WorldWideScience

Sample records for rapid agonist application

  1. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

    DEFF Research Database (Denmark)

    Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny

    2007-01-01

    parameters considered to be key markers of antidepressant action, but that are observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT(1A) autoreceptors, increased tonus on hippocampal postsynaptic 5-HT(1A) receptors, and enhanced phosphorylation of the CREB protein...... intake consecutive to a chronic mild stress. These findings point out 5-HT(4) receptor agonists as a putative class of antidepressants with a rapid onset of action. Udgivelsesdato: 2007-Sep-6...

  2. Profound and Rapid Reduction in Body Temperature Induced by the Melanocortin Receptor Agonists

    Science.gov (United States)

    Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

    2014-01-01

    The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5′AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII’s effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. PMID:25065745

  3. Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists.

    Science.gov (United States)

    Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

    2014-08-22

    The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5'AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII's effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites

    International Nuclear Information System (INIS)

    Forman, S.A.; Miller, K.W.

    1989-01-01

    The relationship between the high-affinity procaine channel inhibition site and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid 86 Rb + quenched-flux assays at 4 degree C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with α-bungarotoxin (α-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations alone, AChR undergoes one phase of inactivation in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting ACh concentrations rapid inactivation complete in 30-75 ms is followed by fast desensitization at the same k d observed without procaine. The dependence of k r on [procaine] is consistent with a bimolecular association between procaine and its AChR site. Inhibition of AChR function by mixtures of procaine plus self-inhibiting concentrations of ACh or suberyldicholine was studied by reducing the level of α-BTX block in vesicles. The data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and k r 's dependence on [ACh] in channel-activating range closely parallels that of 86 Rb + flux response to ACh

  5. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    International Nuclear Information System (INIS)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system

  6. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    Energy Technology Data Exchange (ETDEWEB)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.

  7. [Rapid determination of illicit beta2-agonist additives in health foods and traditional Chinese patent medicines with DCBI-MS/MS method].

    Science.gov (United States)

    Hou, Yu-Lan; Wu, Shuang; Wang, Hua; Zhao, Yong; Liao, Peng; Tian, Qing-Qing; Sun, Wen-Jian; Chen, Bo

    2013-01-01

    A novel rapid method for detection of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines was developed with the desorption corona beam ionization mass spectrometry (DCBI-MS) technique. The DCBI conditions including temperature and sample volume were optimized according to the resulting mass spectra intensity. Matrix effect on 9 beta2-agonists additives was not significant in the proposed rapid determination procedure. All of the 9 target molecules were detected within 1 min. Quantification was achieved based on the typical fragment ion in MS2 spectra of each analyte. The method showed good linear coefficients in the range of 1-100 mg x L(-1) for all analytes. The relative deviation values were between 14.29% and 25.13%. Ten claimed antitussive and antiasthmatic health foods and traditional Chinese patent medicines from local pharmacies were analyzed. All of them were negative with the proposed DCBI-MS method. Without tedious sample pretreatments, the developed DCBI-MS is simple, rapid and sensitive for rapid qualification and semi-quantification of the illicit beta2-agonist additives in health foods and traditional Chinese patent medicines.

  8. 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.

  9. Rapid Prototyping and its Application in Dentistry

    Directory of Open Access Journals (Sweden)

    V. N. V. Madhav

    2013-01-01

    Full Text Available Medical implants and biological models have three main characteristics: low volume, complex shape, and can be customized. These characteristics suit very well with Rapid Prototyping (RP and Rapid Manufacturing (RM processes. RP/RM processes are fabricated part layer- by-layer until complete shape finished from 3D model. Biocompatible materials, such as Titanium and Titanium alloy, Zirconium, Cobalt Chromium, PEEK, etc, are used for fabrication process. Reverse Engineering (RE technology greatly affects RP/RM processes. RE is used to capture or scan image of the limb, cranium, tooth, and other biological objects. Three common methods to get the image are 3D laser scanning, Computer Tomography (CT, and Magnetic Resonance Imaging (MRI. Main RP/RM techniques used in Dentistry are Stereotype Lithography Apparatus (SLA, Fused Deposition Modeling (FDM, Selective Laser Sintering (SLS, and ink jet printing. This article reviews the changing scenario of technology in dentistry with special emphasis on Rapid Prototyping and its various applications in Dentistry.

  10. Rapid desensitization and resensitization of 5-HT2 receptor mediated phosphatidyl inositol hydrolysis by serotonin agonists in quiescent calf aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Pauwels, P.J.; Van Gompel, P.; Leysen, J.E.

    1990-01-01

    Agonist regulation of 5-hydroxytryptamine 2 (5-HT 2 ) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability. In these cells, 5-hydroxytryptamine (5-HT)-induced [ 3 H]inositol phosphates accumulation showed the characteristics of a 5-HT 2 receptor coupled transducing system according to the inhibition of the response by 5-HT 2 antagonists at nanomolar concentrations. The 5-HT 2 receptor coupled response became rapidly desensitized during continued incubation with 5-HT and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM); nearly full desensitization was obtained in two hours with 10 μM 5-HT and DOM pretreatment. The recovery of the response had a half-live of 5 hours after 2 hours pretreatment and of 9.5 to 12.5 hours after 24 to 96 hours agonist pretreatment. The DOM-induced desensitization of the 5-HT 2 receptor coupled response was fully blocked by 0.1 μM cinanserin. Cinanserin alone did not induce desensitization or up-regulation of the 5-HT 2 receptor coupled response at 0.1 μM

  11. Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))

    1991-01-01

    The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

  12. A rapid and reagent-free bioassay for the detection of dioxin-like compounds and other aryl hydrocarbon receptor (AhR) agonists using autobioluminescent yeast.

    Science.gov (United States)

    Xu, Tingting; Young, Anna; Marr, Enolia; Sayler, Gary; Ripp, Steven; Close, Dan

    2018-02-01

    An autonomously bioluminescent Saccharomyces cerevisiae BLYAhS bioreporter was developed in this study for the simple and rapid detection of dioxin-like compounds (DLCs) and aryl hydrocarbon receptor (AhR) agonists. This recombinant yeast reporter was based on a synthetic bacterial luciferase reporter gene cassette (lux) that can produce the luciferase as well as the enzymes capable of self-synthesizing the requisite substrates for bioluminescent production from endogenous cellular metabolites. As a result, bioluminescent signal production is generated continuously and autonomously without cell lysis or exogenous reagent addition. By linking the expression of the autobioluminescent lux reporter cassette to AhR activation via the use of a dioxin-responsive promoter, the S. cerevisiae BLYAhS bioreporter emitted a bioluminescent signal in response to DLC exposure in a dose-responsive manner. The model dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), could be detected within 4 h with a half maximal effective concentration (EC 50 ) of ~ 8.1 nM and a lower detection limit of 500 pM. The autobioluminescent response of BLYAhS to other AhR agonists, including 2,3,7,8-tetrachlorodibenzofuran (TCDF), polychlorinated bisphenyl congener 126 (PCB-126) and 169 (PCB-169), 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin (HxCDD), 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), benzo[a]pyrene (BaP), and β-naphthoflavone (bNF), were also characterized in this study. The non-destructive and reagent-free nature of the BLYAhS reporter assay facilitated near-continuous, automated signal acquisition without additional hands-on effort and cost, providing a simple and cost-effective method for rapid DLC detection.

  13. A Rapid and Efficient Sonogashira Protocol and Improved Synthesis of Free Fatty Acid 1 (FFA1) Receptor Agonists

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Ulven, Trond

    2010-01-01

    A protocol for rapid and efficient Pd/Cu-catalyzed coupling of aryl bromides and iodides to terminal alkynes has been developed with use of 2-(di-tert-butylphosphino)-N-phenylindole (cataCXium PIntB) as ligand in TMEDA and water. The new protocol successfully couples substrates which failed...

  14. Rapidly solidified aluminium for optical applications

    NARCIS (Netherlands)

    Gubbels, G.P.H.; Venrooy, B.W.H. van; Bosch, A.J.; Senden, R.

    2008-01-01

    This paper present the results of a diamond turning study of a rapidly solidified aluminium 6061 alloy grade, known as RSA6061. It is shown that this small grain material can be diamond turned to smaller roughness values than standard AA6061 aluminium grades. Also, the results are nearly as good as

  15. Rapid Prototyping Modules for Remote Engineering Applications

    Directory of Open Access Journals (Sweden)

    Karsten Henke

    2008-07-01

    Full Text Available This contribution describes the concept and implementation for an integration of microcontroller and FPGA based Rapid Prototyping modules into a Remote Lab system. This implementation enables a Web-based access to electro-mechanical models. A student uploads a source file implementation to the Remote Lab server in order to test an implementation directly within a hardware environment. The Remote Lab server offers the interfaces to integrate specific project and hardware plug-ins. These plug-ins access a hardware specific software environment to automatically compile and program the resulting firmware. To stimulate this design, the Remote Lab server exchanges digital signals via a serial interface. To allow the student to compare architectures of different designs using the same hardware model, a specific controller (using the Remote Lab interface can be selected. For this, an IP-based multiplexer provides the control connection between the respective controller and the hardware model. In our contribution we would like to give examples of such a complex design task and how the students can use different tools during several design steps.

  16. CCR4 agonists CCL22 and CCL17 are elevated in pediatric OMS sera: rapid and selective down-regulation of CCL22 by ACTH or corticosteroids.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A; Ransohoff, Richard M

    2013-05-01

    To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy. The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24). Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r = -0.50, p OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect.

  17. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin

    Directory of Open Access Journals (Sweden)

    Fang Zhao

    2016-02-01

    Full Text Available Voltage-gated sodium channels (VGSCs are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1–Nav1.9, Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR membrane potential (FMP blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  18. Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin.

    Science.gov (United States)

    Zhao, Fang; Li, Xichun; Jin, Liang; Zhang, Fan; Inoue, Masayuki; Yu, Boyang; Cao, Zhengyu

    2016-02-16

    Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 α-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 ± 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6-trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists.

  19. Solid modeling and applications rapid prototyping, CAD and CAE theory

    CERN Document Server

    Um, Dugan

    2016-01-01

    The lessons in this fundamental text equip students with the theory of Computer Assisted Design (CAD), Computer Assisted Engineering (CAE), the essentials of Rapid Prototyping, as well as practical skills needed to apply this understanding in real world design and manufacturing settings. The book includes three main areas: CAD, CAE, and Rapid Prototyping, each enriched with numerous examples and exercises. In the CAD section, Professor Um outlines the basic concept of geometric modeling, Hermite and Bezier Spline curves theory, and 3-dimensional surface theories as well as rendering theory. The CAE section explores mesh generation theory, matrix notion for FEM, the stiffness method, and truss Equations. And in Rapid Prototyping, the author illustrates stereo lithographic theory and introduces popular modern RP technologies. Solid Modeling and Applications: Rapid Prototyping, CAD and CAE Theory is ideal for university students in various engineering disciplines as well as design engineers involved in product...

  20. Application of GIS Rapid Mapping Technology in Disaster Monitoring

    Science.gov (United States)

    Wang, Z.; Tu, J.; Liu, G.; Zhao, Q.

    2018-04-01

    With the rapid development of GIS and RS technology, especially in recent years, GIS technology and its software functions have been increasingly mature and enhanced. And with the rapid development of mathematical statistical tools for spatial modeling and simulation, has promoted the widespread application and popularization of quantization in the field of geology. Based on the investigation of field disaster and the construction of spatial database, this paper uses remote sensing image, DEM and GIS technology to obtain the data information of disaster vulnerability analysis, and makes use of the information model to carry out disaster risk assessment mapping.Using ArcGIS software and its spatial data modeling method, the basic data information of the disaster risk mapping process was acquired and processed, and the spatial data simulation tool was used to map the disaster rapidly.

  1. Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711 evoke rapid and transient increases in prefrontal glutamate release

    DEFF Research Database (Denmark)

    Bortz, D M; Mikkelsen, J D; Bruno, J P

    2013-01-01

    The ability of local infusions of the alpha 7 nicotinic acetycholine receptor (α7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal cortex was determined in awake rats using a microelectrode array. Infusions of SSR180711 produced dose-dependent increases in glutamate levels...

  2. 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.

  3. Rapid prototyping technology and its application in bone tissue engineering.

    Science.gov (United States)

    Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

    Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

  4. Rapid prototyping technology and its application in bone tissue engineering*

    Science.gov (United States)

    YUAN, Bo; ZHOU, Sheng-yuan; CHEN, Xiong-sheng

    2017-01-01

    Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects. PMID:28378568

  5. Rapid application development using the Tcl/Tk language

    International Nuclear Information System (INIS)

    van Zeijts, J.

    1995-01-01

    During the last year, high level applications at CEBAF were written using the Tcl/Tk scripting language. This language is rapidly gaining in popularity, in part due to ease of constructing programs with X11 graphical user interfaces, and in part to ease of adding compiled user code for specialized purposes. Extensions to the language provide object oriented programming, which was used to develop a hierarchy of classes relevant for high level accelerator control. We describe basic language features, some 3rd party add-on packages, and local additions to the toolbox. Next we describe features of the accelerator object hierarchy, and finally describe applications written using this toolbox such as the ModelServer prototype, Slow Orbit and Energy Lock, the Linac Energy Management System, and other applications

  6. Nitrous oxide as an opioid agonist: some experimental and clinical applications

    International Nuclear Information System (INIS)

    Gillman, M.A.

    1984-01-01

    The purpose of the present investigation is primarily to determine whether N 2 O at analgesic concentrations acts vid the opioid system. Interaction at an opioid receptor level will be studied by means of a ligand binding study. An in vitro study is presented in which the effect of 50% N 2 O mixed with 50% O 2 and 100% N 2 O on ( 3 H) naloxone binding is presented. Secondly, possible therapeutic and diagnostic applications of the use of N 2 O in conditions possibly related to abnormalities of the opioid system viz alcoholism, depression, schizophrenia and anxiety will be investigated. Thirdly, possible hematological abnormalities induced by the use of N 2 O will be studied

  7. Rapid Application Development with OpenStudio: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, E.; Long, N.; Fleming, K.; Schott, M.; Benne, K.; Hale, E.

    2012-05-01

    This paper presents several case studies of rapidly implemented, audience-specific applications for whole building energy modeling and standards analysis. By tailoring each application to the audience and the task at hand, the required learning curve for new users was greatly reduced. Each case study used OpenStudio, the U.S. Department of Energy's middleware software development kit (SDK). OpenStudio provides an easy interface to the EnergyPlus whole building simulation engine, while extending its capability and providing higher-level functionality such as software interoperability, standards, analysis, and optimization. Each case study is unique in the technology employed to interface with OpenStudio as well as the methods used for user interaction and data presentation. Four case studies are presented.

  8. Development and validation of an UHPLC-MS/MS method for β2-agonists quantification in human urine and application to clinical samples.

    Science.gov (United States)

    Bozzolino, Cristina; Leporati, Marta; Gani, Federica; Ferrero, Cinzia; Vincenti, Marco

    2018-02-20

    A fast analytical method for the simultaneous detection of 24 β 2 -agonists in human urine was developed and validated. The method covers the therapeutic drugs most commonly administered, but also potentially abused β 2 -agonists. The procedure is based on enzymatic deconjugation with β-glucuronidase followed by SPE clean up using mixed-phase cartridges with both ion-exchange and lipophilic properties. Instrumental analysis conducted by UHPLC-MS/MS allowed high peak resolution and rapid chromatographic separation, with reduced time and costs. The method was fully validated according ISO 17025:2005 principles. The following parameters were determined for each analyte: specificity, selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, matrix effect, recovery and carry-over. The method was tested on real samples obtained from patients subjected to clinical treatment under chronic or acute therapy with either formoterol, indacaterol, salbutamol, or salmeterol. The drugs were administered using pressurized metered dose inhalers. All β 2 -agonists administered to the patients were detected in the real samples. The method proved adequate to accurately measure the concentration of these analytes in the real samples. The observed analytical data are discussed with reference to the administered dose and the duration of the therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Basal testosterone concentrations after the application of a slow-release GnRH agonist implant are associated with a loss of response to buserelin, a short-term GnRH agonist, in the tom cat.

    Science.gov (United States)

    Goericke-Pesch, Sandra; Georgiev, Plamen; Fasulkov, Ivan; Vodenicharov, Angel; Wehrend, Axel

    2013-07-01

    Slow-release GnRH agonist implants are considered an effective, reversible alternative to surgical castration in male tom cats. Individual differences exist regarding the onset of efficacy and might be delayed in some animals. Single measurements of testosterone (T) might result in basal concentrations also in intact male cats. Consequently, GnRH stimulation tests are performed to measure T increase in intact animals and to differentiate castrated from intact male cats. In this study, five tom cats were treated with a 4.7-mg deslorelin implant and GnRH stimulation tests using buserelin were performed before treatment and at 4-week intervals afterward until Week 20. After the last test in Week 20 all animals were castrated. Four of five animals had basal T after 4 weeks and-in contrast to pretreatment-application of buserelin did not result in any further T increase. In one animal, T was low after implant insertion, but not basal; however, a GnRH stimulation test induced a slight increase of T in Week 8 and 16 only and no response in Weeks 4, 12, and 20. Testicular volume was significantly decreased and penile spines disappeared in all cats. Testicular histology showed mixed atrophy, but also fully elongated spermatids in three of five male cats making infertility questionable. Because of the loss of the stimulatory effect of short-term GnRH application (buserelin), it can be assumed that long-term GnRH agonists also act by some mechanisms of downregulation of pituitary GnRH receptors in the tom cat. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Raexplore: Enabling Rapid, Automated Architecture Exploration for Full Applications

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yao [Argonne National Lab. (ANL), Argonne, IL (United States); Balaprakash, Prasanna [Argonne National Lab. (ANL), Argonne, IL (United States); Meng, Jiayuan [Argonne National Lab. (ANL), Argonne, IL (United States); Morozov, Vitali [Argonne National Lab. (ANL), Argonne, IL (United States); Parker, Scott [Argonne National Lab. (ANL), Argonne, IL (United States); Kumaran, Kalyan [Argonne National Lab. (ANL), Argonne, IL (United States)

    2014-12-01

    We present Raexplore, a performance modeling framework for architecture exploration. Raexplore enables rapid, automated, and systematic search of architecture design space by combining hardware counter-based performance characterization and analytical performance modeling. We demonstrate Raexplore for two recent manycore processors IBM Blue- Gene/Q compute chip and Intel Xeon Phi, targeting a set of scientific applications. Our framework is able to capture complex interactions between architectural components including instruction pipeline, cache, and memory, and to achieve a 3–22% error for same-architecture and cross-architecture performance predictions. Furthermore, we apply our framework to assess the two processors, and discover and evaluate a list of architectural scaling options for future processor designs.

  11. Penggunaan Metode Rapid Application Development Dalam Perancangan Sistem Informasi Perpustakaan

    Directory of Open Access Journals (Sweden)

    Reza Trimahardhika

    2017-09-01

    Abstract Yayasan Putra Asih Malida in library data processing both in data processing member, book loaning, returning book until making report still using manual method and still using paper media to recording existing data in library. This will certainly slow down the process. On the other hand, students also find it difficult to find a book to read because they do not know where the storage is. To solve the problem it is necessary to create a library information system design that can handle the data processing library so that the process runs efficiently and effectively. In addition to saving expenses to buy paper, this system can also make old archives stored neatly than to be stored in a closet or Warehouse. In the design of information systems libraries based on this wab, the authors use Rapid Application Development (RAD, Netbeans 8.1 application as a script-making software and Xampp 1.7.3 as a software-based database creation MYSQL. The results of this information system design can provide ease of the officers in processing data related to the processing of libraries and can simplify and accelerate and can save time in making reports, and data can be stored safely because it is using the database so that officers do not have to worry about the loss data.   Keywords: System, Information, Library, Web, RAD

  12. Development of Nylon Based FDM Filament for Rapid Tooling Application

    Science.gov (United States)

    Singh, R.; Singh, S.

    2014-04-01

    There has been critical need for development of cost effective nylon based wire to be used as feed stock filament for fused deposition modelling (FDM) machine. But hitherto, very less work has been reported for development of alternate solution of acrylonitrile butadiene styrene (ABS) based wire which is presently used in most of FDM machines. The present research work is focused on development of nylon based wire as an alternative of ABS wire (which is to be used as feedstock filament on FDM) without changing any hardware or software of machine. For the present study aluminium oxide (Al2O3) as additive in different proportion has been used with nylon fibre. Single screw extruder was used for wire preparation and wire thus produced was tested on FDM. Mechanical properties i.e. tensile strength and percentage elongation of finally developed wire have been optimized by Taguchi L9 technique. The work represented major development in reducing cost and time in rapid tooling applications.

  13. Rapid Prototyping of High Performance Signal Processing Applications

    Science.gov (United States)

    Sane, Nimish

    Advances in embedded systems for digital signal processing (DSP) are enabling many scientific projects and commercial applications. At the same time, these applications are key to driving advances in many important kinds of computing platforms. In this region of high performance DSP, rapid prototyping is critical for faster time-to-market (e.g., in the wireless communications industry) or time-to-science (e.g., in radio astronomy). DSP system architectures have evolved from being based on application specific integrated circuits (ASICs) to incorporate reconfigurable off-the-shelf field programmable gate arrays (FPGAs), the latest multiprocessors such as graphics processing units (GPUs), or heterogeneous combinations of such devices. We, thus, have a vast design space to explore based on performance trade-offs, and expanded by the multitude of possibilities for target platforms. In order to allow systematic design space exploration, and develop scalable and portable prototypes, model based design tools are increasingly used in design and implementation of embedded systems. These tools allow scalable high-level representations, model based semantics for analysis and optimization, and portable implementations that can be verified at higher levels of abstractions and targeted toward multiple platforms for implementation. The designer can experiment using such tools at an early stage in the design cycle, and employ the latest hardware at later stages. In this thesis, we have focused on dataflow-based approaches for rapid DSP system prototyping. This thesis contributes to various aspects of dataflow-based design flows and tools as follows: 1. We have introduced the concept of topological patterns, which exploits commonly found repetitive patterns in DSP algorithms to allow scalable, concise, and parameterizable representations of large scale dataflow graphs in high-level languages. We have shown how an underlying design tool can systematically exploit a high

  14. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Virtual Agonist-antagonist Mechanisms Produce Biological Muscle-like Functions: An Application for Robot Joint Control

    DEFF Research Database (Denmark)

    Xiong, Xiaofeng; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Purpose – Biological muscles of animals have a surprising variety of functions, i.e., struts, springs, and brakes. According to this, the purpose of this paper is to apply virtual agonist-antagonist mechanisms to robot joint control allowing for muscle-like functions and variably compliant joint......, variably compliant joint motions can be produced without mechanically bulky and complex mechanisms or complex force/toque sensing at each joint. Moreover, through tuning the damping coefficient of the VAAM, the functions of the VAAM are comparable to biological muscles. Originality/value – The model (i.......e., VAAM) provides a way forward to emulate muscle-like functions that are comparable to those found in physiological experiments of biological muscles. Based on these muscle-like functions, the robotic joints can easily achieve variable compliance that does not require complex physical components...

  16. Application of Microwave Irradiation to Rapid Organic Inclusion Complex

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Microwave irradiation has been used in chemical laboratories for moisture analysis and wet asking procedures of biological and geological materials for a number of years [1]. More recently the microwave irradiation also widely used for rapid organic synthesis [2]. However, there have not yet been any reports concerning the ultilisatioin of microwave ovens in the routine organic inclusion complex regularly in chemical research.

  17. 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.

  18. 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...

  19. Novel method for the rapid and specific extraction of multiple β2 -agonist residues in food by tailor-made Monolith-MIPs extraction disks and detection by gas chromatography with mass spectrometry.

    Science.gov (United States)

    Liu, Haibo; Gan, Ning; Chen, Yinji; Ding, Qingqing; Huang, Jie; Lin, Saichai; Cao, Yuting; Li, Tianhua

    2016-09-01

    A quick and specific pretreatment method based on a series of extraction clean-up disks, consisting of molecularly imprinted polymer monoliths and C18 adsorbent, was developed for the specific enrichment of salbutamol and clenbuterol residues in food. The molecularly imprinted monolithic polymer disk was synthesized using salbutamol as a template through a one-step synthesis process. It can simultaneously and specifically recognize salbutamol and clenbuterol. The monolithic polymer disk and series of C18 disks were assembled with a syringe to form a set of tailor-made devices for the extraction of target molecules. In a single run, salbutamol and clenbuterol can be specifically extracted, cleaned, and eluted by methanol/acetic acid/H2 O. The target molecules, after a silylation derivatization reaction were detected by gas chromatography-mass spectrometry. The parameters including solvent desorption, sample pH, and the cycles of reloading were investigated and discussed. Under the optimized extraction and clean-up conditions, the limits of detection and quantitation were determined as 0.018-0.022 and 0.042-0.049 ng/g for salbutamol and clenbuterol, respectively. The assay described was convenient, rapid, and specific; thereby potentially efficient in the high-throughput analysis of β2 -agonists residues in real food samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. [Application of rapid PCR to authenticate medicinal snakes].

    Science.gov (United States)

    Chen, Kang; Jiang, Chao; Yuan, Yuan; Huang, Lu-Qi; Li, Man

    2014-10-01

    To obtained an accurate, rapid and efficient method for authenticate medicinal snakes listed in Chinese Pharmacopoeia (Zaocysd humnades, Bungarus multicinctus, Agkistrodon acutus), a rapid PCR method for authenticate snakes and its adulterants was established based on the classic molecular authentication methods. DNA was extracted by alkaline lysis and the specific primers were amplified by two-steps PCR amplification method. The denatured and annealing temperature and cycle numbers were optimized. When 100 x SYBR Green I was added in the PCR product, strong green fluorescence was visualized under 365 nm UV whereas adulterants without. The whole process can complete in 30-45 minutes. The established method provides the technical support for authentication of the snakes on field.

  1. Rapid Detection of Herpes Viruses for Clinical Applications

    Science.gov (United States)

    Pierson, Duane; Mehta, Satish

    2013-01-01

    There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

  2. Numerical analysis of rapid drawdown: Applications in real cases

    Directory of Open Access Journals (Sweden)

    Eduardo E. Alonso

    2016-07-01

    Full Text Available In this study, rapid drawdown scenarios were analyzed by means of numerical examples as well as modeling of real cases with in situ measurements. The aim of the study was to evaluate different approaches available for calculating pore water pressure distributions during and after a drawdown. To do that, a single slope subjected to a drawdown was first analyzed under different calculation alternatives, and numerical results were discussed. Simple methods, such as undrained analysis and pure flow analysis, implicitly assuming a rigid soil skeleton, lead to significant errors in pore water pressure distributions when compared with coupled flow-deformation analysis. A similar analysis was performed for the upstream slope of the Glen Shira Dam, Scotland, and numerical results were compared with field measurements during a controlled drawdown. Field records indicate that classical undrained calculations are conservative but unrealistic. Then, a recent case of a major landslide triggered by a rapid drawdown in a reservoir was interpreted. A key aspect of the case was the correct characterization of permeability of a representative soil profile. This was achieved by combining laboratory test results and a back analysis of pore water pressure time records during a period of reservoir water level fluctuations. The results highlight the difficulty of predicting whether the pore water pressure is overestimated or underestimated when using simplified approaches, and it is concluded that predicting the pore water pressure distribution in a slope after a rapid drawdown requires a coupled flow-deformation analysis in saturated and unsaturated porous media.

  3. Application of Self Cleaning Rapid Sand Filter in Water Treatment

    Directory of Open Access Journals (Sweden)

    Ali Reza Rahmani

    2005-08-01

    Full Text Available Rapid sand filter is one of the most important units in the water treatment plants. It has some difficulties in operation such as backwashing. For the solving of this problem a rapid sand filter has designed and built with the self-cleaning backwashing system. This system consist of 3 main constituents; one galvanized siphon and two galvanized steel tanks. One of them is used for filtration and the other used for the storage of filtrated water in elevation for backwashing the system. Water enter from upside of the filter through the inlet pipe, and collected from the under drainage pipe. Then filter water conduct to the storage tank and exit from outlet pipe. In the beginning, the head loss was low, but because of bed clogging by suspended solids, it increases gradually to the designed head loss (1.2m. Then the system is outed of the service automatically and the backwash is began. The main data for the design of system selected from the hydraulic rules of siphons and rapid sand filter criteria. After essential calculations it was constructed and was started operation. For the hydraulic studies a known volume of storage tank was selected and the time needed for the fill (in filtration stage and empty (in backwash stage of water volume with volumetric method were measured. In hydraulic studies the filter surface rate (SOR was selected about 5-7.5m3/m2/hr (1.39-2.08 lit/sec and the flow of water in siphon, during the backwashing was measured 8.7 lit/sec. It can be seen that the siphon passes 4-6 times the inlet raw water thus a negative pressure will created in the siphon which causes the water above the sand bed to be discharged automatically and rinse water from elevated tank flow under the sand bed and back wash it. So according to this study self cleaning rapid sand filter is very useful for water filtration, especially in small population community. The construction of system is rapid, simple and economic.

  4. The application of automatic chemiluminescence machine in rapid immune detection

    International Nuclear Information System (INIS)

    Lin Aizhen; Li Xuanwei; Chen Binhong; Li Zhenqian; Chen Zhaoxuan

    2004-01-01

    Objective: To provide high-quality, rapid and dependable result for clinical practice, and give satisfactory service to patients of different economical status by supplementation with other labeling immune examination. With an innovative attitude, we carried out efficient technical reform on ACS180 automatic chemiluminescence machine, making it possible for patients to complete the whole process including examination, check-out, diagnosis and getting drugs. The reported will be issued within an hour, thus a rapid immune detection service was established in out-patients department. Methods: 1. ACS-180 automatic chemiluminescence machine is used based on the principle of chemiluminescence immune methods. 2. The reagents are provided by Ciba-Comig Company of USA, composed of anti acridinium ester antibody of liquid phase and particulate antigen of solid phase wrapped in magnetic powder. 3. Calibration and quality control: high and low concentration are set for each calibration fluid with attached standard curve. Product for quality controlling includes three concentration of low, moderate and high. Results: 1. rapid machine detection for sample: serum is replaced with plasma coagulated by heparin, and comparison among series of methods using serum or plasma suggest no significant difference exists. 2. The problem about fasting detection: chemiluminescence machine measure optical density directly, with the results hardly being influenced by turbidity. But attention should be paid to the treatment of lipid turbid samples. 3. Other innovations: (1) direct placement of sample tube on machine: a cushion is placed on sample plate to transfer sample to machine directly after centrifugation, saving time and reducing the accident in sample transference. (2) for HCG quantification in blood and urine, 'gold criteria' is used firstly in screening to determine approximately the dilution range, with an advantage of saving time and reagent as well as accuracy. (3) we design a

  5. Rapid thermal processing and beyond applications in semiconductor processing

    CERN Document Server

    Lerch, W

    2008-01-01

    Heat-treatment and thermal annealing are very common processing steps which have been employed during semiconductor manufacturing right from the beginning of integrated circuit technology. In order to minimize undesired diffusion, and other thermal budget-dependent effects, the trend has been to reduce the annealing time sharply by switching from standard furnace batch-processing (involving several hours or even days), to rapid thermal processing involving soaking times of just a few seconds. This transition from thermal equilibrium, to highly non-equilibrium, processing was very challenging a

  6. THE EFFECT OF INTRASTRIATAL APPLICATION OF DIRECTLY AND INDIRECTLY ACTING DOPAMINE AGONISTS AND ANTAGONISTS ON THE INVIVO RELEASE OF ACETYLCHOLINE MEASURED BY BRAIN MICRODIALYSIS - THE IMPORTANCE OF THE POSTSURGERY INTERVAL

    NARCIS (Netherlands)

    DEBOER, P; DAMSMA, G; SCHRAM, Q; STOOF, JC; ZAAGSMA, J; WESTERINK, BHC

    The effect of intrastriatal application of D-1, D-2 and indirect dopaminergic drugs on the release of striatal acetylcholine as a function of the post-implantation intervals was studied using in vivo microdialysis. The dopamine D-2 agonists LY 171555 and (-)N0437 inhibited the release of striatal

  7. Application of artificial seeds in rapid multiplication of ...

    African Journals Online (AJOL)

    ajl user 3

    2011-11-09

    Nov 9, 2011 ... In this study, a method which produces artificial seeds of Pseudostellaria heterophylla was presented. The micro-tubers ... traditional herb used for hundreds of years in China to .... One of the advantages of artificial seed production is that it is not ... neration system, relative cost of a specific application for.

