battery energy storage system equipped with grid-tied power converter and state-of-charge control system. The effectiveness of the proposed rule-based strategy has been evaluated by means of computer simulation analysis based on drilling rig microgrid active and reactive power data recorded during the 30 day period. The analysis has indicated that fuel consumption of

  4. Anticancer Role of PPARγ Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes

    Directory of Open Access Journals (Sweden)

    P. J. Simpson-Haidaris

    2010-01-01

    Full Text Available The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR-γ agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARγ agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARγ agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARγ and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.

  5. Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

    Directory of Open Access Journals (Sweden)

    Chenxi Zhai

    2014-11-01

    Full Text Available The transient receptor potential ankyrin 1 (TRPA1 cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.

  6. Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole.

    Science.gov (United States)

    Modi, Meera E; Inoue, Kiyoshi; Barrett, Catherine E; Kittelberger, Kara A; Smith, Daniel G; Landgraf, Rainer; Young, Larry J

    2015-07-01

    The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process. Peripheral administration of the brain penetrant MC3/4R receptor peptide agonist, Melanotan II (MTII), and the highly selective, small-molecule MC4R agonist, Pf-446687, enhanced partner preference formation in the prairie vole, but not in the non-monogamous meadow vole. MTII-induced partner preferences were enduring, as they were present 1 week after drug manipulation. The prosocial effects of MCR agonists may be mediated, in part, through modulation of OT, as coadministration of an OT receptor antagonist prevented MTII-induced partner preferences. MTII also selectively activated hypothalamic OT neurons and potentiated central OT release. As OT has been shown to enhance some aspects of social cognition in humans, our data suggest that the MC4R may be a viable therapeutic target for enhancing social function in psychiatric disorders, including autism spectrum disorders and schizophrenia, potentially through activation of the OT system.

  7. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

    Directory of Open Access Journals (Sweden)

    Eun Ju Oh

    2016-04-01

    Full Text Available BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2 and microphthalmia-associated transcription factor (MITF in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA and cAMP response element-binding protein (CREB activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

  8. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Lund, Asger; Knop, Filip K; Vilsbøll, Tina

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, secreted in response to ingestion of nutrients, and has important effects on several of the pathophysiological features of type 2 diabetes (T2D). The effects include potentiation of insulin secretion, suppression of glucagon secretion...... effects. This review gives an overview of the clinical data on GLP-1R agonists that have been compared in head-to-head studies and focuses on relevant differences between the compounds. Highlighting these similarities and differences could be beneficial for physicians in choosing the best treatment......, slowing of gastric emptying and suppression of appetite. In circulation, GLP-1 has a half-life of approximately 2min due to rapid degradation by the enzyme dipeptidyl peptidase 4 (DPP-4). Because of this short half-life GLP-1 receptor (GLP-1R) agonists, resistant to degradation by DPP-4 have been...

  9. Potential nitrous oxide yield of AOA vs. AOB and utilization of carbon and nitrogen in the ammonia oxidizing process in the Pearl River Estuary

    Science.gov (United States)

    Ma, L.; Dai, M.; Tan, S.; Xia, X.; Liu, H.

    2016-12-01

    Nitrous oxide (N2O), a greenhouse gas, is a by-product during ammonia oxidation process, the production of which is often stimulated under low dissolved oxygen (DO) in the estuarine environment. The potential yield of N2O has been considered to be driven by ammonia-oxidizing bacteria (AOB) of Betaproteobacteria & Gammaproteobacteria and/or ammonia-oxidizing archaea (AOA) of Thaumarchaeota. In order to examine the relative importance of AOA and AOB in producing N2O and in modulating the potential N2O yield, arch-amoA, beta-amoA, gamma-amoA encoding for the alpha subunit of the ammonia monooxygenase (AMO) are used as biomarkers to identify the distributions and bioactivities of AOA and AOB in the Pearl River Estuary (PRE). Size fractionation experiments were conducted to distinguish AOA and AOB on particles in different size-fractions of > 3 μm, 0.45-3 μm, and 0.22-0.45 μm. Pure culture of N. maritimusSCM1 was studied as a model organism to identify the organic carbon production during ammonia oxidation by SCM1 strains. Our results show that AOA distributes largely in the free-living state and could adapt to very limited ammonia substrate and low saturation of DO; AOB mainly distributes at the particle-attached state under relative richer ammonia and high DO conditions; however, the RNA/DNA ratio of AOB was higher than that of AOA under the same conditions suggesting AOB is relatively more actively expressed. In the upper reach of PRE, the dominant microorganism in the water column was AOB and the in situ N2O/NH3 therein ranged 0.73-3.74 ‰. In the lower PRE, AOA was dominated, and the in situ N2O/NH3 was of 1.17- 7.32‰. At selected sites, we estimated isotope effect (e) of AOA (eDIC/bulk) as -23.94‰ and AOB (eDIC/bulk) as -56.6‰ to -44.8‰, which is consistent with the studies of pure cultures. The coefficient of C sequestration "k", defined as (C biomass / DIC in situ) / (N biomass / ammonia in situ) to differ the utilization of carbon and nitrogen, of

  10. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    Science.gov (United States)

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

  11. MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Ayu Maha Iswari

    2013-04-01

    Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

  12. Factors affecting the potential of direct load control for non-generating utilities. Final report. [Distribution and wholesale power supply interaction

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-04-01

    Several alternatives are available for achieving load management, including direct or voluntary control of customer loads, customer or utility energy storage systems for diurnal load shifting, and expanded interconnection and operation of electric power systems. All of these alternatives are available to the fully integrated (generating, transmitting and distributing) electric utility and the analysis of their effects encompasses the power supply and delivery system. However, the costs and benefits of the alternatives to the fully integrated electric utility are perhaps not so obvious. Therefore, by considering a non-generating utility, this analysis focuses upon the distribution system and wholesale power supply interaction as a step toward an analysis including the power supply and delivery system. This report develops an analysis procedure and discusses some of the relevant factors to be consdered in the application of direct load control for a non-generating utility system. The analysis concentrates on the distribution system only to determine the effect of rates and payback as a result of direct load control. Thus, the study is responsive to the specific needs of the non-generating utility. This analysis of direct load control encompasses the determination of those loads amenable to control, the selection of a suitable one-way communications system to rend control and the estimation of expected benefits and costs. The complementary functions to the application of direct load control such as automatic meter reading via the addition of a bi-directional communications system and voltage control are not included in the analysis but are detailed for future consideration.

  13. Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Jennifer G. Robinson

    2008-01-01

    Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

  14. Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53.

    Science.gov (United States)

    Hsu, Hsi-Hsien; Kuo, Wei-Wen; Ju, Da-Tong; Yeh, Yu-Lan; Tu, Chuan-Chou; Tsai, Ying-Lan; Shen, Chia-Yao; Chang, Sheng-Huang; Chung, Li-Chin; Huang, Chih-Yang

    2014-11-28

    To investigate the effects of 17β-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student's t-test. The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10(-8) mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a potential alternative

  15. A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

    International Nuclear Information System (INIS)

    Finnema, Sjoerd J.; Seneca, Nicholas; Farde, Lars; Shchukin, Evgeny; Sovago, Judit; Gulyas, Balazs; Wikstroem, Hakan V.; Innis, Robert B.; Neumeyer, John L.; Halldin, Christer

    2005-01-01

    This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D 2 -like receptor agonist (R)-2- 11 CH 3 O-N-n-propylnorapomorphine ([ 11 C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D 2 receptor (D 2 R). MNPA is a selective D 2 -like receptor agonist with a high affinity (K i =0.17 nM). [ 11 C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [ 11 C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D 2 R, with a maximum striatum-to-cerebellum ratio of 2.23±0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37±0.06 at 72 min. The pretreatment study demonstrated high specific binding to D 2 R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [ 11 C]MNPA has potential as an agonist radioligand for the D 2 -like receptor and has potential for examination of the high-affinity state of the D 2 R in human subjects and patients with neuropsychiatric disorders

  16. Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

    DEFF Research Database (Denmark)

    Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek

    2008-01-01

    A library of robust ghrelin receptor mutants with single substitutions at 22 positions in the main ligand-binding pocket was employed to map binding sites for six different agonists: two peptides (the 28-amino-acid octanoylated endogenous ligand ghrelin and the hexapeptide growth hormone......, and PheVI:23 on the opposing face of transmembrane domain (TM) VI. Each of the agonists was also affected selectively by specific mutations. The mutational map of the ability of L-692,429 and GHRP-6 to act as allosteric modulators by increasing ghrelin's maximal efficacy overlapped with the common....... It is concluded that although each of the ligands in addition exploits other parts of the receptor, a large, common binding site for both small-molecule agonists--including ago-allosteric modulators--and the endogenous agonist is found on the opposing faces of TM-III and -VI of the ghrelin receptor....

  17. Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.

    Science.gov (United States)

    Tabassum, Nargis; Ma, Qianyun; Wu, Guanzhao; Jiang, Tao; Yu, Rilei

    2017-09-01

    Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure. This approximate treatment of interactions suggested that full agonists, partial agonists, and antagonists of the α7 nAChR possess distinctive binding energy profiles. Results from docking revealed that ligand binding efficacy may be related to the capacity of the ligand to stabilize conformational states with a closed C loop.

  18. Glass melting and its innovation potentials: the impact of the input and output geometries on the utilization of the melting space

    Czech Academy of Sciences Publication Activity Database

    Polák, M.; Němec, Lubomír

    2010-01-01

    Roč. 54, č. 3 (2010), s. 212-218 ISSN 0862-5468 R&D Projects: GA MPO 2A-1TP1/063 Institutional research plan: CEZ:AV0Z40320502 Keywords : space utilization, * sand dissolution * bubble removal * space geometry Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass Impact factor: 0.297, year: 2010

  19. Treatment of type 2 diabetes by free Fatty Acid receptor agonists

    DEFF Research Database (Denmark)

    Watterson, Kenneth R; Hudson, Brian D; Ulven, Trond

    2014-01-01

    been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long-chain FFA receptor, FFA1, improved glycemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand...... was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss, and reduces inflammation and the metabolic and anti...

  20. Nanoparticles containing a liver X receptor agonist inhibit inflammation and atherosclerosis.

    Science.gov (United States)

    Zhang, Xue-Qing; Even-Or, Orli; Xu, Xiaoyang; van Rosmalen, Mariska; Lim, Lucas; Gadde, Suresh; Farokhzad, Omid C; Fisher, Edward A

    2015-01-28

    Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP-LXR) exert anti-inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self-assembly of a biodegradable diblock poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) copolymer. NP-LXR is significantly more effective than free GW3965 at inducing LXR-target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr (-/-) mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP-LXR over 2 weeks markedly reduce the CD68-positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965-encapsulated PLGA-b-PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Beta-Adrenergic Receptors and Mechanisms in Asthma: The New Long-Acting Beta-Agonists

    Directory of Open Access Journals (Sweden)

    Robert G Townley

    1996-01-01

    Full Text Available The objective is to review β-adrenergic receptors and mechanisms in the immediate and late bronchial reaction in asthma and the new long-acting β-agonist. This will be discussed in light of the controversy of the potential adverse effect of regular use of long-acting β-agonists. We studied the effect of formoterol on the late asthmatic response (LAR and airway inflammation in guinea-pigs. Formoterol suppressed the LAR, antigen-induced airway inflammation and hyperresponsiveness, although isoproterenol failed to inhibit these parameters. β-Adrenergic hyporesponsiveness, and cholinergic and a- adrenergic hyperresponsiveness have been implicated in the pathogenesis of asthma. A decrease in β-adrenoreceptor function can result either from exogenously administered β-agonist or from exposure to allergens resulting in a late bronchial reaction. There is increasing evidence that eosinophils, macrophages, and lymphocytes which are of primary importance in the late bronchial reaction are also modulated by β2- adrenoreceptors. In functional studies of guinea-pig or human isolated trachea and lung parenchyma, PAF and certain cytokines significantly reduced the potency of isoproterenol to reverse methacholine- or histamine-induced contraction. The effect of glucocorticoids on pulmonary β-adrenergic receptors and responses suggests an important role for glucocorticoids to increase β-adrenergic receptors and responsiveness.

  2. Effects of local anesthetics on cholinergic agonist binding affinity of central nervous system. cap alpha. -bungarotoxin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.L.; Bennett, E.L.

    1979-12-01

    In general, pharmacological effects of local anesthetics may be attributed to their ability to reversibly block the propagation of nerve and muscle action potentials. At physiologically potent concentrations, local anesthetics (LA) also act as noncompetitive antagonists of the physiological response of post-synaptic nicotinic acetylcholine receptors (nAChR) to cholinergic agonists, and increase agonist binding affinities of nAChR from electric organ. It is postulated that the primary site of LA action on nAChR function is at the receptor-coupled ionophore. Furthermore, LA-nAChR ionophore interactions are thought to accelerate physiological desensitization of nAChR, manifest biochemically as increased affinity of nAChR for agonist. Specific receptors for ..cap alpha..-bungarotoxin (..cap alpha..-Bgt), a potent competitive antagonist at nAChR sites in the periphery, have been detected in rat central nervous system membrane preparations. The affinity of these central ..cap alpha..-Bgt receptors (..cap alpha..-BgtR) for cholinergic agonists is found to increase on exposure to agonist. Nevertheless, on the basis of inconsistent pharmacological and physiological results, uncertainty remains regarding the relationship between ..cap alpha..-BgtR and authentic nAChR in the CNS, despite a wide body of biochemical and histological evidence consistent with their identity. Reasoning that if CNS ..cap alpha..-BgtR are true in nAChR, coupled to functional ion channels, LA might be expected to cause biochemically measurable increases in ..cap alpha..-BgtR affinity for cholinergic agonists, we have undertaken a study of the effects of LA on the ability of acetylcholine (ACh) to inhibit interaction of ..cap alpha..-BgtR with /sup 3/H-labeled ..cap alpha..-Bgt.

  3. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

    Directory of Open Access Journals (Sweden)

    Marios Politis

    2017-01-01

    Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

  4. Prediction of selective estrogen receptor beta agonist using open data and machine learning approach.

    Science.gov (United States)

    Niu, Ai-Qin; Xie, Liang-Jun; Wang, Hui; Zhu, Bing; Wang, Sheng-Qi

    2016-01-01

    Estrogen receptors (ERs) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. ERs have been validated as important drug targets for the treatment of various diseases, including breast cancer, ovarian cancer, osteoporosis, and cardiovascular disease. ERs have two subtypes, ER-α and ER-β. Emerging data suggest that the development of subtype-selective ligands that specifically target ER-β could be a more optimal approach to elicit beneficial estrogen-like activities and reduce side effects. Herein, we focused on ER-β and developed its in silico quantitative structure-activity relationship models using machine learning (ML) methods. The chemical structures and ER-β bioactivity data were extracted from public chemogenomics databases. Four types of popular fingerprint generation methods including MACCS fingerprint, PubChem fingerprint, 2D atom pairs, and Chemistry Development Kit extended fingerprint were used as descriptors. Four ML methods including Naïve Bayesian classifier, k-nearest neighbor, random forest, and support vector machine were used to train the models. The range of classification accuracies was 77.10% to 88.34%, and the range of area under the ROC (receiver operating characteristic) curve values was 0.8151 to 0.9475, evaluated by the 5-fold cross-validation. Comparison analysis suggests that both the random forest and the support vector machine are superior for the classification of selective ER-β agonists. Chemistry Development Kit extended fingerprints and MACCS fingerprint performed better in structural representation between active and inactive agonists. These results demonstrate that combining the fingerprint and ML approaches leads to robust ER-β agonist prediction models, which are potentially applicable to the identification of selective ER-β agonists.

  5. Characterization of 12 GnRH peptide agonists - a kinetic perspective.

    Science.gov (United States)

    Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

    2016-01-01

    Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

  6. Identities of epilithic hydrocarbon-utilizing diazotrophic bacteria from the Arabian Gulf Coasts, and their potential for oil bioremediation without nitrogen supplementation.

    Science.gov (United States)

    Radwan, Samir; Mahmoud, Huda; Khanafer, Majida; Al-Habib, Aamar; Al-Hasan, Redha

    2010-08-01

    Gravel particles from four sites along the Arabian Gulf coast in autumn, winter, and spring were naturally colonized with microbial consortia containing between 7 and 400 × 10(2) cm(-2) of cultivable oil-utilizing bacteria. The 16S rRNA gene sequences of 70 representatives of oil-utilizing bacteria revealed that they were predominantly affiliated with the Gammaproteobacteria and the Actinobacteria. The Gammaproteobacteria comprised among others, the genera Pseudomonas, Pseudoalteromonas, Shewanella, Marinobacter, Psychrobacter, Idiomarina, Alcanivorax, Cobetia, and others. Actinobacteria comprised the genera Dietzia, Kocuria, Isoptericola, Rhodococcus, Microbacterium, and others. In autumn, Firmicutes members were isolated from bay and nonbay stations while Alphaproteobacteria were detected only during winter from Anjefa bay station. Fingerprinting by denaturing gradient gel electrophoresis of amplified 16S rRNA genes of whole microbial consortia confirmed the culture-based bacterial diversities in the various epilithons in various sites and seasons. Most of the representative oil-utilizing bacteria isolated from the epilithons were diazotrophic and could attenuate oil also in nitrogen-rich (7.9-62%) and nitrogen-free (4-54%) cultures, which, makes the microbial consortia suitable for oil bioremediation in situ, without need for nitrogen supplementation. This was confirmed in bench-scale experiments in which unfertilized oily seawater was bioremediated by epilithon-coated gravel particles.