  8. A low cost rapid prototype platform for a three phase PFC rectifier application

    DEFF Research Database (Denmark)

    Haase, Frerk; Kouchaki, Alireza; Nymand, Morten

    2015-01-01

    In this paper the design and development of a low cost rapid prototype platform for a Three Phase PFC rectifier application is presented. The active rectifier consists of a SiC-MOSFET based PWM converter and a low cost rapid prototype platform for simulating and implementing the digital control...

  9. Qualitative CFD for Rapid Learning in Industrial and Academic Applications

    Science.gov (United States)

    Variano, Evan

    2010-11-01

    We present a set of tools that allow CFD to be used at an early stage in the design process. Users can rapidly explore the qualitative aspects of fluid flow using real-time simulations that react immediately to design changes. This can guide the design process by fostering an intuitive understanding of fluid dynamics at the prototyping stage. We use an extremely stable Navier-Stokes solver that is available commercially (and free to academic users) plus a custom user interface. The code is designed for the animation and gaming industry, and we exploit the powerful graphical display capabilities to develop a unique human-machine interface. This interface allows the user to efficiently explore the flow in 3D + real time, fostering an intuitive understanding of steady and unsteady flow patterns. There are obvious extensions to use in an academic setting. The trade-offs between accuracy and speed will be discussed in the context of CFD's role in design and education.

  10. 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

  11. 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.

  12. Rapid deposition process for zinc oxide film applications in pyroelectric devices

    International Nuclear Information System (INIS)

    Hsiao, Chun-Ching; Yu, Shih-Yuan

    2012-01-01

    Aerosol deposition (AD) is a rapid process for the deposition of films. Zinc oxide is a low toxicity and environmentally friendly material, and it possesses properties such as semiconductivity, pyroelectricity and piezoelectricity without the poling process. Therefore, AD is used to accelerate the manufacturing process for applications of ZnO films in pyroelectric devices. Increasing the temperature variation rate in pyroelectric films is a useful method for enhancing the responsivity of pyroelectric devices. In the present study, a porous ZnO film possessing the properties of large heat absorption and high temperature variation rate is successfully produced by the AD rapid process and laser annealing for application in pyroelectric devices. (paper)

  13. The scope of application of incremental rapid prototyping methods in foundry engineering

    Directory of Open Access Journals (Sweden)

    M. Stankiewicz

    2010-01-01

    Full Text Available The article presents the scope of application of selected incremental Rapid Prototyping methods in the process of manufacturing casting models, casting moulds and casts. The Rapid Prototyping methods (SL, SLA, FDM, 3DP, JS are predominantly used for the production of models and model sets for casting moulds. The Rapid Tooling methods, such as: ZCast-3DP, ProMetalRCT and VoxelJet, enable the fabrication of casting moulds in the incremental process. The application of the RP methods in cast production makes it possible to speed up the prototype preparation process. This is particularly vital to elements of complex shapes. The time required for the manufacture of the model, the mould and the cast proper may vary from a few to several dozen hours.

  14. Rapid computation of chemical equilibrium composition - An application to hydrocarbon combustion

    Science.gov (United States)

    Erickson, W. D.; Prabhu, R. K.

    1986-01-01

    A scheme for rapidly computing the chemical equilibrium composition of hydrocarbon combustion products is derived. A set of ten governing equations is reduced to a single equation that is solved by the Newton iteration method. Computation speeds are approximately 80 times faster than the often used free-energy minimization method. The general approach also has application to many other chemical systems.

  15. 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

  16. Adaptive multiparameter control: application to a Rapid Thermal Processing process; Commande Adaptative Multivariable: Application a un Procede de Traitement Thermique Rapide

    Energy Technology Data Exchange (ETDEWEB)

    Morales Mago, S J

    1995-12-20

    In this work the problem of temperature uniformity control in rapid thermal processing is addressed by means of multivariable adaptive control. Rapid Thermal Processing (RTP) is a set of techniques proposed for semiconductor fabrication processes such as annealing, oxidation, chemical vapour deposition and others. The product quality depends on two mains issues: precise trajectory following and spatial temperature uniformity. RTP is a fabrication technique that requires a sophisticated real-time multivariable control system to achieve acceptable results. Modelling of the thermal behaviour of the process leads to very complex mathematical models. These are the reasons why adaptive control techniques are chosen. A multivariable linear discrete time model of the highly non-linear process is identified on-line, using an identification scheme which includes supervisory actions. This identified model, combined with a multivariable predictive control law allows to prevent the controller from systems variations. The control laws are obtained by minimization of a quadratic cost function or by pole placement. In some of these control laws, a partial state reference model was included. This reference model allows to incorporate an appropriate tracking capability into the control law. Experimental results of the application of the involved multivariable adaptive control laws on a RTP system are presented. (author) refs

  17. Validation of a Rapid Bacteria Endospore Enumeration System for Planetary Protection Application

    Science.gov (United States)

    Chen, Fei; Kern, Roger; Kazarians, Gayane; Venkateswaran, Kasthuri

    NASA monitors spacecraft surfaces to assure that the presence of bacterial endospores meets strict criteria at launch, to minimize the risk of inadvertent contamination of the surface of Mars. Currently, the only approved method for enumerating the spores is a culture based assay that requires three days to produce results. In order to meet the demanding schedules of spacecraft assembly, a more rapid spore detection assay is being considered as an alternate method to the NASA standard culture-based assay. The Millipore Rapid Microbiology Detection System (RMDS) has been used successfully for rapid bioburden enumeration in the pharmaceutical and food industries. The RMDS is rapid and simple, shows high sensitivity (to 1 colony forming unit [CFU]/sample), and correlates well with traditional culture-based methods. It combines membrane filtration, adenosine triphosphate (ATP) bioluminescence chemistry, and image analysis based on photon detection with a Charge Coupled Device (CCD) camera. In this study, we have optimized the assay conditions and evaluated the use of the RMDS as a rapid spore detection tool for NASA applications. In order to select for spores, the samples were subjected to a heat shock step before proceeding with the RMDS incubation protocol. Seven species of Bacillus (nine strains) that have been repeatedly isolated from clean room environments were assayed. All strains were detected by the RMDS in 5 hours and these assay times were repeatedly demonstrated along with low image background noise. Validation experiments to compare the Rapid Sore Assay (RSA) and NASA standard assay (NSA) were also performed. The evaluation criteria were modeled after the FDA Guideline of Process Validation, and Analytical Test Methods. This body of research demonstrates that the Rapid Spore Assay (RSA) is quick, and of equivalent sensitivity to the NASA standard assay, potentially reducing the assay time for bacterial endospores from over 72 hours to less than 8 hours

  18. Rapid Methods for the Detection of Foodborne Bacterial Pathogens: Principles, Applications, Advantages and Limitations

    Directory of Open Access Journals (Sweden)

    Law eJodi Woan-Fei

    2015-01-01

    Full Text Available The incidence of foodborne diseases has increased over the years and resulted in major public health problem globally. Foodborne pathogens can be found in various foods and it is important to detect foodborne pathogens to provide safe food supply and to prevent foodborne diseases. The conventional methods used to detect foodborne pathogen are time consuming and laborious. Hence, a variety of methods have been developed for rapid detection of foodborne pathogens as it is required in many food analyses. Rapid detection methods can be categorized into nucleic acid-based, biosensor-based and immunological-based methods. This review emphasizes on the principles and application of recent rapid methods for the detection of foodborne bacterial pathogens. Detection methods included are simple polymerase chain reaction (PCR, multiplex PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA, loop-mediated isothermal amplification (LAMP and oligonucleotide DNA microarray which classified as nucleic acid-based methods; optical, electrochemical and mass-based biosensors which classified as biosensor-based methods; enzyme-linked immunosorbent assay (ELISA and lateral flow immunoassay which classified as immunological-based methods. In general, rapid detection methods are generally time-efficient, sensitive, specific and labor-saving. The developments of rapid detection methods are vital in prevention and treatment of foodborne diseases.

  19. Extending NASA Research Results to Benefit Society: Rapid Prototyping for Coastal Applications

    Science.gov (United States)

    Glorioso, Mark V.; Miller, Richard L.; Hall, Callie M.; McPherson, Terry R.

    2006-01-01

    The mission of the NASA Applied Sciences Program is to expand and accelerate the use of NASA research results to benefit society in 12 application areas of national priority. ONe of the program's major challenges is to perform a quick, efficient, and detailed review (i.e., prototyping) of the large number of combinations of NASA observations and results from Earth system models that may be used by a wide range of decision support tools. A Rapid Prototyping Capacity (RPC) is being developed to accelerate the use of NASA research results. Here, we present the conceptual framework of the Rapid Prototyping Capacity within the context of quickly assessing the efficacy of NASA research results and technologies to support the Coastal Management application. An initial RPC project designed to quickly evaluate the utility of moderate-resolution MODIS products for calibrating/validating coastal sediment transport models is also presented.

  20. Rapid application development by KEKB accelerator operators using EPICS/Python

    International Nuclear Information System (INIS)

    Tanaka, M.; Satoh, Y.; Kitabayashi, T.

    2004-01-01

    In the KEKB accelerator facility, the control system is constructed based on the framework of EPICS. By using EPICS/Python API, which is originated from KEK, we can develop an EPICS channel access application based on simple Python technology with only a few knowledge of EPICS channel access protocols. The operator's new tuning ideas are quickly implemented to the control system. In this paper, we introduce the EPICS/Python API and report the effectiveness of rapid application development by the KEKB operators using the API. (author)

  1. Application tests of a new-type LNG rapid gasification unit

    Directory of Open Access Journals (Sweden)

    Ping Yan

    2017-01-01

    Full Text Available Liquefied natural gas (LNG is stored under low temperature and high pressure. It has to be gasified before it is used. Therefore, LNG gasification unit is essential and it is vital to the high-efficiency utilization of LNG. In this paper, a new-type LNG rapid gasification unit was developed. Adopted in this unit are some innovative technologies authorized with the national patent of invention, such as the umbrella-shape gas flow circle unit, the flue gas circulation system and the water feeding system, which help to guarantee its operation safety and increase its operation efficiency. After it was justified in lab test, the unit for industrial application was designed and manufactured and then tested to verify its design rationality. The results show that the new-type LNG rapid gasification unit meets the design requirements in the aspect of efficiency, exhaust gas loss, radiation loss and fuel gas consumption rate; at a load of 1800–2200 m3/h, its efficiency is over 95%; at a load of 1976.0 m3/h which is close to the design value of 2000 m3/h, its efficiency is 96.34% or even up to 2800 m3/h. This new-type LNG rapid gasification unit is adaptable to a large range of loads and can adapt to the rapid increase of external load. Its fuel gas consumption rate is only 1.5%, which is in the range of energy conservation. It presents the advantages of high heating efficiency, rapid startup, high gasification rate, compact structure, small land occupation and invulnerability to the environment, therefore, it is applicable to the middle and small independent regions which cannot be connected to the natural gas supply pipeline networks due to various reasons.

  2. Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review of Literature.

    Science.gov (United States)

    Torabi, Kianoosh; Farjood, Ehsan; Hamedani, Shahram

    2015-03-01

    The early computer-aided design/computer-aided manufacturing (CAD/CAM) systems were relied exclusively on subtractive methods. In recent years, additive methods by employing rapid prototyping (RP) have progressed rapidly in various fields of dentistry as they have the potential to overcome known drawbacks of subtractive techniques such as fit problems. RP techniques have been exploited to build complex 3D models in medicine since the 1990s. RP has recently proposed successful applications in various dental fields, such as fabrication of implant surgical guides, frameworks for fixed and removable partial dentures, wax patterns for the dental prosthesis, zirconia prosthesis and molds for metal castings, and maxillofacial prosthesis and finally, complete dentures. This paper aimed to offer a comprehensive literature review of various RP methods, particularly in dentistry, that are expected to bring many improvements to the field. A search was made through MEDLINE database and Google scholar search engine. The keywords; 'rapid prototyping' and 'dentistry' were searched in title/abstract of publications; limited to 2003 to 2013, concerning past decade. The inclusion criterion was the technical researches that predominately included laboratory procedures. The exclusion criterion was meticulous clinical and excessive technical procedures. A total of 106 articles were retrieved, recited by authors and only 50 met the specified inclusion criteria for this review. Selected articles had used rapid prototyping techniques in various fields in dentistry through different techniques. This review depicted the different laboratory procedures employed in this method and confirmed that RP technique have been substantially feasible in dentistry. With advancement in various RP systems, it is possible to benefit from this technique in different dental practices, particularly in implementing dental prostheses for different applications.

  3. Rapid Prototyping Technologies and their Applications in Prosthodontics, a Review of Literature

    Science.gov (United States)

    Torabi, Kianoosh; Farjood, Ehsan; Hamedani, Shahram

    2015-01-01

    The early computer-aided design/computer-aided manufacturing (CAD/CAM) systems were relied exclusively on subtractive methods. In recent years, additive methods by employing rapid prototyping (RP) have progressed rapidly in various fields of dentistry as they have the potential to overcome known drawbacks of subtractive techniques such as fit problems. RP techniques have been exploited to build complex 3D models in medicine since the 1990s. RP has recently proposed successful applications in various dental fields, such as fabrication of implant surgical guides, frameworks for fixed and removable partial dentures, wax patterns for the dental prosthesis, zirconia prosthesis and molds for metal castings, and maxillofacial prosthesis and finally, complete dentures. This paper aimed to offer a comprehensive literature review of various RP methods, particularly in dentistry, that are expected to bring many improvements to the field. A search was made through MEDLINE database and Google scholar search engine. The keywords; ‘rapid prototyping’ and ‘dentistry’ were searched in title/abstract of publications; limited to 2003 to 2013, concerning past decade. The inclusion criterion was the technical researches that predominately included laboratory procedures. The exclusion criterion was meticulous clinical and excessive technical procedures. A total of 106 articles were retrieved, recited by authors and only 50 met the specified inclusion criteria for this review. Selected articles had used rapid prototyping techniques in various fields in dentistry through different techniques. This review depicted the different laboratory procedures employed in this method and confirmed that RP technique have been substantially feasible in dentistry. With advancement in various RP systems, it is possible to benefit from this technique in different dental practices, particularly in implementing dental prostheses for different applications. PMID:25759851

  4. Study of a large rapid ashing apparatus and a rapid dry ashing method for biological samples and its application

    International Nuclear Information System (INIS)

    Jin Meisun; Wang Benli; Liu Wencang

    1988-04-01

    A large rapid-dry-ashing apparatus and a rapid ashing method for biological samples are described. The apparatus consists of specially made ashing furnace, gas supply system and temperature-programming control cabinet. The following adventages have been showed by ashing experiment with the above apparatus: (1) high speed of ashing and saving of electric energy; (2) The apparatus can ash a large amount of samples at a time; (3) The ashed sample is pure white (or spotless), loose and easily soluble with few content of residual char; (4) The fresh sample can also be ashed directly. The apparatus is suitable for ashing a large amount of the environmental samples containing low level radioactivity trace elements and the medical, food and agricultural research samples

  5. Penerapan Aplikasi Program Penjualan Dan Pembelian Menggunakan Model Rapid Application Development

    Directory of Open Access Journals (Sweden)

    Annisa Febriani

    2017-09-01

    Abstract The development of information technology at the moment quickly and rapidly, supported by one means namely computer. Of course the computer has been equipped with a particular application is used to help facilitate the work of the man to manage the data of an organization or company so that getting accurate results and according to needs. The results of the observations that have been made, showed a sales and purchase activities are still using manual systems, one of them at a clothing store. Starting from the data processing of the goods, the difficulty of checking stock, purchase transaction, sales transactions, as well as other data storage associated with all types of such activities, so that it could make a loss for the store owner, errors in the logging and less akuratnya the report is made. Judging from the large number of transactions done on clothing stores, required system information more quickly and accurately. Thus, the author makes the program architecture-based computer, use the Microsoft Visual Basic.net programming language and the MySQL database, so that the information and activities that occur can be done quickly and accurately. The methods used in making architecture the program using the model of Rapid Application Development (RAD. This RAD model is an adaptation of the waterfall model for high speed version of the development of each component of its software. Results achieved from the discussion of this theme is the form of the application program selling and buying the ready-made. In this case, the use of the application program is the best solution to solve the existing problems, as well as with the use of application programs can be reached by an activity which is effective and efficient in supporting that activity, especially for addressing the problem of the sale and purchase of.   Keywords: Sales Program, Purchasing Program.

  6. Long-term reclaimed water application effects on phosphorus leaching potential in rapid infiltration basins.

    Science.gov (United States)

    Moura, Daniel R; Silveira, Maria L; O'Connor, George A; Wise, William R

    2011-09-01

    Rapid infiltration basins (RIBs) are effective tools for wastewater treatment and groundwater recharge, but continuous application of wastewater can increase soil P concentrations and subsequently impact groundwater quality. The objectives of this study were to (1) investigate the effects of reclaimed water infiltration rate and "age" of RIBs on soil P concentrations at various depths, and (2) estimate the degree (percentage) of sorption equilibrium reached between effluent P and soil attained during reclaimed water application to different RIBs. The study was conducted in four contrasting cells of a RIB system with up to a 25 year history of secondary wastewater application. Soil samples were collected from 0 to 300 cm depth at 30 cm intervals and analyzed for water extractable phosphorus (WEP) and oxalate extractable P, Al, and Fe concentrations. Water extractable P and P saturation ratio (PSR) values were generally greater in the cells receiving reclaimed water compared to control soils, suggesting that reclaimed water P application can increase soil P concentrations and the risk of P movement to greater depths. Differences between treatment and control samples were more evident in cells with longer histories of reclaimed water application due to greater P loading. Data also indicated considerable spatial variability in WEP concentrations and PSR values, especially within cells from RIBs characterized by fast infiltration rates. This occurs because wastewater-P flows through surface soils much faster than the minimum time required for sorption equilibrium to occur. Studies should be conducted to investigate soil P saturation at deeper depths to assess possible groundwater contamination.

  7. Application of Rapid Prototyping Methods to High-Speed Wind Tunnel Testing

    Science.gov (United States)

    Springer, A. M.

    1998-01-01

    This study was undertaken in MSFC's 14-Inch Trisonic Wind Tunnel to determine if rapid prototyping methods could be used in the design and manufacturing of high speed wind tunnel models in direct testing applications, and if these methods would reduce model design/fabrication time and cost while providing models of high enough fidelity to provide adequate aerodynamic data, and of sufficient strength to survive the test environment. Rapid prototyping methods utilized to construct wind tunnel models in a wing-body-tail configuration were: fused deposition method using both ABS plastic and PEEK as building materials, stereolithography using the photopolymer SL-5170, selective laser sintering using glass reinforced nylon, and laminated object manufacturing using plastic reinforced with glass and 'paper'. This study revealed good agreement between the SLA model, the metal model with an FDM-ABS nose, an SLA nose, and the metal model for most operating conditions, while the FDM-ABS data diverged at higher loading conditions. Data from the initial SLS model showed poor agreement due to problems in post-processing, resulting in a different configuration. A second SLS model was tested and showed relatively good agreement. It can be concluded that rapid prototyping models show promise in preliminary aerodynamic development studies at subsonic, transonic, and supersonic speeds.

  8. Perancangan Aplikasi Presensi Dosen Realtime Dengan Metode Rapid Application Development (RAD Menggunakan Fingerprint Berbasis Web

    Directory of Open Access Journals (Sweden)

    Darma Setiawan Putra

    2018-05-01

    Full Text Available The fingerprint is one of the biometric methods which is can be used in the education field. Attendance monitoring system using fingerprint will make the leaders easily to monitor the attendance of the lecturer and to make decisions. The fingerprint attendance is used to easy students detecting quickly and accurately the lecturer in the classroom. This system aims to provide the lecturer status information, entry or exit for teaching when every lecturer performs a fingerprint scanning. This study uses rapid application development (RAD method to develop attendance system and involves the lecturer who have a teaching schedule in the current semester. To test the system, the lecturer was required to record the fingerprint in fingerprint machine. The result shows that the application of lecturer attendance in real time web-based can be a system provides the lecturers attendance information effectively and efficiently.

  9. 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....

  10. RICHTER: A Smartphone Application for Rapid Collection of Geo-Tagged Pictures of Earthquake Damage

    Science.gov (United States)

    Skinnemoen, H.; Bossu, R.; Furuheim, K.; Bjorgo, E.

    2010-12-01

    RICHTER (Rapid geo-Images for Collaborative Help Targeting Earthquake Response) is a smartphone version of a professional application developed to provide high quality geo-tagged image communication over challenging network links, such as satellites and poor mobile links. Developed for Android mobile phones, it allows eyewitnesses to share their pictures of earthquake damage easily and without cost with the Euro-Mediterranean Seismological Centre (EMSC). The goal is to engage citizens in the collection of the most up-to-date visual information on local damage for improved rapid impact assessment. RICHTER integrates the innovative and award winning ASIGN protocol initially developed for satellite communication between cameras / computers / satcom terminals and servers at HQ. ASIGN is a robust and optimal image and video communication management solution for bandwidth-limited communication networks which was developed for use particularly in emergency and disaster situations. Contrary to a simple Multimedia Messaging System (MMS), RICHTER allows access to high definition images with embedded location information. Location is automatically assigned from either the internal GPS, derived from the mobile network (triangulation) or the current Wi-Fi domain, in that order, as this corresponds to the expected positioning accuracy. Pictures are compressed to 20-30KB of data typically for fast transfer and to avoid network overload. Full size images can be requested by the EMSC either fully automatically, or on a case-by-case basis, depending on the user preferences. ASIGN was initially developed in coordination with INMARSAT and the European Space Agency. It was used by the Rapid Mapping Unit of the United Nations notably for the damage assessment of the January 12, 2010 Haiti earthquake where more than 700 photos were collected. RICHTER will be freely distributed on the EMSC website to eyewitnesses in the event of significantly damaging earthquakes. The EMSC is the second

  11. Fourier-transform infrared spectroscopy for rapid screening and live-cell monitoring: application to nanotoxicology.

    Science.gov (United States)

    Sundaram, S K; Sacksteder, Colette A; Weber, Thomas J; Riley, Brian J; Addleman, R Shane; Harrer, Bruce J; Peterman, John W

    2013-01-01

    A significant challenge to realize the full potential of nanotechnology for therapeutic and diagnostic applications is to understand and evaluate how live cells interact with an external stimulus, such as a nanosized particle, and the toxicity and broad risk associated with these stimuli. It is difficult to capture the complexity and dynamics of these interactions by following omics-based approaches exclusively, which can be expensive and time-consuming. Attenuated total reflectance-Fourier transform infrared spectroscopy is well suited to provide noninvasive live-cell monitoring of cellular responses to potentially toxic nanosized particles or other stimuli. This alternative approach provides the ability to carry out rapid toxicity screenings and nondisruptive monitoring of live-cell cultures. We review the technical basis of the approach, the instrument configuration and interface with the biological media, the various effects that impact the data, subsequent data analysis and toxicity, and present some preliminary results on live-cell monitoring.

  12. A novel low-cost mobile robot for rapid prototyping of precision farming applications

    DEFF Research Database (Denmark)

    Jensen, Kjeld; Neerup, Mathias Mikkel; Larsen, Leon Bonde

    Experimental research in precision farming is a significant challenge due to the considerable resources required to perform field experiments. Simulating the field environment is a frequently used technique which is useful for functional software tests, but beyond that it is necessary to perform...... experiments. In this work we present a novel FrobitPro robot platform designed for rapid prototyping of FroboMind field robot applications. FrobitPro has a fundamental design similar to many current wheeled and tracked robots such as the Kongskilde Robotti, and the workflow of migrating from simulation...... as outdoor driving in semi-rugged terrain such as grass fields and bare soil. This paper presents the FrobitPro robot and describes two use cases in current research projects, namely the Grassbots project which focuses on harvesting of grass on lowland areas for biofuel production and the SAFE project...

  13. Application of rapid thermal processing on SiNx thin film to solar cells

    Institute of Scientific and Technical Information of China (English)

    Youjie LI; Peiqing LUO; Zhibin ZHOU; Rongqiang CUI; Jianhua HUANG; Jingxiao WANG

    2008-01-01

    Rapid thermal processing (RTP) of SiNx thin films from PECVD with low temperature was investigated. A special processing condition of this technique which could greatly increase the minority lifetime was found in the experiments. The processing mechanism and the application of the technique to silicon solar cells fabrication were dis-cussed. A main achievement is an increase of the minority lifetime in silicon wafer with SiNx thin film by about 200% after the RTP was reached. PC-1D simulation results exhibit an enhancement of the efficiency of the solar cell by 0.42% coming from the minority lifetime improvement. The same experiment was also conducted with P-diffusion silicon wafers, but the increment of minority lifetime is just about 55%. It could be expected to improve the solar cell efficiency if it would be used in silicon solar cells fabrication with the combination of laser firing contact technique.

  14. CAD – CAM PROCEDURE USING FOR RAPID PROTOTYPING WITH APPLICATION IN BIOMECHANICS

    Directory of Open Access Journals (Sweden)

    BRAUN Barbu

    2015-06-01

    Full Text Available The paper presents a new and efficient method for modeling some components with application in Biomechanics. It is shown the way in which this method could be successfully applied for orthopedic shoes, namely for foot insoles to correct any plantar deformities. The main advantages of the proposed method refer to low costs, successfully applying for different products for Biomechanics. The prototyped models via CAD/CAM method allowed a rapid and efficient improvement of their design. Another advantage refer to the fact that these can be properly and efficiently tested before prototyping by the point of view of mechanical stress, due to prior simulations, eliminating all costs meaning wastes or adjustments.

  15. Inovasi Layanan Lapor Kehilangan (E-Report Dengan Metode Rapid Application Development

    Directory of Open Access Journals (Sweden)

    Ahmad Chusyairi

    2018-02-01

    Full Text Available Pelayanan kehilangan yang dilakukan Kepolisian Resort (Polres Banyuwangi khususnya Sentra Pelayanan Keamanan Terpadu (SPKT meliputi Surat Tanda Nomor Kendaraan (STNK Mobil/Motor, Surat Izin Mengemudi (SIM Mobil/Motor, Kartu Tanda Penduduk (KTP, Kartu Keluarga (KK, Anjungan Tunai Mandiri (ATM, Buku Tabungan, Paspor, Sertifikat, Surat Tanah dan Surat Lain-lain (Kartu Tanda Mahasiswa, Surat Gadai, Ijazah, Giro Bilyet, Tilang dan Buku Raport dimana pembuatan Surat Keterangan Tanda Lapor Kehilangan (SKTLK masih manual dengan tools pengolah kata dan membutuhkan waktu yang lama, sehingga masyarakat mengalami kesulitan dalam proses pelayanannya. Polres Banyuwangi menjalankan Program Prioritas Promoter (Profesional, Modern dan Terpercaya Kapolri Tahun 2016, khususnya program ke-2: Peningkatan Pelayanan Publik yang Lebih Mudah bagi Masyarakat dan Berbasis Teknologi Informasi. Tujuan dari penelitian ini adalah masyarakat (pemohon SKTLK dapat mengakses layanan dengan mudah dan mendapatkan SKTLK lebih cepat di polres/polsek terdekat pada wilayah hukum kabupaten Banyuwangi. Metode yang digunakan dalam penelitian ini adalah Rapid Application Development (RAD yang terdiri dari: Requirements Planning, User Design, Construction dan Cutover. Hasil penelitian ini adalah web tentang laporan kehilangan (e-report dengan URL http://banyuwangi.jatim.polri.go.id/kehilangan.html. Kesimpulan dari penelitian ini adalah pelayanan publik pada Polres Banyuwangi tentang e-report dengan metode RAD dapat diakses pada web, sehingga pemohon dapat dengan mudah mendapatkan SKTLK di Polres atau Polsek yang terdekat dengan lokasi kehilangan. Metode RAD mempermudah dalam pembangunan layanan e-report berbasis web karena aktivitas dan fasenya melibatkan pengguna khususnya pada user design. Hasil pengujian terhadap fitur pada layanan e-report pada fase construction dan cutover dapat menampilkan  sesuai dengan requirements planning yang ditetapkan pengguna.Kata Kunci: kehilangan, Polres

  16. The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer

    Directory of Open Access Journals (Sweden)

    Gu J

    2015-08-01

    Full Text Available Junsheng Gu, Ranran Sun, Shen Shen, Zujiang Yu Department of Infectious Diseases, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Objective: This study was designed to explore the influence of Toll-like receptor 4 (TLR4 agonist lipopolysaccharides (LPS on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Methods: Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. Results: The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3 signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Conclusion: Thus, TLR4 agonist LPS is proved to be able to

  17. The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer.

    Science.gov (United States)

    Gu, Junsheng; Sun, Ranran; Shen, Shen; Yu, Zujiang

    2015-01-01

    This study was designed to explore the influence of Toll-like receptor 4 (TLR4) agonist lipopolysaccharides (LPS) on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI) single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3) signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Thus, TLR4 agonist LPS is proved to be able to induce liver cancer cells to express inflammation factors and mediate liver cancer cell proliferation and generation of multidrug resistance by activating the cyclooxygenase-2/prostaglandin signal axis as well as the STAT3 pathway.

  18. Status of IGS Ultra-Rapid Products for Real-Time Applications

    Science.gov (United States)

    Ray, J.; Griffiths, J.

    2008-12-01

    Since November 2000 the International GNSS Service (IGS) has produced Ultra-rapid (IGU) products for near real-time and real-time applications. They include GPS orbits, satellite clocks, and Earth rotation parameters for a sliding 48-hr period. The first day of each update is based on the most recent GPS observational data from the IGS hourly tracking network. At the time of release, these observed products have an initial latency of 3 hr. The second day of each update consists of predictions. So the predictions between about 3 and 9 hr into the second half are relevant for true real-time uses. Originally updated twice daily, the IGU products since April 2004 have been issued four times per day, at 3, 9, 15, and 21 UTC. Up to seven Analysis Centers (ACs) contribute to the IGU combinations: Astronomical Institute of the University of Berne (AIUB), European Space Operations Center (ESOC), Geodetic Observatory Pecny (GOP), GeoForschungsZentrum (GFZ) Potsdam, Natural Resources Canada (NRC), Scripps Insitution of Oceanography (SIO), U.S. Naval Observatory (USNO). This redundancy affords a high measure of reliability and enhanced orbit accuracy. IGU orbit precision has improved markedly since late 2007. This is due to a combination of factors: decommissioning of the old, poorly behaved PRN29 in October 2007; upgraded procedures implemented by GOP around the same time, by SIO in spring 2008, and by USNO in June 2008; better handling of maneuvered satellites at the combination level starting June 2008; and stricter AC rejection criteria since July 2008. As a consequence, the weighted 1D RMS residual of the IGU orbit predictions over their first 6 hr is currently about 20 to 30 mm (after a Helmert transformation) compared to the IGS Rapid orbits, averaged over the constellation. The median residual is about 15 to 20 mm. When extended to the full 24 hr prediction period, the IGU orbit errors approximately double. Systematic rotational offsets are probably more important than

  19. VIPER: a web application for rapid expert review of variant calls.

    Science.gov (United States)

    Wöste, Marius; Dugas, Martin

    2018-01-15

    With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10,000 calls. VIPER is implemented in Java and Javascript and is freely available at https://github.com/MarWoes/viper. Marius.Woeste@uni-muenster.de. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. Environmental science applications with Rapid Integrated Mapping and analysis System (RIMS)

    Science.gov (United States)

    Shiklomanov, A.; Prusevich, A.; Gordov, E.; Okladnikov, I.; Titov, A.