  7. G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na+ channel interaction

    International Nuclear Information System (INIS)

    Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

    1988-01-01

    The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na + channels is a coupled event mediated by guanine nucleotide binding protein(s) [G-protein(s)]. These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of [ 3 H] acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of [ 3 H]batrachotoxin to Na + channel(s) in the presence of the muscarinic agonists; and (iii) muscarinically induced 22 Na + uptake in the presence and absence of tetrodotoxin, which blocks Na + channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na + channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na + channel-is such that at resting potential the muscarinic receptor induces opening of Na + channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues

  8. Interaction between corticosteroid and beta-agonist drugs. Biochemical and cardiovascular effects in normal subjects.

    Science.gov (United States)

    Taylor, D R; Wilkins, G T; Herbison, G P; Flannery, E M

    1992-08-01

    The aim of this study was to investigate whether the administration of prednisone potentiates any of the acute biochemical and cardiovascular effects of high-dose inhaled beta-agonist drugs. These agents are known to cause dose-related changes in plasma potassium and glucose, as well as ECG changes in heart rate, corrected QT interval (QTc), T wave, and U wave. On theoretical grounds, the concomitant use of systemic corticosteroids might enhance these actions. Twenty-four healthy subjects were randomized to receive one of three treatments: salbutamol 5 mg or fenoterol 5 mg or normal saline solution. Each drug was administered twice, 30 min apart by nebulizer, and the procedure was repeated after each subject had received prednisone 30 mg daily for one week. Plasma potassium and glucose levels were measured, and ECGs were obtained after each treatment, together with 12-h Holter monitoring for arrhythmias. Changes in plasma potassium and glucose following nebulized beta-agonist were significantly greater after treatment with prednisone. Baseline potassium level fell from 3.75 mmol/L (95 percent CI 3.61, 3.89) to 3.50 mmol/L (95 percent CI 3.36, 3.64), and thereafter all values were significantly lower at each time point (p = 0.003). The lowest mean plasma potassium was obtained 90 min after fenoterol administration with prednisone pretreatment: 2.78 mmol/L (95 percent CI 2.44, 3.13). Increases in heart rate and QTc interval following both beta-agonist drugs were significant, but T-wave amplitude reductions did not reach significance. Prednisone treatment did not significantly alter the cardiovascular responses. Supraventricular and ventricular ectopic activity was related to beta-agonist use, but no potentiating effect was noted following steroid treatment. We conclude that the acute biochemical effects of beta-agonist administration are augmented by prior treatment with prednisone, but this is not the case for ECG effects. However, the degree of hypokalemia noted as

  9. Identification of PPARgamma partial agonists of natural origin (II: in silico prediction in natural extracts with known antidiabetic activity.

    Directory of Open Access Journals (Sweden)

    Laura Guasch

    Full Text Available BACKGROUND: Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. METHODOLOGY/PRINCIPAL FINDINGS: From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally, we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. CONCLUSIONS/SIGNIFICANCE: Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused

  10. Unique interaction pattern for a functionally biased ghrelin receptor agonist

    DEFF Research Database (Denmark)

    Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

    2011-01-01

    Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

  11. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  12. Ecdysone Agonist: New Insecticides with Novel Mode of Action

    Directory of Open Access Journals (Sweden)

    Y. Andi Trisyono

    2002-12-01

    Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

  13. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  14. Metabolic engineering of a glycerol-oxidative pathway in Lactobacillus panis PM1 for utilization of bioethanol thin stillage: potential to produce platform chemicals from glycerol.

    Science.gov (United States)

    Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

    2014-12-01

    Lactobacillus panis PM1 has the ability to produce 1,3-propanediol (1,3-PDO) from thin stillage (TS), which is the major waste material after bioethanol production, and is therefore of significance. However, the fact that L. panis PM1 cannot use glycerol as a sole carbon source presents a considerable problem in terms of utilization of this strain in a wide range of industrial applications. Accordingly, L. panis PM1 was genetically engineered to directly utilize TS as a fermentable substrate for the production of valuable platform chemicals without the need for exogenous nutrient supplementation (e.g., sugars and nitrogen sources). An artificial glycerol-oxidative pathway, comprised of glycerol facilitator, glycerol kinase, glycerol 3-phosphate dehydrogenase, triosephosphate isomerase, and NADPH-dependent aldehyde reductase genes of Escherichia coli, was introduced into L. panis PM1 in order to directly utilize glycerol for the production of energy for growth and value-added chemicals. A pH 6.5 culture converted glycerol to mainly lactic acid (85.43 mM), whereas a significant amount of 1,3-propanediol (59.96 mM) was formed at pH 7.5. Regardless of the pH, ethanol (82.16 to 83.22 mM) was produced from TS fermentations, confirming that the artificial pathway metabolized glycerol for energy production and converted it into lactic acid or 1,3-PDO and ethanol in a pH-dependent manner. This study demonstrates the cost-effective conversion of TS to value-added chemicals by the engineered PM1 strain cultured under industrial conditions. Thus, application of this strain or these research findings can contribute to reduced costs of bioethanol production. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. An evaluation of selected in silico models for the assessment of skin sensitization potential – performance and practical utility considerations (QSAR conference)

    Science.gov (United States)

    Skin sensitization remains an important endpoint for consumers, manufacturers and regulators. Although the development of alternative approaches to assess skin sensitization potential has been extremely active over many years, the implication of regulations such as REACH and the ...

  16. Principles of agonist recognition in Cys-loop receptors

    Directory of Open Access Journals (Sweden)

    Timothy eLynagh

    2014-04-01

    Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

  17. In silico discovery of novel Retinoic Acid Receptor agonist structures

    Directory of Open Access Journals (Sweden)

    Samuels Herbert H

    2001-06-01

    Full Text Available Abstract Background Several Retinoic Acid Receptors (RAR agonists have therapeutic activity against a variety of cancer types; however, unacceptable toxicity profiles have hindered the development of drugs. RAR agonists presenting novel structural and chemical features could therefore open new avenues for the discovery of leads against breast, lung and prostate cancer or leukemia. Results We have analysed the induced fit of the active site residues upon binding of a known ligand. The derived binding site models were used to dock over 150,000 molecules in silico (or virtually to the structure of the receptor with the Internal Coordinates Mechanics (ICM program. Thirty ligand candidates were tested in vitro. Conclusions Two novel agonists resulting from the predicted receptor model were active at 50 nM. One of them displays novel structural features which may translate into the development of new ligands for cancer therapy.

  18. The risky business of dopamine agonists in Parkinson disease and impulse control disorders.

    Science.gov (United States)

    Claassen, Daniel O; van den Wildenberg, Wery P M; Ridderinkhof, K Richard; Jessup, Charles K; Harrison, Madaline B; Wooten, G Frederick; Wylie, Scott A

    2011-08-01

    Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly dopamine agonists (DAA). Behaviors associated with ICD include hypersexuality as well as compulsive gambling, shopping, and eating, and these behaviors are potentially linked to alterations to risk processing. Using the Balloon Analogue Risk Task, we assessed the role of agonist therapy on risk-taking behavior in PD patients with (n = 22) and without (n = 19) active ICD symptoms. Patients performed the task both "on" and "off" DAA. DAA increased risk-taking in PD patients with active ICD symptoms, but it did not affect risk behavior of PD controls. DAA dose was also important in explaining risk behavior. Both groups similarly reduced their risk-taking in high compared to low risk conditions and following the occurrence of a negative consequence, suggesting that ICD patients do not necessarily differ in their abilities to process and adjust to some aspects of negative consequences. Our findings suggest dopaminergic augmentation of risk-taking behavior as a potential contributing mechanism for the emergence of ICD in PD patients. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  19. Metabolic rate in different rat brain areas during seizures induced by a specific delta opiate receptor agonist.

    Science.gov (United States)

    Haffmans, J; De Kloet, R; Dzoljic, M R

    1984-06-04

    The glucose utilization during specific delta opiate agonist-induced epileptiform phenomena, determined by the [14C]2-deoxyglucose technique (2-DG), was examined in various rat brain areas at different time intervals. The peak in EEG spiking response and the most intensive 2-DG uptake occurred 5 min after intraventricular (i.v.t.) administration of the delta opiate receptor agonist. The most pronounced 2-DG uptake at this time interval can be observed in the subiculum, including the CA1 hippocampal area, frontal cortex and central amygdala. A general decrease of glucose consumption, compared to control values, is observed after 10 min, in all regions, with exception of the subiculum. Since functional activity and 2-DG uptake are correlated, we suggest that the subiculum and/or CA1 area, are probably the brain regions most involved in the enkephalin-induced epileptic phenomena.

  20. Estimating Utility

    DEFF Research Database (Denmark)

    Arndt, Channing; Simler, Kenneth R.

    2010-01-01

    A fundamental premise of absolute poverty lines is that they represent the same level of utility through time and space. Disturbingly, a series of recent studies in middle- and low-income economies show that even carefully derived poverty lines rarely satisfy this premise. This article proposes a......, with the current approach tending to systematically overestimate (underestimate) poverty in urban (rural) zones.......A fundamental premise of absolute poverty lines is that they represent the same level of utility through time and space. Disturbingly, a series of recent studies in middle- and low-income economies show that even carefully derived poverty lines rarely satisfy this premise. This article proposes...... an information-theoretic approach to estimating cost-of-basic-needs (CBN) poverty lines that are utility consistent. Applications to date illustrate that utility-consistent poverty measurements derived from the proposed approach and those derived from current CBN best practices often differ substantially...

  1. [Effects of GLP-1 receptor agonists on carbohydrate metabolism control].

    Science.gov (United States)

    Fernández-García, José Carlos; Colomo, Natalia; Tinahones, Francisco José

    2014-09-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  2. Investigation of the mechanism of radioprotective action of adrenoceptor agonists

    International Nuclear Information System (INIS)

    Kulinskij, V.I.; Klimova, A.D.; Yashunskij, V.G.; Alpatova, T.V.; 4205700SU)

    1986-01-01

    α-Adrenoceptor agonists of both main groups, i.e. arylalkylamines and imidazolines, have a pronounced radioprotective effect. Their chemical analogs, which fail to stimulate α-adrenoceptors, do not protect mice. The effect of phenylephrine, adrenaline, and noradrenaline comes into play via α 1 -adrenoceptors and that of clonidine, via α 2 -adrenoceptors and also via α 1 -adrenoceptors. Adrenoceptor agonists can probably manifest their radioprotective action via both subtypes of α-adrenoceptors. Possible intracellular mechanisms of the radioprotective action are discussed

  3. Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

    Science.gov (United States)

    Scarlett, Kisha A; White, El-Shaddai Z; Coke, Christopher J; Carter, Jada R; Bryant, Latoya K; Hinton, Cimona V

    2018-04-01

    G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease. Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728-39. ©2018 AACR . ©2018 American Association for Cancer Research.

  4. Evaluation of Computational Docking to Identify Pregnane X Receptor Agonists in the ToxCast Database

    OpenAIRE

    Kortagere, Sandhya; Krasowski, Matthew D.; Reschly, Erica J.; Venkatesh, Madhukumar; Mani, Sridhar; Ekins, Sean

    2010-01-01

    Background The pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion. Objectives As part of an evaluation of different approaches to predict compound affinity for nuclear hormone receptors, we used the molecular docking program GOLD and a hybrid scoring scheme based on similarity weighted GoldScores to predict potential PXR agonists in the ToxCast database of pesticides...

  5. Essential oils of culinary herbs and spices display agonist and antagonist activities at human aryl hydrocarbon receptor AhR.

    Science.gov (United States)

    Bartoňková, Iveta; Dvořák, Zdeněk

    2018-01-01

    Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise). Major constituents (>10%) of AhR-active EOs were studied in more detail. We identified AhR partial agonists (carvacrol, ligustilide, eugenol, eugenyl acetate, thymol, ar-turmerone) and antagonists (trans-anethole, butylidine phtalide, R/S-carvones, p-cymene), which account for AhR-mediated activities of EOs of fennel, anise, star anise, caraway, spearmint, tarragon, cloves, dill, turmeric, lovage, thyme and oregano. We also show that AhR-mediated effects of some individual constituents of EOs differ from those manifested in mixtures. In conclusion, EOs of culinary herbs and spices are agonists and antagonists of human AhR, implying a potential for food-drug interactions and interference with endocrine pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Water exposure assessment of aryl hydrocarbon receptor agonists in Three Gorges Reservoir, China using SPMD-based virtual organisms.

    Science.gov (United States)

    Wang, Jingxian; Bernhöft, Silke; Pfister, Gerd; Schramm, Karl-Werner

    2014-10-15

    SPMD-based virtual organisms (VOs) were deployed at five to eight sites in the Three Gorges Reservoir (TGR), China for five periods in 2008, 2009 and 2011. The water exposure of aryl hydrocarbon receptor (AhR) agonists was assessed by the VOs. The chosen bioassay response for the extracts of the VOs, the induction of 7-ethoxyresorufin-O-deethylase (EROD) was assayed using a rat hepatoma cell line (H4IIE). The results show that the extracts from the VOs could induce AhR activity significantly, whereas the chemically derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalent (TEQcal) accounted for water level reached a maximum of 175 m. Although the aqueous concentration of AhR agonists of 0.8-4.8 pg TCDDL(-1) in TGR was not alarming, the tendency of accumulating high concentration of AhR agonists in VO lipid and existence of possible synergism or antagonism in the water may exhibit a potential hazard to local biota being exposed to AhR agonists. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero.

    Science.gov (United States)

    Jia, Shihai; Zhou, Jing; Fanelli, Christopher; Wee, Yinshen; Bonds, John; Schneider, Pascal; Mues, Gabriele; D'Souza, Rena N

    2017-10-15

    Clefts of the palate and/or lip are among the most common human craniofacial malformations and involve multiple genetic and environmental factors. Defects can only be corrected surgically and require complex life-long treatments. Our studies utilized the well-characterized Pax9 -/- mouse model with a consistent cleft palate phenotype to test small-molecule Wnt agonist therapies. We show that the absence of Pax9 alters the expression of Wnt pathway genes including Dkk1 and Dkk2 , proven antagonists of Wnt signaling. The functional interactions between Pax9 and Dkk1 are shown by the genetic rescue of secondary palate clefts in Pax9 -/- Dkk1 f/+ ;Wnt1Cre embryos. The controlled intravenous delivery of small-molecule Wnt agonists (Dkk inhibitors) into pregnant Pax9 +/- mice restored Wnt signaling and led to the growth and fusion of palatal shelves, as marked by an increase in cell proliferation and osteogenesis in utero , while other organ defects were not corrected. This work underscores the importance of Pax9-dependent Wnt signaling in palatogenesis and suggests that this functional upstream molecular relationship can be exploited for the development of therapies for human cleft palates that arise from single-gene disorders. © 2017. Published by The Company of Biologists Ltd.

  8. Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.

    Science.gov (United States)

    Liu, Tao; Zhang, Yong; Liu, Yan; Wang, Ying; Jia, Haiqun; Kang, Mingchao; Luo, Xiaozhou; Caballero, Dawna; Gonzalez, Jose; Sherwood, Lance; Nunez, Vanessa; Wang, Danling; Woods, Ashley; Schultz, Peter G; Wang, Feng

    2015-02-03

    On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.

  9. GLP-1 receptor agonists in the treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Lamos, Elizabeth Mary; Malek, Rana; Davis, Stephen N

    2017-04-01

    Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed. Literature was searched from PubMed using appropriate search terms up to November 2016. Expert commentary: The available studies of GLP-1 RA therapy in the treatment of excess body weight in women with PCOS demonstrate that exenatide and liraglutide are effective in weight reduction either as monotherapy or in combination with metformin. A few studies showed that androgens may be modestly decreased and menstrual frequency may be increased. Eating behavior may be improved with liraglutide therapy. Glucose parameters are generally improved. GLP-1RAs were well-tolerated, with nausea being the most significant adverse side effect. Barriers to utilization may be the short duration studies, lack of familiarity of the medication, the route of administration (injection) and the variable outcomes on ovulation and hyperandrogenism.

  10. Potential of solid waste utilization as source of refuse derived fuel (RDF) energy (case study at temporary solid waste disposal site in West Jakarta)

    Science.gov (United States)

    Indrawati, D.; Lindu, M.; Denita, P.

    2018-01-01

    This study aims to measure the volume of solid waste generated as well asits density, composition, and characteristics, to analyze the potential of waste in TPS to become RDF materials and to analyze the best composition mixture of RDF materials. The results show that the average of solid waste generation in TPS reaches 40.80 m3/day, with the largest percentage of its share is the organic waste component of 77.9%, while the smallest amount of its share is metal and rubber of 0.1%. The average water content and ash content of solid waste at the TPS is 27.7% and 6.4% respectively, while the average calorific potential value is 728.71 kcal/kg. The results of solid waste characteristics comparison at three TPS indicate thatTPS Tanjung Duren has the greatest waste potential to be processed into RDF materials with a calorific value of 893.73 kcal/kg, water content level of 24.6%, andlow ash content of 6.11%. This research has also shown that the best composition for RDF composite materials is rubber, wood, and textile mixtureexposed to outdoor drying conditions because it produced low water content and low ash content of 10.8% and 9.6%, thus optimizedthe calorific value of 4,372.896 kcal/kg.

  11. Nutritional and anti-nutritional potential of three accessions of itching bean (Mucuna pruriens (L.) DC var. pruriens): an under-utilized tribal pulse.

    Science.gov (United States)

    Kala, Balasubiramanian Kamatchi; Mohan, Veerabahu Ramasamy

    2010-08-01

    Three accessions of the under-utilized legume itching bean (Mucuna pruriens var. pruriens) were analysed for proximate composition, mineral profiles, vitamins (niacin and ascorbic acid), fatty acid profiles, amino acid profiles of total seed protein, in vitro protein digestibility and certain anti-nutritional factors. All three accessions of M. pruriens var. pruriens contained higher amounts of crude protein and crude lipid when compared with most of the commonly consumed pulses. The fatty acid profiles revealed that the seed lipids contained a higher concentration of palmitic acid and linoleic acids. Amino acid profiles of M. pruriens var. pruriens revealed that the seed protein contained relatively higher levels of certain essential amino acids compared with the FAO/WHO requirement pattern. The investigated seeds are rich in minerals such as potassium, calcium, magnesium, phosphorus, iron and manganese. Anti nutritional substances such as total free phenolics, tannins, 3,4-dihydroxyphenylalanine, phytic acid, hydrogen cyanide, trypsin inhibitor activity, oligosaccharides and phytohaemagglutinating activity were investigated. The anti-nutritional fatty acid, behenic acid, also was detected in the present study.

  12. Method for estimating potential wetland extent by utilizing streamflow statistics and flood-inundation mapping techniques: Pilot study for land along the Wabash River near Terre Haute, Indiana

    Science.gov (United States)

    Kim, Moon H.; Ritz, Christian T.; Arvin, Donald V.

    2012-01-01

    Potential wetland extents were estimated for a 14-mile reach of the Wabash River near Terre Haute, Indiana. This pilot study was completed by the U.S. Geological Survey in cooperation with the U.S. Department of Agriculture, Natural Resources Conservation Service (NRCS). The study showed that potential wetland extents can be estimated by analyzing streamflow statistics with the available streamgage data, calculating the approximate water-surface elevation along the river, and generating maps by use of flood-inundation mapping techniques. Planning successful restorations for Wetland Reserve Program (WRP) easements requires a determination of areas that show evidence of being in a zone prone to sustained or frequent flooding. Zone determinations of this type are used by WRP planners to define the actively inundated area and make decisions on restoration-practice installation. According to WRP planning guidelines, a site needs to show evidence of being in an "inundation zone" that is prone to sustained or frequent flooding for a period of 7 consecutive days at least once every 2 years on average in order to meet the planning criteria for determining a wetland for a restoration in agricultural land. By calculating the annual highest 7-consecutive-day mean discharge with a 2-year recurrence interval (7MQ2) at a streamgage on the basis of available streamflow data, one can determine the water-surface elevation corresponding to the calculated flow that defines the estimated inundation zone along the river. By using the estimated water-surface elevation ("inundation elevation") along the river, an approximate extent of potential wetland for a restoration in agricultural land can be mapped. As part of the pilot study, a set of maps representing the estimated potential wetland extents was generated in a geographic information system (GIS) application by combining (1) a digital water-surface plane representing the surface of inundation elevation that sloped in the downstream

  13. GABA(B) receptors, schizophrenia and sleep dysfunction: a review of the relationship and its potential clinical and therapeutic implications.

    Science.gov (United States)

    Kantrowitz, Joshua; Citrome, Leslie; Javitt, Daniel

    2009-08-01

    Evidence for an intrinsic relationship between sleep, cognition and the symptomatic manifestations of schizophrenia is accumulating. This review presents evidence for the possible utility of GABA(B) receptor agonists for the treatment of subjective and objective sleep abnormalities related to schizophrenia. At the phenotypic level, sleep disturbance occurs in 16-30% of patients with schizophrenia and is related to reduced quality of life and poor coping skills. On the neurophysiological level, studies suggest that sleep deficits reflect a core component of schizophrenia. Specifically, slow-wave sleep deficits, which are inversely correlated with cognition scores, are seen. Moreover, sleep plays an increasingly well documented role in memory consolidation in schizophrenia. Correlations of slow-wave sleep deficits with impaired reaction time and declarative memory have also been reported. Thus, both behavioural insomnia and sleep architecture are critical therapeutic targets in patients with schizophrenia. However, long-term treatment with antipsychotics often results in residual sleep dysfunction and does not improve slow-wave sleep, and adjunctive GABA(A) receptor modulators, such as benzodiazepines and zolpidem, can impair sleep architecture and cognition in schizophrenia. GABA(B) receptor agonists have therapeutic potential in schizophrenia. These agents have minimal effect on rapid eye movement sleep while increasing slow-wave sleep. Preclinical associations with increased expression of genes related to slow-wave sleep production and circadian rhythm function have also been reported. GABA(B) receptor deficits result in a sustained hyperdopaminergic state and can be reversed by a GABA(B) receptor agonist. Genetic, postmortem and electrophysiological studies also associate GABA(B) receptors with schizophrenia. While studies thus far have not shown significant effects, prior focus on the use of GABA(B) receptor agonists has been on the positive symptoms of

  14. Thrombopoietin-receptor agonists in haematological disorders: The Danish experience

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Hasselbalch, Hans

    2011-01-01

    The objective of this study was to investigate the use of thrombopoietin-receptor agonists (TPO-ra) in patients with refractory primary immune thrombocytopenia (ITP) as well as off-label use of TPO-ra in Danish haematology departments. Hospital medical records from 32 of the 39 patients having re...

  15. Use of ß-adrenergic agonists in hybrid catfish

    Science.gov (United States)

    Ractopamine hydrochloride (RH) is a potent ß-adrenergic agonist that has been used in some species of fish to improve growth performance and dress out characteristics. While this metabolic modifier has been shown to have positive effects on growth of fish, little research has focused on the mechani...

  16. Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian

    2012-01-01

    FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metaboli...

  17. Synthesis and pharmacological characterization of novel inverse agonists acting on the viral-encoded chemokine receptor US28.

    Science.gov (United States)

    Hulshof, Janneke W; Vischer, Henry F; Verheij, Mark H P; Fratantoni, Silvina A; Smit, Martine J; de Esch, Iwan J P; Leurs, Rob

    2006-11-01

    G-protein coupled receptors encoded by viruses represent an unexplored class of potential drug targets. In this study, we describe the synthesis and pharmacological characterization of the first class of inverse agonists acting on the HCMV-encoded receptor US28. It is shown that replacement of the 4-hydroxy group of lead compound 1 with a methylamine group results in a significant 6-fold increase in affinity. Interestingly, increasing the rigidity of the spacer by the introduction of a double bond also leads to a significant increase in binding affinity compared to 1. These novel inverse agonists serve as valuable tools to elucidate the role of constitutive signaling in the pathogenesis of viral infection and may have therapeutic potential as leads for new antiviral drugs.

  18. Potential Bedside Utility of the Clock-Drawing Test in Evaluating Rapid Therapeutic Response in the Natural Course of Schizophrenia: A Preliminary Study.

    Science.gov (United States)

    Ransing, Ramdas Sarjerao; Khairkar, Praveen Homdeorao; Mishra, Kshirod; Sakekar, Gajanan

    2017-01-01

    The Clock-Drawing Test (CDT) is a brief, relatively time-efficient, easy to administer at bedside, and well-proven cognitive screening test that assesses a broad range of cognitive abilities in stroke, delirium, and dementia. However, challenges of comprehensive therapeutic outcome evaluations in schizophrenia can also be potentially overcome using CDT. The authors aimed to measure the therapeutic outcome using CDT in 101 schizophrenia patients, irrespective of their diagnostic subtypes. A repeated measures analysis of variance found that improvements on CDT and the Positive and Negative Syndrome Scale were closely correlated, reflecting critical information about therapeutic response measures in schizophrenia.

  19. Utilization of potentials - regular reduction of costs. An intelligent regulation and control of cooling furniture; Potenziale nutzen - Kosten geregelt senken. Intelligente Regelung und Steuerung von Kuehlmoebeln

    Energy Technology Data Exchange (ETDEWEB)

    Di Lieto, Gianluca [Wurm GmbH und Co. KG Elektronische Systeme, Remscheid (Germany). Bereich Vertrieb und Marketing

    2011-02-15

    The trade installs new, energy-efficient refrigerant plants and equips its salesrooms with energy-saving cooling furniture. In order to work in such a way that all potentials are exhausted an intelligent regulation and control is necessary. At the same time these systems help to fulfil legal requirements to a large extent automatically as for example with the security of food by means of a correct storage temperature (HACCP). But in the sense of a positive environmental balance, not all options are used by the users so far. They renounce savings with the energy in the two digit percent area due to an individual adjustment of the plant operation.

  20. Multiattribute Utility Theory without Expected Utility Foundations

    NARCIS (Netherlands)

    Stiggelbout, A.M.; Wakker, P.P.

    1995-01-01

    Methods for determining the form of utilities are needed for the implementation of utility theory in specific decisions. An important step forward was achieved when utility theorists characterized useful parametric families of utilities, and simplifying decompositions of multiattribute utilities.

  1. Multiattribute utility theory without expected utility foundations

    NARCIS (Netherlands)

    Wakker, P.P.; Miyamoto, J.

    1996-01-01

    Methods for determining the form of utilities are needed for the implementation of utility theory in specific decisions. An important step forward was achieved when utility theorists characterized useful parametric families of utilities, and simplifying decompositions of multiattribute utilities.

  2. Effect of beta-agonists on LAM progression and treatment.

    Science.gov (United States)

    Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

    2018-01-30

    Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

  3. Bio-energy utilizes surplusses at the agricultural commodity markets. Large potentials of the biomass; Bioenergie verwertet Ueberschuesse an den Agrarmaerkten. Grosse Potenziale der Biomasse

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-03-19

    At the beginning of spring in the northern hemisphere, the situation in agricultural markets relaxes visibly. After the year 2012 was characterized by periods of drought in the United States and some Eastern European countries, in recent months good harvests in major producing countries in the southern hemisphere have provided that the stocks of major agricultural commodities are grown again. Thus, enough resources are still available for the supply of food and energy. There still exists land potential in Europe and on other continents for the use of bio-energy. In addition to new power plant crops, known arable crop cultures contribute to the exploration of such a potential: An example of this is the sugar beet. The view on the global supply balance in agricultural goods inter alia the major staple food rice shows that there exist large surpluses on the food markets. However, these surpluses do not benefit the hungry persons in the world. Hunger is a problem of distribution which is not associated with the growth of bio-energy.

  4. Identifying patterns of general practitioner service utilisation and their relationship with potentially preventable hospitalisations in people with diabetes: The utility of a cluster analysis approach.

    Science.gov (United States)

    Ha, Ninh Thi; Harris, Mark; Preen, David; Robinson, Suzanne; Moorin, Rachael

    2018-04-01

    We aimed to characterise use of general practitioners (GP) simultaneously across multiple attributes in people with diabetes and examine its impact on diabetes related potentially preventable hospitalisations (PPHs). Five-years of panel data from 40,625 adults with diabetes were sourced from Western Australian administrative health records. Cluster analysis (CA) was used to group individuals with similar patterns of GP utilisation characterised by frequency and recency of services. The relationship between GP utilisation cluster and the risk of PPHs was examined using multivariable random-effects negative binomial regression. CA categorised GP utilisation into three clusters: moderate; high and very high usage, having distinct patient characteristics. After adjusting for potential confounders, the rate of PPHs was significantly lower across all GP usage clusters compared with those with no GP usage; IRR = 0.67 (95%CI: 0.62-0.71) among the moderate, IRR = 0.70 (95%CI 0.66-0.73) high and IRR = 0.76 (95%CI 0.72-0.80) very high GP usage clusters. Combination of temporal factors with measures of frequency of use of GP services revealed patterns of primary health care utilisation associated with different underlying patient characteristics. Incorporation of multiple attributes, that go beyond frequency-based approaches may better characterise the complex relationship between use of GP services and diabetes-related hospitalisation. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.

    Science.gov (United States)

    Newman-Tancredi, A; Gavaudan, S; Conte, C; Chaput, C; Touzard, M; Verrièle, L; Audinot, V; Millan, M J

    1998-08-21

    ' antipsychotic agents displayed antagonist properties at h5-HT1A sites with generally much lower affinity than at hD2 dopamine receptors. It is suggested that agonist activity at 5-HT1A receptors may be of utility for certain antipsychotic agents.

  6. Bilateral deficit in explosive force production is not caused by changes in agonist neural drive.

    Directory of Open Access Journals (Sweden)

    Matthew W Buckthorpe

    Full Text Available Bilateral deficit (BLD describes the phenomenon of a reduction in performance during synchronous bilateral (BL movements when compared to the sum of identical unilateral (UL movements. Despite a large body of research investigating BLD of maximal voluntary force (MVF there exist a paucity of research examining the BLD for explosive strength. Therefore, this study investigated the BLD in voluntary and electrically-evoked explosive isometric contractions of the knee extensors and assessed agonist and antagonist neuromuscular activation and measurement artefacts as potential mechanisms. Thirteen healthy untrained males performed a series of maximum and explosive voluntary contractions bilaterally (BL and unilaterally (UL. UL and BL evoked twitch and octet contractions were also elicited. Two separate load cells were used to measure MVF and explosive force at 50, 100 and 150 ms after force onset. Surface EMG amplitude was measured from three superficial agonists and an antagonist. Rate of force development (RFD and EMG were reported over consecutive 50 ms periods (0-50, 50-100 and 100-150 ms. Performance during UL contractions was compared to combined BL performance to measure BLD. Single limb performance during the BL contractions was assessed and potential measurement artefacts, including synchronisation of force onset from the two limbs, controlled for. MVF showed no BLD (P = 0.551, but there was a BLD for explosive force at 100 ms (11.2%, P = 0.007. There was a BLD in RFD 50-100 ms (14.9%, P = 0.004, but not for the other periods. Interestingly, there was a BLD in evoked force measures (6.3-9.0%, P<0.001. There was no difference in agonist or antagonist EMG for any condition (P≥0.233. Measurement artefacts contributed minimally to the observed BLD. The BLD in volitional explosive force found here could not be explained by measurement issues, or agonist and antagonist neuromuscular activation. The BLD in voluntary and evoked explosive force

  7. [The receptorial responsiveness method (RRM): a new possibility to estimate the concentration of pharmacologic agonists at their receptors].