    2016-11-01

    The Rapid Integrated Mapping and analysis System (RIMS) has been developed at the University of New Hampshire as an online instrument for multidisciplinary data visualization, analysis and manipulation with a focus on hydrological applications. Recently it was enriched with data and tools to allow more sophisticated analysis of interdisciplinary data. Three different examples of specific scientific applications with RIMS are demonstrated and discussed. Analysis of historical changes in major components of the Eurasian pan-Arctic water budget is based on historical discharge data, gridded observational meteorological fields, and remote sensing data for sea ice area. Express analysis of the extremely hot and dry summer of 2010 across European Russia is performed using a combination of near-real time and historical data to evaluate the intensity and spatial distribution of this event and its socioeconomic impacts. Integrative analysis of hydrological, water management, and population data for Central Asia over the last 30 years provides an assessment of regional water security due to changes in climate, water use and demography. The presented case studies demonstrate the capabilities of RIMS as a powerful instrument for hydrological and coupled human-natural systems research.

  1. Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

    Science.gov (United States)

    Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

    2017-11-17

    Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

  2. Pocket pathologist: A mobile application for rapid diagnostic surgical pathology consultation

    Directory of Open Access Journals (Sweden)

    Douglas J Hartman

    2014-01-01

    Full Text Available Introduction: Telepathology allows the digital transmission of images for rapid access to pathology experts. Recent technologic advances in smartphones have allowed them to be used to acquire and transmit digital images of the glass slide, representing cost savings and efficiency gains over traditional forms of telepathology. We report our experience with developing an iPhone application (App - Pocket Pathologist to facilitate rapid diagnostic pathology teleconsultation utilizing a smartphone. Materials and Methods: A secure, web-based portal (http://pathconsult.upmc.com/ was created to facilitate remote transmission of digital images for teleconsultation. The App augments functionality of the web-based portal and allows the user to quickly and easily upload digital images for teleconsultation. Image quality of smartphone cameras was evaluated by capturing images using different adapters that directly attach phones to a microscope ocular lens. Results: The App was launched in August 2013. The App facilitated easy submission of cases for teleconsultation by limiting the number of data entry fields for users and enabling uploading of images from their smartphone′s gallery wirelessly. Smartphone cameras properly attached to a microscope create static digital images of similar quality to a commercial digital microscope camera. Conclusion: Smartphones have great potential to support telepathology because they are portable, provide ubiquitous internet connectivity, contain excellent digital cameras, and can be easily attached to a microscope. The Pocket Pathologist App represents a significant reduction in the cost of creating digital images and submitting them for teleconsultation. The iPhone App provides an easy solution for global users to submit digital pathology images to pathology experts for consultation.

  3. Testing the applicability of rapid on-site enzymatic activity detection for surface water monitoring

    Science.gov (United States)

    Stadler, Philipp; Vogl, Wolfgang; Juri, Koschelnik; Markus, Epp; Maximilian, Lackner; Markus, Oismüller; Monika, Kumpan; Peter, Strauss; Regina, Sommer; Gabriela, Ryzinska-Paier; Farnleitner Andreas, H.; Matthias, Zessner

    2015-04-01

    bacteria. Therefore the applicability of on-site enzymatic activity determination as a direct surrogate or proxy parameter for microbiological standard assays and quantification of fecal indicator bacteria (FIB) concentration could not be approved and further research in this field is necessary. Presently we conclude that rapid on-site detection of enzymatic activity is applicable for surface water monitoring and that it constitutes a complementary on-site monitoring parameter with high potential. Selection of the type of measured enzymatic activities has to be done on a catchment-specific basis and further work is needed to learn more about its detailed information characteristics in different habitats. The accomplishment of this method detecting continuous data of enzymatic activity in high temporal resolution caused by a target bacterial member is on the way of becoming a powerful tool for water quality monitoring, health related water quality- and early warning requirements.

  4. A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2013-08-01

    Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  5. 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....

  6. Design and rapid prototyping of DLC coated fractal surfaces for tissue engineering applications

    International Nuclear Information System (INIS)

    Diaz-Lantada, A; Mosquera, A; Endrino, J L; Lafont, P

    2010-01-01

    Several medical devices (both implantable and for in vitro diagnosis) benefit greatly from having microtextured surfaces that help to improve and promote phenomena such as osteointegracion and cell / tissue growth on the surface of a device. Normally, the use of abrasives or chemical attacks are employed for obtaining such surface microtextures, however, it is sometimes difficult to precisely control the final surface characteristics (porosity, roughness, among others) and consequently the related biological aspects. In this work, we propose an alternative process based on the use of fractal surface models for designing special surfaces, which helps controlling the desired contact properties (from the design stage) in multiple applications within biomedical engineering, especially regarding tissue engineering tasks. Manufacturing can be directly accomplished by means of rapid prototyping technologies. This method supposes a focus change from a conventional 'top-down' to a more versatile 'bottom-up' approach. Finally, in order to improve the possible biological response, the surfaces of the designed devices were coated with hydrogen-free amorphous carbon (a-C) thin films, known to be highly biocompatible materials. The films were deposited at room temperature using the vacuum filter cathodic arc technique. Our first prototypes have helped verify the viability of the approach and to validate the design, manufacturing and coating processes.

  7. Rapid Object Detection Systems, Utilising Deep Learning and Unmanned Aerial Systems (uas) for Civil Engineering Applications

    Science.gov (United States)

    Griffiths, D.; Boehm, J.

    2018-05-01

    With deep learning approaches now out-performing traditional image processing techniques for image understanding, this paper accesses the potential of rapid generation of Convolutional Neural Networks (CNNs) for applied engineering purposes. Three CNNs are trained on 275 UAS-derived and freely available online images for object detection of 3m2 segments of railway track. These includes two models based on the Faster RCNN object detection algorithm (Resnet and Incpetion-Resnet) as well as the novel onestage Focal Loss network architecture (Retinanet). Model performance was assessed with respect to three accuracy metrics. The first two consisted of Intersection over Union (IoU) with thresholds 0.5 and 0.1. The last assesses accuracy based on the proportion of track covered by object detection proposals against total track length. In under six hours of training (and two hours of manual labelling) the models detected 91.3 %, 83.1 % and 75.6 % of track in the 500 test images acquired from the UAS survey Retinanet, Resnet and Inception-Resnet respectively. We then discuss the potential for such applications of such systems within the engineering field for a range of scenarios.

  8. Application of adjustable pulse lasers to studying rapid reaction kinetics of excited lanthanide complexing

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, V.P. (Gosudarstvennyj Opticheskij Inst., Leningrad (USSR))

    1983-12-01

    Using some europium (3) ion complexes new possibilities to be opened by application of adjustable pulse lasers for studying rapid reactions of electron-excited metal ion complexing are demonstrated. The 6Zh rhodamine pulse laser is used as a source of nonequilibrium photoexcitation of an array of Eu/sup 3 +/ complexes in the luminescent kinetic spectroscopy method. The following results are obtained: for the first time the rate of reaction of acetate ion substitution for water molecules of an excited (/sup 5/D/sub 0/) ion of Eu/sup 3 +/ was measured to be (0.7+-0.2)x10/sup 7/ s/sup -1/; using direct experiments the lower limit for the rate of transition of one isomeric form of the excited Eu x EDTA complex into another one in an aqueous solution is determined to be 5x10/sup 5/ s/sup -1/ at 295 K; the kinetics of the excitation energy migration beteen aqueous solvates of Eu/sup 3 +/ and EuxEDTA complexes is investigated.

  9. Design and rapid prototyping of DLC coated fractal surfaces for tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Lantada, A; Mosquera, A; Endrino, J L; Lafont, P, E-mail: adiaz@etsii.upm.es

    2010-11-01

    Several medical devices (both implantable and for in vitro diagnosis) benefit greatly from having microtextured surfaces that help to improve and promote phenomena such as osteointegracion and cell / tissue growth on the surface of a device. Normally, the use of abrasives or chemical attacks are employed for obtaining such surface microtextures, however, it is sometimes difficult to precisely control the final surface characteristics (porosity, roughness, among others) and consequently the related biological aspects. In this work, we propose an alternative process based on the use of fractal surface models for designing special surfaces, which helps controlling the desired contact properties (from the design stage) in multiple applications within biomedical engineering, especially regarding tissue engineering tasks. Manufacturing can be directly accomplished by means of rapid prototyping technologies. This method supposes a focus change from a conventional 'top-down' to a more versatile 'bottom-up' approach. Finally, in order to improve the possible biological response, the surfaces of the designed devices were coated with hydrogen-free amorphous carbon (a-C) thin films, known to be highly biocompatible materials. The films were deposited at room temperature using the vacuum filter cathodic arc technique. Our first prototypes have helped verify the viability of the approach and to validate the design, manufacturing and coating processes.

  10. Modeling cavitation in a rapidly changing pressure field - application to a small ultrasonic horn.

    Science.gov (United States)

    Žnidarčič, Anton; Mettin, Robert; Dular, Matevž

    2015-01-01

    Ultrasonic horn transducers are frequently used in applications of acoustic cavitation in liquids. It has been observed that if the horn tip is sufficiently small and driven at high amplitude, cavitation is very strong, and the tip can be covered entirely by the gas/vapor phase for longer time intervals. A peculiar dynamics of the attached cavity can emerge with expansion and collapse at a self-generated frequency in the subharmonic range, i.e. below the acoustic driving frequency. The term "acoustic supercavitation" was proposed for this type of cavitation Žnidarčič et al. (2014) [1]. We tested several established hydrodynamic cavitation models on this problem, but none of them was able to correctly predict the flow features. As a specific characteristic of such acoustic cavitation problems lies in the rapidly changing driving pressures, we present an improved approach to cavitation modeling, which does not neglect the second derivatives in the Rayleigh-Plesset equation. Comparison with measurements of acoustic supercavitation at an ultrasonic horn of 20kHz frequency revealed a good agreement in terms of cavity dynamics, cavity volume and emitted pressure pulsations. The newly developed cavitation model is particularly suited for simulation of cavitating flow in highly fluctuating driving pressure fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Rapid monitoring particulate radiocesium with nonwoven fabric cartridge filter and application to field monitoring

    International Nuclear Information System (INIS)

    Tsuji, Hideki; Yasutaka, Tetsuo; Kondo, Yoshihiko; Kawashima, Shoji

    2013-01-01

    A method for rapid monitoring particulate radiocesium using a nonwoven fabric cartridge filter was developed, which needs no further preprocessing before served to a detector. By a performance test, more than 98% of suspended solid (SS) was collected. This method showed the same radioactivity measurement accuracy as filtration by membrane filter and more rapid extraction capability of SS. (author)

  12. Recent applications for rapid estimation of earthquake shaking and losses with ELER Software

    International Nuclear Information System (INIS)

    Demircioglu, M.B.; Erdik, M.; Kamer, Y.; Sesetyan, K.; Tuzun, C.

    2012-01-01

    A methodology and software package entitled Earthquake Loss Estimation Routine (ELER) was developed for rapid estimation of earthquake shaking and losses throughout the Euro-Mediterranean region. The work was carried out under the Joint Research Activity-3 (JRA3) of the EC FP6 project entitled Network of Research Infrastructures for European Seismology (NERIES). The ELER methodology anticipates: 1) finding of the most likely location of the source of the earthquake using regional seismo-tectonic data base; 2) estimation of the spatial distribution of selected ground motion parameters at engineering bedrock through region specific ground motion prediction models, bias-correcting the ground motion estimations with strong ground motion data, if available; 3) estimation of the spatial distribution of site-corrected ground motion parameters using regional geology database using appropriate amplification models; and 4) estimation of the losses and uncertainties at various orders of sophistication (buildings, casualties). The multi-level methodology developed for real time estimation of losses is capable of incorporating regional variability and sources of uncertainty stemming from ground motion predictions, fault finiteness, site modifications, inventory of physical and social elements subjected to earthquake hazard and the associated vulnerability relationships which are coded into ELER. The present paper provides brief information on the methodology of ELER and provides an example application with the recent major earthquake that hit the Van province in the east of Turkey on 23 October 2011 with moment magnitude (Mw) of 7.2. For this earthquake, Kandilli Observatory and Earthquake Research Institute (KOERI) provided almost real time estimations in terms of building damage and casualty distribution using ELER. (author)

  13. Development of field-applicable tests for rapid and sensitive detection of Candidatus Phytoplasma oryzae.

    Science.gov (United States)

    Wambua, Lillian; Schneider, Bernd; Okwaro, Allan; Wanga, Joseph Odhiambo; Imali, Olive; Wambua, Peninah Nduku; Agutu, Lavender; Olds, Cassandra; Jones, Chris Stephen; Masiga, Daniel; Midega, Charles; Khan, Zeyaur; Jores, Joerg; Fischer, Anne

    2017-10-01

    Napier grass Stunt Disease (NSD) is a severe disease of Napier grass (Pennisetum purpureum) in Eastern Africa, caused by the leafhopper-transmitted bacterium Candidatus Phytoplasma oryzae. The pathogen severely impairs the growth of Napier grass, the major fodder for dairy cattle in Eastern Africa. NSD is associated with biomass losses of up to 70% of infected plants. Diagnosis of NSD is done by nested PCR targeting the phytoplasma DNA, which is difficult to perform in developing countries with little infrastructure. We report the development of an easy to use, rapid, sensitive and specific molecular assay for field diagnosis of NSD. The procedure is based on recombinase polymerase amplification and targets the imp gene encoding a pathogen-specific immunodominant membrane protein. Therefore we followed a two-step process. First we developed an isothermal DNA amplification method for real time fluorescence application and then transferred this assay to a lateral flow format. The limit of detection for both procedures was estimated to be 10 organisms. We simplified the template preparation procedure by using freshly squeezed phloem sap from Napier grass. Additionally, we developed a laboratory serological assay with the potential to be converted to a lateral flow assay. Two murine monoclonal antibodies with high affinity and specificity to the immunodominant membrane protein IMP of Candidatus Phytoplasma oryzae were generated. Both antibodies specifically reacted with the denatured or native 17 kDa IMP protein. In dot blot experiments of extracts from infected plant, phytoplasmas were detected in as little as 12,5 μg of fresh plant material. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Advantages of utilizing DMD based rapid manufacturing systems in mass customization applications

    Science.gov (United States)

    El-Siblani, A.

    2010-02-01

    The Use of DMD based Rapid Manufacturing Systems has proven to be very advantageous in the production of highly accurate plastic based components for use in mass customization market such as hearing aids, and dental markets. The voxelization process currently afforded with the DLP technology eliminates any layering effect associated with all existing additive Rapid Manufacturing technologies. The smooth accurate surfaces produced in an additive process utilizing DLP technology, through the voxelization approach, allow for the production of custom finished products. The implementation of DLP technology in rapid prototyping and rapid manufacturing systems allow for the usage of highly viscous photopolymer based liquid and paste composites for rapid manufacturing that could not be used in any other additive process prior to implementation of DLP technology in RP and RM systems. It also allowed for the greater throughput in production without sacrificing quality and accuracy.

  15. Rapid application design of an electronic clinical skills portfolio for undergraduate medical students.

    Science.gov (United States)

    Dornan, Tim; Lee, Catherine; Stopford, Adam; Hosie, Liam; Maredia, Neil; Rector, Alan

    2005-04-01

    The aim was to find how to use information and communication technology to present the clinical skills content of an undergraduate medical curriculum. Rapid application design was used to develop the product, and technical action research was used to evaluate the development process. A clinician-educator, two medical students, two computing science masters students, two other project workers, and a hospital education informatics lead, formed a design team. A sample of stakeholders took part in requirements planning workshops and continued to advise the team throughout the project. A university hospital had many features that favoured fast, inexpensive, and successful system development: a clearly defined and readily accessible user group; location of the development process close to end-users; fast, informal communication; leadership by highly motivated and senior end-users; devolved authority and lack of any rigidly imposed management structure; cooperation of clinicians because the project drew on their clinical expertise to achieve scholastic goals; a culture of learning and involvement of highly motivated students. A detailed specification was developed through storyboarding, use case diagramming, and evolutionary prototyping. A very usable working product was developed within weeks. "SkillsBase" is a database web application using Microsoft Active Server Pages, served from a Microsoft Windows 2000 Server operating system running Internet Information Server 5.0. Graphing functionality is provided by the KavaChart applet. It presents the skills curriculum, provides a password-protected portfolio function, and offers training materials. The curriculum can be presented in several different ways to help students reflect on their objectives and progress towards achieving them. The reflective portfolio function is entirely private to each student user and allows them to document their progress in attaining skills, as judged by self, peer and tutor assessment, and

  16. Design guidelines for rapid and simple context-aware mobile application development – an android case study

    Directory of Open Access Journals (Sweden)

    Hossein Shams

    2015-11-01

    Full Text Available Presenting a context-aware service and information is a key aspect of ubiquitous computing, but development of such applications is quite complicated. Context-aware applications should be able to obtain raw data fromsensors, create highlevel context information, detect the user’s situation, and adapt the behavior of the application to the recognized situation . These complexities caused to reduce the impact of context -awareness in mobile computing while sensors of smartphones have made huge potential for developing context aware mobile applications. In this paper, we explain some guidelines to overcome the existing obstacles by separating the context -aware application layers and make a loosely coupled connection between them. These guidelines will bring easy and rapid development, reusability of the code and flexibility for developers. Finally, we provide a case study example in the Android platform to demonstrate how the guidelines can be used in a real application.

  17. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol

    International Nuclear Information System (INIS)

    Gao, Hongfei; Han, Jing; Yang, Shijia; Wang, Zhenxing; Wang, Lin; Fu, Zhifeng

    2014-01-01

    Graphical abstract: A multianalyte immunochromatographic test strip was developed for the rapid detection of two β 2 -agonists. Due to the application of chemiluminescent detection, this quantitative method shows much higher sensitivity. - Highlights: • An immunochromatographic test strip was developed for detection of multiple β 2 -agonists. • The whole assay process can be completed within 20 min. • The proposed method shows much higher sensitivity due to the application of CL detection. • It is a portable analytical tool suitable for field analysis and rapid screening. - Abstract: A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β 2 -agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β 2 -agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50–40 and 0.10–50 ng mL −1 , with the detection limits of 0.20 and 0.040 ng mL −1 (S/N = 3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β 2 -agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety

  18. 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

  19. Application of portable XRF and VNIR sensors for rapid assessment of soil heavy metal pollution

    OpenAIRE

    Hu, Bifeng; Chen, Songchao; Hu, Jie; Xia, Fang; Xu, Junfeng; Li, Yan; Shi, Zhou

    2017-01-01

    Rapid heavy metal soil surveys at large scale with high sampling density could not be conducted with traditional laboratory physical and chemical analyses because of the high cost, low efficiency and heavy workload involved. This study explored a rapid approach to assess heavy metals contamination in 301 farmland soils from Fuyang in Zhejiang Province, in the southern Yangtze River Delta, China, using portable proximal soil sensors. Portable X-ray fluorescence spectroscopy (PXRF) was used to ...

  20. Application of rapid prototyping technology in the prototype manufacturing for evaluation of NPP components and equipments

    International Nuclear Information System (INIS)

    Park, C. Y.; Kim, J. W.; Shon, H. K.; Choi, H. S.; Yang, D. Y.

    2001-01-01

    A brief overview of rapid prototyping technology in which a part with complex shape can be produced easily and rapidly in a layer-by-layer additive manner is given in this article. In addition, a prototype model of a complex fan is manufactured using three-dimensional solid CAD modeling and Laminated Object Manufacturing (LOM), a rapid prototyping technology. This enables designers to verify and modify design rapidly at an early stage of product development; and the prototype model of a fan can be used as a pattern for various secondary casting process such as vacumm casting, lost-paper casting to make prototypes of a fan. It has been shown that the combination of three-dimensional solid CAD modeling and rapid prototyping technology can reduce greatly the cost and time of prototyping of fans and turbine blades in comparison with conventional CNC machining. It should also be noted that rapid prototyping technology enables the visualization of various physical and chemical defects at a nuclear power plant so that it can help engineers understand those defects in an effective way

  1. Binding free energy predictions of farnesoid X receptor (FXR) agonists using a linear interaction energy (LIE) approach with reliability estimation: application to the D3R Grand Challenge 2

    Science.gov (United States)

    Rifai, Eko Aditya; van Dijk, Marc; Vermeulen, Nico P. E.; Geerke, Daan P.

    2018-01-01

    Computational protein binding affinity prediction can play an important role in drug research but performing efficient and accurate binding free energy calculations is still challenging. In the context of phase 2 of the Drug Design Data Resource (D3R) Grand Challenge 2 we used our automated eTOX ALLIES approach to apply the (iterative) linear interaction energy (LIE) method and we evaluated its performance in predicting binding affinities for farnesoid X receptor (FXR) agonists. Efficiency was obtained by our pre-calibrated LIE models and molecular dynamics (MD) simulations at the nanosecond scale, while predictive accuracy was obtained for a small subset of compounds. Using our recently introduced reliability estimation metrics, we could classify predictions with higher confidence by featuring an applicability domain (AD) analysis in combination with protein-ligand interaction profiling. The outcomes of and agreement between our AD and interaction-profile analyses to distinguish and rationalize the performance of our predictions highlighted the relevance of sufficiently exploring protein-ligand interactions during training and it demonstrated the possibility to quantitatively and efficiently evaluate if this is achieved by using simulation data only.

  2. Research on the Application of Rapid Surveying and Mapping for Large Scare Topographic Map by Uav Aerial Photography System

    Science.gov (United States)

    Gao, Z.; Song, Y.; Li, C.; Zeng, F.; Wang, F.

    2017-08-01

    Rapid acquisition and processing method of large scale topographic map data, which relies on the Unmanned Aerial Vehicle (UAV) low-altitude aerial photogrammetry system, is studied in this paper, elaborating the main work flow. Key technologies of UAV photograph mapping is also studied, developing a rapid mapping system based on electronic plate mapping system, thus changing the traditional mapping mode and greatly improving the efficiency of the mapping. Production test and achievement precision evaluation of Digital Orth photo Map (DOM), Digital Line Graphic (DLG) and other digital production were carried out combined with the city basic topographic map update project, which provides a new techniques for large scale rapid surveying and has obvious technical advantage and good application prospect.

  3. Application of a rapid screening method to detect irradiated meat in Brazil

    International Nuclear Information System (INIS)

    Villavicencio, A.L.C.H.; Delincee, H.

    1998-01-01

    Complete text of publication follows. Based on the enormous potential for food irradiation in Brazil, and to ensure free consumer choice, there is a need to find a convenient and rapid method for detection of irradiated food. Since treatment with ionizing radiation causes DNA fragmentation, the analysis of DNA damage might be promising. In fact, DNA fragmentation measured in single cells by agarose gel electrophoresis - DNA Comet Assay - has shown to offer great potential as a rapid tool to detect whether a wide variety of foodstuffs has been radiation processed. However, more work is needed to exploit the full potential of this promising technique. In this paper, the DNA Comet Assay was used to identify exotic meat (boar, jacare and capybara), irradiated with 60 Co gamma-rays. The applied radiation doses were 0, 1.5, 3.0 and 4.5 kGy. Analysis of the DNA migration enable a rapid identification of the radiation treatment

  4. Applications and control of air conditioning systems using rapid cycling to modulate capacity

    Energy Technology Data Exchange (ETDEWEB)

    Poort, M.J.; Bullard, C.W. [Department of Mechanical and Industrial Engineering, Air Conditioning and Refrigeration Center, University of Illinois, 1206 W. Green St., Urbana, IL 61801 (United States)

    2006-08-15

    Rapid cycling the compressor of an air conditioning or refrigeration system can be used to modulate capacity, thus offering an alternative to a variable speed compressor. This paper explores design tradeoffs to optimize rapid cycling performance based on experimental results using two different evaporators and changing other components of an air conditioning system. Rapid cycling has inherent compressor lift penalties associated with larger mass flow rates, which need to be minimized. Preventing dryout (superheating) in the evaporator during the off cycle, a major penalty as cycles are lengthened, is also important. Evaporator dryout is minimized by increasing the refrigerant side area and reducing off cycle drainage. Combining a flash gas bypass with a suction line heat exchanger was found to maximize performance during the off cycle while allowing increased cycle lengths without incurring major penalties. (author)

  5. Oracle Application Express 5 for beginners a practical guide to rapidly develop data-centric web applications accessible from desktop, laptops, tablets, and smartphones

    CERN Document Server

    2015-01-01

    Oracle Application Express has taken another big leap towards becoming a true next generation RAD tool. It has entered into its fifth version to build robust web applications. One of the most significant feature in this release is a new page designer that helps developers create and edit page elements within a single page design view, which enormously maximizes developer productivity. Without involving the audience too much into the boring bits, this full colored edition adopts an inspiring approach that helps beginners practically evaluate almost every feature of Oracle Application Express, including all features new to version 5. The most convincing way to explore a technology is to apply it to a real world problem. In this book, you’ll develop a sales application that demonstrates almost every feature to practically expose the anatomy of Oracle Application Express 5. The short list below presents some main topics of Oracle APEX covered in this book: Rapid web application development for desktops, la...

  6. Application of a rapid screening method to detect irradiated meat in Brazil

    International Nuclear Information System (INIS)

    Villavicencio, A.L.C.H.; Mancini-Filho, J.; Delincee, H.

    2000-01-01

    Based on the enormous potential for food irradiation in Brazil, and to ensure free consumer choice, there is a need to find a convenient and rapid method for detection of irradiated food. Since treatment with ionising radiation causes DNA fragmentation, the analysis of DNA damage might be promising. In this paper, the DNA Comet Assay was used to identify exotic meat (boar, jacare and capybara), irradiated with 60 Co gamma rays. The applied radiation doses were 0, 1.5, 3.0 and 4.5 kGy. Analysis of the DNA migration enabled a rapid identification of the radiation treatment

  7. 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.

  8. Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

    Directory of Open Access Journals (Sweden)

    Merk Martina

    2011-09-01

    Full Text Available Abstract Background Active dendritic cell (DC immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML. Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR agonists in intensively pretreated patients with AML. Methods Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C, induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70, showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells. Conclusions Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

  9. 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...

  10. Potential applications of rapid/elementary nonparametric statistical techniques (NST) to electrochemical problems

    International Nuclear Information System (INIS)

    Fahidy, Thomas Z.

    2009-01-01

    A major advantage of NST lies in the unimportance of the probability distribution of observations. In this paper, the sign test, the rank-sum test, the Kruskal-Wallis test, the Friedman test, and the runs test illustrate the potential of certain rapid NST for the evaluation of electrochemical process performance.

  11. Design and Applications of Rapid Image Tile Producing Software Based on Mosaic Dataset

    Science.gov (United States)

    Zha, Z.; Huang, W.; Wang, C.; Tang, D.; Zhu, L.

    2018-04-01

    Map tile technology is widely used in web geographic information services. How to efficiently produce map tiles is key technology for rapid service of images on web. In this paper, a rapid producing software for image tile data based on mosaic dataset is designed, meanwhile, the flow of tile producing is given. Key technologies such as cluster processing, map representation, tile checking, tile conversion and compression in memory are discussed. Accomplished by software development and tested by actual image data, the results show that this software has a high degree of automation, would be able to effectively reducing the number of IO and improve the tile producing efficiency. Moreover, the manual operations would be reduced significantly.

  12. DESIGN AND APPLICATIONS OF RAPID IMAGE TILE PRODUCING SOFTWARE BASED ON MOSAIC DATASET

    Directory of Open Access Journals (Sweden)

    Z. Zha

    2018-04-01

    Full Text Available Map tile technology is widely used in web geographic information services. How to efficiently produce map tiles is key technology for rapid service of images on web. In this paper, a rapid producing software for image tile data based on mosaic dataset is designed, meanwhile, the flow of tile producing is given. Key technologies such as cluster processing, map representation, tile checking, tile conversion and compression in memory are discussed. Accomplished by software development and tested by actual image data, the results show that this software has a high degree of automation, would be able to effectively reducing the number of IO and improve the tile producing efficiency. Moreover, the manual operations would be reduced significantly.

  13. Ultrathin Oxide Passivation Layer by Rapid Thermal Oxidation for the Silicon Heterojunction Solar Cell Applications

    OpenAIRE

    Lee, Youngseok; Oh, Woongkyo; Dao, Vinh Ai; Hussain, Shahzada Qamar; Yi, Junsin

    2012-01-01

    It is difficult to deposit extremely thin a-Si:H layer in heterojunction with intrinsic thin layer (HIT) solar cell due to thermal damage and tough process control. This study aims to understand oxide passivation mechanism of silicon surface using rapid thermal oxidation (RTO) process by examining surface effective lifetime and surface recombination velocity. The presence of thin insulating a-Si:H layer is the key to get high Voc by lowering the leakage current (I0) which improves the efficie...

  14. Application of portable XRF and VNIR sensors for rapid assessment of soil heavy metal pollution.

    Science.gov (United States)

    Hu, Bifeng; Chen, Songchao; Hu, Jie; Xia, Fang; Xu, Junfeng; Li, Yan; Shi, Zhou

    2017-01-01

    Rapid heavy metal soil surveys at large scale with high sampling density could not be conducted with traditional laboratory physical and chemical analyses because of the high cost, low efficiency and heavy workload involved. This study explored a rapid approach to assess heavy metals contamination in 301 farmland soils from Fuyang in Zhejiang Province, in the southern Yangtze River Delta, China, using portable proximal soil sensors. Portable X-ray fluorescence spectroscopy (PXRF) was used to determine soil heavy metals total concentrations while soil pH was predicted by portable visible-near infrared spectroscopy (PVNIR). Zn, Cu and Pb were successfully predicted by PXRF (R2 >0.90 and RPD >2.50) while As and Ni were predicted with less accuracy (R2 heavy metals contamination grades in farmland soils was conducted based on previous results; the Kappa coefficient was 0.87, which showed that the combination of PXRF and PVNIR was an effective and rapid method to determine the degree of pollution with soil heavy metals. This study provides a new approach to assess soil heavy metals pollution; this method will facilitate large-scale surveys of soil heavy metal pollution.

  15. Experimental study and field application of calcium sulfoaluminate cement for rapid repair of concrete pavements

    Institute of Scientific and Technical Information of China (English)

    Yanhua GUAN; Ying GAO; Renjuan SUN; Moon C.WON; Zhi GE

    2017-01-01

    The fast-track repair of deteriorated concrete pavement requires materials that can be placed,cured,and opened to the traffic in a short period.Type Ⅲ cement and Calcium Sulfoaluminate (CSA) cement are the most commonly used fast-setting hydraulic cement (FSHC).In this study,the properties of Type Ⅲ and CSA cement concrete,including compressive strength,coefficient of thermal expansion (CTE) and shrinkage were evaluated.The test results indicate that compressive strength of FSHC concrete increased rapidly at the early age.CSA cement concrete had higher early-age and long term strength.The shrinkage of CSA cement concrete was lower than that of Type Ⅲ cement concrete.Both CSA and Type Ⅲ cement concrete had similar CTE values.Based on the laboratory results,the CSA cement was selected as the partial-depth rapid repair material for a distressed continuously reinforced concrete pavement.The data collected during and after the repair show that the CSA cement concrete had good short-term and long-term performances and,therefore,was suitable for the rapid repair of concrete pavement.