    Science.gov (United States)

    Pák, Krisztián; Kiss, Zsuzsanna; Erdei, Tamás; Képes, Zita; Gesztelyi, Rudolf

    2014-01-01

    Cardiovascular disease is the biggest challenge in terms of life expectancy in developed countries. Adenosine contributes to the adaptation of the heart to ischemia and hypoxia, because adenosine, in addition to its metabolite role in the nucleic acid metabolism, is the endogenous agonist of the ubiquitous adenosine receptor family. Adenosine receptor activation is beneficial in most cases, it improves the balance between energy supply and consumption, reduces injury caused by stressors and inhibits the unfavorable tissue remodeling. Pharmacological manipulation of cardioprotective effects evoked by adenosine is an important, although to date not sufficiently utilized endeavor that may have therapeutic and preventive implications in cardiovascular diseases. As the ligand binding site of adenosine receptors is accessible from the extracellular space, it is especially important to know the adenosine concentration of the interstitial fluid ([Ado](ISF)). However, in the functioning heart, [Ado](ISF) values range in an extremely wide interval, spanning from nano- to micromolar concentrations, as estimated by the commonly used methods. Our recently developed procedure, the receptorial responsiveness method (RRM), may resolve this problem in certain cases. RRM enables quantification of an acute increase in the concentration of a pharmacological agonist, uniquely in the microenvironment of the receptors of the given agonist. As a limitation, concentration of agonists with short half-life (just like adenosine) at their receptors can only be quantified with the equieffective concentration of a stable agonist exerting the same action. In a previous study using RRM, inhibition of the transmembrane nucleoside transport in the euthyroid guinea pig atrium produced an increase in [Ado](ISF) that was equieffective with 18.8 +/- 3 nM CPA (N6-cyclopentyladenosine, a stable, selective A1 adenosine receptor agonist). This finding is consistent with observations of others, i.e., in the

  8. Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects

    Directory of Open Access Journals (Sweden)

    Esposito Emanuela

    2011-04-01

    Full Text Available Abstract Background Permanent functional deficits following spinal cord injury (SCI arise both from mechanical injury and from secondary tissue reactions involving inflammation. Enhanced release of adenosine and glutamate soon after SCI represents a component in the sequelae that may be responsible for resulting functional deficits. The role of adenosine A2A receptor in central ischemia/trauma is still to be elucidated. In our previous studies we have demonstrated that the adenosine A2A receptor-selective agonist CGS21680, systemically administered after SCI, protects from tissue damage, locomotor dysfunction and different inflammatory readouts. In this work we studied the effect of the adenosine A2A receptor antagonist SCH58261, systemically administered after SCI, on the same parameters. We investigated the hypothesis that the main action mechanism of agonists and antagonists is at peripheral or central sites. Methods Spinal trauma was induced by extradural compression of SC exposed via a four-level T5-T8 laminectomy in mouse. Three drug-dosing protocols were utilized: a short-term systemic administration by intraperitoneal injection, a chronic administration via osmotic minipump, and direct injection into the spinal cord. Results SCH58261, systemically administered (0.01 mg/kg intraperitoneal. 1, 6 and 10 hours after SCI, reduced demyelination and levels of TNF-α, Fas-L, PAR, Bax expression and activation of JNK mitogen-activated protein kinase (MAPK 24 hours after SCI. Chronic SCH58261 administration, by mini-osmotic pump delivery for 10 days, improved the neurological deficit up to 10 days after SCI. Adenosine A2A receptors are physiologically expressed in the spinal cord by astrocytes, microglia and oligodendrocytes. Soon after SCI (24 hours, these receptors showed enhanced expression in neurons. Both the A2A agonist and antagonist, administered intraperitoneally, reduced expression of the A2A receptor, ruling out the possibility that the

  9. Agonists and partial agonists of rhodopsin: retinal polyene methylation affects receptor activation.

    Science.gov (United States)

    Vogel, Reiner; Lüdeke, Steffen; Siebert, Friedrich; Sakmar, Thomas P; Hirshfeld, Amiram; Sheves, Mordechai

    2006-02-14

    Using Fourier transform infrared (FTIR) difference spectroscopy, we have studied the impact of sites and extent of methylation of the retinal polyene with respect to position and thermodynamic parameters of the conformational equilibrium between the Meta I and Meta II photoproducts of rhodopsin. Deletion of methyl groups to form 9-demethyl and 13-demethyl analogues, as well as addition of a methyl group at C10 or C12, shifted the Meta I/Meta II equilibrium toward Meta I, such that the retinal analogues behaved like partial agonists. This equilibrium shift resulted from an apparent reduction of the entropy gain of the transition of up to 65%, which was only partially offset by a concomitant reduction of the enthalpy increase. The analogues produced Meta II photoproducts with relatively small alterations, while their Meta I states were significantly altered, which accounted for the aberrant transitions to Meta II. Addition of a methyl group at C14 influenced the thermodynamic parameters but had little impact on the position of the Meta I/Meta II equilibrium. Neutralization of the residue 134 in the E134Q opsin mutant increased the Meta II content of the 13-demethyl analogue, but not of the 9-demethyl analogue, indicating a severe impairment of the allosteric coupling between the conserved cytoplasmic ERY motif involved in proton uptake and the Schiff base/Glu 113 microdomain in the 9-demethyl analogue. The 9-methyl group appears therefore essential for the correct positioning of retinal to link protonation of the cytoplasmic motif with protonation of Glu 113 during receptor activation.

  10. An Experimental Determination of the Quasi-Rest Potential of Copper Indium Disulfide Utilizing the Novel Open-Circuit Voltage Transient

    Science.gov (United States)

    Newell, Michael Jason

    Environmental sustainability requires resource management that takes future generations into account. The present generation has witnessed changes across the planet, unprecedented in human history and disrupting communities and cities around the world, due to shifting global climate. This is primarily the result of fossil fuels, which powered modern civilization but dramatically increased levels of CO2 and other greenhouse gases, and may be the least sustainable aspect of human civilization. Chapter 1 justifies the research from an environmental perspective and provides initial research parameters. Thin film photovoltaic (PV) modules are reported the most sustainable among energy production technologies currently available. Electrodeposited PV layers offer significant improvement to sustainability metrics over current thin film production methods, at reduced cost, but have rarely been demonstrated on an industrial scale. Quasi-rest potential (QRP) ultimately led to large-scale, electrodeposited thin film CdTe modules. An in-situ material characterization technique that allows adjustment of the deposition voltage (Vdep) to match the exact experimental conditions, QRP enabled precise control of deposit stoichiometry and crystallinity. Chapter 2 discusses theory and literature regarding QRP, and introduces the open-circuit voltage transient (Voc T), developed by the present research for analyzing QRP as a function of both Vdep and time. VocT data from a CdTe ethylene glycol bath matches details and speculations from the literature. Although predicted to have wide applicability, experimental QRP data have never been published for compounds unrelated to CdTe. Chapter 3 discusses VocTs performed in pursuit of electrodeposited CuInS2, demonstrating functionality as a QRP scan in a variety of ethylene glycol solutions. Stoichiometries of deposited films were improved by using the V ocT to determine appropriate plating voltages. VocTs enabled QRP, in-situ rest potential (EM

  11. Quantitative determination of biological activity of botulinum toxins utilizing compound muscle action potentials (CMAP), and comparison of neuromuscular transmission blockage and muscle flaccidity among toxins.

    Science.gov (United States)

    Torii, Yasushi; Goto, Yoshitaka; Takahashi, Motohide; Ishida, Setsuji; Harakawa, Tetsuhiro; Sakamoto, Takashi; Kaji, Ryuji; Kozaki, Shunji; Ginnaga, Akihiro

    2010-01-01

    The biological activity of various types of botulinum toxin has been evaluated using the mouse intraperitoneal LD(50) test (ip LD(50)). This method requires a large number of mice to precisely determine toxin activity, and so has posed a problem with regard to animal welfare. We have used a direct measure of neuromuscular transmission, the compound muscle action potential (CMAP), to evaluate the effect of different types of botulinum neurotoxin (NTX), and we compared the effects of these toxins to evaluate muscle relaxation by employing the digit abduction scoring (DAS) assay. This method can be used to measure a broad range of toxin activities the day after administration. Types A, C, C/D, and E NTX reduced the CMAP amplitude one day after administration at below 1 ip LD(50), an effect that cannot be detected using the mouse ip LD(50) assay. The method is useful not only for measuring toxin activity, but also for evaluating the characteristics of different types of NTX. The rat CMAP test is straightforward, highly reproducible, and can directly determine the efficacy of toxin preparations through their inhibition of neuromuscular transmission. Thus, this method may be suitable for pharmacology studies and the quality control of toxin preparations. Copyright 2009 Elsevier Ltd. All rights reserved.

  12. Serum-Based Quantification of MYCN Gene Amplification in Young Patients with Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Shigeki Yagyu

    Full Text Available We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB. Here, we analyzed the relationship between MYCN amplification (MNA status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86% and very high specificity (95%. The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4. MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01. The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00-24.78, and 1.41 (95% confidence interval, 0.63-3.14 for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status.

  13. The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin

    Directory of Open Access Journals (Sweden)

    Hung-Wen Lai

    2012-01-01

    Full Text Available HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3 cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr. In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer.

  14. β2 agonists in athletes. An ergogenic aid? = β2 agonistas en deportistas. ¿Una ayuda ergogénica?

    Directory of Open Access Journals (Sweden)

    Ospina Uribe, Carlos Fernando

    2013-01-01

    Full Text Available Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB. Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency, except salbutamol (maximum dose: 1.600 μg over 24 hours and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

  15. Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

    Science.gov (United States)

    Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

    2012-08-01

    Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Computer-aided discovery of aromatic L-α-amino acids as agonists of the orphan G protein-coupled receptor GPR139

    DEFF Research Database (Denmark)

    Ísberg, Vignir; Andersen, Kirsten Bayer; Bisig, Christoph

    2014-01-01

    GPR139 is an orphan G protein-coupled receptor expressed mainly in the central nervous system. We developed a pharmacophore model based on known GPR139 surrogate agonists which led us to propose aromatic-containing dipeptides as potential ligands. Upon testing, the dipeptides demonstrated agonism...... in the Gq pathway. Next, testing all 20 proteinogenic L-α-amino acids; L-tryptophan and L-phenylalanine were found to have EC50 values of 220 µM and 320 µM, respectively, making them the first putative endogenous agonists for GPR139....

  17. Prediction of selective estrogen receptor beta agonist using open data and machine learning approach

    Directory of Open Access Journals (Sweden)

    Niu AQ

    2016-07-01

    for the classification of selective ER-β agonists. Chemistry Development Kit extended fingerprints and MACCS fingerprint performed better in structural representation between active and inactive agonists. Conclusion: These results demonstrate that combining the fingerprint and ML approaches leads to robust ER-β agonist prediction models, which are potentially applicable to the identification of selective ER-β agonists. Keywords: estrogen receptor subtype β, selective estrogen receptor modulators, quantitative structure-activity relationship models, machine learning approach

  18. Intradermally administered TLR4 agonist GLA-SE enhances the capacity of human skin DCs to activate T cells and promotes emigration of Langerhans cells

    NARCIS (Netherlands)

    Schneider, Laura P.; Schoonderwoerd, Antoinet J.; Moutaftsi, Magdalini; Howard, Randall F.; Reed, Steven G.; de Jong, Esther C.; Teunissen, Marcel B. M.

    2012-01-01

    The natural TLR4 agonist lipopolysaccharide (LPS) has notable adjuvant activity. However, it is not useful as a vaccine adjuvant due to its toxicity. Glucopyranosyl lipid A (GLA) is a synthetic derivative of the lipid A tail of LPS with limited cytotoxicity, but strong potential to induce immune

  19. GnRH antagonist versus long agonist protocols in IVF

    DEFF Research Database (Denmark)

    Lambalk, C B; Banga, F R; Huirne, J A

    2017-01-01

    BACKGROUND: Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist...... was not the only variable between the compared study arms. OBJECTIVE AND RATIONALE: The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. SEARCH...... in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF...

  20. Utilities objectives

    International Nuclear Information System (INIS)

    Cousin, Y.; Fabian, H.U.

    1996-01-01

    The policy of French and german utilities is to make use of nuclear energy as a long term, competitive and environmentally friendly power supply. The world electricity generation is due to double within the next 30 years. In the next 20 to 30 years the necessity of nuclear energy will be broadly recognized. More than for most industries, to deal properly with nuclear energy requires the combination of a consistent political will, of a proper institutional framework, of strong and legitimate control authorities, of a sophisticated industry and of operators with skilled management and human resources. One of the major risk facing nuclear energy is the loss of competitiveness. This can be achieved only through the combination of an optimized design, a consistent standardization, a proper industrial partnership and a stable long term strategy. Although the existing plants in Western Europe are already very safe, the policy is clearly to enhance the safety of the next generation of nuclear plants which are designing today. The French and German utilities have chosen an evolutionary approach based on experience and proven technologies, with an enhanced defense in depth and an objective of easier operation and maintenance. The cost objective is to maintain and improve what has been achieved in the best existing power plants in both countries. This calls for rational choices and optimized design to meet the safety objectives, a strong standardization policy, short construction times, high availability and enough flexibility to enable optimization of the fuel cycle throughout the lifetime of the plants. The conceptual design phase has proven that the French and German teams from industry and from the utilities are able to pursue both the safety and the cost objectives, basing their decision on a rational approach which could be accepted by the safety authorities. (J.S.)

  1. Thorium utilization

    Energy Technology Data Exchange (ETDEWEB)

    Trauger, D B [Oak Ridge National Lab., TN (USA)

    1978-01-01

    Some of the factors that provide incentive for the utilization of thorium in specific reactor types are explored and the constraints that stand in the way are pointed out. The properties of thorium and derived fuels are discussed, and test and reactor operating experience is reviewed. In addition, symbiotic systems of breeder and converter reactor are suggested as being particularly attractive systems for energy production. Throughout the discussion, the High-Temperature Gas-Cooled Reactor and Molten Salt Reactor are treated in some detail because they have been developed primarily for use with thorium fuel cycles.

  2. Japanese utilities' plutonium utilization program

    International Nuclear Information System (INIS)

    Matsuo, Yuichiro.

    1996-01-01

    Japan's 10 utility companies are working and will continue to work towards establishing a fully closed nuclear fuel cycle. The key goals of which are: (1) reprocessing spent fuel; (2) recycling recovered uranium and plutonium; and (3) commercializing fast breeder technology by around the year 2030. This course of action by the Japanese electric power industry is in full accordance with Japan's national policy outlined in the government's report ''The Long-Term Program for Research, Development, and Nuclear Energy,'' which was published in June 1994. The Japanese civilian nuclear program is a long-term program that looks into the 21st century and beyond. It is quite true that sustaining the recycling option for energy security and the global environment demands a large investment. For it to be accepted by the public, safety must be the highest priority and will be pursued at a great cost if necessary. In its history, Japan has learned that as technology advances, costs will come down. The Japanese utility industry will continue investment in technology without compromising safety until the recycling option becomes more competitive with other options. This effort will be equally applied to the development of the commercial FBRs. The Japanese utility industry is confident that Japan's stable policy and strong objective to develop competitive and peaceful technology will contribute to the global economy and the environment without increasing the threat of plutonium proliferation

  3. Virtual screening studies of Chinese medicine Coptidis Rhizoma as alpha7 nicotinic acetylcholine receptor agonists for treatment of Alzheimer's disease

    Science.gov (United States)

    Xiang, Li; Xu, Youdong; Zhang, Yan; Meng, Xianli; Wang, Ping

    2015-04-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease. Extensive in vitro and in vivo experiments have proved that the decreased activity of the cholinergic neuron is responsible for the memory and cognition deterioration. The alpha7 nicotinic acetylcholine receptor (α7-nAChR) is proposed to a drug target of AD, and compounds which acting as α7-nAChR agonists are considered as candidates in AD treatment. Chinese medicine CoptidisRhizoma and its compounds are reported in various anti-AD effects. In this study, virtual screening, docking approaches and hydrogen bond analyses were applied to screen potential α7-nAChR agonists from CoptidisRhizome. The 3D structure of the protein was obtained from PDB database. 87 reported compounds were included in this research and their structures were accessed by NCBI Pubchem. Docking analysis of the compounds was performed using AutoDock 4.2 and AutoDock Vina. The images of the binding modes hydrogen bonds and the hydrophobic interaction were rendered with PyMOL1.5.0.4. and LigPlot+ respectively. Finally, N-tran-feruloyltyramine, isolariciresinol, flavanone, secoisolariciresinol, (+)-lariciresinol and dihydrochalcone, exhibited the lowest docking energy of protein-ligand complex. The results indicate these 6 compounds are potential α7 nAChR agonists, and expected to be effective in AD treatment.

  4. Open absorption heat pump for waste heat utilization in the forest industry. A study of technical and economic potential; Oeppen absorptionsvaermepump foer uppgradering av spillvaerme fraan skogsindustrin. Studie av teknisk och ekonomisk potential

    Energy Technology Data Exchange (ETDEWEB)

    Westermark, Mats; Vidlund, Anna

    2006-02-15

    Waste heat from the forest industry is mainly humid air or humid flue gases with somewhat too low dew point for direct use as district heating or for other qualified purposes. Upgrading of the temperature by heat pumps is thus often necessary for the full use of the waste heat. This study evaluates an open absorption heat, based on hygroscopic condensation. The hygroscopic condenser has the potential to replace mechanical heat pumps or conventional absorption heat pumps (based on lithium bromide) for the upgrading of heat from humid gases. The goal for the project is to evaluate technology and potential for an open absorption heat pump for heat recovery from humid gases in the forest industry. In an open heat pump the humid gas is brought in direct contact with the hygroscopic liquid (whereas a conventional heat pump uses an intermediate circuit with evaporation of water in the evaporator). The direct contact makes it possible to recover the heat at a higher temperature than the dew point of the humid gas without the use of evaporator. The target group for the study is the forest industry and its suppliers of technology and knowledge. The study has been carried out in cooperation with representatives from the forest industry and from suppliers of equipment. The study shows that the forest industry has good potential to upgrade waste heat from humid air to district heating. The waste heat can be extracted from various humid gases such as exit air from paper machines, wood driers, green liquid quenchers and flue gases from soda boilers, mesa kilns, bark-fired boilers and gas engines. Hygroscopic condensation is considered to give economic and environmental advantages compared to conventional absorption heat pumps due to much less consumption of driving heat. An interesting special case is the regeneration of the hygroscopic medium by direct contact with hot flue gases and for this application a patent application has been filed. Upgrading of waste heat to process

  5. Dopamine agonists and risk: impulse control disorders in Parkinson's; disease

    OpenAIRE

    Voon, Valerie; Gao, Jennifer; Brezing, Christina; Symmonds, Mkael; Ekanayake, Vindhya; Fernandez, Hubert; Dolan, Raymond J.; Hallett, Mark

    2011-01-01

    Impulse control disorders are common in Parkinson's; disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's; disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a ‘Sure’ choice an...