  16. Application of portable XRF and VNIR sensors for rapid assessment of soil heavy metal pollution

    Science.gov (United States)

    Hu, Bifeng; Chen, Songchao; Hu, Jie; Xia, Fang; Xu, Junfeng; Li, Yan; Shi, Zhou

    2017-01-01

    Rapid heavy metal soil surveys at large scale with high sampling density could not be conducted with traditional laboratory physical and chemical analyses because of the high cost, low efficiency and heavy workload involved. This study explored a rapid approach to assess heavy metals contamination in 301 farmland soils from Fuyang in Zhejiang Province, in the southern Yangtze River Delta, China, using portable proximal soil sensors. Portable X-ray fluorescence spectroscopy (PXRF) was used to determine soil heavy metals total concentrations while soil pH was predicted by portable visible-near infrared spectroscopy (PVNIR). Zn, Cu and Pb were successfully predicted by PXRF (R2 >0.90 and RPD >2.50) while As and Ni were predicted with less accuracy (R2 heavy metals contamination grades in farmland soils was conducted based on previous results; the Kappa coefficient was 0.87, which showed that the combination of PXRF and PVNIR was an effective and rapid method to determine the degree of pollution with soil heavy metals. This study provides a new approach to assess soil heavy metals pollution; this method will facilitate large-scale surveys of soil heavy metal pollution. PMID:28234944

  17. STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice.

    Science.gov (United States)

    Skouboe, Morten K; Knudsen, Alice; Reinert, Line S; Boularan, Cedric; Lioux, Thierry; Perouzel, Eric; Thomsen, Martin K; Paludan, Søren R

    2018-04-01

    In recent years, there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions, including infectious diseases. For instance, Toll-like receptor (TLR) agonists have been evaluated for treatment of genital herpes. However, although the TLR7 agonist imiquimod was shown to have antiviral activity in individual patients, no significant effects were observed in clinical trials, and the compound also exhibited significant side effects, including local inflammation. Cytosolic DNA is detected by the enzyme cyclic GMP-AMP (2'3'-cGAMP) synthase (cGAS) to stimulate antiviral pathways, mainly through induction of type I interferon (IFN)s. cGAS is activated upon DNA binding to produce the cyclic dinucleotide (CDN) 2'3'-cGAMP, which in turn binds and activates the adaptor protein Stimulator of interferon genes (STING), thus triggering type I IFN expression. In contrast to TLRs, STING is expressed broadly, including in epithelial cells. Here we report that natural and non-natural STING agonists strongly induce type I IFNs in human cells and in mice in vivo, without stimulating significant inflammatory gene expression. Systemic treatment with 2'3'-cGAMP reduced genital herpes simplex virus (HSV) 2 replication and improved the clinical outcome of infection. More importantly, local application of CDNs at the genital epithelial surface gave rise to local IFN activity, but only limited systemic responses, and this treatment conferred total protection against disease in both immunocompetent and immunocompromised mice. In direct comparison between CDNs and TLR agonists, only CDNs acted directly on epithelial cells, hence allowing a more rapid and IFN-focused immune response in the vaginal epithelium. Thus, specific activation of the STING pathway in the vagina evokes induction of the IFN system but limited inflammatory responses to allow control of HSV2 infections in vivo.

  18. A rapid method of estimating the solar irradiance spectra with potential lighting applications

    NARCIS (Netherlands)

    Gao, Y.; Dong, J.; Isabella, O.; Zeman, M.; Zhang, G

    2016-01-01

    Diverse solar irradiance spectra can be observed under different conditions of time, date, location, weather, etc. Since the solar irradiance spectrum is required by certain scientific and engineering applications, obtaining accurate spectral data is essential. Measurements by spectrophotometers are

  19. Rapid Development of Guidance, Navigation, and Control Core Flight System Software Applications Using Simulink Models

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of this proposal is to demonstrate a new Guidance, Navigation, and Control (GNC) Flight Software (FSW) application development paradigm which takes...

  20. 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....

  1. 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.

  2. Rapid DNA haplotyping using a multiplex heteroduplex approach: Application to Duchenne muscula dystrophy carrier detection

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Wenger, G.D.; Moore, J. [Ohio State Univ., Columbus, OH (United States)] [and others

    1994-09-01

    A new strategy has been developed for rapid haplotype analysis. It is based on an initial multiplex amplification of several polymorphic sites, followed by heteroduplex detection. Heteroduplexes formed between two different alleles are detected because they migrate differently than the corresponding homoduplexes in Hydrolink-MDE gel. The method is simple, rapid, does not depend on specific sequences such as restriction enzyme sites or CA boxes and does not require the use of isotope. This approach has been tested using 12 commonly occurring polymorphisms spanning the dystrophin gene as a model. We describe the use of the method to assign the carrier status of females in Duchenne muscular dystrophy (DMD) pedigrees. As a result of expanding the number of detectable polymorphisms throughout the dystrophin gene, we show how the method can easily be combined with dinucleotide analysis to improve the accuracy of carrier detection in the nondeletion cases. The technique is also shown to be used as an effective screen for improving carrier detection in several families with deletions. The finding of heterozygosity within the deletion identifies the at-risk female as a noncarrier. Using this method, we have identified and incorporated 3 new dystrophin polymorphisms (one of which in exon 16 is unique to African Americans). The method may be used other genetic diseases when mutations are unknown, or there are few dinucleotide markers in the gene proximity, or for the identification of haplotype backgrounds of mutant alleles.

  3. Application of rapid-sampling, online microdialysis to the monitoring of brain metabolism during aneurysm surgery.

    Science.gov (United States)

    Bhatia, Robin; Hashemi, Parastoo; Razzaq, Ashfaq; Parkin, Mark C; Hopwood, Sarah E; Boutelle, Martyn G; Strong, Anthony J

    2006-04-01

    To introduce rapid-sampling microdialysis for the early detection of adverse metabolic changes in tissue at risk during aneurysm surgery. A microdialysis catheter was inserted under direct vision into at-risk cortex at the start of surgery. This monitoring was sustained throughout the course of the operation, during which intraoperative events, for example, temporary arterial occlusion or lobe retraction, were precisely documented. A continuous online flow of dialysate was fed into a mobile bedside glucose and lactate analyser. This comprises flow-injection dual-assay enzyme-based biosensors capable of determining values of metabolites every 30 seconds. Eight patients underwent clipping or wrapping of intracranial aneurysms and were monitored. Time between events and detection: 9 minutes. Mean change in metabolite value +/- standard deviation: temporal lobe retraction lactate, +656 +/- 562 micromol/L (n = 7, P glucose, -123 +/- 138 micromol/L (n = 6, P = 0.08). Glucose intravenous bolus infusion glucose, +512 +/- 244 micromol/L (n = 5, P lactate, +731 +/- 346 micromol/L (n = 6, P glucose, -139 +/- 96 micromol/L (n = 5, P glucose and lactate in dialysate, particularly when rapid, transient changes in brain analyte levels need to be determined and the alternative offline methodology would be inadequate.

  4. Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

    Directory of Open Access Journals (Sweden)

    Min Gao

    Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

  5. 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.

  6. Validation and application of an improved method for the rapid determination of proline in grape berries.

    Science.gov (United States)

    Rienth, Markus; Romieu, Charles; Gregan, Rebecca; Walsh, Caroline; Torregrosa, Laurent; Kelly, Mary T

    2014-04-16

    A rapid and sensitive method is presented for the determination of proline in grape berries. Following acidification with formic acid, proline is derivatized by heating at 100 °C for 15 min with 3% ninhydrin in dimethyl sulfoxide, and the absorbance, which is stable for at least 60 min, is read at 520 nm. The method was statistically validated in the concentration range from 2.5 to 15 mg/L, giving a repeatability and intermediate precision of generally amino acid analyzer. In terms of sample preparation, a simple dilution (5-20-fold) is required, and sugars, primary amino acids, and anthocyanins were demonstrated not to interfere, as the latter are bleached by ninhydrin under the experimental conditions. The method was applied to the study of proline accumulation in the fruits of microvines grown in phytotrons, and it was established that proline accumulation and concentrations closely resemble those of field-grown macrovines.

  7. A novel approach for high precision rapid potentiometric titrations: application to hydrazine assay.

    Science.gov (United States)

    Sahoo, P; Malathi, N; Ananthanarayanan, R; Praveen, K; Murali, N

    2011-11-01

    We propose a high precision rapid personal computer (PC) based potentiometric titration technique using a specially designed mini-cell to carry out redox titrations for assay of chemicals in quality control laboratories attached to industrial, R&D, and nuclear establishments. Using this technique a few microlitre of sample (50-100 μl) in a total volume of ~2 ml solution can be titrated and the waste generated after titration is extremely low comparing to that obtained from the conventional titration technique. The entire titration including online data acquisition followed by immediate offline analysis of data to get information about concentration of unknown sample is completed within a couple of minutes (about 2 min). This facility has been created using a new class of sensors, viz., pulsating sensors developed in-house. The basic concept in designing such instrument and the salient features of the titration device are presented in this paper. The performance of the titration facility was examined by conducting some of the high resolution redox titrations using dilute solutions--hydrazine against KIO(3) in HCl medium, Fe(II) against Ce(IV) and uranium using Davies-Gray method. The precision of titrations using this innovative approach lies between 0.048% and 1.0% relative standard deviation in different redox titrations. With the evolution of this rapid PC based titrator it was possible to develop a simple but high precision potentiometric titration technique for quick determination of hydrazine in nuclear fuel dissolver solution in the context of reprocessing of spent nuclear fuel in fast breeder reactors. © 2011 American Institute of Physics

  8. Service platform for rapid development and deployment of context-Aware, mobile applications

    NARCIS (Netherlands)

    Pokraev, S.; Koolwaaij, Johan; van Setten, Mark; Broens, Tom; Dockhorn Costa, Patrícia; Wibbels, Martin; Ebben, Peter; Strating, Patrick

    2005-01-01

    In this paper we present a web services-based platform that facilitates and speeds up the development and deployment of context-aware, integrated mobile speech and data applications. The platform is capable of handling different types of context and offers sophisticated personalization mechanisms.

  9. Rapid and Efficient Conversion of (11) CO2 to (11) CO through Silacarboxylic Acids: Applications in Pd-Mediated Carbonylations.

    Science.gov (United States)

    Nordeman, Patrik; Friis, Stig D; Andersen, Thomas L; Audrain, Hélène; Larhed, Mats; Skrydstrup, Troels; Antoni, Gunnar

    2015-12-01

    Herein, we present a new rapid, efficient, and low-cost radiosynthetic protocol for the conversion of (11) CO2 to (11) CO and its subsequent application in Pd-mediated reactions of importance for PET applications. This room-temperature methodology, using readily available chemical reagents, is carried out in simple glass vials, thus eliminating the need for expensive and specialized high-temperature equipment to access (11) CO. With this fast and near-quantitative conversion of (11) CO2 into (11) CO, aryl and heteroaryl iodides were easily converted into a broad selection of biologically active amides in radiochemical yields ranging from 29-84 %. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Preparation of stir cake sorptive extraction based on poly(4-vinylbenzoic acid-divinylbenzene) monolith and its application in sensitive determination of β-agonists in milk and swine urine samples

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xiaojia, E-mail: hxj@xmu.edu.cn; Chen, Linli; Yuan, Dongxing

    2013-11-15

    Highlights: • A new poly(4-vinylbenzoic acid-divinylbenzene) monolith was first prepared. • The porous monolith was used as sorbent of stir cake sorptive extraction. • The new sorbent could extract β-agonists effectively by multiple interactions. • Method of determination of trace β-agonists in milk and urine samples was developed. -- Abstract: In this study, a new stir cake sorptive extraction (SCSE) based on poly(4-vinylbenzoic acid-divinylbenzene) (VBADB) monolith was prepared. The effect of preparation conditions of monolith on extraction efficiencies was investigated in detail. Several characteristic techniques, such as elemental analysis, infrared spectroscopy, mercury intrusion porosimetry and scanning electron microscopy were used to characterize the monolithic material. The combination of SCSE-VBADB with high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS) detection was developed for sensitive determination of ultra-trace β-agonists in milk and swine urine samples. In order to obtain the optimal extraction conditions of SCSE-VBADB for β-agonists, several extractive parameters, including pH values and ionic strength in sample matrix, extraction and desorption time were optimized. Under the optimum conditions, the limits of detection (S/N = 3) for the target analytes were 0.007–0.030 μg/L in milk and 0.002–0.011 μg/L in swine urine, respectively. Excellent method reproducibility was achieved in terms of intraday and interday precisions, indicated by the RSDs of both <10.0%, respectively. Finally, the proposed method was successfully used to detect β-agonists in different milk and swine urines samples. Acceptable recoveries ranged from 50.3% to 113% and 50.1% to 92.2% for milk and swine urine samples, respectively; and the RSDs for reproducibility were less than 8.0% for target analytes in all real samples.

  11. Application of rapid artificial cardiac pacing in thoracic endovascular aortic repair in aged patients

    Directory of Open Access Journals (Sweden)

    Chen J

    2013-12-01

    Full Text Available Jun Chen,1,* Wenhui Huang,2,* Songyuan Luo,2,* Dahao Yang,1 Zhengrong Xu,1 Jianfang Luo21Department of Angiocardiopathy, Affiliated Baoan Hospital of Southern Medical University, Shenzhen City, People's Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China*These authors contributed equally to this workObjective: To compare the safety, efficacy, and impact on stent graft positioning between rapid artificial cardiac pacing (RACP, induced hypotension and sodium nitroprusside (SNP induced hypotension during thoracic endovascular aortic repair (TEVAR for Stanford B aortic dissection.Methods: One hundred and sixty-eight patients, who were diagnosed with Stanford B aortic dissection and who underwent selective TEVAR in Guangdong General Hospital and the People's Hospital of Baoan District, Shenzhen, People's Republic of China, were enrolled in this study. Patients were randomly divided into a RACP group (n=77 and a SNP group (n=91. During localization and deployment of the stent graft, hypotension was induced by RACP or intravenous SNP, according to randomization. Hemodynamics, landing precision (deviation from planned placement site, duration of procedure, renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia were compared. Except for methods of inducing hypotension, TEVAR was performed according to the same protocol in each group.Results: RACP was successfully performed in all patients assigned to the RACP group. Compared with the SNP group, blood pressure was significantly lower (43±5 versus 81±6 mmHg, P=0.003 and the restoration time of blood pressure and the operation duration were significantly shorter (7±2 versus 451±87 seconds, P<0.001; 87±15 versus 106±18 minutes, P<0.001, respectively in the RACP group. Stent graft localization/deployment was more precise in the RACP

  12. Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

    Science.gov (United States)

    Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

    2006-01-01

    The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

  13. A jumping spark counter for various applications; rapid determination of its counting parameters

    International Nuclear Information System (INIS)

    Varnagy, M.; Vasvary, L.; Gyarmati, E.; Juhasz, S.; Scharbert, T.; Sztaricskai, T.

    1977-01-01

    On the basis of the method proposed by Cross and Tommasino a jumping spark counter (JSC) has been constructed which is applicable for the counting (continuously or 'step by step') of the perforations in thin (5-20μm) polymer foils. The JSC was combined with a DIDAC 4000 multichannel pulse-height analyser and multiscaler to determine automatically the best parameters and procedures for spark counting as well as to study the working mechanism of the JSC. Investigations were performed on etched Markrofol GK foils irradiated with fission fragments and exposed to 0.35 MRad gamma-rays. The track density interval studies was 0-50000 tracks/cm 2 . The possibility of the adoption of JSC for neutron dosimetric application, evaluation of angular distribution and for safegaurd purposes was tested. The possible consequences of the results are discussed. (Auth.)

  14. A Survey of the Rapidly Emerging Field of Nanotechnology: Potential Applications for Scientific Instruments and Technologies for Atmospheric Entry Probes

    Science.gov (United States)

    Meyyappan, M.; Arnold, J. O.

    2005-01-01

    The field of Nanotechnology is well funded worldwide and innovations applicable to Solar System Exploration are emerging much more rapidly than thought possible just a few years ago. This presentation will survey recent innovations from nanotechnololgy with a focus on novel applications to atmospheric entry science and probe technology, in a fashion similar to that presented by Arnold and Venkatapathy at the previous workshop forum at Lisbon Portugal, October 6-9, 2003. Nanotechnology is a rapidly emerging field that builds systems, devices and materials from the bottom up, atom by atom, and in so doing provides them with novel and remarkable macro-scale performance. This technology has the potential to revolutionize space exploration by reducing mass and simultaneously increasing capability. Thermal, Radiation, Impact Protective Shields: Atmospheric probes and humans on long duration deep space missions involved in Solar System Exploration must safely endure 3 significant hazards: (i) atmospheric entry; (ii) radiation; and (iii) micrometeorite or debris impact. Nanostructured materials could be developed to address all three hazards with a single protective shield, which would involve much less mass than a traditional approach. The concept can be ready in time for incorporation into NASA s Crew Exploration Vehicle, and possible entry probes to fly on the Jupiter Icy Moons

  15. Applicability of two automated disintegration apparatuses for rapidly disintegrating (mini)tablets.

    Science.gov (United States)

    Sieber, Daniel; Lazzari, Alessia; Quodbach, Julian; Pein, Miriam

    2017-03-01

    Orally disintegrating (mini)tablets (OD(M)Ts) are of interest in the field of pharmaceutics. Their orodispersible character is defined by the disintegration time, which is measured with a basket apparatus according to the European Pharmacopoeia. This method, however, lacks applicability for ODTs and especially ODMTs. New disintegration apparatuses have been described in literature, but a qualification to assess the applicability has not been described. A qualification procedure for two automated disintegration apparatuses, OD-mate and Hermes apparatus, is introduced. Aspects of the operational qualification as well as precision and accuracy regarding a performance qualification were evaluated for both apparatuses analog to the ICH guideline Q2. While the OQ study is performed separately for each apparatus, accuracy and precision were performed following the same protocol for both testers. Small RSDs (16.9% OD-mate; 15.2% Hermes compared to 32.3% for the pharmacopeial method) were found despite very fast disintegration times (1.5 s for both apparatuses). By comparing these RSDs to practical examples, the authors propose threshold values for repeatability depending on the mean disintegration time. Obtained results from the qualification were used to assess the applicability of both apparatuses.

  16. Physically Transient Memory on a Rapidly Dissoluble Paper for Security Application

    Science.gov (United States)

    Bae, Hagyoul; Lee, Byung-Hyun; Lee, Dongil; Seol, Myeong-Lok; Kim, Daewon; Han, Jin-Woo; Kim, Choong-Ki; Jeon, Seung-Bae; Ahn, Daechul; Park, Sang-Jae; Park, Jun-Young; Choi, Yang-Kyu

    2016-12-01

    We report the transient memory device by means of a water soluble SSG (solid sodium with glycerine) paper. This material has a hydroscopic property hence it can be soluble in water. In terms of physical security of memory devices, prompt abrogation of a memory device which stored a large number of data is crucial when it is stolen because all of things have identified information in the memory device. By utilizing the SSG paper as a substrate, we fabricated a disposable resistive random access memory (RRAM) which has good data retention of longer than 106 seconds and cycling endurance of 300 cycles. This memory device is dissolved within 10 seconds thus it can never be recovered or replicated. By employing direct printing but not lithography technology to aim low cost and disposable applications, the memory capacity tends to be limited less than kilo-bits. However, unlike high memory capacity demand for consumer electronics, the proposed device is targeting for security applications. With this regards, the sub-kilobit memory capacity should find the applications such as one-time usable personal identification, authentication code storage, cryptography key, and smart delivery tag. This aspect is attractive for security and protection system against unauthorized accessibility.

  17. Field application of a rapid spectrophotometric method for determination of persulfate in soil.

    Directory of Open Access Journals (Sweden)

    Colin J Cunningham

    Full Text Available Remediation of hydrocarbon contaminated soils can be performed both in situ and ex situ using chemical oxidants such as sodium persulfate. Standard methods for quantifying persulfate require either centrifugation or prolonged settling times. An optimized soil extraction procedure was developed for persulfate involving simple water extraction using a modified disposable syringe. This allows considerable saving of time and removes the need for centrifugation. The extraction time was reduced to only 5 min compared to 15 min for the standard approach. A comparison of the two approaches demonstrated that each provides comparable results. Comparisons were made using high (93 g kg(-1 soil and low (9.3 g kg(-1 soil additions of sodium persulfate to a petroleum hydrocarbon-contaminated soil, as well as sand spiked with diesel. Recoveries of 95±1% and 96±10% were observed with the higher application rate in the contaminated soil and spiked sand, respectively. Corresponding recoveries of 86±5% and 117±19% were measured for the lower application rate. Results were obtained in only 25 min and the method is well suited to batch analyses. In addition, it is suitable for application in a small field laboratory or even a mobile, vehicle-based system, as it requires minimal equipment and reagents.

  18. Field Application of a Rapid Spectrophotometric Method for Determination of Persulfate in Soil

    Science.gov (United States)

    Cunningham, Colin J.; Pitschi, Vanessa; Anderson, Peter; Barry, D. A.; Patterson, Colin; Peshkur, Tanya A.

    2013-01-01

    Remediation of hydrocarbon contaminated soils can be performed both in situ and ex situ using chemical oxidants such as sodium persulfate. Standard methods for quantifying persulfate require either centrifugation or prolonged settling times. An optimized soil extraction procedure was developed for persulfate involving simple water extraction using a modified disposable syringe. This allows considerable saving of time and removes the need for centrifugation. The extraction time was reduced to only 5 min compared to 15 min for the standard approach. A comparison of the two approaches demonstrated that each provides comparable results. Comparisons were made using high (93 g kg−1 soil) and low (9.3 g kg−1 soil) additions of sodium persulfate to a petroleum hydrocarbon-contaminated soil, as well as sand spiked with diesel. Recoveries of 95±1% and 96±10% were observed with the higher application rate in the contaminated soil and spiked sand, respectively. Corresponding recoveries of 86±5% and 117±19% were measured for the lower application rate. Results were obtained in only 25 min and the method is well suited to batch analyses. In addition, it is suitable for application in a small field laboratory or even a mobile, vehicle-based system, as it requires minimal equipment and reagents. PMID:23776446

  19. Mechanism of the rapid dissolution of Pu02 under oxidizing conditions and applications

    International Nuclear Information System (INIS)

    Madic, C.; Lecomte, M.; Bourges, J.; Koehly, G.

    1991-01-01

    Until the recent years, plutonium dioxide was known to be among the metallic oxides the most difficult to dissolve. From thermodynamic calculations it can be predicted that PuO 2 will dissolve under oxidizing conditions. This can be achieved using Ag(II) species possibly regenerated by electrochemical means. The mechanism of such a process has been elucidated using carbon paste electrochemistry and 18 O labelling. These studies demonstrate that the chemical reaction limiting the overall proces is located on the surface of the solid PuO 2 , and that the first step consists in the oxidation of the plutonium into Pu(V) species. Applications of the dissolution process of PuO 2 by electrogenerated Ag(II) were growing in the recent years in FRANCE. These applications developed often in collaboration with SGN and COGEMA, concern the treatment of: out of specifications PuO 2 , incineration ashes, wastes produced during MOX fuel fabrication, and during the dismantling of old nuclear facilities. A general overview of these different applications is given

  20. Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists.

    Science.gov (United States)

    Schaeffer, J I; Haddad, G G

    1985-09-01

    To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40-60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002-2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5-25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

  1. Rapid Assessment of the Ce-Co-Fe-Cu System for Permanent Magnetic Applications

    Science.gov (United States)

    Meng, F.; Chaudhary, R. P.; Gandha, K.; Nlebedim, I. C.; Palasyuk, A.; Simsek, E.; Kramer, M. J.; Ott, R. T.

    2018-04-01

    This work focuses on the rapid synthesis and characterization of quaternary Ce(CoFeCu)5 alloy libraries to assess their potential viability as permanent magnets. Arrays of bulk specimens with controlled compositions were synthesized via laser engineered net shaping (LENS) by feeding different ratios of alloy powders into a melt pool created by a laser. Based on the assessment of the magnetic properties of the LENS printed samples, arc-melted and cast ingots were prepared with varying Fe (5-20 at.%) and Co (60-45 at.%) compositions while maintaining constant Ce (16 at.%) and Cu (19 at.%) content. The evolution of the microstructure and phases with varying chemical compositions and their dependence on magnetic properties are analyzed in as-cast and heat-treated samples. In both the LENS printed and cast samples, we find the best magnetic properties correspond to a predominantly single-phase Ce(CoFeCu)5 microstructure in which high coercivity (H c > 10 kOe) can be achieved without any microstructural refinement.

  2. Ultrathin Oxide Passivation Layer by Rapid Thermal Oxidation for the Silicon Heterojunction Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Youngseok Lee

    2012-01-01

    Full Text Available It is difficult to deposit extremely thin a-Si:H layer in heterojunction with intrinsic thin layer (HIT solar cell due to thermal damage and tough process control. This study aims to understand oxide passivation mechanism of silicon surface using rapid thermal oxidation (RTO process by examining surface effective lifetime and surface recombination velocity. The presence of thin insulating a-Si:H layer is the key to get high Voc by lowering the leakage current (I0 which improves the efficiency of HIT solar cell. The ultrathin thermal passivation silicon oxide (SiO2 layer was deposited by RTO system in the temperature range 500–950°C for 2 to 6 minutes. The thickness of the silicon oxide layer was affected by RTO annealing temperature and treatment time. The best value of surface recombination velocity was recorded for the sample treated at a temperature of 850°C for 6 minutes at O2 flow rate of 3 Lpm. A surface recombination velocity below 25 cm/s was obtained for the silicon oxide layer of 4 nm thickness. This ultrathin SiO2 layer was employed for the fabrication of HIT solar cell structure instead of a-Si:H, (i layer and the passivation and tunneling effects of the silicon oxide layer were exploited. The photocurrent was decreased with the increase of illumination intensity and SiO2 thickness.

  3. Application of Fourier Transform Infrared (FTIR) Spectroscopy for Rapid Detection of Fumonisin B2 in Raisins.

    Science.gov (United States)

    Heperkan, Dilek; Gökmen, Ece

    2016-07-01

    The aim of this study was to investigate the potential use of FTIR spectroscopy as a rapid screening method to detect fumonisin produced by Aspergillus niger. A. niger spore suspensions isolated from raisins were inoculated in Petri dishes prepared with sultana raisin or black raisin extracts containing agar and malt extract agar (MEA). After 9 days of incubation at 25°C, fumonisin B2 (FB2) production on each agar plate was determined by subjecting the agar plugs to IR spectroscopy. The presence of amino group (at 1636-1639 cm(-1)) was especially indicative of fumonisin production in MEA and the raisin extracts containing agar. The results were confirmed by HPLC analysis of the agar sample extracts after immunoaffinity column cleanup. It was determined that A. niger produced more FB2 in sultana raisins than in MEA, with no FB2 being produced in black raisin extract agar. This study demonstrated that proper sample preparation procedure followed by FTIR analysis is a useful technique for identifying toxigenic molds and their mycotoxin production in agricultural commodities.

  4. Application of near-infrared spectroscopy for the rapid quality assessment of Radix Paeoniae Rubra

    Science.gov (United States)

    Zhan, Hao; Fang, Jing; Tang, Liying; Yang, Hongjun; Li, Hua; Wang, Zhuju; Yang, Bin; Wu, Hongwei; Fu, Meihong

    2017-08-01

    Near-infrared (NIR) spectroscopy with multivariate analysis was used to quantify gallic acid, catechin, albiflorin, and paeoniflorin in Radix Paeoniae Rubra, and the feasibility to classify the samples originating from different areas was investigated. A new high-performance liquid chromatography method was developed and validated to analyze gallic acid, catechin, albiflorin, and paeoniflorin in Radix Paeoniae Rubra as the reference. Partial least squares (PLS), principal component regression (PCR), and stepwise multivariate linear regression (SMLR) were performed to calibrate the regression model. Different data pretreatments such as derivatives (1st and 2nd), multiplicative scatter correction, standard normal variate, Savitzky-Golay filter, and Norris derivative filter were applied to remove the systematic errors. The performance of the model was evaluated according to the root mean square of calibration (RMSEC), root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), and correlation coefficient (r). The results show that compared to PCR and SMLR, PLS had a lower RMSEC, RMSECV, and RMSEP and higher r for all the four analytes. PLS coupled with proper pretreatments showed good performance in both the fitting and predicting results. Furthermore, the original areas of Radix Paeoniae Rubra samples were partly distinguished by principal component analysis. This study shows that NIR with PLS is a reliable, inexpensive, and rapid tool for the quality assessment of Radix Paeoniae Rubra.

  5. Rapid Application of Space Effects for the Small Satellites Systems and Services Symposium

    Science.gov (United States)

    Tsairides, Demosthenes; Finley, Charles; Moretti, George

    2016-01-01

    NASA Ames Research Center (ARC) has engaged Military Branches, the Department of Defense, and other Government Agencies in successful partnerships to design, develop, deliver and support various space effects capabilities and space vehicles on timeline of need. Contracts with Industry are in place to execute operational and enabler missions using physical and informational infrastructures including Responsive Manufacturing capabilities and Digital Assurance. The intent is to establish a secure, web-enabled "store front" for ordering and delivering any capabilities required as defined by the users and directed by NASA ARC and Partner Organizations. The capabilities are envisioned to cover a broad range and include 6U CubeSats, 50-100 kg Space Vehicles, Modular Space Vehicle architecture variations, as well as rapid payload integration on various Bus options. The paper will discuss the efforts underway to demonstrate autonomous manufacturing of low-volume, high-value assets, to validate the ability of autonomous digital techniques to provide Mission Assurance, and to demonstrate cost savings through the identification, characterization, and utilization of Responsive Space components. The culmination of this effort will be the integration of several 6U satellites and their launch in 2016.

  6. Application of rapid microbiological screening methods for detection of irradiated frozen foods

    International Nuclear Information System (INIS)

    Hussain, A.A.; Rady, A.H.; ElBary, N.A.A.

    2003-01-01

    The exposure of food to ionizing radiation is being progressively used in many countries to, inactivate food pathogens, eradicate pests and extend shelf-life. To ensure free consumer choice, irradiated food. The direct epi fluorescent filter technique (DEFT) was applied as recent and rapid technique for determination of total bacterial count in irradiated minced chicken (2,4,6, and 8 kGy) as well as non-irradiated samples. Also aerobic plate count (APC) was used to determine the viable bacterial cells. A large significant differences between the profiteered DEFT and APC counts were obtained with the irradiated samples of each chicken and fish where the conventional plating gives a much lower values than the (DEFT) technique compared with non-irradiated samples. A highly correlation (r=0.99 and 1.00) were detected at 8 and 6 kGy with irradiated minced chicken and fish respectively. The Gram-negative bacteria belonging to (Enterobacteriaceae and fluorescence pseudomonas) showed very low count in the irradiated selected fish samples compared with control while the endotoxin selected fish samples compared with control while the endotoxin levels did not affect under the same conditions. Micro-gel electrophoresis indicated that gamma irradiation at 8 kGy can induce DNA damage in the cells of both minced chicken and fish where, some bands disappeared compared with the non-irradiated samples

  7. Miniature silicon electronic biological assay chip and applications for rapid battlefield diagnostics

    Science.gov (United States)

    Cunningham, Brian T.; Regan, Robert A.; Clapp, Christopher; Hildebrant, Eric; Weinberg, Marc S.; Williams, John

    1999-07-01

    Assessing the medical condition of battlefield personnel requires the development of rapid, portable biological diagnostic assays for a wide variety of antigens and enzymes. Ideally, such an assay would be inexpensive, small, and require no added reagents while maintaining the sensitivity and accuracy of laboratory-based assays. In this work, a microelectromechanical (MEMS) based biological assay sensor is presented which is expected to meet the above requirements. The sensor is a thin silicon membrane resonator (SMR) which registers a decrease in resonant frequency when mass is adsorbed onto its surface. By coating the sensor surface with a monolayer of antibody, for example, we have detected the corresponding antigen with a detection resolution of 0.25 ng/ml in phosphate buffer solution. Micromachining techniques are being used to integrate many (64 elements on the first test chip) identical SMR sensors into a single silicon chip which would be capable of simultaneously performing a wide variety of biomedical assays. The sensors require only a small printed circuit board and 8V power supply to operate and provide a readout. The presentation will describe the operation of the SMR sensor, the fabrication of the sensor array, and initial test results using commercially available animal immunoglobulins in laboratory-prepared test solutions.