  6. Improving the developability profile of pyrrolidine progesterone receptor partial agonists

    Energy Technology Data Exchange (ETDEWEB)

    Kallander, Lara S.; Washburn, David G.; Hoang, Tram H.; Frazee, James S.; Stoy, Patrick; Johnson, Latisha; Lu, Qing; Hammond, Marlys; Barton, Linda S.; Patterson, Jaclyn R.; Azzarano, Leonard M.; Nagilla, Rakesh; Madauss, Kevin P.; Williams, Shawn P.; Stewart, Eugene L.; Duraiswami, Chaya; Grygielko, Eugene T.; Xu, Xiaoping; Laping, Nicholas J.; Bray, Jeffrey D.; Thompson, Scott K. (GSKPA)

    2010-09-17

    The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.

  7. Pharmacophore-driven identification of PPARγ agonists from natural sources

    DEFF Research Database (Denmark)

    Petersen, R. K.; Christensen, Kathrine Bisgaard; Assimopoulou, A. N.

    2011-01-01

    mastic gum fractions, whereas some other sub-fractions exhibited also biological activity towards PPARγ. The results from the present work are two-fold: on the one hand we demonstrate that the pharmacophore model we developed is able to select novel ligand scaffolds that act as PPARγ agonists; while...... at the same time it manifests that natural products are highly relevant for use in virtual screening-based drug discovery....

  8. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

    OpenAIRE

    Dietrich, Johannes W.; Landgrafe, Gabi; Fotiadou, Elisavet H.

    2012-01-01

    This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of th...

  9. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nic

    2010-01-01

    PET brain imaging of the serotonin 2A (5-hydroxytryptamine 2A, or 5-HT(2A)) receptor has been widely used in clinical studies, and currently, several well-validated radiolabeled antagonist tracers are used for in vivo imaging of the cerebral 5-HT(2A) receptor. Access to 5-HT(2A) receptor agonist...... PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3......)]methoxybenzyl)ethanamine ((11)C-CIMBI-5) and investigate its potential as a PET tracer....

  10. On the Pharmacology of Farnesoid X Receptor Agonists: Give me an “A”, Like in “Acid”

    Directory of Open Access Journals (Sweden)

    Eva Hambruch

    2016-06-01

    Full Text Available The Farnesoid X Receptor (FXR has recently moved into the spotlight through the release of clinical data using Obeticholic Acid, an FXR agonist, that demonstrated effectiveness of this bile acid-like drug in patients with Primary Biliary Cirrhosis and Non-alcoholic Steatohepatitis (NASH. FXR holds the promise to become an attractive drug target for various conditions, from Non-alcoholic Fatty Liver Disease (NAFLD, NASH, liver cirrhosis, portal hypertension and a variety of cholestatic disorders to intestinal diseases including inflammatory bowel disease and bile acid diarrhea. Despite the wide therapeutic potential, surprisingly little is known about the pharmacology, pharmacokinetics and tissue distribution properties of drugs targeting FXR. Are tissue specific FXR agonists preferable for different indications, or might one type of ligand fit all purposes? This review aims to summarize the sparse data which are available on this clinically and pharmacologically relevant topic and provides a mechanistic model for understanding tissue-specific effects in vivo.

  11. The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns (Review)

    Science.gov (United States)

    Zhou, Hongyan; Zhang, Wensong; Bi, Miaomiao; Wu, Jie

    2016-01-01

    Corneal alkali burns (CAB) are characterized by injury-induced inflammation, fibrosis and neovascularization (NV), and may lead to blindness. This review evaluates the current knowledge of the molecular mechanisms responsible for CAB. The processes of cytokine production, chemotaxis, inflammatory responses, immune response, cell signal transduction, matrix metalloproteinase production and vascular factors in CAB are discussed. Previous evidence indicates that peroxisome proliferator-activated receptor γ (PPAR-γ) agonists suppress immune responses, inflammation, corneal fibrosis and NV. This review also discusses the role of PPAR-γ as an anti-inflammatory, anti-fibrotic and anti-angiogenic agent in the treatment of CAB, as well as the potential role of PPAR-γ in the pathological process of CAB. There have been numerous studies evaluating the clinical profiles of CAB, and the aim of this systematic review was to summarize the evidence regarding the treatment of CAB with PPAR-γ agonists. PMID:27499172

  12. The potential of utilizing wood ash and peat ash on organic soils in Sweden; Arealer foer skogsgoedsling med traeaska och torvaska paa organogena jordar i Sverige

    Energy Technology Data Exchange (ETDEWEB)

    Haanell, Bjoern [Swedish Univ. of Agricultural Sciences, Umeaa (Sweden). Dept. of Silviculture

    2004-01-01

    Nutrients removed from the forest when branches and treetops are harvested as fuel can be returned to the site by recycling the remaining wood ash after combustion. This compensation measure is presently not carried out to any appreciable extent, partly because there is no economic incentive for the landowner. In sites where this measure has been applied, only on mineral soils (e.g. moraine) until now, greater margins for sustainable maintenance of the long-term site productivity can be expected. The ash contains all elements required for tree growth except for nitrogen (N). Therefore the ash amendment does not result in increased stand growth on these soils because the most important element for a growth response (N) is missing. In contrast, on organic soils N is often abundant whereas the amounts of other mineral nutrients are small. Thus, the elements lacking in the soils of peatland forests are available in the ash. This is especially true for phosphorus (P) and potassium (K). This means that peatland forests provide an opportunity for ash amendment in order to increase forest production. Old fertilization trials using wood ash show that the growth increase can be very large. The aim of this study was to (i) calculate the area of peat covered land that with respect to stand growth responses could be regarded as most suitable for bio-ash (wood ash and peat ash) fertilization, and (ii) assess the amount of bio-ash needed for fertilizing this area. Peat ash, although not as much studied, also has potential to be used to provide nutrients for increasing peatland forest growth. Most of the area calculations were based on data from the National Forest Inventory (NFI) 1997-2001. Sites were selected with guidance from existing knowledge about ash fertilization effects on tree growth and with the aid of registrations made in NFI regarding peat depth, site productivity, drainage, condition of drains, dominating field vegetation, and degree of stand development

  13. Multiattribute Utility Theory without Expected Utility Foundations

    NARCIS (Netherlands)

    J. Miyamoto (John); P.P. Wakker (Peter)

    1996-01-01

    textabstractMethods for determining the form of utilities are needed for the implementation of utility theory in specific decisions. An important step forward was achieved when utility theorists characterized useful parametric families of utilities and simplifying decompositions of multiattribute

  14. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  15. Dopamine agonist activity of EMD 23,448

    Energy Technology Data Exchange (ETDEWEB)

    Martin, G E; Pettibone, D J [Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania (USA). Dept. of Pharmacology

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED/sub 50/ greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81..mu..g/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses <=50 mg/i.p.). Moreover, EMD 23,448 was relatively weak in competing for (/sup 3/H)-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED/sub 50/ value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the ..gamma..-butyrolactone-induced increase in striatal dopa levels (ED/sub 50/ = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP.

  16. Dopamine agonist activity of EMD 23,448

    International Nuclear Information System (INIS)

    Martin, G.E.; Pettibone, D.J.

    1985-01-01

    EMD 23,448 was examined in tests of dopaminergic function and was found to be an atypical dopamine (DA) agonist. EMD 23,448 was a weak or inactive DA agonist when examined in tests of normal postsynaptic DA receptor function: production of stereotypy in the rat (ED 50 greater than sign 5.0 mg/kg.i.p.); production of emesis in beagles (minimum effective dose = 81μg/kg i.v.); and, enhanced locomotor activity of the mouse (no excitation in doses 3 H]-apomorphine binding to rat striatal membranes (Ki, 205 nM). On the other hand, this indolyl-3-butylamine did activate supersensitive postsynaptic DA receptors. Specifically, it elicited contralateral turning in rats with a unilateral 6-hydroxydopamine lesion of the substantia nigra (ED 50 value = 0.9 mg/kg) and did elicit stereotypy in rats given chronic daily haloperidol treatments. EMD 23,448 also exerted pharmacological effects in tests designed to measure activation of dopamine autoreceptors. It inhibited the γ-butyrolactone-induced increase in striatal dopa levels (ED 50 = 1 mg/kg i.p.) and produced a dose-related fall in the locomotor activity of the mouse. The results are discussed and contrasted with data derived for apomorphine and the putatively selective autoreceptor agonist (+-)-3-PPP. (Author)

  17. Agonizing care: care ethics, agonistic feminism and a political theory of care.

    Science.gov (United States)

    Cloyes, Kristin G

    2002-09-01

    'Care' is central to nursing theory and practice, and has been described in a variety of ways. Intense conversations about care have been developing in other fields of study as well, from the social sciences to the humanities. Care ethics has grown out of intellectual exchange between feminist thought, moral theory and the critique of traditional western political philosophy. However, care ethics is not without its critics, as these accounts of care have also sparked vigorous challenges. This paper traces the construct of care through nursing theory, care ethics, feminist critiques of moral and political theory and agonistic feminism to outline a set of problematics that a political theory of care should engage. It discusses how care is conventionally posited in more or less essentialist, universalizing and naturalizing terms. It introduces the ideas of feminist theorists who resist dichotomizing care and the political, and situate care in the context of power and politics. The tensions between care feminism and agonistic feminism are highlighted in order to explore the potential of theorizing both care and nursing in political terms.

  18. Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.

    Science.gov (United States)

    Ciancetta, Antonella; Jacobson, Kenneth A

    2017-03-11

    Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A₁, A 2A , A 2B and A₃, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A₃AR (hA₃AR) subtype is implicated in several cytoprotective functions. Therefore, hA₃AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure-activity relationships (SARs) of newly emerged A₃AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A₃AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates.

  19. Structural Probing and Molecular Modeling of the A3 Adenosine Receptor: A Focus on Agonist Binding

    Science.gov (United States)

    Ciancetta, Antonella; Jacobson, Kenneth A.

    2017-01-01

    Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR) subtypes, termed A1, A2A, A2B and A3, which belong to the G protein-coupled receptor (GPCR) superfamily. The human A3AR (hA3AR) subtype is implicated in several cytoprotective functions. Therefore, hA3AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure-activity relationships (SARs) of newly emerged A3AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM) data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A3AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates. PMID:28287473

  20. Structural Probing and Molecular Modeling of the A3 Adenosine Receptor: A Focus on Agonist Binding

    Directory of Open Access Journals (Sweden)

    Antonella Ciancetta

    2017-03-01

    Full Text Available Adenosine is an endogenous modulator exerting its functions through the activation of four adenosine receptor (AR subtypes, termed A1, A2A, A2B and A3, which belong to the G protein-coupled receptor (GPCR superfamily. The human A3AR (hA3AR subtype is implicated in several cytoprotective functions. Therefore, hA3AR modulators, and in particular agonists, are sought for their potential application as anti-inflammatory, anticancer, and cardioprotective agents. Structure-based molecular modeling techniques have been applied over the years to rationalize the structure–activity relationships (SARs of newly emerged A3AR ligands, guide the subsequent lead optimization, and interpret site-directed mutagenesis (SDM data from a molecular perspective. In this review, we showcase selected modeling-based and guided strategies that were applied to elucidate the binding of agonists to the A3AR and discuss the challenges associated with an accurate prediction of the receptor extracellular vestibule through homology modeling from the available X-ray templates.

  1. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors.

    Science.gov (United States)

    Secrest, Matthew H; Udell, Jacob A; Filion, Kristian B

    2017-04-01

    In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The effect of GLP-1 agonists on retinopathy remains a potential concern. In the only completed trial to date to assess a sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin reduced the risk of composite cardiovascular endpoints, predominantly through its impact on cardiovascular mortality and heart failure hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The electrophysiological effects of the serotonin 1A receptor agonist buspirone in emotional face processing.

    Science.gov (United States)

    Bernasconi, Fosco; Kometer, Michael; Pokorny, Thomas; Seifritz, Erich; Vollenweider, Franz X

    2015-04-01

    Emotional face processing is critically modulated by the serotonergic system, and serotonin (5-HT) receptor agonists impair emotional face processing. However, the specific contribution of the 5-HT1A receptor remains poorly understood. Here we investigated the spatiotemporal brain mechanisms underpinning the modulation of emotional face processing induced by buspirone, a partial 5-HT1A receptor agonist. In a psychophysical discrimination of emotional faces task, we observed that the discrimination fearful versus neutral faces were reduced, but not happy versus neutral faces. Electrical neuroimaging analyses were applied to visual evoked potentials elicited by emotional face images, after placebo and buspirone administration. Buspirone modulated response strength (i.e., global field power) in the interval 230-248ms after stimulus onset. Distributed source estimation over this time interval revealed that buspirone decreased the neural activity in the right dorsolateral prefrontal cortex that was evoked by fearful faces. These results indicate temporal and valence-specific effects of buspirone on the neuronal correlates of emotional face processing. Furthermore, the reduced neural activity in the dorsolateral prefrontal cortex in response to fearful faces suggests a reduced attention to fearful faces. Collectively, these findings provide new insights into the role of 5-HT1A receptors in emotional face processing and have implications for affective disorders that are characterized by an increased attention to negative stimuli. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  3. Sirtuin 1 Agonist Minimizes Injury and Improves the Immune Response Following Traumatic Shock.

    Science.gov (United States)

    Luciano, Jason A; Kautza, Benjamin; Darwiche, Sophie; Martinez, Silvia; Stratimirovic, Sladjana; Waltz, Paul; Sperry, Jason; Rosengart, Matthew; Shiva, Sruti; Zuckerbraun, Brian S

    2015-08-01

    Survival from traumatic injury requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a sirtuin 1 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following trauma. C57Bl/6 mice were subjected to a multiple trauma model. Mice were pretreated with either 100 mg/kg per day of the sirtuin 1 agonist, Srt1720, via oral gavage for 2 days prior to trauma and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) siRNA via hydrodynamic tail vein injection 48 h prior to trauma. Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following traumatic injury (P hepatic injury with significant reductions in serum alanine aminotransferase levels seen in mice treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following trauma-hemorrhage. Treatment with Srt1720 minimized the trauma-induced decreases in splenocyte proliferation (P clearance. The PGC1α signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against hepatic injury and minimize the immunosuppression that is seen following trauma-hemorrhage.

  4. Examining the safety of PPAR agonists - current trends and future prospects.

    Science.gov (United States)

    Bortolini, Michele; Wright, Matthew B; Bopst, Martin; Balas, Bogdana

    2013-01-01

    The peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists, fibrates and glitazones, are effective treatments for dyslipidemia and type 2 diabetes mellitus, respectively, but exhibit class-related, as well as compound-specific safety characteristics. This article reviews the profiles of PPAR-α, PPAR-γ, and dual PPAR-α/γ agonists with regard to class-related and compound-specific efficacy and adverse effects. We explore how learnings from first-generation drugs are being applied to develop safer PPAR-targeted therapies. The finding that rosiglitazone may increase risk for cardiovascular events has led to regulatory guidelines requiring demonstration of cardiovascular safety in appropriate outcome trials for new type 2 diabetes mellitus drugs. The emerging data on the possibly increased risk of bladder cancer with pioglitazone may prompt the need for post-approval safety studies for new drugs. Since PPAR-α and -γ affect key cardiometabolic risk factors (diabetic dyslipidemia, insulin resistance, hyperglycemia, and inflammation) in a complementary fashion, combining their benefits has emerged as a particularly attractive option. New PPAR-targeted therapies that balance the relative potency and/or activity toward PPAR-α and -γ have shown promise in retaining efficacy while reducing potential side effects.

  5. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  6. Agonistic behaviour in juvenile southern rock lobster, Jasus edwardsii (Decapoda, Palinuridae: implications for developing aquaculture

    Directory of Open Access Journals (Sweden)

    Chris Carter

    2014-11-01

    Full Text Available The Southern rock lobster, Jasus edwardsii, is a temperate species of spiny lobster with established well managed fisheries in Australia and New Zealand. It has also been under consideration as a species with aquaculture potential. Agonistic behaviour has important consequences under aquaculture conditions that encompass direct effects, such as damage or death of protagonists, and indirect effects on growth that relate to resource access, principally food and refuge. This study aimed to identify and characterize behaviours and to make a preliminary investigation of their occurrence under tank culture. Juvenile Jasus edwardsii were examined in a flow-through seawater system using a remote video camera system. Twenty-nine behaviours were divided into three sub-groups: aggressive (11, avoidance (6 and others (12. Aggressive behaviours included attacks, pushing, lifting, clasping and carrying an opponent. Avoidance behaviours included moving away in a backwards-, forwards- or side-stepping motion as well as with more vigorous tail flips. These behaviours were components of twelve behavioural groups that described contact, attack and displacement between individuals. Activity was crepuscular with two clear peaks, one in the morning and the other in the evening. The occurrence of behavioural groups was not different between the morning and evening. The frequency of aggressive behaviours was not affected by changes made to stocking density or access to food. The implications of agonistic behaviours are discussed further in relation to developing aquaculture.