  8. Rapid wasted-free microfluidic fabrication based on ink-jet approach for microfluidic sensing applications

    Science.gov (United States)

    Jarujareet, Ungkarn; Amarit, Rattasart; Sumriddetchkajorn, Sarun

    2016-11-01

    Realizing that current microfluidic chip fabrication techniques are time consuming and labor intensive as well as always have material leftover after chip fabrication, this research work proposes an innovative approach for rapid microfluidic chip production. The key idea relies on a combination of a widely-used inkjet printing method and a heat-based polymer curing technique with an electronic-mechanical control, thus eliminating the need of masking and molds compared to typical microfluidic fabrication processes. In addition, as the appropriate amount of polymer is utilized during printing, there is much less amount of material wasted. Our inkjet-based microfluidic printer can print out the desired microfluidic chip pattern directly onto a heated glass surface, where the printed polymer is suddenly cured. Our proof-of-concept demonstration for widely-used single-flow channel, Y-junction, and T-junction microfluidic chips shows that the whole microfluidic chip fabrication process requires only 3 steps with a fabrication time of 6 minutes.

  9. Rapid Assessment of the Ce-Co-Fe-Cu System for Permanent Magnetic Applications

    Science.gov (United States)

    Meng, F.; Chaudhary, R. P.; Gandha, K.; Nlebedim, I. C.; Palasyuk, A.; Simsek, E.; Kramer, M. J.; Ott, R. T.

    2018-06-01

    This work focuses on the rapid synthesis and characterization of quaternary Ce(CoFeCu)5 alloy libraries to assess their potential viability as permanent magnets. Arrays of bulk specimens with controlled compositions were synthesized via laser engineered net shaping (LENS) by feeding different ratios of alloy powders into a melt pool created by a laser. Based on the assessment of the magnetic properties of the LENS printed samples, arc-melted and cast ingots were prepared with varying Fe (5-20 at.%) and Co (60-45 at.%) compositions while maintaining constant Ce (16 at.%) and Cu (19 at.%) content. The evolution of the microstructure and phases with varying chemical compositions and their dependence on magnetic properties are analyzed in as-cast and heat-treated samples. In both the LENS printed and cast samples, we find the best magnetic properties correspond to a predominantly single-phase Ce(CoFeCu)5 microstructure in which high coercivity ( H c > 10 kOe) can be achieved without any microstructural refinement.

  10. Application of two electrical methods for the rapid assessment of freezing resistance in Salix epichloro

    Energy Technology Data Exchange (ETDEWEB)

    Tsarouhas, V.; Kenney, W.A.; Zsuffa, L. [University of Toronto, Ontario (Canada). Faculty of Forestry

    2000-09-01

    The importance of early selection of frost-resistant Salix clones makes it desirable to select a rapid and accurate screening method for assessing freezing resistance among several genotypes. Two electrical methods, stem electrical impedance to 1 and 10 khz alternating current, and electrolyte leakage of leaf tissue, were evaluated for detecting freezing resistance on three North America Salix epichloro Michx., clones after subjecting them to five different freezing temperatures (-1, -2, -3, -4, and -5 deg C). Differences in the electrical impedance to 1 and 10 kHz, and the ratio of the impedance at the two frequencies (low/high) before and after the freezing treatment (DZ{sub low}, DZ{sub high}, and DZ{sub ratio}, respectively) were estimated. Electrolyte leakage was expressed as relative conductivity (RC{sub t}) and index of injury (IDX{sub t}). Results from the two methods, obtained two days after the freezing stress, showed that both electrical methods were able to detect freezing injury in S. eriocephala. However, the electrolyte leakage method detected injury in more levels of freezing stress (-3, -4, and -5 deg C) than the impedance (-4, and -5 deg C), it assessed clonal differences in S. eriocephala freezing resistance, and it was best suited to correlate electrical methods with the visual assessed freezing injury. No significant impedance or leakage changes were found after the -1 and -2 deg C freezing temperatures. (author)

  11. Design and testing of RapidIO application and verification model%RapidIO应用系统及其验证模型的设计与测试

    Institute of Scientific and Technical Information of China (English)

    梁光胜; 刘倩茹; 姚海洋

    2011-01-01

    Aiming at the problem existed in the traditional interconnection of embedded system, a scheme of RapidIO application and verification model, which can be used for the communication in the embedded system, is proposed. Based on the IP Core and Cyclone serial FPGA of Ahera Company, this scheme builds communication system of Serial RapidIO (SRIO) whose functions are verified. The structure and operation principle of RapidIO application and verification model are elaborated, which give a solution to the improvement of communication rate in the embedded system.%针对传统嵌入式系统中互连通信的问题.提出一种可用于嵌入式系统内部通信的基于RapidIO的应用系统及其验证模型。该方案采/8Ahera公司的IP核和Cyclone系列FPGA,建立了串行RapidIO(SRIO)4g-口通信系统,并对其功能进行验证。详细分析了RapidIO应用系统及其验证模型的功能结构和运行原理.为提高嵌入式系统内部模块的通信速率提供了解决方案。

  12. 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...

  13. Reads2Type: a web application for rapid microbial taxonomy identification

    DEFF Research Database (Denmark)

    Saputra, Dhany; Rasmussen, Simon; Larsen, Mette Voldby

    2015-01-01

    genome of microbial isolates. Therefore we have developed Reads2Type, a web-based tool for taxonomy identification based on whole bacterial genome sequence data. Raw sequencing data provided by the user are mapped against a set of marker probes that are derived from currently available bacteria complete......, as the entire computational analysis is done on the computer of whom utilizes the web application. This also prevents data privacy issues to arise. The Reads2Type tool is available at http://www.cbs.dtu.dk/~dhany/reads2type.html ....

  14. ApplBuilder - an Object-Oriented Application Generator Supporting Rapid Prototyping

    DEFF Research Database (Denmark)

    Grønbæk, Kaj; Hviid, Anette; Trigg, Randall Hagner

    1991-01-01

    , and windows are designed using direct manipulation graphical editors. Actions behind buttons and menu items are programmed as ''scripts'' in textual editors activated from within a graphical editor. The editors reflect changes in the code directly in an underlying Abstract Syntax Tree (AST) thus saving...... compilation time. Moreover, generated applications are modularized so that editing, for instance the script for a button, only requires re-compilation of the script itself. An advantage of APPLBUILDER compared to other user-interface design tools such as HyperCard is that APPLBUILDER's scripts are embedded...

  15. 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.

  16. Electrowetting-based microfluidic operations on rapid-manufactured devices for heat pipe applications

    Science.gov (United States)

    Hale, Renee S.; Bahadur, Vaibhav

    2017-07-01

    The heat transport capacity of traditional heat pipes is limited by the capillary pressure generated in the internal wick that pumps condensate to the evaporator. Recently, the authors conceptualized a novel heat pipe architecture, wherein wick-based pumping is replaced by electrowetting (EW)-based pumping of microliter droplets in the adiabatic section. An electrowetting heat pipe (EHP) can overcome the capillary limit to heat transport capacity and enable compact, planar, gravity-insensitive, and ultralow power consumption heat pipes that transport kiloWatt heat loads over extended distances. This work develops a novel technique for rapid, scalable fabrication of EW-based devices and studies critical microfluidic operations underlying the EHP, with the objective of predicting the key performance parameters of the EHP. Devices are fabricated on a printed circuit board (PCB) substrate with mechanically-milled electrodes, and a removable polyimide dielectric film. The first set of experiments uncovers the maximum channel gap (1 mm) for reliable EW-based pumping; this parameter determines the heat transport capacity of the EHP, which scales linearly with the channel gap. The second set of experiments uncovers the maximum channel gap (375 microns) at which EW voltages can successfully split droplets. This is an important consideration which ensures EHP operability in the event of unintentional droplet merging. The third set of experiments demonstrate and study EW-induced droplet generation from an open-to-air reservoir, which mimics the interface between the condenser and adiabatic sections of the EHP. The experimental findings predict that planar, water-based EHPs with a (10 cm by 4 mm) cross section can transport 1.6 kW over extended distances (>1 m), with a thermal resistance of 0.01 K W-1.

  17. Affinity reagent technology development and application to rapid immunochromatographic pathogen detection

    Science.gov (United States)

    Sooter, Letha J.; Stratis-Cullum, Dimitra N.; Zhang, Yanting; Daugherty, Patrick S.; Soh, H. Tom; Pellegrino, Paul; Stagliano, Nancy

    2007-09-01

    Immunochromatography is a rapid, reliable, and cost effective method of detecting biowarfare agents. The format is similar to that of an over-the-counter pregnancy test. A sample is applied to one end of a cassette and then a control line, and possibly a sample line, are visualized at the other end of the cassette. The test is based upon a sandwich assay. For the control, a line of Protein A is immobilized on the membrane. Gold nanoparticle bound IgG flows through the membrane and binds the Protein A, creating a visible line on the membrane. For the sample, one epitope is immobilized on the membrane and another epitope is attached to gold nanoparticles. The sample binds gold bound epitope, travels through the membrane, and binds membrane bound epitope. The two epitopes are not cross-reactive, therefore a sample line is only visible if the sample is present. In order to efficiently screen for binders to a sample target, a novel, Continuous Magnetic Activated Cell Sorter (CMACS) has been developed on a disposable, microfluidic platform. The CMACS chip quickly sorts E. coli peptide libraries for target binders with high affinity. Peptide libraries, are composed of approximately ten million bacteria, each displaying a different peptide on their surface. The target of interest is conjugated to a micrometer sized magnetic particle. After the library and the target are incubated together to allow binding, the mixture is applied to the CMACS chip. In the presence of patterned nickel and an external magnet, separation occurs of the bead-bound bacteria from the bulk material. The bead fraction is added to bacterial growth media where any attached E. coli grow and divide. These cells are cloned, sequenced, and the peptides are assayed for target binding affinity. As a proof-of-principle, assays were developed for human C-reactive protein. More defense relevant targets are currently being pursued.

  18. Rapid End-Group Modification of Polysaccharides for Biomaterial Applications in Regenerative Medicine.

    Science.gov (United States)

    Bondalapati, Somasekhar; Ruvinov, Emil; Kryukov, Olga; Cohen, Smadar; Brik, Ashraf

    2014-09-15

    Polysaccharides have emerged as important functional materials because of their unique properties such as biocompatibility, biodegradability, and availability of reactive sites for chemical modifications to optimize their properties. The overwhelming majority of the methods to modify polysaccharides employ random chemical modifications, which often improve certain properties while compromising others. On the other hand, the employed methods for selective modifications often require excess of coupling partners, long reaction times and are limited in their scope and wide applicability. To circumvent these drawbacks, aniline-catalyzed oxime formation is developed for selective modification of a variety of polysaccharides through their reducing end. Notably, it is found that for efficient oxime formation, different conditions are required depending on the composition of the specific polysaccharide. It is also shown how our strategy can be applied to improve the physical and functional properties of alginate hydrogels, which are widely used in tissue engineering and regenerative medicine applications. While the randomly and selectively modified alginate exhibits similar viscoelastic properties, the latter forms significantly more stable hydrogel and superior cell adhesive and functional properties. Our results show that the developed conjugation reaction is robust and should open new opportunities for preparing polysaccharide-based functional materials with unique properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Low-Cost Rapid Usability Testing: Its Application in Both Product Development and System Implementation.

    Science.gov (United States)

    Kushniruk, Andre; Borycki, Elizabeth

    2017-01-01

    In recent years there has been considerable discussion around the need for certification and regulation of healthcare information technology (IT). In particular, the usability of the products being developed needs to be evaluated. This has included the application of standards designed to ensure the process of system development is user-centered and takes usability into consideration while a product is being developed. In addition to this, in healthcare, organizations in the United States and Europe have also addressed the need and requirement for product certification. However, despite these efforts there are continued reports of unusable and unsafe implementations. In this paper we discuss the need to not only include (and require) usability testing in the one-time development process of health IT products (such as EHRs), but we also argue for the need to additionally develop specific usability standards and requirements for usability testing during the implementation of vendor products (i.e. post product development) in healthcare settings. It is further argued that health IT products that may have been certified regarding their development process will still require application of usability testing in the process of implementing them in real hospital settings in order to ensure usability and safety. This is needed in order to ensure that the final result of both product development and implementation processes take into account and apply the latest usability principles and methods.

  20. The Restoration Rapid Assessment Tool: An Access/Visual Basic application

    Science.gov (United States)

    Hiebert, Ron; Larson, D.L.; Thomas, K.; Tancreto, N.; Haines, D.; Richey, A.; Dow, T.; Drees, L.

    2009-01-01

    Managers of parks and natural areas are increasingly faced with difficult decisions concerning restoration of disturbed lands. Financial and workforce resources often limit these restoration efforts, and rarely can a manager afford to address all concerns within the region of interest. With limited resources, managers and scientists have to decide which areas will be targeted for restoration and the restoration treatments to use in these areas. A broad range of approaches are used to make such decisions, from well-researched expert opinions (Cipollini et al. 2005) to gut feeling, with variable degrees of input from site visits, data collection, and data analysis used to support the decision. A standardized approach including an analytical assessment of site characteristics based on the best information available, with a written or electronic record of all the steps taken along the way, would make comparisons among a group of sites easier and lend credibility through use of common, documented criteria at all sites. In response to these concerns, we have developed the Restoration Rapid Assessment Tool (RRAT). RRAT is based on field observations of key indicators of site degradation, stressors influencing the site, value of the site with respect to larger management objectives, likelihood of achieving the management goals, and logistical constraints to restoration. The purpose of RRAT is not to make restoration decisions or prescribe methods, but rather to ensure that a basic set of pertinent issues are considered for each site and to facilitate comparisons among sites. Several concepts have been central to the development of RRAT. First, the management goal (also known as desired future condition) of any site under evaluation should be defined before the field evaluation begins. Second, the evaluation should be based upon readily observable indicators so as to avoid cumbersome field methods. Third, the ease with which site stressors can be ameliorated must be

  1. RADII OF RAPIDLY ROTATING STARS, WITH APPLICATION TO TRANSITING-PLANET HOSTS

    International Nuclear Information System (INIS)

    Brown, Timothy M.

    2010-01-01

    The currently favored method for estimating radii and other parameters of transiting-planet host stars is to match theoretical models to observations of the stellar mean density ρ * , the effective temperature T eff , and the composition parameter [Z]. This explicitly model-dependent approach is based on readily available observations, and results in small formal errors. Its performance will be central to the reliability of results from ground-based transit surveys such as TrES, HAT, and SuperWASP, as well as to the space-borne missions MOST, CoRoT, and Kepler. Here, I use two calibration samples of stars (eclipsing binaries (EBs) and stars for which asteroseismic analyses are available) having well-determined masses and radii to estimate the accuracy and systematic errors inherent in the ρ * method. When matching to the Yonsei-Yale stellar evolution models, I find the most important systematic error results from selection bias favoring rapidly rotating (hence probably magnetically active) stars among the EB sample. If unaccounted for, this bias leads to a mass-dependent underestimate of stellar radii by as much as 4% for stars of 0.4 M sun , decreasing to zero for masses above about 1.4 M sun . Relative errors in estimated stellar masses are three times larger than those in radii. The asteroseismic sample suggests (albeit with significant uncertainty) that systematic errors are small for slowly rotating, inactive stars. Systematic errors arising from failings of the Yonsei-Yale models of inactive stars probably exist, but are difficult to assess because of the small number of well-characterized comparison stars having low mass and slow rotation. Poor information about [Z] is an important source of random error, and may be a minor source of systematic error as well. With suitable corrections for rotation, it is likely that systematic errors in the ρ * method can be comparable to or smaller than the random errors, yielding radii that are accurate to about 2% for

  2. FIRESTORM: a collaborative network suite application for rapid sensor data processing and precise decisive responses

    Science.gov (United States)

    Kaniyantethu, Shaji

    2011-06-01

    This paper discusses the many features and composed technologies in Firestorm™ - a Distributed Collaborative Fires and Effects software. Modern response management systems capitalize on the capabilities of a plethora of sensors and its output for situational awareness. Firestorm utilizes a unique networked lethality approach by integrating unmanned air and ground vehicles to provide target handoff and sharing of data between humans and sensors. The system employs Bayesian networks for track management of sensor data, and distributed auction algorithms for allocating targets and delivering the right effect without information overload to the Warfighter. Firestorm Networked Effects Component provides joint weapon-target pairing, attack guidance, target selection standards, and other fires and effects components. Moreover, the open and modular architecture allows for easy integration with new data sources. Versatility and adaptability of the application enable it to devise and dispense a suitable response to a wide variety of scenarios. Recently, this application was used for detecting and countering a vehicle intruder with the help of radio frequency spotter sensor, command driven cameras, remote weapon system, portable vehicle arresting barrier, and an unmanned aerial vehicle - which confirmed the presence of the intruder, as well as provided lethal/non-lethal response and battle damage assessment. The completed demonstrations have proved Firestorm's™ validity and feasibility to predict, detect, neutralize, and protect key assets and/or area against a variety of possible threats. The sensors and responding assets can be deployed with numerous configurations to cover the various terrain and environmental conditions, and can be integrated to a number of platforms.

  3. Oracle application express 5.1 basics and beyond a practical guide to rapidly develop data-centric web applications accessible from desktop, laptops, tablets, and smartphones

    CERN Document Server

    2017-01-01

    You will find stuff about workspace, application, page, and so on in every APEX book. But this book is unique because the information it contains is not available anywhere else! Unlike other books, it adopts a stimulating approach to reveal almost every feature necessary for the beginners of Oracle APEX and also takes them beyond the basics. As a technology enthusiast I write on a variety of new technologies, but writing books on Oracle Application Express is my passion. The blood pumping comments I get from my readers on Amazon (and in my inbox) are the main forces that motivate me to write a book whenever a new version of Oracle APEX is launched. This is my fifth book on Oracle APEX (and the best so far) written after discovering the latest 5.1 version. As usual, I’m sharing my personal learning experience through this book to expose this unique rapid web application development platform. In Oracle Application Express you can build robust web applications. The new version is launched with some more prol...

  4. Rapid Formation of Metal-Organic Frameworks (MOFs) Based Nanocomposites in Microdroplets and Their Applications for CO2 Photoreduction.

    Science.gov (United States)

    He, Xiang; Gan, Zhuoran; Fisenko, Sergey; Wang, Dawei; El-Kaderi, Hani M; Wang, Wei-Ning

    2017-03-22

    A copper-based metal-organic framework (MOF), [Cu 3 (TMA) 2 (H 2 O) 3 ] n (also known as HKUST-1, where TMA stands for trimesic acid), and its TiO 2 nanocomposites were directly synthesized in micrometer-sized droplets via a rapid aerosol route for the first time. The effects of synthesis temperature and precursor component ratio on the physicochemical properties of the materials were systematically investigated. Theoretical calculations on the mass and heat transfer within the microdroplets revealed that the fast solvent evaporation and high heat transfer rates are the major driving forces. The fast droplet shrinkage because of evaporation induces the drastic increase in the supersaturation ratio of the precursor, and subsequently promotes the rapid nucleation and crystal growth of the materials. The HKUST-1-based nanomaterials synthesized via the aerosol route demonstrated good crystallinity, large surface area, and great photostability, comparable with those fabricated by wet-chemistry methods. With TiO 2 embedded in the HKUST-1 matrix, the surface area of the composite is largely maintained, which enables significant improvement in the CO 2 photoreduction efficiency, as compared with pristine TiO 2 . In situ diffuse reflectance infrared Fourier transform spectroscopy analysis suggests that the performance enhancement was due to the stable and high-capacity reactant adsorption by HKUST-1. The current work shows great promise in the aerosol route's capability to address the mass and heat transfer issues of MOFs formation at the microscale level, and ability to synthesize a series of MOFs-based nanomaterials in a rapid and scalable manner for energy and environmental applications.

  5. Application Values of T-SPOT.TB in Clinical Rapid Diagnosis of Tuberculosis.

    Science.gov (United States)

    Zhu, Feng; Ou, Qinfang; Zheng, Jian

    2018-01-01

    This paper aims to explore the application value of tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) in the diagnosis of tuberculosis. Fifty one patients with tuberculosis (TB) admitted to Wuxi No.5 People's Hospital, Wuxi, China from June 2015 to June 2017 were selected as the TB group, and 40 patients without tuberculosis admitted in the same period were randomly selected as the non-TB group. Patients in the two groups received T-SPOT.TB, TB antibody (TB-Ab) test and mycobacterium TB deoxyribonucleic acid (TB-DNA) test, and the results were compared. Comparisons of the sensitivity of the three methods showed that the sensitivity of T-SPOT.TB was the highest, followed by TB-DNA from sputum samples, and that of TB-Ab was the lowest. The specificity of TB-Ab was the highest, followed by T-SPOT.TB, and that of TB-DNA from sputum samples was the lowest. In the receiver operating characteristic (ROC) curve analysis, the area under curve (AUC) of T-SPOT.TB (0.896) was the highest, followed by TB-DNA from sputum samples (0.772), and that of sputum smears (0.698) was the lowest. T-SPOT.TB can quickly and accurately determine the presence of tuberculosis infection, and it is a non-invasive examination, which can further assist in the diagnosis and guide the treatment.

  6. Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption.

    Science.gov (United States)

    Cai, Zhu-Yun; Peng, Fan; Zi, Yun-Peng; Chen, Feng; Qian, Qi-Rong

    2015-07-31

    Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.

  7. Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption

    Directory of Open Access Journals (Sweden)

    Zhu-Yun Cai

    2015-07-01

    Full Text Available Synthetic calcium phosphate (CaP-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP nanostructure was prepared under weak acidic conditions (pH 5, while the HAP nanorod was prepared under neutral (pH 7 and weak alkali (pH 9 condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.

  8. Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

    Full Text Available Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

  9. Integration of Simulink, MARTe and MDSplus for rapid development of real-time applications

    Energy Technology Data Exchange (ETDEWEB)

    Manduchi, G., E-mail: gabriele.manduchi@igi.cnr.it [Consorzio RFX (CNR, ENEA, INFN, Università di Padova, Acciaierie Venete SpA), Padova (Italy); Luchetta, A.; Taliercio, C. [Consorzio RFX (CNR, ENEA, INFN, Università di Padova, Acciaierie Venete SpA), Padova (Italy); Neto, A.; Sartori, F. [Fusion for Energy, Barcelona (Spain); De Tommasi, G. [Fusion for Energy, Barcelona (Spain); Consorzio CREATE/DIETI, Università degli Studi di Napoli Federico II, Via Claudio 21, 80125 Napoli (Italy)

    2015-10-15

    Highlights: • The integration of two frameworks for real-time control and data acquisition is described. • The integration may significantly fasten the development of system components. • The system includes also a code generator for the integration of code written in Simulink. • A real-time control systemcan be implemented without the need of writing any line of code. - Abstract: Simulink is a graphical data flow programming tool for modeling and simulating dynamic systems. A component of Simulink, called Simulink Coder, generates C code from Simulink diagrams. MARTe is a framework for the implementation of real-time systems, currently in use in several fusion experiments. MDSplus is a framework widely used in the fusion community for the management of data. The three systems provide a solution to different facets of the same process, that is, real-time plasma control development. Simulink diagrams will describe the algorithms used in control, which will be implemented as MARTe GAMs and which will use parameters read from and produce results written to MDSplus pulse files. The three systems have been integrated in order to provide a tool suitable to speed up the development of real-time control applications. In particular, it will be shown how from a Simulink diagram describing a given algorithm to be used in a control system, it is possible to generate in an automated way the corresponding MARTe and MDSplus components that can be assembled to implement the target system.

  10. Integration of Simulink, MARTe and MDSplus for rapid development of real-time applications

    International Nuclear Information System (INIS)

    Manduchi, G.; Luchetta, A.; Taliercio, C.; Neto, A.; Sartori, F.; De Tommasi, G.

    2015-01-01

    Highlights: • The integration of two frameworks for real-time control and data acquisition is described. • The integration may significantly fasten the development of system components. • The system includes also a code generator for the integration of code written in Simulink. • A real-time control systemcan be implemented without the need of writing any line of code. - Abstract: Simulink is a graphical data flow programming tool for modeling and simulating dynamic systems. A component of Simulink, called Simulink Coder, generates C code from Simulink diagrams. MARTe is a framework for the implementation of real-time systems, currently in use in several fusion experiments. MDSplus is a framework widely used in the fusion community for the management of data. The three systems provide a solution to different facets of the same process, that is, real-time plasma control development. Simulink diagrams will describe the algorithms used in control, which will be implemented as MARTe GAMs and which will use parameters read from and produce results written to MDSplus pulse files. The three systems have been integrated in order to provide a tool suitable to speed up the development of real-time control applications. In particular, it will be shown how from a Simulink diagram describing a given algorithm to be used in a control system, it is possible to generate in an automated way the corresponding MARTe and MDSplus components that can be assembled to implement the target system.

  11. Numerical simulation of a plane turbulent mixing layer, with applications to isothermal, rapid reactions

    Science.gov (United States)

    Lin, P.; Pratt, D. T.

    1987-01-01

    A hybrid method has been developed for the numerical prediction of turbulent mixing in a spatially-developing, free shear layer. Most significantly, the computation incorporates the effects of large-scale structures, Schmidt number and Reynolds number on mixing, which have been overlooked in the past. In flow field prediction, large-eddy simulation was conducted by a modified 2-D vortex method with subgrid-scale modeling. The predicted mean velocities, shear layer growth rates, Reynolds stresses, and the RMS of longitudinal velocity fluctuations were found to be in good agreement with experiments, although the lateral velocity fluctuations were overpredicted. In scalar transport, the Monte Carlo method was extended to the simulation of the time-dependent pdf transport equation. For the first time, the mixing frequency in Curl's coalescence/dispersion model was estimated by using Broadwell and Breidenthal's theory of micromixing, which involves Schmidt number, Reynolds number and the local vorticity. Numerical tests were performed for a gaseous case and an aqueous case. Evidence that pure freestream fluids are entrained into the layer by large-scale motions was found in the predicted pdf. Mean concentration profiles were found to be insensitive to Schmidt number, while the unmixedness was higher for higher Schmidt number. Applications were made to mixing layers with isothermal, fast reactions. The predicted difference in product thickness of the two cases was in reasonable quantitative agreement with experimental measurements.

  12. The application of the rapid assessment and response methodology for cannabis prevention research among youth in the Netherlands.

    Science.gov (United States)

    Dupont, Hans B; Kaplan, Charles D; Braam, Richard V; Verbraeck, Hans T; de Vries, Nanne K

    2015-08-01

    Drug prevention methods tailored to specific target groups have become increasingly important. There is a growing need to find ways to rapidly assess and situate target groups in their particular contexts. This need is associated with the implementation of evidence-based interventions (EBIs) for these specific target groups. This article describes the application of Rapid Assessment and Response (RAR) as a necessary first step in designing and implementing a prevention intervention plan for problematic cannabis use among "loitering" youth in the South of the Netherlands. Seven RAR studies were conducted using an innovative stepwise model in which the prevention field worker is central. The normative structure for the use of cannabis was found to vary across the neighborhoods of the RAR studies and emerged as the focal point in designing a suitable response. The RAR studies also identified the need in the prevention toolbox for a tailored, low-threshold, effective, individual brief intervention for youth problematic cannabis use. The RAR was found to provide a powerful methodology for detecting target groups and generating contextual and normative data that enable the prevention field worker to select and adapt from the spectrum of existing Evidence based Interventions (EBIs) or develop the most promising model for implementation with the specific target group. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Rapid access to information resources in clinical biochemistry: medical applications of Personal Digital Assistants (PDA).

    Science.gov (United States)

    Serdar, Muhittin A; Turan, Mustafa; Cihan, Murat

    2008-06-01

    Laboratory specialists currently need to access scientific-based information at anytime and anywhere. A considerable period of time and too much effort are required to access this information through existing accumulated data. Personal digital assistants (PDA) are supposed to provide an effective solution with commercial software for this problem. In this study, 11 commercial software products (UpToDate, ePocrates, Inforetrive, Pepid, eMedicine, FIRST Consult, and 5 laboratory e-books released by Skyscape and/or Isilo) were selected and the benefits of their use were evaluated by seven laboratory specialists. The assessment of the software was performed based on the number of the tests included, the software content of detailed information for each test-like process, method, interpretation of results, reference ranges, critical values, interferences, equations, pathophysiology, supplementary technical details such as sample collection principles, and additional information such as linked references, evidence-based data, test cost, etc. In terms of technique, the following items are considered: the amount of memory required to run the software, the graphical user interface, which is a user-friendly instrument, and the frequency of new and/or up-date releases. There is still no perfect program, as we have anticipated. Interpretation of laboratory results may require software with an integrated program. However, methodological data are mostly not included in the software evaluated. It seems that these shortcomings will be fixed in the near future, and PDAs and relevant medical applications will also become indispensable for all physicians including laboratory specialists in the field of training/education and in patient care.

  14. 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.

  15. 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.

  16. 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.

  17. Rapid prototyping of SoC-based real-time vision system: application to image preprocessing and face detection

    Science.gov (United States)

    Jridi, Maher; Alfalou, Ayman

    2017-05-01

    By this paper, the major goal is to investigate the Multi-CPU/FPGA SoC (System on Chip) design flow and to transfer a know-how and skills to rapidly design embedded real-time vision system. Our aim is to show how the use of these devices can be benefit for system level integration since they make possible simultaneous hardware and software development. We take the facial detection and pretreatments as case study since they have a great potential to be used in several applications such as video surveillance, building access control and criminal identification. The designed system use the Xilinx Zedboard platform. The last is the central element of the developed vision system. The video acquisition is performed using either standard webcam connected to the Zedboard via USB interface or several camera IP devices. The visualization of video content and intermediate results are possible with HDMI interface connected to HD display. The treatments embedded in the system are as follow: (i) pre-processing such as edge detection implemented in the ARM and in the reconfigurable logic, (ii) software implementation of motion detection and face detection using either ViolaJones or LBP (Local Binary Pattern), and (iii) application layer to select processing application and to display results in a web page. One uniquely interesting feature of the proposed system is that two functions have been developed to transmit data from and to the VDMA port. With the proposed optimization, the hardware implementation of the Sobel filter takes 27 ms and 76 ms for 640x480, and 720p resolutions, respectively. Hence, with the FPGA implementation, an acceleration of 5 times is obtained which allow the processing of 37 fps and 13 fps for 640x480, and 720p resolutions, respectively.

  18. Reliable TLDA-microvolume UV spectroscopy with applications in chemistry and biosciences for microlitre analysis and rapid pipette calibration

    Science.gov (United States)

    McMillan, Norman; O'Neill, Martina; Smith, Stephen; Hammond, John; Riedel, Sven; Arthure, Kevin; Smith, S.

    2009-05-01

    A TLDA-microvolume (transmitted light drop analyser) accessory for use with a standard UV-visible fibre spectrophotometer is described. The physics of the elegantly simple optical design is described along with the experimental testing of this accessory. The modelling of the arrangement is fully explored to investigate the performance of the drop spectrophotometer. The design optimizes the focusing to deliver the highest quality spectra, rapid and simple sample handling and, importantly, no detectable carryover on the single quartz drophead. Results of spectral measurements in a laboratory providing NIST standards show the closest correlation between modelled pathlength and experimental measurement for different drop volumes in the range 0.7-3 µl. This instrument accessory delivers remarkably accurate and reproducible results that are good enough to allow the accessory to be used for rapid pipette calibration to avoid the laborious weighing methods currently employed. Measurements on DNA standards and proteins are given to illustrate the main application area of biochemistry for this accessory. The accessory has a measurement range of at least 0-60 A units without sample dilution and, since there exists an accurate volume-pathlength relationship, the drop volume used in any specific measurement or assay should be optimized to minimize the photometric error. Studies demonstrate that the cleaning of the drophead with lab wipes results in no measurable carryover. This important practical result is confirmed from direct reading of the accessory and an analytical balance which was used to perform carryover studies. For further information on the TLDA please contact: Drop Technology, Unit 2, Tallaght Business Park, Whitestown, Dublin 24, Republic of Ireland. email: info@droptechnology.com.