  7. In vivo and in vitro studies on a muscarinic presynaptic antagonist and postsynaptic agonist: BM-5

    International Nuclear Information System (INIS)

    Nordstrom, O.; Bartafi, T.; Frieder, B.; Grimm, V.; Ladinsky, H.; Unden, A.

    1986-01-01

    This paper reports on in vitro and in vivo studies with compound BM-5 which, at proper dosage, could have great potential since it could enhance cholinergic transmission by being a presynaptic antagonist and postsynaptic agonist. Binding studies are described in which tritium-4-NMPB, a muscarinic antagonist, was displaced by compound BM-5 in membranes from striatum, cerebral cortex, cerebellum and hippocampus. The binding data are summarized, which for each brain area involved 86-92 data points evaluated by means of nonlinear regression methods. Compound BM-5 recognized in each brain region a population of high and a population of low affinity binding sites; both of which were labelled with tritium-4-NMPB. It is shown that compound BM-5 causes muscarinic cholinergic agonist-like effects such as redness of the eye, increased motility in the gut, and impairment of locomotor behavior. It also produces muscarinic super-sensitivity upon chronic treatment, and decreases rat striatial ACh content by acute treatment

  8. Vitamin D Receptor Agonists Target CXCL10: New Therapeutic Tools for Resolution of Inflammation

    Directory of Open Access Journals (Sweden)

    Sabino Scolletta

    2013-01-01

    Full Text Available Understanding the many biological extraskeletal actions of vitamin D has increased in the past decades. Indeed, vitamin D and analogue molecules, besides the classical actions on bone metabolism, exert several beneficial effects on metabolic homeostasis, heart-cardiovascular, brain, and muscle physiological functions, throughout the interaction with the specific vitamin D receptor (VDR. In particular, VDR agonists powerfully control innate and adaptive immune system with favorable effects on human health. VDR ligands act as immunomodulators that are potent enough to retain anti-inflammatory effects, even though the mechanism underlying those effects is not yet fully elucidated. VDR agonists exert a significant suppression of inflammatory processes switching the immune response from T helper 1 (Th1 to T helper 2 (Th2 dominance and counteracting the self-enhancing inflammatory loop between immune and resident cells, especially by cytokine release impairment. Those molecules are able, indeed, to reduce the release of the interferon (IFN-induced 10 kDa protein IP-10/CXCL10, a powerful chemokine driving Th1-mediated inflammation. Based on their features, VDR ligands show the potentiality to be included in immunosuppressive regimens, aimed to control auto- and alloimmune Th1-driven overreactivity, occurring, for example, in autoimmune disease or graft rejection.

  9. β-agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms.

    Directory of Open Access Journals (Sweden)

    Krzysztof Kolmus

    Full Text Available The proinflammatory cytokine Tumour Necrosis Factor (TNF-α is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with β-agonists modulates the TNF-α-induced inflammatory program. We observed that C2C12 myotubes express functional TNF receptor 1 (TNF-R1 and β2-adrenoreceptors (β2-ARs. TNF-α activated the canonical Nuclear Factor-κB (NF-κB pathway and Mitogen-Activated Protein Kinases (MAPKs, culminating in potent induction of NF-κB-dependent proinflammatory genes. Cotreatment with the β-agonist isoproterenol potentiated the expression of inflammatory mediators, including Interleukin-6 (IL-6 and several chemokines. The enhanced production of chemotactic factors upon TNF-α/isoproterenol cotreatment was also suggested by the results from migrational analysis. Whereas we could not explain our observations by cytoplasmic crosstalk, we found that TNF-R1-and β2-AR-induced signalling cascades cooperate in the nucleus. Using the IL-6 promoter as a model, we demonstrated that TNF-α/isoproterenol cotreatment provoked phosphorylation of histone H3 at serine 10, concomitant with enhanced promoter accessibility and recruitment of the NF-κB p65 subunit, cAMP-response element-binding protein (CREB, CREB-binding protein (CBP and RNA polymerase II. In summary, we show that β-agonists potentiate TNF-α action, via nuclear crosstalk, that promotes chromatin relaxation at selected gene promoters. Our data warrant further study into the mode of action of β-agonists and urge for caution in their use as therapeutic agents for muscular disorders.

  10. Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats.

    Directory of Open Access Journals (Sweden)

    Morten S Thomsen

    Full Text Available The α7 nicotinic acetylcholine receptor (nAChR is a potential target for the treatment of cognitive deficits in patients with schizophrenia, ADHD and Alzheimer's disease. Here we test the hypothesis that upregulation of α7 nAChR levels underlies the enhanced and sustained procognitive effect of repeated administration of α7 nAChR agonists. We further compare the effect of agonists to that of α7 nAChR positive allosteric modulators (PAMs, which do not induce upregulation of the α7 nAChR. Using the social discrimination test as a measure of short-term memory, we show that the α7 nAChR agonist A-582941 improves short-term memory immediately after repeated (7× daily, but not a single administration. The α7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects of agonists and PAMs that may be relevant for clinical development. Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration, suggesting that repeated administration of both agonists and PAMs may produce sustained effects on cognitive performance. Subsequent [(125I]-bungarotoxin autoradiography revealed no direct correlation between α7 nAChR levels in frontal cortical or hippocampal brain regions and short-term memory with either compound. Additionally, repeated treatment with A-582941 did not affect mRNA expression of RIC-3 or the lynx-like gene products lynx1, lynx2, PSCA, or Ly6H, which are known to affect nAChR function. In conclusion, both α7 nAChR agonists and PAMs exhibit sustained pro-cognitive effects after repeated administration, and altered levels of the α7 nAChR per se, or that of endogenous regulators of nAChR function, are likely not the major cause of this effect.

  11. The treatment of Parkinson's disease with dopamine agonists

    Directory of Open Access Journals (Sweden)

    Frank, Wilhelm

    2008-06-01

    Full Text Available Parkinson’s disease is a chronic degenerative organic disease with unknown causes. A disappearance of cells with melanin in the substantia nigra is considered as biological artefact of the disease, which causes a degenerative loss of neurons in the corpus striatum of mesencephalon. This structure produces also the transmitter substance dopamine. Due to this disappearance of cells dopamine is not produced in a sufficient quantity which is needed for movement of the body. The questions of this report are concerned the efficiency and safety of a treatment with dopamine agonists. Furthermore the cost-effectiveness is investigated as well as ethic questions. The goal is to give recommendation for the use of dopamine agonists to the German health system. A systematic literature search was done. The identified studies have different methodological quality and investigate different hypothesis and different outcome criteria. Therefore a qualitative method of information synthesis was chosen. Since the introduction of L-Dopa in the 1960´s it is considered as the most effective substance to reduce all the cardinal symptoms of Parkinson disease. This substance was improved in the course of time. Firstly some additional substances were given (decarbonxylase inhibitors, catechol-o-transferase inhibitors (COMT-inhibitors, monoaminoxydase-inhibitors (MAO-inhibitors and NMDA-antagonists (N-Methyl-d-aspartat-antagonists. In the practical therapy of Parkinson dopamine agonists play an important role, because they directly use the dopamine receptors. The monotherapy of Parkinson disease is basically possible and is used in early stages of the disease. Clinical practise has shown, that an add on therapy with dopamine agonists can led to a reduction of the dose of L-dopa and a reduction of following dyskinesia. The studies for effectiveness include studies for the initial therapy, monotherapy and add-on-therapy. Basically there is a good effectiveness of dopamine

  12. A pepducin derived from the third intracellular loop of FPR2 is a partial agonist for direct activation of this receptor in neutrophils but a full agonist for cross-talk triggered reactivation of FPR2.

    Directory of Open Access Journals (Sweden)

    Michael Gabl

    Full Text Available We recently described a novel receptor cross-talk mechanism in neutrophils, unique in that the signals generated by the PAF receptor (PAFR and the ATP receptor (P2Y2R transfer formyl peptide receptor 1 (FPR1 from a desensitized (non-signaling state back to an actively signaling state (Forsman H et al., PLoS One, 8:e60169, 2013; Önnheim K, et al., Exp Cell Res, 323∶209, 2014. In addition to the G-protein coupled FPR1, neutrophils also express the closely related receptor FPR2. In this study we used an FPR2 specific pepducin, proposed to work as an allosteric modulator at the cytosolic signaling interface, to determine whether the cross-talk pathway is utilized also by FPR2. The pepducin used contains a fatty acid linked to a peptide sequence derived from the third intracellular loop of FPR2, and it activates as well as desensensitizes this receptor. We now show that neutrophils desensitized with the FPR2-specific pepducin display increased cellular responses to stimulation with PAF or ATP. The secondary PAF/ATP induced response was sensitive to FPR2-specific inhibitors, disclosing a receptor cross-talk mechanism underlying FPR2 reactivation. The pepducin induced an activity in naïve cells similar to that of a conventional FPR2 agonist, but with lower potency (partial efficacy, meaning that the pepducin is a partial agonist. The PAF- or ATP-induced reactivation was, however, much more pronounced when neutrophils had been desensitized to the pepducin as compared to cells desensitized to conventional agonists. The pepducin should thus in this respect be classified as a full agonist. In summary, we demonstrate that desensitized FPR2 can be transferred back to an actively signaling state by receptor cross-talk signals generated through PAFR and P2Y2R, and the difference in agonist potency with respect to pepducin-induced direct receptor activation and cross-talk reactivation of FPR2 puts the concept of functional selectivity in focus.

  13. MELATONIN: POTENTIAL UTILITY FOR IMPROVING PUBLIC HEALTH

    Directory of Open Access Journals (Sweden)

    Russel J REITER; Fatih GULTEKIN; Luis J FLORES; Ma Pilar TERRON; Dun-Xian TAN

    2006-04-01

    Full Text Available This review summarizes the beneficial actions of melatonin in various experimental conditions/diseases and identifies where the use of melatonin may be helpful in improving public health. The nightly use of melatonin supplements by humans often improves their sleep and helps correct the circadian dyssynchronization associated with “jet lag”. Additionally, melatonin has been found effective in curtailing the growth of a variety of experimental cancers. Mechanistically, this is achieved by melatonin’s ability to limit fatty acid uptake, especially linoleic acid, by tumor cells. Fatty acids are growth factors for many tumors. Additionally, melatonin inhibits the elevated telomerase activity of tumor cells thus making them more fragile and vulnerable to chemotherapies. Melatonin also may inhibit angiogenesis in tumors by suppressing endothelin-1 production and the indole interferes with the stimulatory action of steroids on hormone-responsive tumors. As an ubiquitously-acting antioxidant, melatonin reduces cardiac damage during ischemia/reperfusion (I/R injury (heart attack and during I/R to the brain (stroke. Melatonin also limits the toxicity of amyloid  peptide and of neurofibrillary tangles, two of the cardinal signs of Alzheimer’s disease. Collectively, these data suggest supplementation with melatonin, whose endogenous levels decrease with age, may improve the quality of life in the aged and, as a consequence, be beneficial for public health generally. [TAF Prev Med Bull 2006; 5(2.000: 131-158

  14. characterization qualitative and potentialities of utilization of ...

    African Journals Online (AJOL)

    Y. M’Sadak et A. Ben M’Barek

    1 sept. 2016 ... e is obtained from the digester and the other two from the decanter (d. ) ...... Landry Ch., Lavallée S., Paré M. et Tremblay F. Recherche et ... Gauthier F., Gagnon S. et Dansereau B. Canadian Journal of Plant Science, 1998, vol.

  15. Zolpidem, a selective GABA(A) receptor alpha1 subunit agonist, induces comparable Fos expression in oxytocinergic neurons of the hypothalamic paraventricular and accessory but not supraoptic nuclei in the rat

    DEFF Research Database (Denmark)

    Kiss, Alexander; Søderman, Andreas; Bundzikova, Jana

    2006-01-01

    Functional activation of oxytocinergic (OXY) cells in the hypothalamic paraventricular (PVN), supraoptic (SON), and accessory (ACC) nuclei was investigated in response to acute treatment with Zolpidem (a GABA(A) receptor agonist with selectivity for alpha(1) subunits) utilizing dual Fos/OXY immun...

  16. Economic and environmental advantages for the utilization of the industrial potential of cogeneration in Mexico; Ventajas economicas y ambientales para el aprovechamiento del potencial industrial de cogeneracion en Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Leon de los Santos, G [Division de Estudios Posgrado, Facultad de ingenieria, Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    2003-01-15

    Mexico has an industrial cogeneration potential very important, not evaluated or projected within its historical growth. The objective of the present work consist of studying the industrial cogeneration potential that exists in Mexico, as well as the economic and environmental savings that it would be achieved if one took advantage of this potential. As a result of the present work we can conclude that the cogeneration in Mexico offers a theoretical potential middle of 28,000 MWe to the 2007. It is estimated an economic saving potential in the construction of generation infrastructure electrical, for the high stage of its utilization of almost 7000 million dollars and a stage of emissions reduction of 2007- 21.4%, instead of 2007- 0.35%, for the industrial sector of the country. Provided that change the vision of the government of seeing to the cogeneration as a measure of energy saving and substitute it by that of political of complement to the development of the national electrical sector. [Spanish] Mexico tiene un importante potencial de cogeneracion industrial que no ha sido evaluado ni proyectado dentro de su crecimiento historico, por ello, el objetito de este trabajo consiste en estudiar y conocer los ahorros economicos y ambientales que se podrian lograr si se aprovechara dicho potencial. Como resultado, se muestra que la cogeneracion en Mexico ofrece un potencial teorico medio de 28,000 MW e al ano 2007. Se estima tambien un ahorro economico en la construccion de infraestructura de generacion electrica para el escenario alto de su aprovechamiento de casi 7000 mdd, y un escenario de reduccion de emisiones para el sector industrial del pais de un 0.35% a un 21.47% para el ano 2007. Estos pronosticos se pueden lograr, siempre y cunado el gobierno cambie la vision de manejar este tema como una medida de ahorro de energia, y la sustituya por la politica de complemento al desarrollo del sector electrico nacional.

  17. Utility planning for decommissioning

    International Nuclear Information System (INIS)

    Williams, D.H.

    1982-01-01

    Though the biggest impact on a utility of nuclear power plant decommissioning may occur many years from now, procrastination of efforts to be prepared for that time is unwarranted. Foresight put into action through planning can significantly affect that impact. Financial planning can assure the recovery of decommissioning costs in a manner equitable to customers. Decision-making planning can minimize adverse affects of current decisions on later decommissioning impacts and prepare a utility to be equipped to make later decommissioning decisions. Technological knowledge base planning can support all other planning aspects for decommissioning and prepare a utility for decommissioning decisions. Informed project planning can ward off potentially significant pitfalls during decommissioning and optimize the effectiveness of the actual decommissioning efforts

  18. Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.

    Science.gov (United States)

    Hsieh, Wen-Chuan; Lan, Bau-Shin; Chen, Yi-Ling; Chang, Yao; Chuang, Huai-Chia; Su, Ih-Jen

    2010-01-01

    Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein-Barr virus and H5N1 influenza, that results from macrophage activation and pro inflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion. In this study, we adopted rosiglitazone, a PPAR-gamma agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5 x 10(7) copies of HVP. The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection (P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease (P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-alpha levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo. PPAR agonists could represent a potentially new agent for the therapy of VAHS.

  19. Simultaneous determination of β-agonists and monitoring in bovine tissues by liquid chromatography-tandem mass spectrometry

    Directory of Open Access Journals (Sweden)

    Kyunghun Jeong

    2018-01-01

    Full Text Available The misuse of β-agonists leads to a potential risk to public health and is forbidden in many countries. We developed a rapid, sensitive and reliable multi-residue detection method for zilpaterol, ractopamine, and clenbuterol in bovine tissues by liquid chromatography–tandem mass spectrometry. Residues were extracted in ethyl acetate after protein precipitation, and then analyzed by the developed method. Good linearities (R2 > 0.99 were observed, and the recoveries of zilpaterol, ractopamine, and clenbuterol were 99%, 74%, and 102%, respectively. The limits of quantitation for zilpaterol, ractopamine, and clenbuterol were 1.3, 5.0, and 1.7 ng/g, respectively. The method is also applied successfully to bovine tissues within the Korean National Residue Programme. None of the 3 β-agonists were detected from 50 domestic samples. However, zilpaterol (6.3 ng/g was quantified in one out of the 50 imported samples. The application of this method will be helpful in quality control analysis of β-agonists residues in bovine tissues.