  19. Application of laboratory and portable attenuated total reflectance infrared spectroscopic approaches for rapid quantification of alpaca serum immunoglobulin G

    Science.gov (United States)

    Burns, Jennifer B.; Riley, Christopher B.; Shaw, R. Anthony; McClure, J. Trenton

    2017-01-01

    The objective of this study was to develop and compare the performance of laboratory grade and portable attenuated total reflectance infrared (ATR-IR) spectroscopic approaches in combination with partial least squares regression (PLSR) for the rapid quantification of alpaca serum IgG concentration, and the identification of low IgG (portable ATR-IR spectrometers. Various pre-processing strategies were applied to the ATR-IR spectra that were linked to corresponding RID-IgG concentrations, and then randomly split into two sets: calibration (training) and test sets. PLSR was applied to the calibration set and calibration models were developed, and the test set was used to assess the accuracy of the analytical method. For the test set, the Pearson correlation coefficients between the IgG measured by RID and predicted by both laboratory grade and portable ATR-IR spectrometers was 0.91. The average differences between reference serum IgG concentrations and the two IR-based methods were 120.5 mg/dL and 71 mg/dL for the laboratory and portable ATR-IR-based assays, respectively. Adopting an IgG concentration portable ATR-IR assay were 95, 99 and 99%, respectively. These results suggest that the two different ATR-IR assays performed similarly for rapid qualitative evaluation of alpaca serum IgG and for diagnosis of IgG portable ATR-IR spectrometer performed slightly better, and provides more flexibility for potential application in the field. PMID:28651006

  20. The convulsive and electroencephalographic changes produced by nonpeptidic delta-opioid agonists in rats: comparison with pentylenetetrazol.

    Science.gov (United States)

    Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

    2006-06-01

    delta-Opioid agonists produce convulsions and antidepressant-like effects in rats. It has been suggested that the antidepressant-like effects are produced through a convulsant mechanism of action either through overt convulsions or nonconvulsive seizures. This study evaluated the convulsive and seizurogenic effects of nonpeptidic delta-opioid agonists at doses that previously were reported to produce antidepressant-like effects. In addition, delta-opioid agonist-induced electroencephalographic (EEG) and behavioral changes were compared with those produced by the chemical convulsant pentylenetetrazol (PTZ). For these studies, EEG changes were recorded using a telemetry system before and after injections of the delta-opioid agonists [(+)-4-[(alphaR)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-methoxyphenyl)methyl]-N,N-diethylbenz (SNC80) and [(+)-4-[alpha(R)-alpha-[(2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide [(+)-BW373U86]. Acute administration of nonpeptidic delta-opioid agonists produced bilateral ictal and paroxysmal spike and/or sharp wave discharges. delta-Opioid agonists produced brief changes in EEG recordings, and tolerance rapidly developed to these effects; however, PTZ produced longer-lasting EEG changes that were exacerbated after repeated administration. Studies with antiepileptic drugs demonstrated that compounds used to treat absence epilepsy blocked the convulsive effects of nonpeptidic delta-opioid agonists. Overall, these data suggest that delta-opioid agonist-induced EEG changes are not required for the antidepressant-like effects of these compounds and that neural circuitry involved in absence epilepsy may be related to delta-opioid agonist-induced convulsions. In terms of therapeutic development, these data suggest that it may be possible to develop delta-opioid agonists devoid of convulsive properties.

  1. Application of a regularized model inversion system (REGFLEC) to multi-temporal RapidEye imagery for retrieving vegetation characteristics

    KAUST Repository

    Houborg, Rasmus

    2015-10-14

    Accurate retrieval of canopy biophysical and leaf biochemical constituents from space observations is critical to diagnosing the functioning and condition of vegetation canopies across spatio-temporal scales. Retrieved vegetation characteristics may serve as important inputs to precision farming applications and as constraints in spatially and temporally distributed model simulations of water and carbon exchange processes. However significant challenges remain in the translation of composite remote sensing signals into useful biochemical, physiological or structural quantities and treatment of confounding factors in spectrum-trait relations. Bands in the red-edge spectrum have particular potential for improving the robustness of retrieved vegetation properties. The development of observationally based vegetation retrieval capacities, effectively constrained by the enhanced information content afforded by bands in the red-edge, is a needed investment towards optimizing the benefit of current and future satellite sensor systems. In this study, a REGularized canopy reFLECtance model (REGFLEC) for joint leaf chlorophyll (Chll) and leaf area index (LAI) retrieval is extended to sensor systems with a band in the red-edge region for the first time. Application to time-series of 5 m resolution multi-spectral RapidEye data is demonstrated over an irrigated agricultural region in central Saudi Arabia, showcasing the value of satellite-derived crop information at this fine scale for precision management. Validation against in-situ measurements in fields of alfalfa, Rhodes grass, carrot and maize indicate improved accuracy of retrieved vegetation properties when exploiting red-edge information in the model inversion process. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  2. Development of a polymerase chain reaction applicable to rapid and sensitive detection of Clonorchis sinensis eggs in human stool samples

    Science.gov (United States)

    Cho, Pyo Yun; Na, Byoung-Kuk; Mi Choi, Kyung; Kim, Jin Su; Cho, Shin-Hyeong; Lee, Won-Ja; Lim, Sung-Bin; Cha, Seok Ho; Park, Yun-Kyu; Pak, Jhang Ho; Lee, Hyeong-Woo; Hong, Sung-Jong; Kim, Tong-Soo

    2013-01-01

    Microscopic examination of eggs of parasitic helminths in stool samples has been the most widely used classical diagnostic method for infections, but tiny and low numbers of eggs in stool samples often hamper diagnosis of helminthic infections with classical microscopic examination. Moreover, it is also difficult to differentiate parasite eggs by the classical method, if they have similar morphological characteristics. In this study, we developed a rapid and sensitive polymerase chain reaction (PCR)-based molecular diagnostic method for detection of Clonorchis sinensis eggs in stool samples. Nine primers were designed based on the long-terminal repeat (LTR) of C. sinensis retrotransposon1 (CsRn1) gene, and seven PCR primer sets were paired. Polymerase chain reaction with each primer pair produced specific amplicons for C. sinensis, but not for other trematodes including Metagonimus yokogawai and Paragonimus westermani. Particularly, three primer sets were able to detect 10 C. sinensis eggs and were applicable to amplify specific amplicons from DNA samples purified from stool of C. sinensis-infected patients. This PCR method could be useful for diagnosis of C. sinensis infections in human stool samples with a high level of specificity and sensitivity. PMID:23916334

  3. Application of Rapid Prototyping Technique and Intraoperative Navigation System for the Repair and Reconstruction of Orbital Wall Fractures

    Science.gov (United States)

    Cha, Jong Hyun; Lee, Yong Hae; Ruy, Wan Chul; Roe, Young; Moon, Myung Ho

    2016-01-01

    Background Restoring the orbital cavity in large blow out fractures is a challenge for surgeons due to the anatomical complexity. This study evaluated the clinical outcomes and orbital volume after orbital wall fracture repair using a rapid prototyping (RP) technique and intraoperative navigation system. Methods This prospective study was conducted on the medical records and radiology records of 12 patients who had undergone a unilateral blow out fracture reconstruction using a RP technique and an intraoperative navigation system from November 2014 to March 2015. The surgical results were assessed by an ophthalmic examination and a comparison of the preoperative and postoperative orbital volume ratio (OVR) values. Results All patients had a successful treatment outcome without complications. Volumetric analysis revealed a significant decrease in the mean OVR from 1.0952±0.0662 (ranging from 0.9917 to 1.2509) preoperatively to 0.9942±0.0427 (ranging from 0.9394 to 1.0680) postoperatively. Conclusion The application of a RP technique for the repair of orbital wall fractures is a useful tool that may help improve the clinical outcomes by understanding the individual anatomy, determining the operability, and restoring the orbital cavity volume through optimal implant positioning along with an intraoperative navigation system. PMID:28913272

  4. Highly sensitive multianalyte immunochromatographic test strip for rapid chemiluminescent detection of ractopamine and salbutamol

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hongfei; Han, Jing; Yang, Shijia; Wang, Zhenxing; Wang, Lin; Fu, Zhifeng, E-mail: fuzf@swu.edu.cn

    2014-08-11

    Graphical abstract: A multianalyte immunochromatographic test strip was developed for the rapid detection of two β{sub 2}-agonists. Due to the application of chemiluminescent detection, this quantitative method shows much higher sensitivity. - Highlights: • An immunochromatographic test strip was developed for detection of multiple β{sub 2}-agonists. • The whole assay process can be completed within 20 min. • The proposed method shows much higher sensitivity due to the application of CL detection. • It is a portable analytical tool suitable for field analysis and rapid screening. - Abstract: A novel immunochromatographic assay (ICA) was proposed for rapid and multiple assay of β{sub 2}-agonists, by utilizing ractopamine (RAC) and salbutamol (SAL) as the models. Owing to the introduction of chemiluminescent (CL) approach, the proposed protocol shows much higher sensitivity. In this work, the described ICA was based on a competitive format, and horseradish peroxidase-tagged antibodies were used as highly sensitive CL probes. Quantitative analysis of β{sub 2}-agonists was achieved by recording the CL signals of the probes captured on the two test zones of the nitrocellulose membrane. Under the optimum conditions, RAC and SAL could be detected within the linear ranges of 0.50–40 and 0.10–50 ng mL{sup −1}, with the detection limits of 0.20 and 0.040 ng mL{sup −1} (S/N = 3), respectively. The whole process for multianalyte immunoassay of RAC and SAL can be completed within 20 min. Furthermore, the test strip was validated with spiked swine urine samples and the results showed that this method was reliable in measuring β{sub 2}-agonists in swine urine. This CL-based multianalyte test strip shows a series of advantages such as high sensitivity, ideal selectivity, simple manipulation, high assay efficiency and low cost. Thus, it opens up new pathway for rapid screening and field analysis, and shows a promising prospect in food safety.

  5. Application of laboratory and portable attenuated total reflectance infrared spectroscopic approaches for rapid quantification of alpaca serum immunoglobulin G.

    Directory of Open Access Journals (Sweden)

    Ibrahim Elsohaby

    Full Text Available The objective of this study was to develop and compare the performance of laboratory grade and portable attenuated total reflectance infrared (ATR-IR spectroscopic approaches in combination with partial least squares regression (PLSR for the rapid quantification of alpaca serum IgG concentration, and the identification of low IgG (<1000 mg/dL, which is consistent with the diagnosis of failure of transfer of passive immunity (FTPI in neonates. Serum samples (n = 175 collected from privately owned, healthy alpacas were tested by the reference method of radial immunodiffusion (RID assay, and laboratory grade and portable ATR-IR spectrometers. Various pre-processing strategies were applied to the ATR-IR spectra that were linked to corresponding RID-IgG concentrations, and then randomly split into two sets: calibration (training and test sets. PLSR was applied to the calibration set and calibration models were developed, and the test set was used to assess the accuracy of the analytical method. For the test set, the Pearson correlation coefficients between the IgG measured by RID and predicted by both laboratory grade and portable ATR-IR spectrometers was 0.91. The average differences between reference serum IgG concentrations and the two IR-based methods were 120.5 mg/dL and 71 mg/dL for the laboratory and portable ATR-IR-based assays, respectively. Adopting an IgG concentration <1000 mg/dL as the cut-point for FTPI cases, the sensitivity, specificity, and accuracy for identifying serum samples below this cut point by laboratory ATR-IR assay were 86, 100 and 98%, respectively (within the entire data set. Corresponding values for the portable ATR-IR assay were 95, 99 and 99%, respectively. These results suggest that the two different ATR-IR assays performed similarly for rapid qualitative evaluation of alpaca serum IgG and for diagnosis of IgG <1000 mg/dL, the portable ATR-IR spectrometer performed slightly better, and provides more flexibility for

  6. Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

    Directory of Open Access Journals (Sweden)

    Martin B. Oleksiewicz

    2008-01-01

    Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

  7. Development of 7TM receptor-ligand complex models using ligand-biased, semi-empirical helix-bundle repacking in torsion space: application to the agonist interaction of the human dopamine D2 receptor.

    Science.gov (United States)

    Malo, Marcus; Persson, Ronnie; Svensson, Peder; Luthman, Kristina; Brive, Lars

    2013-03-01

    Prediction of 3D structures of membrane proteins, and of G-protein coupled receptors (GPCRs) in particular, is motivated by their importance in biological systems and the difficulties associated with experimental structure determination. In the present study, a novel method for the prediction of 3D structures of the membrane-embedded region of helical membrane proteins is presented. A large pool of candidate models are produced by repacking of the helices of a homology model using Monte Carlo sampling in torsion space, followed by ranking based on their geometric and ligand-binding properties. The trajectory is directed by weak initial restraints to orient helices towards the original model to improve computation efficiency, and by a ligand to guide the receptor towards a chosen conformational state. The method was validated by construction of the β1 adrenergic receptor model in complex with (S)-cyanopindolol using bovine rhodopsin as template. In addition, models of the dopamine D2 receptor were produced with the selective and rigid agonist (R)-N-propylapomorphine ((R)-NPA) present. A second quality assessment was implemented by evaluating the results from docking of a library of 29 ligands with known activity, which further discriminated between receptor models. Agonist binding and recognition by the dopamine D2 receptor is interpreted using the 3D structure model resulting from the approach. This method has a potential for modeling of all types of helical transmembrane proteins for which a structural template with sequence homology sufficient for homology modeling is not available or is in an incorrect conformational state, but for which sufficient empirical information is accessible.

  8. 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...

  9. Field application of SD bioline malaria Ag Pf/Pan rapid diagnostic test for malaria in Greece.

    Science.gov (United States)

    Tseroni, Maria; Pervanidou, Danai; Tserkezou, Persefoni; Rachiotis, George; Pinaka, Ourania; Baka, Agoritsa; Georgakopoulou, Theano; Vakali, Annita; Dionysopoulou, Martha; Terzaki, Irene; Marka, Andriani; Detsis, Marios; Evlampidou, Zafiroula; Mpimpa, Anastasia; Vassalou, Evdokia; Tsiodras, Sotirios; Tsakris, Athanasios; Kremastinou, Jenny; Hadjichristodoulou, Christos

    2015-01-01

    Greece, a malaria-free country since 1974, has experienced re-emergence of Plasmodium vivax autochthonous malaria cases in some agriculture areas over the last three years. In early 2012, an integrated control programme (MALWEST Project) was launched in order to prevent re-establishment of the disease. In the context of this project, the rapid diagnostic tests (RDT) of SD Bioline Malaria Ag Pf/Pan that detects hrp-2 and pan-LDH antigens were used. The aim of this study was to assess the field application of the RDT for the P. vivax diagnosis in comparison to light microscopy and polymerase chain reaction (PCR). A total of 955 samples were tested with all three diagnostic tools. Agreement of RDT against microscopy and PCR for the diagnosis of P. vivax was satisfactory (K value: 0.849 and 0.976, respectively). The sensitivity, specificity and positive predictive value of RDT against PCR was 95.6% (95% C.I.: 84.8-99.3), 100% (95% C.I.: 99.6-100.0) and 100% (95% CI: 91.7-100.0) respectively, while the sensitivity, specificity and positive predictive value of RDT against microscopic examination was 97.4% (95% C.I.: 86.1-99.6), 99.4% (95% C.I.: 98.6-99.8) and 86.1% (95% CI: 72.1-94.7), respectively. Our results indicate that RDT performed satisfactory in a non-endemic country and therefore is recommended for malaria diagnosis, especially in areas where health professionals lack experience on light microscopy.

  10. 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...

  11. 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.

  12. Applications of RIGAKU Dmax Rapid II micro-X-ray diffractometer in the analysis of archaeological metal objects

    Science.gov (United States)

    Mozgai, Viktória; Szabó, Máté; Bajnóczi, Bernadett; Weiszburg, Tamás G.; Fórizs, István; Mráv, Zsolt; Tóth, Mária

    2017-04-01

    During material analysis of archaeological metal objects, especially their inlays or corrosion products, not only microstructure and chemical composition, but mineralogical composition is necessary to be determined. X-ray powder diffraction (XRD) is a widely-used method to specify the mineralogical composition. However, when sampling is not or limitedly allowed due to e.g. the high value of the object, the conventional XRD analysis can hardly be used. Laboratory micro-XRD instruments provide good alternatives, like the RIGAKU Dmax Rapid II micro-X-ray diffractometer, which is a unique combination of a MicroMax-003 third generation microfocus, sealed tube X-ray generator and a curved 'image plate' detector. With this instrument it is possible to measure as small as 10 µm area in diameter on the object. Here we present case studies for the application of the micro-XRD technique in the study of archaeological metal objects. In the first case niello inlay of a Late Roman silver augur staff was analysed. Due to the high value of the object, since it is the only piece known from the Roman Empire, only non-destructive analyses were allowed. To reconstruct the preparation of the niello, SEM-EDX analysis was performed on the niello inlays to characterise their chemical composition and microstructure. Two types of niello are present: a homogeneous, silver sulphide niello (acanthite) and an inhomogeneous silver-copper sulphide niello (exsolution of acanthite and jalpaite or jalpaite and stromeyerite). The micro-X-ray diffractometer was used to verify the mineralogical composition of the niello, supposed on the base of SEM results. In the second case corrosion products of a Late Roman copper cauldron with uncertain provenance were examined, since they may hold clues about the burial conditions (pH, Eh, etc.) of the object. A layer by layer analysis was performed in cross sections of small metal samples by using electron microprobe and micro-X-ray diffractometer. The results

  13. Response of microbial community of organic-matter-impoverished arable soil to long-term application of soil conditioner derived from dynamic rapid fermentation of food waste.

    Science.gov (United States)

    Hou, Jiaqi; Li, Mingxiao; Mao, Xuhui; Hao, Yan; Ding, Jie; Liu, Dongming; Xi, Beidou; Liu, Hongliang

    2017-01-01

    Rapid fermentation of food waste can be used to prepare soil conditioner. This process consumes less time and is more cost-effective than traditional preparation technology. However, the succession of the soil microbial community structure after long-term application of rapid fermentation-derived soil conditioners remains unclear. Herein, dynamic rapid fermentation (DRF) of food waste was performed to develop a soil conditioner and the successions and diversity of bacterial communities in an organic-matter-impoverished arable soil after six years of application of DRF-derived soil conditioner were investigated. Results showed that the treatment increased soil organic matter (SOM) accumulation and strawberry yield by 5.3 g/kg and 555.91 kg/ha, respectively. Proteobacteria, Actinobacteria, Acidobacteria, and Firmicutes became the dominant phyla, occupying 65.95%-77.52% of the bacterial sequences. Principal component analysis (PCA) results showed that the soil bacterial communities were largely influenced by the treatment. Redundancy analysis (RDA) results showed that the relative abundances of Gemmatimonadetes, Chloroflexi, Verrucomicrobia, Nitrospirae, and Firmicutes were significantly correlated with soil TC, TN, TP, NH4+-N, NO3--N, OM, and moisture. These communities were all distributed in the soil samples collected in the sixth year of application. Long-term treatment did not enhance the diversity of bacterial species but significantly altered the distribution of major functional bacterial communities in the soils. Application of DRF-derived soil conditioner could improve the soil quality and optimize the microbial community, ultimately enhancing fruit yields.

  14. 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.

  15. 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

  16. 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)

  17. Acoustic transfer function of cavity and its application to rapid evaluation of sound field at low frequency band

    Institute of Scientific and Technical Information of China (English)

    YIN Gang; CHEN Hualing; HU Xuanli; HUANG Xieqing

    2001-01-01

    A new method to obtain numerical solution of Acoustic Transfer Function (ATF) by BEM is presented. For a simply supported panel backed by a rectangular cavity at low frequency band (0-200 Hz), the frequency property of ATF is analyzed. The relation between the accuracy of the rapid evaluation of sound field and the discretization schemes of the vibrational panel is discussed. The result shows that the method to obtain ATF and the rapid evaluation of sound field using the ATF is suitable to low frequency band. If an appropriate discretization scheme is choosed based on the frequency involved and the effort to obtain ATF, the accuracy of the rapid evaluation of sound field is acceptable.

  18. Rapid Tooling via Stereolithography

    OpenAIRE

    Montgomery, Eva

    2006-01-01

    Approximately three years ago, composite stereolithography (SL) resins were introduced to the marketplace, offering performance features beyond what traditional SL resins could offer. In particular, the high heat deflection temperatures and high stiffness of these highly filled resins have opened the door to several new rapid prototyping (RP) applications, including wind tunnel test modelling and, more recently, rapid tooling.

  19. Application of a regularized model inversion system (REGFLEC) to multi-temporal RapidEye imagery for retrieving vegetation characteristics

    KAUST Repository

    Houborg, Rasmus; McCabe, Matthew

    2015-01-01

    to time-series of 5 m resolution multi-spectral RapidEye data is demonstrated over an irrigated agricultural region in central Saudi Arabia, showcasing the value of satellite-derived crop information at this fine scale for precision management. Validation

  20. Integration of Nanoparticle-Based Paper Sensors into the Classroom: An Example of Application for Rapid Colorimetric Analysis of Antioxidants

    Science.gov (United States)

    Sharpe, Erica; Andreescu, Silvana

    2015-01-01

    We describe a laboratory experiment that employs the Nanoceria Reducing Antioxidant Capacity (or NanoCerac) Assay to introduce students to portable nanoparticle-based paper sensors for rapid analysis and field detection of polyphenol antioxidants. The experiment gives students a hands-on opportunity to utilize nanoparticle chemistry to develop…

  1. Interaction between Mu and Delta Opioid Receptor Agonists in an Assay of Capsaicin-Induced Thermal Allodynia in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    S. Stevens Negus

    2012-01-01

    Full Text Available Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+-4-[(αR-α-((2S,5R-4-allyl-2,5-dimethyl-1-piperazinyl-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of these mu agonists in rhesus monkeys (0.9 : 1 SNC80/methadone; 0.29 : 1 SNC80/morphine; 3.6 : 1 SNC80/nalbuphine. Methadone, morphine, and nalbuphine each produced dose-dependent antiallodynia. SNC80 produced partial antiallodynia up to the highest dose tested (5.6 mg/kg. SNC80 produced a modest, enantioselective, and naltrindole-reversible enhancement of methadone-induced antiallodynia. However, SNC80 did not enhance morphine antiallodynia and only weakly enhanced nalbuphine antiallodynia. Overall, SNC80 produced modest or no enhancement of the antiallodynic effects of the three mu agonists evaluated. These results suggest that delta agonist-induced enhancement of mu agonist antiallodynia may be weaker and less reliable than previously demonstrated enhancement of mu agonist acute thermal nociception.

  2. 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.

  3. 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.

  4. 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...

  5. Application of Portable Raman Spectrometers for Rapid Production Control and Analysis at the Point Of-Need

    Directory of Open Access Journals (Sweden)

    Voyevoda, V.M.

    2014-03-01

    Full Text Available Basic theory of Raman spectroscopy and its application in various fields are described. A world leader in high-tech in s truments, Thermo Fіsher Scіentіfіc designed a series of portable Raman spectrometers for a broad range of applications.

  6. Rapid and simple preparation of thiol-ene emulsion-templated monoliths and their application as enzymatic microreactors

    DEFF Research Database (Denmark)

    Lafleur, Josiane P; Senkbeil, Silja; Novotny, Jakub

    2015-01-01

    A novel, rapid and simple method for the preparation of emulsion-templated monoliths in microfluidic channels based on thiol-ene chemistry is presented. The method allows monolith synthesis and anchoring inside thiol-ene microchannels in a single photoinitiated step. Characterization by scanning...... electron microscopy showed that the methanol-based emulsion templating process resulted in a network of highly interconnected and regular thiol-ene beads anchored solidly inside thiol-ene microchannels. Surface area measurements indicate that the monoliths are macroporous, with no or little micro...

  7. Clinical application of RapidArc volumetric modulated arc therapy as a component in whole brain radiation therapy for poor prognostic, four or more multiple brain metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jin Ho; Kim, Hye Young; Lee, Seok Ho; Sung, Ki Hoon; Kim, Yun Mi [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2012-06-15

    To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Nine patients with multiple ({>=}4) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10- 12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. The median biologically effective dose to metastatic tumors was 68.1 Gy10 and 67.2 Gy10 and the median brain volume irradiated more than 100 Gy3 were 1.9% (24 cm3) and 0.8% (13 cm3) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

  8. Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

    Science.gov (United States)

    Kataria, Hardeep; Lutz, David; Chaudhary, Harshita; Schachner, Melitta; Loers, Gabriele

    2016-09-01

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries.

  9. 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

  10. Rapid and selective detection of acetone using hierarchical ZnO gas sensor for hazardous odor markers application.

    Science.gov (United States)

    Jia, Qianqian; Ji, Huiming; Zhang, Ying; Chen, Yalu; Sun, Xiaohong; Jin, Zhengguo

    2014-07-15

    Hierarchical nanostructured ZnO dandelion-like spheres were synthesized via solvothermal reaction at 200°C for 4h. The products were pure hexagonal ZnO with large exposure of (002) polar facet. Side-heating gas sensor based on hierarchical ZnO spheres was prepared to evaluate the acetone gas sensing properties. The detection limit to acetone for the ZnO sensor is 0.25ppm. The response (Ra/Rg) toward 100ppm acetone was 33 operated at 230°C and the response time was as short as 3s. The sensor exhibited remarkable acetone selectivity with negligible response toward other hazardous gases and water vapor. The high proportion of electron depletion region and oxygen vacancies contributed to high gas response sensitivity. The hollow and porous structure of dandelion-like ZnO spheres facilitated the diffusion of gas molecules, leading to a rapid response speed. The largely exposed (002) polar facets could adsorb acetone gas molecules easily and efficiently, resulting in a rapid response speed and good selectivity of hierarchical ZnO spheres gas sensor at low operating temperature. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. 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...

  14. 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.

  15. A rapid green strategy for the synthesis of Au "meatball"-like nanoparticles using green tea for SERS applications

    Science.gov (United States)

    Wu, Shichao; Zhou, Xi; Yang, Xiangrui; Hou, Zhenqing; Shi, Yanfeng; Zhong, Lubin; Jiang, Qian; Zhang, Qiqing

    2014-09-01

    We report a simple and rapid biological approach to synthesize water-soluble and highly roughened "meatball"-like Au nanoparticles using green tea extract under microwave irradiation. The synthesized Au meatball-like nanoparticles possess excellent monodispersity and uniform size (250 nm in diameter). Raman measurements show that these tea-generated meatball-like gold nanostructures with high active surface areas exhibit a high enhancement of surface-enhanced Raman scattering. In addition, the Au meatball-like nanoparticles demonstrate good biocompatibility and remarkable in vitro stability at the biological temperature. Meanwhile, the factors that influence the Au meatball-like nanoparticles morphology are investigated, and the mechanisms behind the nonspherical shape evolution are discussed.

  16. Application of Rapid Prototyping Pelvic Model for Patients with DDH to Facilitate Arthroplasty Planning: A Pilot Study.

    Science.gov (United States)

    Xu, Jie; Li, Deng; Ma, Ruo-fan; Barden, Bertram; Ding, Yue

    2015-11-01

    Total hip arthroplasty (THA) is challenging in cases of osteoarthritis secondary to developmental dysplasia of the hip (DDH). Acetabular deficiency makes the positioning of the acetabular component difficult. Computer tomography based, patient-individual three dimensional (3-D) rapid prototype technology (RPT)-models were used to plan the placement of acetabular cup so that a surgeon was able to identify pelvic structures, assess the ideal extent of reaming and determine the size of cup after a reconstructive procedure. Intraclass correlation coefficients (ICCs) were used to analyze the agreement between the sizes of chosen components on the basis of preoperative planning and the actual sizes used in the operation. The use of the 3-D RPT-model facilitates the surgical procedures due to better planning and improved orientation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Development of a Novel, Bicombinatorial Approach to Alloy Development, and Application to Rapid Screening of Creep Resistant Titanium Alloys

    Science.gov (United States)

    Martin, Brian

    Combinatorial approaches have proven useful for rapid alloy fabrication and optimization. A new method of producing controlled isothermal gradients using the Gleeble Thermomechanical simulator has been developed, and demonstrated on the metastable beta-Ti alloy beta-21S, achieving a thermal gradient of 525-700 °C. This thermal gradient method has subsequently been coupled with existing combinatorial methods of producing composition gradients using the LENS(TM) additive manufacturing system, through the use of elemental blended powders. This has been demonstrated with a binary Ti-(0-15) wt% Cr build, which has subsequently been characterized with optical and electron microscopy, with special attention to the precipitate of TiCr2 Laves phases. The TiCr2 phase has been explored for its high temperature mechanical properties in a new oxidation resistant beta-Ti alloy, which serves as a demonstration of the new bicombinatorial methods developed as applied to a multicomponent alloy system.

  18. Carbon nanotubes growing on rapid thermal annealed Ni and their application to a triode-type field emission device

    International Nuclear Information System (INIS)

    Uh, Hyung Soo; Park, Sang Sik

    2006-01-01

    In this paper, we demonstrate a new triode-type field emitter arrays using carbon nanotubes (CNTs) as an electron emitter source. In the proposed structure, the gate electrode is located underneath the cathode electrode and the extractor electrode is surrounded by CNT emitters. CNTs were selectively grown on the patterned Ni catalyst layer by using plasma-enhanced chemical vapor deposition (PECVD). Vertically aligned CNTs were grown with gas mixture of acetylene and ammonia under external DC bias. Compared with a conventional under-gate structure, the proposed structure reduced the turn-on voltage by about 30%. In addition, with a view to controlling the density of CNTs, Ni catalyst thickness was varied and rapid thermal annealing (RTA) treatment was optionally adopted before CNT growth. With controlled Ni thickness and RTA condition, field emission efficiency was greatly improved by reducing the density of CNTs, which is due to the reduction of the electric field screening effect caused by dense CNTs

  19. Characterization of a Reconfigurable Free-Space Optical Channel for Embedded Computer Applications with Experimental Validation Using Rapid Prototyping Technology

    Directory of Open Access Journals (Sweden)

    Rafael Gil-Otero

    2007-02-01

    Full Text Available Free-space optical interconnects (FSOIs are widely seen as a potential solution to current and future bandwidth bottlenecks for parallel processors. In this paper, an FSOI system called optical highway (OH is proposed. The OH uses polarizing beam splitter-liquid crystal plate (PBS/LC assemblies to perform reconfigurable beam combination functions. The properties of the OH make it suitable for embedding complex network topologies such as completed connected mesh or hypercube. This paper proposes the use of rapid prototyping technology for implementing an optomechanical system suitable for studying the reconfigurable characteristics of a free-space optical channel. Additionally, it reports how the limited contrast ratio of the optical components can affect the attenuation of the optical signal and the crosstalk caused by misdirected signals. Different techniques are also proposed in order to increase the optical modulation amplitude (OMA of the system.

  20. Characterization of a Reconfigurable Free-Space Optical Channel for Embedded Computer Applications with Experimental Validation Using Rapid Prototyping Technology

    Directory of Open Access Journals (Sweden)

    Lim Theodore

    2007-01-01

    Full Text Available Free-space optical interconnects (FSOIs are widely seen as a potential solution to current and future bandwidth bottlenecks for parallel processors. In this paper, an FSOI system called optical highway (OH is proposed. The OH uses polarizing beam splitter-liquid crystal plate (PBS/LC assemblies to perform reconfigurable beam combination functions. The properties of the OH make it suitable for embedding complex network topologies such as completed connected mesh or hypercube. This paper proposes the use of rapid prototyping technology for implementing an optomechanical system suitable for studying the reconfigurable characteristics of a free-space optical channel. Additionally, it reports how the limited contrast ratio of the optical components can affect the attenuation of the optical signal and the crosstalk caused by misdirected signals. Different techniques are also proposed in order to increase the optical modulation amplitude (OMA of the system.