  20. Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

    Science.gov (United States)

    Kim, Seong Min; Lee, Bonggi; An, Hye Jin; Kim, Dae Hyun; Park, Kyung Chul; Noh, Sang-Gyun; Chung, Ki Wung; Lee, Eun Kyeong; Kim, Kyung Mok; Kim, Do Hyun; Kim, Su Jeong; Chun, Pusoon; Lee, Ho Jeong; Moon, Hyung Ryong; Chung, Hae Young

    2017-07-11

    Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

  1. Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

    Science.gov (United States)

    Wang, Fei; Gao, Hua; Li, Chuzhong; Bai, Jiwei; Lu, Runchun; Cao, Lei; Wu, Yongtu; Hong, Lichuan; Wu, Yonggang; Lan, Xiaolei; Zhang, Yazhuo

    2014-01-01

    Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

  2. Utility training

    International Nuclear Information System (INIS)

    Villaros, P.E.; Luxo, Armando; Bruant, Jacques

    1977-01-01

    The study of operational training systems for electro-nuclear utilities may be conducted through two different approaches. A first analytical approach consists of determining, for each position of a given organization chart, the necessary qualifications required and the corresponding complementary training to be provided. This approach applies preferentially to existing classical systems which are converted to nuclear operation with objectives of minimum structural changes and conservation of maximum efficiency. A second synthetical approach consists of determining the specific characteristics of nuclear plant operation, then, of deducting the training contingencies and the optimized organization chart of the plant, while taking into account, at each step, the parameters linked to local conditions. This last approach is studied in some detail in the present paper, taking advantage of its better suitability to the problems raised at the first stage of an electro-nuclear program development. In this respect, the possibility offered by this apprach to coordinate the training system of a given nuclear power station personnel with the overall problem of developing a skilled industrial labor force in the country, may lead to reconsideration of some usual priorities in the economy of operation of the nuclear power plant

  3. Development of a novel severe triple allergen asthma model in mice which is resistant to dexamethasone and partially resistant to TLR7 and TLR9 agonist treatment.

    Directory of Open Access Journals (Sweden)

    Matthias J Duechs

    Full Text Available Severe asthma is characterised by persistent inflammation, hyperreactivity and remodeling of the airways. No efficient treatment is available, this is particularly the case for steroid resistant phenotypes. Our aim therefore was to develop a preclinical model showing characteristics of severe human asthma including steroid insensitivity. Mice were first sensitized with ovalbumin, extracts of cockroach or house dust mite followed by a challenge period of seven weeks. Further to this, an additional group of mice was sensitized with all three allergens and then challenged with allergen alternating weekly between allergens. All three allergens applied separately to the mice induced comparably strong Th2-type airway inflammation, airway hyperreactivity and airway remodeling, which was characterised by fibrosis and increased smooth muscle thickness. In contrast, application of all three allergens together resulted in a greater Th2 response and increased airway hyperreactivity and a stronger albeit not significant remodeling phenotype compared to using HDM or CRA. In this triple allergen model dexamethasone application, during the last 4 weeks of challenge, showed no suppressive effects on any of these parameters in this model. In contrast, both TLR7 agonist resiquimod and TLR9 agonist CpG-ODN reduced allergen-specific IgE, eosinophils, and collagen I in the lungs. The TLR9 agonist also reduced IL-4 and IL-5 whilst increasing IFN-γ and strongly IL-10 levels in the lungs, effects not seen with the TLR7 agonist. However, neither TLR agonist had any effect on airway hyperreactivity and airway smooth muscle mass. In conclusion we have developed a severe asthma model, which is steroid resistant and only partially sensitive to TLR7 and TLR9 agonist treatment. This model may be particular useful to test new potential therapeutics aiming at treating steroid resistant asthma in humans and investigating the underlying mechanisms responsible for steroid

  4. Statins and PPARα agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    International Nuclear Information System (INIS)

    Johnson, Timothy E.; Zhang, Xiaohua; Shi, Shu; Umbenhauer, Diane R.

    2005-01-01

    Statins and fibrates (weak PPARα agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPARα agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPARα compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPARγ agonist Rosiglitazone caused little or no cell death at up to 10 μM and the PPARδ ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPARα agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPARα agonism mediates in part the toxicity response to PPARα compounds. Furthermore, PPARα agonists and statins cause myotoxicity through distinct and independent pathways

  5. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Timothy E [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Zhang, Xiaohua [Department of Biometrics Research, Merck Research Laboratories, West Point, PA 19486 (United States); Shi, Shu [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Umbenhauer, Diane R [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States)

    2005-11-01

    Statins and fibrates (weak PPAR{alpha} agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPAR{alpha} agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPAR{alpha} compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPAR{gamma} agonist Rosiglitazone caused little or no cell death at up to 10 {mu}M and the PPAR{delta} ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPAR{alpha} agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPAR{alpha} agonism mediates in part the toxicity response to PPAR{alpha} compounds. Furthermore, PPAR{alpha} agonists and statins cause myotoxicity through distinct and independent pathways.

  6. The impact of therapeutic opioid agonists on driving-related psychomotor skills assessed by a driving simulator or an on-road driving task: A systematic review.

    Science.gov (United States)

    Ferreira, Diana H; Boland, Jason W; Phillips, Jane L; Lam, Lawrence; Currow, David C

    2018-04-01

    Driving cessation is associated with poor health-related outcomes. People with chronic diseases are often prescribed long-term opioid agonists that have the potential to impair driving. Studies evaluating the impact of opioids on driving-related psychomotor skills report contradictory results likely due to heterogeneous designs, assessment tools and study populations. A better understanding of the effects of regular therapeutic opioid agonists on driving can help to inform the balance between individual's independence and community safety. To identify the literature assessing the impact of regular therapeutic opioid agonists on driving-related psychomotor skills for people with chronic pain or chronic breathlessness. Systematic review reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement; PROSPERO Registration CRD42017055909. Six electronic databases and grey literature were systematically searched up to January, 2017. Inclusion criteria were as follows: (1) empirical studies reporting data on driving simulation, on-the-road driving tasks or driving outcomes; (2) people with chronic pain or chronic breathlessness; and (3) taking regular therapeutic opioid agonists. Critical appraisal used the National Institutes of Health's quality assessment tools. From 3809 records screened, three studies matched the inclusion criteria. All reported data on people with chronic non-malignant pain. No significant impact of regular therapeutic opioid agonists on people's driving-related psychomotor skills was reported. One study reported more intense pain significantly worsened driving performance. This systematic review does not identify impaired simulated driving performance when people take regular therapeutic opioid agonists for symptom control, although more prospective studies are needed.

  7. The effects of dopamine receptor 1 and 2 agonists and antagonists on sexual and aggressive behaviors in male green anoles.

    Science.gov (United States)

    Smith, Alexandra N; Kabelik, David

    2017-01-01

    The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa. In reptiles there have been few studies examining the relationship between dopaminergic receptors and social behaviors. We therefore examined the effects of D1 and D2 agonists and antagonists on sexual and aggressive behaviors in the male green anole lizard (Anolis carolinensis). Treatment with high doses of both D1 and D2 agonists was found to impair both sexual and aggressive behaviors. However, the D1 agonist treatment was also found to impair motor function, suggesting that those effects were likely nonspecific. Lower doses of both agonists and antagonists failed to affect social behaviors. These findings provide some evidence for D2 receptor regulation of social behaviors, but in contrast with previous research, these effects are all inhibitory and no effects were found for manipulations of D1 receptors. A potential reason for the lack of more widespread effects on social behaviors using moderate or low drug doses is that systemic injection of drugs resulted in effects throughout the whole brain, thus affecting counteracting circuits which negated one another, making measurable changes in behavioral output difficult to detect. Future studies should administer drugs directly into brain regions known to regulate sexual and aggressive behaviors.

  8. A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Wei-Hsuan; Lee, Bao-Hong; Chang, Yu-Ying [Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan (China); Hsu, Ya-Wen [SunWay Biotechnology Company, Taipei, Taiwan (China); Pan, Tzu-Ming, E-mail: tmpan@ntu.edu.tw [Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan (China)

    2013-11-01

    Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-γ (PPARγ) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPARγ agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to D-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPARγ-agonist activity were confirmed by Nrf2 and PPARγ reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes. - Highlights: • Monascin acts as a PPARgamma agonist. • Monascin activates Nrf2 and AMPK. • Monascin promotes MG metabolism into D-lactic acid. • Monascin attenuates inflammation and diabetes in vivo.

  9. Neuroprotective and memory-related actions of novel alpha-7 nicotinic agents with different mixed agonist/antagonist properties.

    Science.gov (United States)

    Meyer, E M; Tay, E T; Zoltewicz, J A; Meyers, C; King, M A; Papke, R L; De Fiebre, C M

    1998-03-01

    The goals of this study were to develop compounds that were selective and highly efficacious agonists at alpha-7 receptors, while varying in antagonist activity; and to test the hypothesis that these compounds had memory-related and neuroprotective actions associated with both agonist and antagonist alpha-7 receptor activities. Three compounds were identified; E,E-3-(cinnamylidene)anabaseine (3-CA), E,E-3-(2-methoxycinnamylidene) anabaseine (2-MeOCA) and E,E-3-(4-methoxycinnamylidene) anabaseine (4-MeOCA) each displaced [125I]alpha-bungarotoxin binding from rat brain membranes and activated rat alpha-7 receptors in a Xenopus oocyte expression system fully efficaciously. The potency series for binding and receptor activation was 2-MeOCA > 4-MeOCA = 3-CA and 2-MeOCA = 3-CA > 4-MeOCA, respectively. No compound significantly activated oocyte-expressed alpha-4beta-2 receptors. Although each cinnamylidene-anabaseine caused a long-term inhibition of alpha-7 receptors, as measured by ACh-application 5 min later, this inhibition ranged considerably, from less than 20% (3-CA) to 90% (2-MeOCA) at an identical concentration (10 microM). These compounds improved passive avoidance behavior in nucleus basalis lesioned rats, with 2-MeOCA most potent in this respect. In contrast, only 3-CA was neuroprotective against neurite loss during nerve growth factor deprivation in differentiated rat pheochromocytoma (PC12) cells. Choline, an efficacious alpha-7 agonist without antagonist activity, was also protective in this model. These results suggest that the neurite-protective action of alpha-7 receptor agonists may be more sensitive to potential long-term antagonist properties than acute behavioral actions are.

  10. Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis.

    LENUS (Irish Health Repository)

    McNally, P

    2011-07-22

    BACKGROUND: 1,25-Dihydroxycholecalciferol (1,25(OH)(2)D(3)) has been shown to mitigate epithelial inflammatory responses after antigen exposure. Patients with cystic fibrosis (CF) are at particular risk for vitamin D deficiency. This may contribute to the exaggerated inflammatory response to pulmonary infection in CF. METHODS: CF respiratory epithelial cell lines were exposed to Pseudomonas aeruginosa lipopolysaccharide (LPS) and Pseudomonas conditioned medium (PCM) in the presence or absence of 1,25(OH)(2)D(3) or a range of vitamin D receptor (VDR) agonists. Levels of IL-6 and IL-8 were measured in cell supernatants, and cellular total and phosphorylated IκBα were determined. Levels of human cathelicidin antimicrobial peptide (hCAP18) mRNA and protein were measured in cells after treatment with 1,25(OH)(2)D(3). RESULTS: Pretreatment with 1,25(OH)(2)D(3) was associated with significant reductions in IL-6 and IL-8 protein secretion after antigen exposure, a finding reproduced with a range of low calcaemic VDR agonists. 1,25(OH)(2)D(3) treatment led to a decrease in IκBα phosphorylation and increased total cellular IκBα. Treatment with 1,25(OH)(2)D(3) was associated with an increase in hCAP18\\/LL-37 mRNA and protein levels. CONCLUSIONS: Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.

  11. The effects of dopamine receptor 1 and 2 agonists and antagonists on sexual and aggressive behaviors in male green anoles.

    Directory of Open Access Journals (Sweden)

    Alexandra N Smith

    Full Text Available The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa. In reptiles there have been few studies examining the relationship between dopaminergic receptors and social behaviors. We therefore examined the effects of D1 and D2 agonists and antagonists on sexual and aggressive behaviors in the male green anole lizard (Anolis carolinensis. Treatment with high doses of both D1 and D2 agonists was found to impair both sexual and aggressive behaviors. However, the D1 agonist treatment was also found to impair motor function, suggesting that those effects were likely nonspecific. Lower doses of both agonists and antagonists failed to affect social behaviors. These findings provide some evidence for D2 receptor regulation of social behaviors, but in contrast with previous research, these effects are all inhibitory and no effects were found for manipulations of D1 receptors. A potential reason for the lack of more widespread effects on social behaviors using moderate or low drug doses is that systemic injection of drugs resulted in effects throughout the whole brain, thus affecting counteracting circuits which negated one another, making measurable changes in behavioral output difficult to detect. Future studies should administer drugs directly into brain regions known to regulate sexual and aggressive behaviors.

  12. Estrogen receptor beta-selective agonists stimulate calcium oscillations in human and mouse embryonic stem cell-derived neurons.

    Directory of Open Access Journals (Sweden)

    Lili Zhang

    2010-07-01

    Full Text Available Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERalpha and ERbeta on calcium oscillations in neurons derived from human (hES and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERbeta, but not ERalpha. The non-selective ER agonist 17beta-estradiol (E(2 rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERalpha agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyltrisphenol (PPT. In contrast, the selective ERbeta agonists, 2,3-bis(4-Hydroxyphenyl-propionitrile (DPN, MF101, and 2-(3-fluoro-4-hydroxyphenyl-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041 stimulated calcium oscillations similar to E(2. The ERbeta agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERbeta activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERbeta signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds.

  13. Build Resilience at Your Utility

    Science.gov (United States)

    CREAT allows users to evaluate potential impacts of climate change on their utility and to evaluate adaptation options to address them using both traditional risk assessment and scenario-based decision making.

  14. FY 1999 report on the potential survey of the environmentally friendly type coal utilization system - Dispatch of engineers. A. Project for supporting the introduction of the environmentally friendly type coal utilization system (model project)/pre-survey for the potential survey; 1999 nendo kankyo chowa gata sekitan riyo system kanosei chosa. Senmomka haken A. kankyo chowa gata sekitan riyo system donyu shien jigyo (model jigyo) - Kanosei chosa no jizen chosa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    For the purpose of the improvement of coal utilization technology and environmental preservation, the paper conducted the pre-survey of the introduction of coke oven gas desulfurization facilities in China and pre-survey of potentiality of the environmentally friendly type coal utilization system in India. The pre-survey in China was made for Anyang Steel Group Co. Ltd. and Laiwu Steel Group Co. Ltd. to judge their adaptability as site for the demonstrative project on the introduction of coke oven gas desulfurization facilities. As a result, it was confirmed that the former satisfied the conditions on Japan side such as the space for installation and prospect for fund raising. However, the amount of COG treatment was larger than that planned at Japan side, and it was found that as to the recovered sulfur, the company wanted the solid sulfur different from the fused sulfur planned at Japan side. In the survey in India, explanations were made to India of CFBC and the fluidized bed cement sintering system, bio-briquette production facilities, facilities for environmental measures, coal reforming technology, etc. At the same time, the site survey was made to examine/analyze possibilities of spread/development of Japan's CCT. (NEDO)

  15. Discovery of Nanomolar Desmuramylpeptide Agonists of the Innate Immune Receptor Nucleotide-Binding Oligomerization Domain-Containing Protein 2 (NOD2) Possessing Immunostimulatory Properties.

    Science.gov (United States)

    Gobec, Martina; Tomašič, Tihomir; Štimac, Adela; Frkanec, Ruža; Trontelj, Jurij; Anderluh, Marko; Mlinarič-Raščan, Irena; Jakopin, Žiga

    2018-04-12

    Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants, and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis, and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date. Compound 9 augmented pro-inflammatory cytokine release from human peripheral blood mononuclear cells in synergy with lipopolysaccharide. Furthermore, it was able to induce ovalbumin-specific IgG titers in a mouse model of adjuvancy. These findings provide deeper insights into the structural requirements of desmuramylpeptides for NOD2-activation and highlight the potential use of NOD2 agonists as adjuvants for vaccines.

  16. Cardiovascular safety and benefits of GLP-1 receptor agonists

    DEFF Research Database (Denmark)

    Dalsgaard, Niels B; Brønden, Andreas; Lauritsen, Tina Vilsbøll

    2017-01-01

    INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) constitute a class of drugs for the treatment of type 2 diabetes, and currently, six different GLP-1RAs are approved. Besides improving glycemic control, the GLP-1RAs have other beneficial effects such as weight loss...... and a low risk of hypoglycemia. Treatment with the GLP-1RA lixisenatide has been shown to be safe in patients with type 2 diabetes and recent acute coronary syndrome. Furthermore, liraglutide and semaglutide have been shown to reduce cardiovascular (CV) disease (CVD) risk in type 2 diabetes patients...