  1. Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet.

    Science.gov (United States)

    Jung, Huijeong Ashley; Augsburger, Larry L

    2012-07-01

    An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab® concentration, DiPac®/Xylitab® ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab® and/or Xylitab®, magnesium stearate, and Explotab® suggested that the amount of Explotab® was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel® and Explotab®, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone® XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol® showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.

  2. RAPID, MACHINE-LEARNED RESOURCE ALLOCATION: APPLICATION TO HIGH-REDSHIFT GAMMA-RAY BURST FOLLOW-UP

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, A N; Richards, Joseph W; Butler, Nathaniel R; Bloom, Joshua S [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Long, James; Broderick, Tamara [Department of Statistics, University of California, Berkeley, CA 94720-3860 (United States)

    2012-02-20

    As the number of observed gamma-ray bursts (GRBs) continues to grow, follow-up resources need to be used more efficiently in order to maximize science output from limited telescope time. As such, it is becoming increasingly important to rapidly identify bursts of interest as soon as possible after the event, before the afterglows fade beyond detectability. Studying the most distant (highest redshift) events, for instance, remains a primary goal for many in the field. Here, we present our Random Forest Automated Triage Estimator for GRB redshifts (RATE GRB-z ) for rapid identification of high-redshift candidates using early-time metrics from the three telescopes onboard Swift. While the basic RATE methodology is generalizable to a number of resource allocation problems, here we demonstrate its utility for telescope-constrained follow-up efforts with the primary goal to identify and study high-z GRBs. For each new GRB, RATE GRB-z provides a recommendation-based on the available telescope time-of whether the event warrants additional follow-up resources. We train RATE GRB-z using a set consisting of 135 Swift bursts with known redshifts, only 18 of which are z > 4. Cross-validated performance metrics on these training data suggest that {approx}56% of high-z bursts can be captured from following up the top 20% of the ranked candidates, and {approx}84% of high-z bursts are identified after following up the top {approx}40% of candidates. We further use the method to rank 200 + Swift bursts with unknown redshifts according to their likelihood of being high-z.

  3. Application of the polystyrene model made by 3-D printing rapid prototyping technology for operation planning in revision lumbar discectomy.

    Science.gov (United States)

    Li, Chao; Yang, Mingyuan; Xie, Yang; Chen, Ziqiang; Wang, Chuanfeng; Bai, Yushu; Zhu, Xiaodong; Li, Ming

    2015-05-01

    The objective was to evaluate the effectiveness of 3-D rapid prototyping technology in revision lumbar discectomy. 3-D rapid prototyping technology has not been reported in the treatment of revision lumbar discectomy. Patients with recurrent lumbar disc herniation who were preparing to undergo revision lumbar discectomy from a single center between January 2011 and 2013 were included in this analysis. Patients were divided into two groups. In group A, 3-D printing technology was used to create subject-specific lumbar vertebral models in the preoperative planning process. Group B underwent lumbar revision as usual. Preoperative and postoperative clinical outcomes were compared between groups included operation time, perioperative blood loss, postoperative complications, Oswestry Disability Index (ODI), Japan Orthopaedics Association (JOA) scores, and visual analogue scale (VAS) scores for back pain and leg pain. A total of 37 patients were included in this study (Group A = 15, Group B = 22). Group A had a significantly shorter operation time (106.53 ± 11.91 vs. 131.92 ± 10.81 min, P < 0.001) and significantly less blood loss (341.67 ± 49.45 vs. 466.77 ± 71.46 ml, P < 0.001). There was no difference between groups for complication rate. There were also no differences between groups for any clinical metric. Using the 3-D printing technology before revision lumbar discectomy may reduce the operation time and the perioperative blood loss. There does not appear to be a benefit to using the technology with respect to clinical outcomes. Future prospective studies are needed to further elucidate the efficacy of this emerging technology.

  4. The Use of Surveillance Cameras for the Rapid Mapping of Lava Flows: An Application to Mount Etna Volcano

    Directory of Open Access Journals (Sweden)

    Mauro Coltelli

    2017-02-01

    Full Text Available In order to improve the observation capability in one of the most active volcanic areas in the world, Mt. Etna, we developed a processing method to use the surveillance cameras for a quasi real-time mapping of syn-eruptive processes. Following an evaluation of the current performance of the Etna permanent ground NEtwork of Thermal and Visible Sensors (Etna_NETVIS, its possible implementation and optimization was investigated to determine the locations of additional observation sites to be rapidly set up during emergencies. A tool was then devised to process time series of ground-acquired images and extract a coherent multi-temporal dataset of georeferenced map. The processed datasets can be used to extract 2D features such as evolution maps of active lava flows. The tool was validated on ad-hoc test fields and then adopted to map the evolution of two recent lava flows. The achievable accuracy (about three times the original pixel size and the short processing time makes the tool suitable for rapidly assessing lava flow evolutions, especially in the case of recurrent eruptions, such as those of the 2011–2015 Etna activity. The tool can be used both in standard monitoring activities and during emergency phases (eventually improving the present network with additional mobile stations when it is mandatory to carry out a quasi-real-time mapping to support civil protection actions. The developed tool could be integrated in the control room of the Osservatorio Etneo, thus enabling the Etna_NETVIS for mapping purposes and not only for video surveillance.

  5. Phytoscreening for chlorinated solvents using rapid in vitro SPME sampling: Application to urban plume in Verl, Germany

    Science.gov (United States)

    Limmer, M.A.; Balouet, J.-C.; Karg, F.; Vroblesky, D.A.; Burken, J.G.

    2011-01-01

    Rapid detection and delineation of contaminants in urban settings is critically important in protecting human health. Cores from trees growing above a plume of contaminated groundwater in Verl, Germany, were collected in 1 day, with subsequent analysis and plume mapping completed over several days. Solid-phase microextraction (SPME) analysis was applied to detect tetrachloroethene (PCE) and trichloroethene (TCE) to below nanogram/liter levels in the transpiration stream of the trees. The tree core concentrations showed a clear areal correlation to the distribution of PCE and TCE in the groundwater. Concentrations in tree cores were lower than the underlying groundwater, as anticipated; however, the tree core water retained the PCE:TCE signature of the underlying groundwater in the urban, populated area. The PCE:TCE ratio can indicate areas of differing degradation activity. Therefore, the phytoscreening analysis was capable not only of mapping the spatial distribution of groundwater contamination but also of delineating zones of potentially differing contaminant sources and degradation. The simplicity of tree coring and the ability to collect a large number of samples in a day with minimal disruption or property damage in the urban setting demonstrates that phytoscreening can be a powerful tool for gaining reconnaissance-level information on groundwater contaminated by chlorinated solvents. The use of SPME decreases the detection level considerably and increases the sensitivity of phytoscreening as an assessment, monitoring, and phytoforensic tool. With rapid, inexpensive, and noninvasive methods of detecting and delineating contaminants underlying homes, as in this case, human health can be better protected through screening of broader areas and with far faster response times. ?? 2011 American Chemical Society.

  6. Rapid and selective detection of acetone using hierarchical ZnO gas sensor for hazardous odor markers application

    International Nuclear Information System (INIS)

    Jia, Qianqian; Ji, Huiming; Zhang, Ying; Chen, Yalu; Sun, Xiaohong; Jin, Zhengguo

    2014-01-01

    Highlights: • ZnO spheres fabricated via solvothermal method are with (0 0 2) polar facet exposed. • Response time of ZnO sensor for detecting 100 ppm acetone is as short as 3 s. • R a /R g toward 100 ppm acetone is 33 when operated at 230 °C. • ZnO sensor exhibits good selectivity against other toxic gases and water vapor. • Porous structure and exposure of polar facet contribute to good sensing properties. - Abstract: Hierarchical nanostructured ZnO dandelion-like spheres were synthesized via solvothermal reaction at 200 °C for 4 h. The products were pure hexagonal ZnO with large exposure of (0 0 2) polar facet. Side-heating gas sensor based on hierarchical ZnO spheres was prepared to evaluate the acetone gas sensing properties. The detection limit to acetone for the ZnO sensor is 0.25 ppm. The response (R a /R g ) toward 100 ppm acetone was 33 operated at 230 °C and the response time was as short as 3 s. The sensor exhibited remarkable acetone selectivity with negligible response toward other hazardous gases and water vapor. The high proportion of electron depletion region and oxygen vacancies contributed to high gas response sensitivity. The hollow and porous structure of dandelion-like ZnO spheres facilitated the diffusion of gas molecules, leading to a rapid response speed. The largely exposed (0 0 2) polar facets could adsorb acetone gas molecules easily and efficiently, resulting in a rapid response speed and good selectivity of hierarchical ZnO spheres gas sensor at low operating temperature

  7. 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...

  8. The diode pump: its application to nuclear particle counting and to the detection of rapid neutronic power excursions in atomic piles (1962); La pompe a diodes, son application au comptage de particules nucleaires et a la detection des excursions rapides de puissance neutronique d'une pile atomique (1962)

    Energy Technology Data Exchange (ETDEWEB)

    Nicolo, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1962-05-15

    This work deals in particular with three applications of an electronic device whose principle is based on that of the diode pump. 1- Linear response circuit 2- Logarithmic response circuit 3- Detection of neutronic power excursions in atomic piles using a circuit or a combination of several circuits of the linear response type. Each of the applications has been studied theoretically and experimentally. Finally, the detection of rapid power excursions is extensively discussed with reference to the many methods available, emphasis being laid on the rapidity of the electronic response. (author) [French] Cet ouvrage traite plus particulierement de trois applications d'un dispositif electronique dont le principe de fonctionnement est base sur celui de la pompe a diodes. 1- Circuit a reponse lineaire 2- Circuit a reponse logarithmique 3- Detection des excursions de puissance neutronique d'une pile atomique a l'aide d'un circuit ou d'une association de plusieurs circuits a reponse lineaire. Chacune des applications fait l'objet d'une etude theorique et experimentale. Enfin, la detection des excursions rapides de puissance est tres largement discutee a travers plusieurs methodes, notamment sur la partie concernant la rapidite de reponse de l'electronique. (auteur)

  9. Confidence ellipses: A variation based on parametric bootstrapping applicable on Multiple Factor Analysis results for rapid graphical evaluation

    DEFF Research Database (Denmark)

    Dehlholm, Christian; Brockhoff, Per B.; Bredie, Wender L. P.

    2012-01-01

    A new way of parametric bootstrapping allows similar construction of confidence ellipses applicable on all results from Multiple Factor Analysis obtained from the FactoMineR package in the statistical program R. With this procedure, a similar approach will be applied to Multiple Factor Analysis r...... in different studies performed on the same set of products. In addition, the graphical display of confidence ellipses eases interpretation and communication of results....

  10. Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

    Directory of Open Access Journals (Sweden)

    Zhenzhen Cai

    2013-02-01

    Full Text Available A rapid sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS method was developed for determination of timosaponin AIII (TA-III in rat plasma, using ginsenoside Re as an internal standard (IS. TA-III and the IS were detected in MRM mode with a negative ionization electrospray mass spectrometer. The calibration curves were linear over the concentration ranges from 11.14 to 1114 ng/mL and the lower limit of quantification (LLOQ was 11.14 ng/mL. Intra-day and inter-day precisions (RSD were within 10%, and accuracy ranged from 6.4% to 9.1%. The extraction recovery at three concentrations ranged from 92.3% to 95.5%. The validated method was successfully applied to monitor the concentrations of TA-III in rat plasma after intragastric administration. The best fit pharmacokinetic model to estimate the pharmacokinetic parameters was a single compartment model with weight of 1/x2 for oral administration groups of rats for TA-III.

  11. A highly selective and sensitive fluorescent chemosensor and its application for rapid on-site detection of Al3 +

    Science.gov (United States)

    Yue, Xiao-li; Wang, Zhao-qing; Li, Chao-rui; Yang, Zheng-yin

    2018-03-01

    In this paper, a simple naphthalene-based derivative (HL) has been designed and synthesized as a Al3 +-selective fluorescent chemosensor based on the PET mechanism. HL exhibited high selectivity and sensitivity towards Al3 + over other commonly coexisting metal ions in ethanol with a detection limit of 2.72 nM. The 1:1 binding stoichiometry of the complex (HL-Al3 +) was determined from the Job's plot based on fluorescence titrations and the ESI-MS spectrum data. Moreover, the binding site of HL with Al3 + was assured by the 1H NMR titration experiment. The binding constant (Ka) of the complex (HL-Al3 +) was calculated to be 5.06 × 104 M- 1 according to the Benesi-Hildebrand equation. In addition, the recognizing process of HL towards Al3 + was chemically reversible by adding Na2EDTA. Importantly, HL could directly and rapidly detect aluminum ion through the filter paper without resorting to additional instrumental analysis.

  12. Recent Trends in Rapid Environmental Monitoring of Pathogens and Toxicants: Potential of Nanoparticle-Based Biosensor and Applications

    Science.gov (United States)

    Koedrith, Preeyaporn; Thasiphu, Thalisa; Weon, Jong-Il; Boonprasert, Rattana; Tuitemwong, Kooranee; Tuitemwong, Pravate

    2015-01-01

    Of global concern, environmental pollution adversely affects human health and socioeconomic development. The presence of environmental contaminants, especially bacterial, viral, and parasitic pathogens and their toxins as well as chemical substances, poses serious public health concerns. Nanoparticle-based biosensors are considered as potential tools for rapid, specific, and highly sensitive detection of the analyte of interest (both biotic and abiotic contaminants). In particular, there are several limitations of conventional detection methods for water-borne pathogens due to low concentrations and interference with various enzymatic inhibitors in the environmental samples. The increase of cells to detection levels requires long incubation time. This review describes current state of biosensor nanotechnology, the advantage over conventional detection methods, and the challenges due to testing of environmental samples. The major approach is to use nanoparticles as signal reporter to increase output rather than spending time to increase cell concentrations. Trends in future development of novel detection devices and their advantages over other environmental monitoring methodologies are also discussed. PMID:25884032

  13. Rapid and sensitive analysis of cyclobenzaprine by LC–MS/MS: Application to a pharmacokinetic study of cyclobenzaprine in dog

    Directory of Open Access Journals (Sweden)

    Wenhong Yu

    2014-04-01

    Full Text Available A rapid and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma. After extracted with organic solvent, post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode. Multiple reaction monitoring was performed using the transitions of m/z 276.2 → 216.1 and m/z 325.1 → 109.0 to quantify cyclobenzaprine and escitalopram (internal standard, respectively. The mobile phase consisted of acetonitrile: 5 mM ammonium acetate: formic acid (90:10:0.01, v/v/v at a flow rate of 0.3 ml/min. The total analysis time was 2.4 min. The method was linear over the concentration range of 0.0200–10.0 ng/ml. The intra- and inter-day precision was within 12.8% in terms of relative standard deviation (RSD% and the accuracy within 5.6% in terms of relative error. This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.

  14. Rapid and sensitive analysis of melatonin by LC-MS/MS and its application to pharmacokinetic study in dogs

    Directory of Open Access Journals (Sweden)

    Huimin Zhao

    2016-04-01

    Full Text Available A rapid and sensitive liquid chromatography tandem mass spectrometry method was established and validated for determination of melatonin in dog plasma using desvenlafaxine as an internal standard (IS. Plasma samples were pretreated by liquid–liquid extraction with ethyl acetate. Chromatographic separation was carried out on a C18 column at a flow rate of 0.2 ml/min by an isocratic mobile phase of methanol : 5 mM ammonium acetate : formic acid (40:60:0.1, v/v/v. Positive ion mode detection was performed using multiple reaction monitoring (MRM at m/z 233.2→174.2 for melatonin and m/z 264.2→58.2 for desvenlafaxine. The method was linear in the concentration range of 0.020–10 ng/ml with a correlation coefficient ≥0.996. The intra- and inter-assay precision (%RSD values were within 12.6% (LLOQ 15.2%, and accuracy (%RE ranged from −1.8% to 5.0% (LLOQ ±16.5%. The total analysis time was 3.0 min. The method was fully validated and successfully applied to a pharmacokinetic study of melatonin prolonged-release tablet in Beagle dogs. The values of half-life and Tmax were similar to the corresponding data reported before.

  15. Rectangular coordination polymer nanoplates: large-scale, rapid synthesis and their application as a fluorescent sensing platform for DNA detection.

    Directory of Open Access Journals (Sweden)

    Yingwei Zhang

    Full Text Available In this paper, we report on the large-scale, rapid synthesis of uniform rectangular coordination polymer nanoplates (RCPNs assembled from Cu(II and 4,4'-bipyridine for the first time. We further demonstrate that such RCPNs can be used as a very effective fluorescent sensing platform for multiple DNA detection with a detection limit as low as 30 pM and a high selectivity down to single-base mismatch. The DNA detection is accomplished by the following two steps: (1 RCPN binds dye-labeled single-stranded DNA (ssDNA probe, which brings dye and RCPN into close proximity, leading to fluorescence quenching; (2 Specific hybridization of the probe with its target generates a double-stranded DNA (dsDNA which detaches from RCPN, leading to fluorescence recovery. It suggests that this sensing system can well discriminate complementary and mismatched DNA sequences. The exact mechanism of fluorescence quenching involved is elucidated experimentally and its use in a human blood serum system is also demonstrated successfully.

  16. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Science.gov (United States)

    Frank, Guido K. W.

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

  17. Could dopamine agonists aid in drug development for anorexia nervosa?

    Science.gov (United States)

    Frank, Guido K W

    2014-01-01

    Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  18. Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

    Directory of Open Access Journals (Sweden)

    Guido eFrank

    2014-11-01

    Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

  19. Rapid Calibration of High Resolution Geologic Models to Dynamic Data Using Inverse Modeling: Field Application and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Akhil Datta-Gupta

    2008-03-31

    Streamline-based assisted and automatic history matching techniques have shown great potential in reconciling high resolution geologic models to production data. However, a major drawback of these approaches has been incompressibility or slight compressibility assumptions that have limited applications to two-phase water-oil displacements only. We propose an approach to history matching three-phase flow using a novel compressible streamline formulation and streamline-derived analytic sensitivities. First, we utilize a generalized streamline model to account for compressible flow by introducing an 'effective density' of total fluids along streamlines. Second, we analytically compute parameter sensitivities that define the relationship between the reservoir properties and the production response, viz. water-cut and gas/oil ratio (GOR). These sensitivities are an integral part of history matching, and streamline models permit efficient computation of these sensitivities through a single flow simulation. We calibrate geologic models to production data by matching the water-cut and gas/oil ratio using our previously proposed generalized travel time inversion (GTTI) technique. For field applications, however, the highly non-monotonic profile of the gas/oil ratio data often presents a challenge to this technique. In this work we present a transformation of the field production data that makes it more amenable to GTTI. Further, we generalize the approach to incorporate bottom-hole flowing pressure during three-phase history matching. We examine the practical feasibility of the method using a field-scale synthetic example (SPE-9 comparative study) and a field application. Recently Ensemble Kalman Filtering (EnKF) has gained increased attention for history matching and continuous reservoir model updating using data from permanent downhole sensors. It is a sequential Monte-Carlo approach that works with an ensemble of reservoir models. Specifically, the method

  20. How citizen seismology is transforming rapid public earthquake information: the example of LastQuake smartphone application and Twitter QuakeBot

    Science.gov (United States)

    Bossu, R.; Etivant, C.; Roussel, F.; Mazet-Roux, G.; Steed, R.

    2014-12-01

    Smartphone applications have swiftly become one of the most popular tools for rapid reception of earthquake information for the public. Wherever someone's own location is, they can be automatically informed when an earthquake has struck just by setting a magnitude threshold and an area of interest. No need to browse the internet: the information reaches you automatically and instantaneously! One question remains: are the provided earthquake notifications always relevant for the public? A while after damaging earthquakes many eyewitnesses scrap the application they installed just after the mainshock. Why? Because either the magnitude threshold is set too high and many felt earthquakes are missed, or it is set too low and the majority of the notifications are related to unfelt earthquakes thereby only increasing anxiety among the population at each new update. Felt and damaging earthquakes are the ones of societal importance even when of small magnitude. LastQuake app and Twitter feed (QuakeBot) focuses on these earthquakes that matter for the public by collating different information threads covering tsunamigenic, damaging and felt earthquakes. Non-seismic detections and macroseismic questionnaires collected online are combined to identify felt earthquakes regardless their magnitude. Non seismic detections include Twitter earthquake detections, developed by the USGS, where the number of tweets containing the keyword "earthquake" is monitored in real time and flashsourcing, developed by the EMSC, which detect traffic surges on its rapid earthquake information website caused by the natural convergence of eyewitnesses who rush to the Internet to investigate the cause of the shaking that they have just felt. We will present the identification process of the felt earthquakes, the smartphone application and the 27 automatically generated tweets and how, by providing better public services, we collect more data from citizens.

  1. 3D Rapid Prototyping for Otolaryngology—Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling

    Science.gov (United States)

    Chan, Harley H. L.; Siewerdsen, Jeffrey H.; Vescan, Allan; Daly, Michael J.; Prisman, Eitan; Irish, Jonathan C.

    2015-01-01

    The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques

  2. 3D Rapid Prototyping for Otolaryngology-Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling.

    Science.gov (United States)

    Chan, Harley H L; Siewerdsen, Jeffrey H; Vescan, Allan; Daly, Michael J; Prisman, Eitan; Irish, Jonathan C

    2015-01-01

    The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques

  3. 3D Rapid Prototyping for Otolaryngology-Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling.

    Directory of Open Access Journals (Sweden)

    Harley H L Chan

    Full Text Available The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i a mono-material paranasal sinus phantom for endoscopy training ii a multi-material skull base simulator and iii 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and

  4. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data

    Directory of Open Access Journals (Sweden)

    Zhaodi Wang

    2018-04-01

    Full Text Available Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN, viz. Residual Network (ResNet and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO, Linear Regression (LR, Random Forest (RF, Bagging and Multilayer Perceptron (MLP, are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great

  5. Atmospheric Infrared Sounder on NASA's Aqua Satellite: Applications for Volcano Rapid Response, Influenza Outbreak Prediction, and Drought Onset Prediction

    Science.gov (United States)

    Ray, S. E.; Fetzer, E. J.; Lambrigtsen, B.; Olsen, E. T.; Licata, S. J.; Hall, J. R.; Penteado, P. F.; Realmuto, V. J.; Thrastarson, H. T.; Teixeira, J.; Granger, S. L.; Behrangi, A.; Farahmand, A.

    2017-12-01

    The Atmospheric Infrared Sounder (AIRS) has been returning daily global observations of Earth's atmospheric constituents and properties since 2002. With its 15-year data record and near real-time capability, AIRS data are being used in the development of applications that fall within many of the NASA Applied Science focus areas. An automated alert system for volcanic plumes has been developed that triggers on threshold breaches of SO2, ash and dust in granules of AIRS data. The system generates a suite of granule-scale maps that depict both plume and clouds, all accessible from the AIRS web site. Alerts are sent to a curated list of volcano community members, and links to views in NASA Worldview and Google Earth are also available. Seasonal influenza epidemics are major public health concern with millions of cases of severe illness and large economic impact. Recent studies have highlighted the role of absolute or specific humidity as a likely player in the seasonal nature of these outbreaks. A quasi-operational influenza outbreak prediction system has been developed based on the SIRS model which uses AIRS and NCEP humidity data, Center for Disease Control reports on flu and flu-like illnesses, and results from Google Flu Trends. Work is underway to account for diffusion (spatial) in addition to the temporal spreading of influenza. The US Drought Monitor (USDM) is generated weekly by the National Drought Mitigation Center (NDMC) and is used by policymakers for drought decision-making. AIRS data have demonstrated utility in monitoring the development and detection of meteorological drought with both AIRS-derived standardized vapor pressure deficit and standardized relative humidity, showing early detection lead times of up to two months. An agreement was secured with the NDMC to begin a trial period using AIRS products in the production of the USDM, and in July of 2017 the operational delivery of weekly CONUS AIRS images of Relative Humidity, Surface Air Temperature

  6. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data.

    Science.gov (United States)

    Wang, Zhaodi; Hu, Menghan; Zhai, Guangtao

    2018-04-07

    Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for

  7. Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data

    Science.gov (United States)

    Hu, Menghan; Zhai, Guangtao

    2018-01-01

    Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for

  8. Heavy-metal-induced Inhibition of Aspergillus niger nitrate reductase: Applications for Rapid Contaminant Detection in Aqueous Samples

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William Arnold; Aiken, Abigail Marie; Peyton, Brent Michael; Petersen, James N.

    2003-03-01

    Enzyme inhibition assays have the potential to rapidly screen and identify heavy metals in environmental samples. Inhibition of nitrate reductase (NR) was examined as a method for detecting toxic metals. The activity of NR (EC 1.6.6.2) from Aspergillus niger was assayed as a function of metal concentration in the presence of Cd2+, Cr3+, Cr6+, Cu2+, Ni2+, Pb2+, and Zn2+. NR exhibited sensitivity to these metals at concentrations below 10 µM. Various buffers were screened for their ability to protect NR activity from metal inhibition, and 3-(N-morpholino) propanesulfonic acid (MOPS) was selected as the buffering system for the NR assays as it exhibited the least interference with metal inhibition, thus providing increased assay sensitivity. The hypothesis that chelating agents could prevent the inhibition of NR activity by metal ions was also tested. Results indicated that 10 mM ethylenediaminetetraacetic acid (EDTA) could protect NR activity from inhibition by Cr3+, Cu2+, Cd2+, Ni2+, and Zn2+ at concentrations below 100 µM, but that the EDTA had no effect on NR inhibition by Cr6+. An amount of 10 mM nitrilotriacetic acid (NTA) prevented NR inhibition by Cd2+, Cu2+, Ni2+, Pb2+, and Zn2+ at metal concentrations below 100 µM. However, 10 mM NTA was unable to protect the enzyme from inhibition by either Cr3+ or Cr6+. These results indicated that through specific metal chelation, a NR-based method for individually quantifying Cr3+ and Cr6+ species in aqueous solutions could be developed. The ability to restore activity to NR which been previously inhibited by exposure to 100 µM Pb2+, Cd2+, Zn2+, Cu2+, and Cr3+ was explored to determine whether NR activity could be recovered by EDTA additions for use in consecutive metal inhibition assays. The results showed NR activity could not be regained after exposure to Cr3+ or Cu2+, but did partially recover activity after Cd2+, Pb2+, and Zn2+ exposure.

  9. A Simple and Rapid Gene Disruption Strategy in Mycobacterium abscessus: On the Design and Application of Glycopeptidolipid Mutants.

    Science.gov (United States)

    Viljoen, Albertus; Gutiérrez, Ana Victoria; Dupont, Christian; Ghigo, Eric; Kremer, Laurent

    2018-01-01

    Little is known about the disease-causing genetic determinants that are used by Mycobacterium abscessus , increasingly acknowledged as an important emerging pathogen, notably in cystic fibrosis. The presence or absence of surface exposed glycopeptidolipids (GPL) conditions the smooth (S) or rough (R) M. abscessus subsp. abscessus ( M. abscessus ) variants, respectively, which are characterized by distinct infective programs. However, only a handful of successful gene knock-out and conditional mutants have been reported in M. abscessus , testifying that genetic manipulation of this mycobacterium is difficult. To facilitate gene disruption and generation of conditional mutants in M. abscessus , we have designed a one-step single cross-over system that allows the rapid and simple generation of such mutants. Cloning of as small as 300 bp of the target gene allows for efficient homologous recombination to occur without additional exogenous recombination-promoting factors. The presence of tdTomato on the plasmids allows easily sifting out the large background of mutants spontaneously resistant to antibiotics. Using this strategy in the S genetic background and the target gene mmpL4a , necessary for GPL synthesis and transport, nearly 100% of red fluorescent clones exhibited a rough morphotype and lost GPL on the surface, suggesting that most red fluorescent colonies obtained after transformation incorporated the plasmid through homologous recombination into the chromosome. This system was further exploited to generate another strain with reduced GPL levels to explore how the presence of these cell wall-associated glycolipids influences M. abscessus hydrophobicity as well as virulence in the zebrafish model of infection. This mutant exhibited a more pronounced killing phenotype in zebrafish embryos compared to its S progenitor and this effect correlated with the production of abscesses in the central nervous system. Overall, these results suggest that the near

  10. Application of Reverse Transcriptase-PCR-DGGE as a rapid method for routine determination of Vibrio spp. in foods.

    Science.gov (United States)

    Chahorm, Kanchana; Prakitchaiwattana, Cheunjit

    2018-01-02

    The aim of this research was to evaluate the feasibility of PCR-DGGE and Reverse Transcriptase-PCR-DGGE techniques for rapid detection of Vibrio species in foods. Primers GC567F and 680R were initially evaluated for amplifying DNA and cDNA of ten references Vibrio species by PCR method. The GC-clamp PCR amplicons were separated according to their sequences by the DGGE using 10% (w/v) polyacrylamide gel containing 45-70% urea and formamide denaturants. Two pair of Vibrio species, which could not be differentiated on the gel, was Vibrio fluvialis - Vibrio furnissii and Vibrio parahaemolyticus - Vibrio harveyi. To determine the detection limit, in the community of 10 reference strains containing the same viable population, distinct DNA bands of 3 species; Vibrio cholerae, Vibrio mimicus and Vibrio alginolyticus were consistently observed by PCR-DGGE technique. In fact, 5 species; Vibrio cholerae, Vibrio mimicus, Vibrio alginolyticus, Vibrio parahaemolyticus and Vibrio fluvialis consistently observed by Reverse Transcriptase-PCR-DGGE. In the community containing different viable population increasing from 10 2 to 10 5 CFU/mL, PCR-DGGE analysis only detected the two most prevalent species, while RT-PCR-DGGE detected the five most prevalent species. Therefore, Reverse Transcriptase-PCR-DGGE was also selected for detection of various Vibrio cell conditions, including viable cell (VC), injured cells from frozen cultures (IVC) and injured cells from frozen cultures with pre-enrichment (PIVC). It was found that cDNA band of all cell conditions gave the same migratory patterns, except that multiple cDNA bands of Plesiomonas shigelloides under IVC and PIVC conditions were found. When Reverse Transcriptase-PCR-DGGE was used for detecting Vibrio parahaemolyticus in the pathogen-spiked food samples, Vibrio parahaemolyticus could be detected in the spiked samples containing at least 10 2 CFU/g of this pathogen. The results obtained also corresponded to standard method (USFDA, 2004

  11. Applicability of rapid and on-site measured enzyme activity for surface water quality monitoring in an agricultural catchment

    Science.gov (United States)

    Stadler, Philipp; Farnleitner, Andreas H.; Sommer, Regina; Kumpan, Monika; Zessner, Matthias

    2014-05-01

    For the near real time and on-site detection of microbiological fecal pollution of water, the measurement of beta-D- Glucuronidase (GLUC) enzymatic activity has been suggested as a surrogate parameter and has been already successfully operated for water quality monitoring of ground water resources (Ryzinska-Paier et al. 2014). Due to possible short measure intervals of three hours, this method has high potential as a water quality monitoring tool. While cultivation based standard determination takes more than one working day (Cabral 2010) the potential advantage of detecting the GLUC activity is the high temporal measuring resolution. Yet, there is still a big gap of knowledge on the fecal indication capacity of GLUC (specificity, sensitivity, persistence, etc.) in relation to potential pollution sources and catchment conditions (Cabral 2010, Ryzinska-Paier et al. 2014). Furthermore surface waters are a big challenge for automated detection devices in a technical point of view due to the high sediment load during event conditions. This presentation shows results gained form two years of monitoring in an experimental catchment (HOAL) dominated by agricultural land use. Two enzymatic measurement devices are operated parallel at the catchment outlet to test the reproducibility and precision of the method. Data from continuous GLUC monitoring under both base flow and event conditions is compared with reference samples analyzed by standardized laboratory methods for fecal pollution detection (e.g. ISO 16649-1, Colilert18). It is shown that rapid enzymatic on-site GLUC determination can successfully be operated from a technical point of view for surface water quality monitoring under the observed catchment conditions. The comparison of enzyme activity with microbiological standard analytics reveals distinct differences in the dynamic of the signals during event conditions. Cabral J. P. S. (2010) "Water Microbiology. Bacterial Pathogens and Water" International Journal of

  12. Rapid synthesis of flower shaped Cu_2ZnSnS_4 nanoparticles by microwave irradiation for solar cell application

    International Nuclear Information System (INIS)

    Ansari, Mohd Zubair; Khare, Neeraj

    2016-01-01

    Single phase Cu_2ZnSnS__4 (CZTS) nanoparticles have been synthesized by the microwave-assisted solution method in a one step process. Structural, morphological and optical characterizations of the CZTS nanoparticles have been carried out. X-ray diffraction confirms the single phase formation of CZTS nanoparticles with kesterite structure. SEM confirms the homogenous distribution of CZTS nanoparticles flower like assemblies. High resolution TEM image confirms the good crystallinity of the CZTS nanoparticles with the average grain size ~20 nm. The CZTS nanoparticles have strong optical absorption in the visible region with direct band gap as ~1.6 eV which is optimal for photovoltaic application

  13. Simple, Rapid and Reliable Preparation of [11C]-(+-a-DTBZ of High Quality for Routine Applications

    Directory of Open Access Journals (Sweden)

    Jiahe Tian

    2012-06-01

    Full Text Available [11C]-(+-a-DTBZ has been used as a marker of dopaminergic terminal densities in human striatum and expressed in islet beta cells in the pancreas. We aimed to establish a fully automated and simple procedure for the synthesis of [11C]-(+-a-DTBZ for routine applications. [11C]-(+-a-DTBZ was synthesized from a 9-hydroxy precursor in acetone and potassium hydroxide with [11C]-methyl triflate and was purified by solid phase extraction using a Vac tC-18 cartridge. Radiochemical yields based on [11C]-methyl triflate (corrected for decay were 82.3% ± 3.6%, with a specific radioactivity of 60 GBq/mmol. Time elapsed was less than 20 min from end of bombardment to release of the product for quality control.

  14. 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...

  15. 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...

  16. 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

  17. Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

    Directory of Open Access Journals (Sweden)

    Theron AJ

    2013-11-01

    Full Text Available Annette J Theron,1,2 Helen C Steel,1 Gregory R Tintinger,1 Charles Feldman,3 Ronald Anderson1 1Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, 2Tshwane Academic Division of the National Health Laboratory Service, Pretoria, 3Division of Pulmonology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand and Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa Abstract: Beta2-adrenoreceptor agonists (β2-agonists are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3',5'-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells. Keywords: adenylyl cyclase, corticosteroids, cyclic AMP, muscarinic

  18. 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

  19. Microstructure and corrosion properties of as sub-rapid solidification Mg-Zn-Y-Nd alloy in dynamic simulated body fluid for vascular stent application.

    Science.gov (United States)

    Wang, Jun; Wang, Liguo; Guan, Shaokang; Zhu, Shijie; Ren, Chenxing; Hou, Shusen

    2010-07-01

    Magnesium alloy stent has been employed in animal and clinical experiment in recent years. It has been verified to be biocompatible and degradable due to corrosion after being implanted into blood vessel. Mg-Y-Gd-Nd alloy is usually used to construct an absorbable magnesium alloy stent. However, the corrosion resistant of as cast Mg-Y-Gd-Nd alloy is poor relatively and the control of corrosion rate is difficult. Aiming at the requirement of endovascular stent in clinic, a new biomedical Mg-Zn-Y-Nd alloy with low Zn and Y content (Zn/Y atom ratio 6) was designed, which exists quasicrystals to improve its corrosion resistance. Additionally, sub-rapid solidification processing was applied for preparation of corrosion-resisting Mg-Zn-Y-Nd and Mg-Y-Gd-Nd alloys. Compared with the as cast sample, the corrosion behavior of alloys in dynamic simulated body fluid (SBF) (the speed of body fluid: 16 ml/800 ml min(-1)) was investigated. The results show that as sub-rapid solidification Mg-Zn-Y-Nd alloy has the better corrosion resistance in dynamic SBF due to grain refinement and fine dispersion distribution of the quasicrystals and intermetallic compounds in alpha-Mg matrix. In the as cast sample, both Mg-Zn-Y-Nd and Mg-Y-Gd-Nd alloys exhibit poor corrosion resistance. Mg-Zn-Y-Nd alloy by sub-rapid solidification processing provides excellent corrosion resistance in dynamic SBF, which open a new window for biomedical materials design, especially for vascular stent application.

  20. [Fabrication of 3-dimensional skull model with rapid prototyping technique and its primary application in repairing one case of cranio-maxillo-facial trauma].

    Science.gov (United States)

    Xia, Delin; Gui, Lai; Zhang, Zhiyong; Lu, Changsheng; Niu, Feng; Jin, Ji; Liu, Xiaoqing

    2005-10-01

    To investigate the methods of establishing 3-dimensional skull model using electron beam CT (EBCT) data rapid prototyping technique, and to discuss its application in repairing cranio-maxillo-facial trauma. The data were obtained by EBCT continuous volumetric scanning with 1.0 mm slice at thickness. The data were transferred to work-station for 3-dimensional surface reconstruction by computer-aided design software and the images were saved as STL file. The data can be used to control a laser rapid-prototyping device (AFS-320QZ) to construct geometric model. The material for the model construction is a kind of laser-sensitive resin power, which will become a mass when scanned by laser beam. The design and simulation of operation can be done on the model. The image data were transferred to the device slice by slice. Thus a geometric model is constructed according to the image data by repeating this process. Preoperative analysis, surgery simulation and implant of bone defect could be done on this computer-aided manufactured 3D model. One case of cranio-maxillo-facial bone defect resulting from trauma was reconstructed with this method. The EBCT scanning showed that the defect area was 4 cm x 6 cm. The nose was flat and deviated to left. The 3-dimensional skull was reconstructed with EBCT data and rapid prototyping technique. The model can display the structure of 3-dimensional anatomy and their relationship. The prefabricated implant by 3-dimensional model was well-matched with defect. The deformities of flat and deviated nose were corrected. The clinical result was satisfactory after a follow-up of 17 months. The 3-dimensional model of skull can replicate the prototype of disease and play an important role in the diagnosis and simulation of operation for repairing cranio-maxillo-facial trauma.

  1. Design of a macroalgae amperometric biosensor; application to the rapid monitoring of organophosphate insecticides in an agroecosystem.

    Science.gov (United States)

    Nunes, G S; Lins, J A P; Silva, F G S; Araujo, L C; Silva, F E P S; Mendonça, C D; Badea, M; Hayat, A; Marty, J-L

    2014-09-01

    The immobilization of enzymes onto transducer support is a mature technology and has been successfully implemented to improve biocatalytic processes for diverse applications. However, there exists still need to design more sophisticated and specialized strategies to enhance the functional properties of the biosensors. In this work, a biosensor platform based on innovative fabrication strategy was designed, and employed for the detection of organophosphate (OP) in natural waters. The biosensor was prepared by incorporating acetylcholinesterase enzyme (AChE) to the graphite paste modified with tetracyanoquinodimethane (TCNQ) mediator, along with the use of a macroalgae (Cladaphropsis membranous) as a functional immobilization support. The novel immobilization design resulted in a synergic effect, and led to enhanced stability and sensitivity of the biosensor. The designed biosensor was used to analyze methyl parathion OP insecticide in water samples collected from a demonstrably contaminated lake of São Luis Island, Maranhão, Northeast of Brazil. Water analysis revealed that the aquatic ecosystem was polluted by sub-ppm concentrations of the OP insecticide, and a good correlation was found between values obtained through biosensor and GC-MS techniques. Our results demonstrated that macroalgae-biosensor could be used as a low-cost and sensitive screening method to detect target analyte. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications

    International Nuclear Information System (INIS)

    Haeusler, D.; Mien, L.-K.; Nics, L.; Ungersboeck, J.; Philippe, C.; Lanzenberger, R.R.; Kletter, K.; Dudczak, R.; Mitterhauser, M.; Wadsak, W.

    2009-01-01

    [ 11 C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [ 11 C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [ 11 C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3±1.6 GBq). Radiochemical yields based on [ 11 C]CH 3 I, (corrected for decay) were 66.3±6.9% with a specific radioactivity (A s ) of 86.8±24.3 GBq/μmol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. Form our data, it is evident that the presented method can be implemented for routine preparations of [ 11 C]DASB with high reliability.

  3. Large-scale, rapid synthesis and application in surface-enhanced Raman spectroscopy of sub-micrometer polyhedral gold nanocrystals

    International Nuclear Information System (INIS)

    Guo Shaojun; Wang Yuling; Wang Erkang

    2007-01-01

    Macromolecule-protected sub-micrometer polyhedral gold nanocrystals have been facilely prepared by heating an aqueous solution containing poly (N-vinyl-2-pyrrolidone) (PVP) and HAuCl 4 without adding other reducing agents. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), ultraviolet-visible-near-infrared spectroscopy (UV-vis-NIR), and x-ray diffraction (XRD) were employed to characterize the obtained polyhedral gold nanocrystals. It is found that the 10:1 molar ratio of PVP to gold is a key factor for obtaining quasi-monodisperse polyhedral gold nanocrystals. Furthermore, the application of polyhedral gold nanocrystals in surface-enhanced Raman scattering (SERS) was investigated by using 4-aminothiophenol (4-ATP) as a probe molecule. The results indicated that the sub-micrometer polyhedral gold nanocrystals modified on the ITO substrate exhibited higher SERS activity compared to the traditional gold nanoparticle modified film. The enhancement factor (EF) on polyhedral gold nanocrystals was about six times larger than that obtained on aggregated gold nanoparticles (∼25 nm)

  4. Simple and rapid preparation of [{sup 11}C]DASB with high quality and reliability for routine applications

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, D.; Mien, L.-K. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Nics, L. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Nutritional Sciences, University of Vienna, A-1090 Vienna (Austria); Ungersboeck, J. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna (Austria); Philippe, C. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Lanzenberger, R.R. [Department of Psychiatry and Psychotherapy, Medical University of Vienna, A-1090 Vienna (Austria); Kletter, K.; Dudczak, R. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria); Wadsak, W. [Department of Nuclear Medicine, PET, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna (Austria)], E-mail: wolfgang.wadsak@meduniwien.ac.at

    2009-09-15

    [{sup 11}C]DASB combines all major prerequisites for a successful SERT-ligand, providing excellent biological properties and in-vivo behaviour. Thus, we aimed to establish a fully automated procedure for the synthesis and purification of [{sup 11}C]DASB with a high degree of reliability reducing the overall synthesis time while conserving high yields and purity. The optimized [{sup 11}C]DASB synthesis was applied in more than 60 applications with a very low failure rate (3.2%). We obtained yields up to 8.9 GBq (average 5.3{+-}1.6 GBq). Radiochemical yields based on [{sup 11}C]CH{sub 3}I, (corrected for decay) were 66.3{+-}6.9% with a specific radioactivity (A{sub s}) of 86.8{+-}24.3 GBq/{mu}mol (both at the end of synthesis, EOS). Time consumption was kept to a minimum, resulting in 43 min from end of bombardment to release of the product after quality control. Form our data, it is evident that the presented method can be implemented for routine preparations of [{sup 11}C]DASB with high reliability.

  5. Application of rapid solidification powder metallurgy to the fabrication of high-strength, high-ductility Mg-Al-Zn-Ca-La alloy through hot extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Ayman, Elsayed, E-mail: ayman@jwri.osaka-u.ac.jp [Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Junko, Umeda; Katsuyoshi, Kondoh [Joining and Welding Research Institute, Osaka University, 11-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)

    2011-01-15

    The microstructure and mechanical properties of hot extruded Mg-7Al-1Zn-1Ca powder alloys with an addition of 1.5% La or 3.3% La were investigated. Both rapidly solidified powders, produced via spinning water atomization process, and cast billets were extruded at 573, 623 and 673 K to optimize the processing conditions for obtaining better mechanical response. Powders were consolidated using both cold compaction and spark plasma sintering. The tensile properties of the extruded alloys were then evaluated and correlated to their microstructures. The results showed that the use of rapidly solidified Mg-7Al-1Zn-1Ca alloy powders with La additions could lead to effective grain refinement and super saturation of alloying elements, which in turn resulted in the improved mechanical response. The Mg-7Al-1Zn-1Ca-1.5La alloy extruded at 573 K attained ultimate tensile strength of 450 {+-} xx MPa and elongation of 17 {+-} xx%, superior to the Mg-7Al-1Zn-1Ca-3.3La alloy and other Mg alloys like Mg-Al-Mn-Ca. This may help extend the application of Mg alloys to higher load-carrying parts while maintaining the excellent advantage of light weight.

  6. A rapid procedure for the determination of thorium, uranium, cadmium and molybdenum in small sediment samples by inductively coupled plasma-mass spectrometry: application in Chesapeake Bay

    International Nuclear Information System (INIS)

    Zheng, Y.; Weinman, B.; Cronin, T.; Fleisher, M.Q.; Anderson, R.F.

    2003-01-01

    This paper describes a rapid procedure that allows precise analysis of Mo, Cd, U and Th in sediment samples as small as 10 mg by using a novel approach that utilizes a 'pseudo' isotope dilution for Th and conventional isotope dilution for Mo, Cd and U by ICP-MS. Long-term reproducibility of the method is between 2.5 and 5% with an advantage of rapid analysis on a single digestion of sediment sample and the potential of adding other elements of interest if so desired. Application of this method to two piston cores collected near the mouth of the Patuxent River in Chesapeake Bay showed that the accumulation of authigenic Mo and Cd varied in response to the changing bottom water redox conditions, with anoxia showing consistent oscillations throughout both pre-industrial and industrial times. Accumulation of authigenic U shows consistent oscillations as well, without any apparent increase in productivity related to anoxic trends. Degrees of Mo and Cd enrichment also inversely correlate to halophilic microfaunal assemblages already established as paleoclimate proxies within the bay indicating that bottom water anoxia is driven in part by the amount of freshwater discharge that the area receives

  7. Application of reflectance colorimeter measurements and infrared spectroscopy methods to rapid and nondestructive evaluation of carotenoids content in apricot (Prunus armeniaca L.).

    Science.gov (United States)

    Ruiz, David; Reich, Maryse; Bureau, Sylvie; Renard, Catherine M G C; Audergon, Jean-Marc

    2008-07-09

    The importance of carotenoid content in apricot (Prunus armeniaca L.) is recognized not only because of the color that they impart but also because of their protective activity against human diseases. Current methods to assess carotenoid content are time-consuming, expensive, and destructive. In this work, the application of rapid and nondestructive methods such as colorimeter measurements and infrared spectroscopy has been evaluated for carotenoid determination in apricot. Forty apricot genotypes covering a wide range of peel and flesh colors have been analyzed. Color measurements on the skin and flesh ( L*, a*, b*, hue, chroma, and a*/ b* ratio) as well as Fourier transform near-infrared spectroscopy (FT-NIR) on intact fruits and Fourier transform mid-infrared spectroscopy (FT-MIR) on ground flesh were correlated with the carotenoid content measured by high-performance liquid chromatography. A high variability in color values and carotenoid content was observed. Partial least squares regression analyses between beta-carotene content and provitamin A activity and color measurements showed a high fit in peel, flesh, and edible apricot portion (R(2) ranged from 0.81 to 0.91) and low prediction error. Regression equations were developed for predicting carotenoid content by using color values, which appeared as a simple, rapid, reliable, and nondestructive method. However, FT-NIR and FT-MIR models showed very low R(2) values and very high prediction errors for carotenoid content.

  8. Procedure for rapid determination of δ15N and δ18O values of nitrate: development and application to an irrigated rice paddy watershed.

    Science.gov (United States)

    Yada, Saeko; Nakajima, Yasuhiro; Itahashi, Sunao; Asada, Kei; Yoshikawa, Seiko; Eguchi, Sadao

    2016-01-01

    The dual isotope approach using the stable isotope ratios of nitrate nitrogen (δ(15)N(NO3)) and oxygen (δ(18)O(NO3)) is a strong tool for identifying the history of nitrate in various environments. Basically, a rapid procedure for determining δ(15)N(NO3) and δ(18)O(NO3) values is required to analyze many more samples quickly and thus save on the operational costs of isotope-ratio mass spectrometry (IRMS). We developed a new rapid procedure to save time by pre-treating consecutive samples of nitrous oxide microbially converted from nitrate before IRMS determination. By controlling two six-port valves of the pre-treatment system separately, IRMS determination of the current sample and backflush during the next sample pre-treatment period could be conducted simultaneously. A set of 89 samples was analyzed precisely during a 25-h continuous run (17 min per sample), giving the fastest reported processing time, and simultaneously reducing liquid nitrogen and carrier helium gas consumption by 35%. Application of the procedure to an irrigated rice paddy watershed suggested that nitrate concentrations in river waters decreased in a downstream direction, mainly because of the mixing of nitrate from different sources, without distinct evidence of denitrification. Our procedure should help with more detailed studies of nitrate formation processes in watersheds.

  9. Rapid concentration and dialysis of proteins with single hollow fibers: possible applications in analysis of protein secretion by isolated cells and steroid radioimmunoassays

    International Nuclear Information System (INIS)

    Rommerts, F.F.G.; Clotscher, W.F.; Van der Molen, H.J.

    1977-01-01

    Single hollow fibers were used in specially made cells for fast concentration and dialysis of solutions containing macromolecules. Volumes on the order of 5 ml of diluted protein solutions could be concentrated to 50--100 μl or less within 7 min with a protein recovery of 60--80%. More than 99% of the molecules with a molecular weight less than 500 could be removed in less than 1 hr. A possible application of the rapid dialysis method for the mechanization of radioimmunoassays is indicated. It was shown that in the radioimmunoassay of steriods the unbound steroids could be removed after incubation with antiserum, within 10 min and without a change in volume

  10. AVSynDEx: A Rapid Prototyping Process Dedicated to the Implementation of Digital Image Processing Applications on Multi-DSP and FPGA Architectures

    Directory of Open Access Journals (Sweden)

    Fresse Virginie

    2002-01-01

    Full Text Available We present AVSynDEx (concatenation of AVS SynDEx, a rapid prototyping process aiming to the implementation of digital signal processing applications on mixed architectures (multi-DSP FPGA. This process is based on the use of widely available and efficient CAD tools established along the design process so that most of the implementation tasks become automatic. These tools and architectures are judiciously selected and integrated during the implementation process to help a signal processing specialist without relevant hardware experience. We have automated the translation between the different levels of the process to increase and secure it. One main advantage is that only a signal processing designer is needed, all the other specialized manual tasks being transparent in this prototyping methodology, hereby reducing the implementation time.

  11. Rapid Biosynthesis of AgNPs Using Soil Bacterium Azotobacter vinelandii With Promising Antioxidant and Antibacterial Activities for Biomedical Applications

    Science.gov (United States)

    Karunakaran, Gopalu; Jagathambal, Matheswaran; Gusev, Alexander; Torres, Juan Antonio Lopez; Kolesnikov, Evgeny; Kuznetsov, Denis

    2017-07-01

    Silver nanoparticles (AgNPs) are applied in various fields from electronics to biomedical applications as a result of their high surface-to-volume ratio. Even though different approaches are available for synthesis of AgNPs, a nontoxic method for the synthesis has not yet been developed. Thus, this study focused on developing an easy and ecofriendly approach to synthesize AgNPs using Azotobacter vinelandii culture extracts. The biosynthesized nanoparticles were further characterized by ultraviolet-visible (UV-Vis) spectroscopy, x-ray diffraction (XRD), Fourier transform infrared (FTIR), energy-dispersive spectrum, particle size distribution (PSD), and transmission electron microscopy (TEM). UV absorption noticed at 435 nm showed formation of AgNPs. The XRD pattern showed a face-centered cubic structure with broad peaks of 28.2°, 32.6°, 46.6°, 55.2°, 57.9°, and 67.8°. The FTIR confirmed the involvement of various functional groups in the biosynthesis of AgNPs. The PSD and TEM analyses showed spherical, well-distributed nanoparticles with an average size of 20-70 nm. The elemental studies confirmed the existence of pure AgNPs. The bacterial extract containing extracellular enzyme nitrate reductase converted silver nitrate into AgNPs. AgNPs significantly inhibited the growth of pathogenic bacteria such as Streptomyces fradiae (National Collection of Industrial Microorganisms (NCIM) 2419), Staphylococcus aureus (NCIM 2127), Escherichia coli (NCIM 2065), and Serratia marcescens (NCIM 2919). In addition, biosynthesized AgNPs were found to possess strong antioxidant activity. Thus, the results of this study revealed that biosynthesized AgNPs could serve as a lead in the development of nanomedicine.

  12. Application of a bacterial whole cell biosensor for the rapid detection of cytotoxicity in heavy metal contaminated seawater.

    Science.gov (United States)

    Cui, Zhisong; Luan, Xiao; Jiang, Huichao; Li, Qian; Xu, Guangfei; Sun, Chengjun; Zheng, Li; Song, Yizhi; Davison, Paul A; Huang, Wei E

    2018-06-01

    A toxicity biosensor Acinetobacter baylyi Tox2 was constructed with the host strain A. baylyi ADP1 harboring a new and medium-copy-number plasmid pWH1274_lux, and was applied to detect the cytotoxicity of heavy metal contaminated seawater. The gene cassette luxCDABE was controlled by constitutively expressed promoter P tet on pWH1274_lux and the bioluminescence intensity of the biosensor reduces in proportional to the concentrations of toxic compounds. A. baylyi Tox2 exhibits tolerance to salinity, hence it is applicable to seawater samples. A. baylyi Tox2 and Mugilogobius chulae were exposed to different concentrations of heavy metals (Hg 2+ , Zn 2+ , Cu 2+ , and Cd 2+ ) in artificial seawater for performance comparison and Pearson correlation analysis showed a significant correlation (p heavy metal contaminated seawater. Furthermore, A. baylyi Tox2 was used to evaluate cytotoxicity of field-collected seawater samples. The results indicate that there was a significant correlation between the luminescence inhibition ratio (IR) of A. baylyi Tox2 and heavy metal concentrations detected by ICP-MS in the samples. Two seawater samples, which contained a high concentration of total heavy metals, exhibited stronger cytotoxicity than the samples containing low concentrations of heavy metals. In conclusion, A. baylyi Tox2 can be used as an alternative tool to aquatic animals for the evaluation of the cytotoxicity of heavy metal contamination in the marine environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Microwave assisted rapid growth of Mg(OH){sub 2} nanosheet networks for ethanol chemical sensor application

    Energy Technology Data Exchange (ETDEWEB)

    Al-Hazmi, Faten [Department of Physics, College of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21569 (Saudi Arabia); Umar, Ahmad, E-mail: ahmadumar786@gmail.com [Promising Centre for Sensors and Electronic Devices (PCSED) and Centre for Advanced Materials and Nano-Research (CAMNR), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Dar, G.N. [Promising Centre for Sensors and Electronic Devices (PCSED) and Centre for Advanced Materials and Nano-Research (CAMNR), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Al-Ghamdi, A.A.; Al-Sayari, S.A. [Department of Physics, College of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21569 (Saudi Arabia); Al-Hajry, A. [Promising Centre for Sensors and Electronic Devices (PCSED) and Centre for Advanced Materials and Nano-Research (CAMNR), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Department of Physics, College of Science and Arts, Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Kim, S.H. [Promising Centre for Sensors and Electronic Devices (PCSED) and Centre for Advanced Materials and Nano-Research (CAMNR), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Al-Tuwirqi, Reem M. [Department of Physics, College of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21569 (Saudi Arabia); Alnowaiserb, Fowzia [Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); El-Tantawy, Farid [Department of Physics, Faculty of Science, Suez Canal University, Ismailia (Egypt)

    2012-04-05

    Highlights: Black-Right-Pointing-Pointer A facile microwave-assisted synthesis and characterizations of magnesium hydroxide (Mg(OH){sub 2}) nanosheet networks. Black-Right-Pointing-Pointer Fabrication of ethanol sensor based on (Mg(OH){sub 2}) nanosheet networks. Black-Right-Pointing-Pointer Good sensitivity ({approx}3.991 {mu}A cm{sup -2} mM{sup -1}) and lower detection limit (5 {mu}M). Black-Right-Pointing-Pointer This research opens a way to utilize Mg(OH){sub 2} nanostructures for chemical sensors applications. - Abstract: This paper reports a facile microwave-assisted synthesis of magnesium hydroxide (Mg(OH){sub 2}) nanosheet networks and their utilization for the fabrication of efficient ethanol chemical sensor. The synthesized nanosheets networks were characterized in terms of their morphological, structural and optical properties using various analysis techniques such as field emission scanning electron microscopy (FESEM), X-ray diffraction pattern (XRD), Fourier transform infrared (FTIR) and UV-Vis spectroscopy. The detailed morphological and structural investigations reveal that the synthesized (Mg(OH){sub 2}) products are nanosheet networks, grown in high density, and possessing hexagonal crystal structure. The optical band gap of as-synthesized Mg(OH){sub 2} nanosheet networks was examined by UV-Vis absorption spectrum, and found to be 5.76 eV. The synthesized nanosheet networks were used as supporting matrices for the fabrication of I-V technique based efficient ethanol chemical sensor. The fabricated ethanol sensor based on nanosheet networks exhibits good sensitivity ({approx}3.991 {mu}A cm{sup -2} mM{sup -1}) and lower detection limit (5 {mu}M), with linearity (R = 0.9925) in short response time (10.0 s). This work demonstrate that the simply synthesized Mg(OH){sub 2} nanosheet networks can effectively be used for the fabrication of efficient ethanol chemical sensors.

  14. Boehringer Ingleheim's selective glucocorticoid receptor agonist development candidate: evaluation of WO2010141331, WO2010141332 and WO2010141333.

    Science.gov (United States)

    Norman, Peter

    2011-07-01

    Three applications from Boehringer Ingelheim all relate to the preparation of non-steroidal glucocorticoid receptor agonists useful in the treatment of inflammatory respiratory diseases. The first two applications claim chiral processes for the preparation of these compounds or intermediates useful therein. These provide two alternative routes, respectively, using achiral and chiral reagents. The third application relates to the preparation of a crystalline salt of the preferred compound on a multi-kilogram scale in micronised form.

  15. Inhibition of oxidative stress-elicited AKT activation facilitates PPARγ agonist-mediated inhibition of stem cell character and tumor growth of liver cancer cells.

    Directory of Open Access Journals (Sweden)

    Lanlan Liu

    Full Text Available Emerging evidence suggests that tumor-initiating cells (TICs are the most malignant cell subpopulation in tumors because of their resistance to chemotherapy or radiation treatment. Targeting TICs may be a key innovation for cancer treatment. In this study, we found that PPARγ agonists inhibited the cancer stem cell-like phenotype and attenuated tumor growth of human hepatocellular carcinoma (HCC cells. Reactive oxygen species (ROS initiated by NOX2 upregulation were partially responsible for the inhibitory effects mediated by PPARγ agonists. However, PPARγ agonist-mediated ROS production significantly activated AKT, which in turn promoted TIC survival by limiting ROS generation. Inhibition of AKT, by either pharmacological inhibitors or AKT siRNA, significantly enhanced PPARγ agonist-mediated inhibition of cell proliferation and stem cell-like properties in HCC cells. Importantly, in nude mice inoculated with HCC Huh7 cells, we demonstrated a synergistic inhibitory effect of the PPARγ agonist rosiglitazone and the AKT inhibitor triciribine on tumor growth. In conclusion, we observed a negative feedback loop between oxidative stress and AKT hyperactivation in PPARγ agonist-mediated suppressive effects on HCCs. Combinatory application of an AKT inhibitor and a PPARγ agonist may provide a new strategy for inhibition of stem cell-like properties in HCCs and treatment of liver cancer.

  16. 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.

  17. STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice

    DEFF Research Database (Denmark)

    Skouboe, Morten K; Knudsen, Alice; Reinert, Line S

    2018-01-01

    In recent years, there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions, including infectious diseases. For instance, Toll-like receptor (TLR) agonists have been evaluated for treatment of genital herpes. However, although the TLR7 agonist imiquimod...... herpes simplex virus (HSV) 2 replication and improved the clinical outcome of infection. More importantly, local application of CDNs at the genital epithelial surface gave rise to local IFN activity, but only limited systemic responses, and this treatment conferred total protection against disease...... to TLRs, STING is expressed broadly, including in epithelial cells. Here we report that natural and non-natural STING agonists strongly induce type I IFNs in human cells and in mice in vivo, without stimulating significant inflammatory gene expression. Systemic treatment with 2'3'-cGAMP reduced genital...

  18. [Development of rapid setting-drying device for herbarium specimens and its application in survey of Chinese materia medica resources in Anhui].

    Science.gov (United States)

    Zheng, Han; Xu, Tao; Li, Chuan-Run; Sun, Xiao-Mei; Xiang, Long; Zhao, Wei-Bo; Liu, He-Ling; Zhou, Jian-Li; Yang, Qing-Shan; Peng, Dai-Yin

    2016-07-01

    Herbarium specimens are the basis for the plant classification and indispensable media in teaching, scientific research and resources investigation. They have also played an important role in identifying and producing traditional Chinese medicine. High-quality herbarium specimens shall meet high requirements for integrity, smoothness, color and fabricating efficiency. Therefore, we designed a rapid setting and drying device for herbarium specimens, which could make the herbarium specimens smooth, colorful and not easy to mildew. In this paper, we pointed out the deficiency of traditional methods in making herbarium specimens, and introduced the structure and working principle of the device. Besides, we also discussed the effect of the device in setting and drying herbarium specimens and its application in the fourth national survey of the Chinese material medica resources (CMMR) in Anhui province. As a result, the device provides new ideas for producing herbarium specimens, with a reasonable design, good uniformity, high efficiency, safety and portability, and so is worthy of promotion and application in the national survey of CMMR. Copyright© by the Chinese Pharmaceutical Association.

  19. 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.

  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. Rapid world modeling

    International Nuclear Information System (INIS)

    Little, Charles; Jensen, Ken

    2002-01-01

    Sandia National Laboratories has designed and developed systems capable of large-scale, three-dimensional mapping of unstructured environments in near real time. This mapping technique is called rapid world modeling and has proven invaluable when used by prototype systems consisting of sensory detection devices mounted on mobile platforms. These systems can be deployed into previously unmapped environments and transmit real-time 3-D visual images to operators located remotely. This paper covers a brief history of the rapid world modeling system, its implementation on mobile platforms, and the current state of the technology. Applications to the nuclear power industry are discussed. (author)

  3. Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda.

    Science.gov (United States)

    Brooker, Simon; Kabatereine, Narcis B; Myatt, Mark; Russell Stothard, J; Fenwick, Alan

    2005-07-01

    Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis.

  4. 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.

  5. 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.  

  6. 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.

  7. 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.

  8. 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....

  9. 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.

  10. Rapid evaporative ionisation mass spectrometry and chemometrics for high-throughput screening of growth promoters in meat producing animals.

    Science.gov (United States)

    Guitton, Yann; Dervilly-Pinel, Gaud; Jandova, Renata; Stead, Sara; Takats, Zoltan; Le Bizec, Bruno

    2018-01-17

    In a proof of concept perspective, Rapid Evaporative Ionisation Mass Spectrometry (REIMS) was explored for the direct analysis of meat samples from β-agonist treated livestock. In this context, the combination of REIMS with untargeted metabolomics was investigated to identify carcasses from treated animals on the basis of a modification of indirect metabolites profile. The REIMS analysis generated specific lipid profiles which enabled the differentiation of meat samples collected from