  17. Mechanical stress activates NMDA receptors in the absence of agonists

    OpenAIRE

    Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K.; Sachs, Frederick; Hua, Susan Z.

    2017-01-01

    While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor i...

  18. Anti-tumor Activity of Toll-Like Receptor 7 Agonists

    Directory of Open Access Journals (Sweden)

    Huju Chi

    2017-05-01

    Full Text Available Toll-like receptors (TLRs are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy. This article reviewed the anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations, and mainly focused on small synthetic molecules, including imiquimod, resiquimod, gardiquimod, and 852A, etc.

  19. Synthesis of Naphthyl-, Quinolin- and Anthracenyl Analogues of Clofibric Acid as PPARα Agonists.

    Science.gov (United States)

    Giampietro, Letizia; Ammazzalorso, Alessandra; Bruno, Isabella; Carradori, Simone; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giancristofaro, Antonella; Maccallini, Cristina; Amoroso, Rosa

    2016-03-01

    PPARα is a ligand activated transcription factor belonging to the nuclear receptor subfamily, involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver. PPARα activation is important in steatosis, inflammation and fibrosis in preclinical models of non-alcoholic fatty liver disease identifying a new potential therapeutic area. In this work, three series of clofibric acid analogues conjugated with naphthyl, quinolin, chloroquinolin and anthracenyl scaffolds were synthesized. In an effort to obtain new compounds active as PPARα agonists, these molecules were evaluated for PPARα transactivation activity. Naphthyl and quinolin derivatives showed a good activation of PPARα; noteworthy, optically active naphthyl derivatives activated PPARα better than corresponding parent compound. © 2015 John Wiley & Sons A/S.

  20. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  1. Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody

    DEFF Research Database (Denmark)

    Segal, Neil H; Logan, Theodore F; Hodi, F Stephen

    2017-01-01

    Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors...... and lymphoma.Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose-escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included...... the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines.Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg...

  2. D-Arg0-Bradykinin-Arg-Arg, a Latent Vasoactive Bradykinin B2 Receptor Agonist Metabolically Activated by Carboxypeptidases

    Directory of Open Access Journals (Sweden)

    Hélène Bachelard

    2018-03-01

    Full Text Available We previously reported hypotensive and vasodilator effects from C-terminally extended bradykinin (BK sequences that behave as B2 receptor (B2R agonists activated by vascular or plasma peptidases. D-Arg0-BK-Arg-Arg (r-BK-RR is a novel prodrug peptide hypothetically activated by two catalytic cycles of Arg-carboxypeptidases (CPs to release the direct agonist D-Arg0-BK. N-terminally extending the BK sequence with D-Arg0 in the latter peptide was meant to block the second kinin inactivation pathway in importance, aminopeptidase P. The affinity of r-BK and r-BK-RR for recombinant B2R was assessed using a [3H]BK binding displacement assay. Their pharmacology was evaluated in human isolated umbilical vein, a contractile bioassay for the B2R, in a morphological assay involving the endocytosis of B2R-green fusion protein (GFP and in anesthetized rats instrumented to record hemodynamic responses to bolus intravenous injection of both peptides. r-BK exhibited an affinity equal to that of BK for the rat B2R, while r-BK-RR was 61-fold less potent. In the vein and the B2R-GFP internalization assay, r-BK was a direct agonist unaffected by the blockade of angiotensin converting enzyme (ACE with enalaprilat, or Arg-CPs with Plummer’s inhibitor. However, the in vitro effects of r-BK-RR were reduced by these inhibitors, more so by enalaprilat. In anesthetized rats, r-BK and r-BK-RR were equipotent hypotensive agents and their effects were inhibited by icatibant (a B2R antagonist. The hypotensive effects of r-BK were potentiated by enalaprilat, but not influenced by the Arg-CPs inhibitor, which is consistent with a minor role of Arg-CPs in the metabolism of r-BK. However, in rats pretreated with both enalaprilat and Plummer’s inhibitor, the hypotensive responses and the duration of the hypotensive episode to r-BK were significantly potentiated. The hypotensive responses to r-BK-RR were not affected by enalaprilat, but were reduced by pre-treatment with the Arg

  3. FY 1999 report on the potential survey of the environmentally friendly type coal utilization system. Potential survey of the environmentally friendly type coal utilization system in the Philippines; 1999 nendo chosa hokokusho. Kankyo chowa gata sekitan riyo system kanosei chosa (Firipin ni okeru kankyo chowa gata system kanosei chosa)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    For the purpose of contributing to working out a master plan for the introduction of the environmentally friendly type coal utilization system in the Philippines, analysis was made of the state of coal use/the state of spread by industry mostly including the electric power industry, cement industry and residential/commercial use fuel sector. In the Philippines, the amount of coal use has rapidly been increasing since coal-fired power plants started operation. For the promotion of the use of domestic coals, it is important to reform low grade coal. Moreover, the technology is required which copes with the reinforced regulation against SOx emissions. In the cement industry, coal and coal ash have not yet been effectively used. Therefore, the following measures should be taken to increase the competitive force: energy conservation measures, reinforcement of environmental measures such as dust prevention, and effective use of the fly ash emitted from power plants. In general households and small-/medium-sized industries such as tobacco drying, they still use a large amount of charcoals and firewood, which is approximately 86% of the residential/commercial use energy. There is a growing tendency for the development/spread of coal briquette as substituting energy. (NEDO)

  4. Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa.

    Directory of Open Access Journals (Sweden)

    Hana Moon

    Full Text Available Transient receptor potential ankyrin1 (TRPA1 and transient receptor potential vanilloid 1 (TRPV1 are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer O. Kuntze (A.rugosa, commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM, our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.

  5. The Good, the Bad, and the Ugly: Agonistic Behaviour in Juvenile Crocodilians

    OpenAIRE

    Brien, Matthew L.; Lang, Jeffrey W.; Webb, Grahame J.; Stevenson, Colin; Christian, Keith A.

    2013-01-01

    We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4) under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds), and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact...

  6. Innate Immune Responses to TLR2 and TLR4 Agonists Differ between Baboons, Chimpanzees and Humans

    Science.gov (United States)

    Brinkworth, Jessica F.; Pechenkina, Ekaterina A.; Silver, Jack; Goyert, Sanna M.

    2012-01-01

    Background African catarrhine primates differ in bacterial disease susceptibility. Methods Human, chimpanzee, and baboon blood was stimulated with TLR-detected bacterial agonists and cytokine/chemokine induction assessed by real-time pcr. Results Humans and chimpanzees shared similar cytokine/chemokine responses, while baboon cytokine/chemokine induction differed. Generally, responses were agonist-independent. Conclusions These primates tend to generate species rather than agonist–specific responses to bacterial agonists. PMID:22978822

  7. Utilization of biomass in the U.S. for the production of ethanol fuel as a gasoline replacement. I - Terrestrial resource potential. II - Energy requirements, with emphasis on lignocellulosic conversion

    Science.gov (United States)

    Ferchak, J. D.; Pye, E. K.

    The paper assesses the biomass resource represented by starch derived from feed corn, surplus and distressed grain, and high-yield sugar crops planted on set-aside land in the U.S. It is determined that the quantity of ethanol produced may be sufficient to replace between 5 to 27% of present gasoline requirements. Utilization of novel cellulose conversion technology may in addition provide fermentable sugars from municipal, agricultural and forest wastes, and ultimately from highly productive silvicultural operations. The potential additional yield of ethanol from lignocellulosic biomass appears to be well in excess of liquid fuel requirements of an enhanced-efficiency transport sector at present mileage demands. No conflict with food production would be entailed. A net-energy assessment is made for lignocellulosic biomass feedstocks' conversion to ethanol and an almost 10:1 energy yield/energy cost ratio determined. It is also found that novel cellulose pretreatment and enzymatic conversion methods still under development may significantly improve even that figure, and that both chemical-feedstocks and energy-yielding byproducts such as carbon dioxide, biogas and lignin make ethanol production potentially energy self-sufficient. A final high-efficiency production approach incorporates site-optimized, nonpolluting energy sources such as solar and geothermal.

  8. Analysis of agonist dissociation constants as assessed by functional antagonism in guinea pig left atria

    International Nuclear Information System (INIS)

    Molenaar, P.; Malta, E.

    1986-01-01

    In electrically driven guinea pig left atria, positive inotropic responses to (-)-isoprenaline and the selective beta 1-adrenoceptor agonist RO363 were obtained in the absence and in the presence of the functional antagonists adenosine, carbachol, gallopamil, nifedipine, and Ro 03-7894. Each of the functional antagonists reduced the maximum response to both agonists and produced nonparallel rightward shifts in the cumulative concentration effect curves. For both agonists, dissociation constants (KA) were calculated using the equation described by Furchgott (1966) for irreversible antagonism. For RO363, which is a partial agonist with high agonist activity, the equations outlined for functional interaction by Mackay (1981) were also employed to calculate KA values. The KA values obtained by each method were compared with the dissociation constants (KD) for the two agonists determined from their ability to displace the radioligand (-)-[ 125 I]iodocyanopindolol from beta 1-adrenoceptors in guinea pig left atrial membrane preparations. The estimates of KA varied substantially from KD values. The KD values were taken as more accurate estimates of the true values for the dissociation constants because a high degree of correlation exists between pKD and pD2 values for a number of other beta-adrenoceptor agonists that behave as partial agonists and between pKD and pKB values for a number of beta-adrenoceptor antagonists. Thus, it appears that there are serious limitations in the current theory for using functional antagonism as a means of obtaining agonist dissociation constants

  9. Long-acting beta(2)-agonists in management of childhood asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

  10. Hypertrophic effect of inhaled beta -agonist with and without concurrent exercise training

    DEFF Research Database (Denmark)

    Jessen, Søren; Onslev, Johan; Lemminger, Anders

    2018-01-01

    INTRODUCTION: Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after...... chronic beta2 -agonist inhalation. METHODS: We investigated if inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a four-week intervention of daily terbutaline (8×0.5 mg...

  11. Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lukas, R.J.; Bennett, E.L.

    1979-01-01

    The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

  12. Identification and in vitro pharmacological characterization of a novel and selective α7 nicotinic acetylcholine receptor agonist, Br-IQ17B.

    Science.gov (United States)

    Tang, Jing-shu; Xie, Bing-xue; Bian, Xi-ling; Xue, Yu; Wei, Ning-ning; Zhou, Jing-heng; Hao, Yu-chen; Li, Gang; Zhang, Liang-ren; Wang, Ke-wei

    2015-07-01

    Alpha7-nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca(2+)-permeable ion channel implicated in cognition and neuropsychiatric disorders. Activation of α7 nAChR improves learning, memory, and sensory gating in animal models. To identify novel α7 nAChR agonists, we synthesized a series of small molecules and characterized a representative compound, Br-IQ17B, N-[(3R)-1-azabicyclo[2,2,2]oct-3-yl]-5-bromoindolizine-2-carboxamide, which specifically activates α7 nAChR. Two-electrode voltage clamp (TEVC) recordings were primarily used for screening in Xenopus oocytes expressing human α7 nAChR. Assays, including radioisotope ligand binding, Western blots, whole-cell recordings of hippocampal culture neurons, and spontaneous IPSC recordings of brain slices, were also utilized to evaluate and confirm the specific activation of α7 nAChR by Br-IQ17B. Br-IQ17B potently activates α7 nAChR with an EC50 of 1.8±0.2 μmol/L. Br-IQ17B is selective over other subtypes such as α4β2 and α3β4, but it blocks 5-HT3A receptors. Br-IQ17B displaced binding of the α7 blocker [(3)H]-MLA to hippocampal crude membranes with a Ki of 14.9±3.2 nmol/L. In hippocampal neurons, Br-IQ17B evoked α7-like currents that were inhibited by MLA and enhanced in the presence of the α7 PAM PNU-120596. In brain slice recordings, Br-IQ17B enhanced GABAergic synaptic transmission in CA1 neurons. Mechanistically, Br-IQ17B increased ERK1/2 phosphorylation that was MLA-sensitive. We identified the novel, potent, and selective α7 agonist Br-IQ17B, which enhances synaptic transmission. Br-IQ17B may be a helpful tool to understand new aspects of α7 nAChR function, and it also has potential for being developed as therapy for schizophrenia and cognitive deficits.

  13. AMP is an adenosine A1 receptor agonist.

    Science.gov (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J

    2012-02-17

    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  14. Mood Disorders, Circadian Rhythms, Melatonin and Melatonin Agonists

    Directory of Open Access Journals (Sweden)

    M.A. Quera Salva

    2012-04-01

    Full Text Available Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC. Melatonin (N-acetyl-5-hydroxytryptamine is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.

  15. Identification of agonists for a group of human odorant receptors

    Directory of Open Access Journals (Sweden)

    Daniela eGonzalez-Kristeller

    2015-03-01

    Full Text Available Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10% have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs.

  16. How does agonistic behaviour differ in albino and pigmented fish?

    Directory of Open Access Journals (Sweden)

    Ondřej Slavík

    2016-04-01

    Full Text Available In addition to hypopigmentation of the skin and red iris colouration, albino animals also display distinct physiological and behavioural alterations. However, information on the social interactions of albino animals is rare and has mostly been limited to specially bred strains of albino rodents and animals from unique environments in caves. Differentiating between the effects of albinism and domestication on behaviour in rodents can be difficult, and social behaviour in cave fish changes according to species-specific adaptations to conditions of permanent darkness. The agonistic behaviours of albino offspring of pigmented parents have yet to be described. In this study, we observed agonistic behaviour in albino and pigmented juvenile Silurus glanis catfish. We found that the total number of aggressive interactions was lower in albinos than in pigmented catfish. The distance between conspecifics was also analysed, and albinos showed a tendency towards greater separation from their same-coloured conspecifics compared with pigmented catfish. These results demonstrate that albinism can be associated with lower aggressiveness and with reduced shoaling behaviour preference, as demonstrated by a tendency towards greater separation of albinos from conspecifics.

  17. Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

    Science.gov (United States)

    Gerra, Gilberto; Zaimovic, Amir; Gerra, Maria L; Ciccocioppo, Roberto; Cippitelli, Andrea; Serpelloni, Giovanni; Somaini, Lorenzo

    2010-01-01

    For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.

  18. Economic and environmental impact of the utilization of the industrial potential of viable cogeneration for period 1998 - 2007; Impacto economico y ambiental de aprovechamiento del potencial industrial de cogeneracion viable para el periodo 1998 - 2007

    Energy Technology Data Exchange (ETDEWEB)

    Leon de los Santos, Gabriel; Mendoza Gonzslez, Lourdes [Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico)

    2001-07-01

    The utilization of the industrial potential of cogeneration offers a significant contribution to the construction of the electrical infrastructure that the growth of the country will require for the period 1998 - 2007. The conditions of growth of the co-generation potential and their levels of utilization are related to a on isolated growth of the other inter actors of the processes of power supply; As levels of economic viability, economic savings to industry, requirements of additional electrical capacity, growth of the industrial activity, costs, use of fuels, environmental impact. Rates of average growth for period 1998 - 2007 are considered and what levels of economic and environmental benefit offers this development to the industry, to the electrical company and to the country. And to what proportion can contribute the utilization of the industrial potential of electrical cogeneration to the requirements of additional electrical capacity that will require the development of the country during this period. With the rates of viable growth of the co-generation the equivalent reduction of fuel consumption is estimated for the industrial sector, given by the improvement in the generation efficiency and with the change in the proportion of fuels used in Comision Federal de Electricidad (CFE) for this period. Evaluating the emissions of the main fuels avoided with this growth and its repercussion at national level via the CFE, and showing the possible international implications of this reduction. [Spanish] El aprovechamiento del potencial industrial de cogeneracion ofrece una significativa aportacion a la construccion de la infraestructura electrica que el crecimiento del pais requerira para el periodo 1998 -2007. Las condiciones de crecimiento del potencial de cogeneracion y sus niveles de aprovechamiento estan relacionados con un crecimiento o aislado de los demas inter actores de los procesos de abasto energetico; Como niveles de viabilidad economica, ahorros

  19. Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Folkers, K.; Bowers, C.Y.; Tang, P.L.; Kubota, M.

    1986-01-01

    Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known agonist analogs of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. The authors have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and they found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His 5 ,Trp 7 ,Gln 8 ]LHRH; [His 5 ,Trp 7 ,Leu 8 ]LHRH; [His 5 ,Trp 7 ]LHRH; [Trp 7 ]LHRH; [His 5 ]LHRH. These structures are a basis for the design of antagonists without Arg 8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg 8 and Gln 8 or Leu 8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas. Radioreceptor assays and radioimmunoassays were utilized

  20. Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats.

    Science.gov (United States)

    Beas, B Sofia; Setlow, Barry; Bizon, Jennifer L

    2016-07-01

    The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (rule 1: correct lever signaled by a cue light; rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (intraperitoneal, 0, 1.0, 2.5, and 4.0 mg/kg) administered acutely before the shift to the second rule. Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders.

  1. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    Science.gov (United States)

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic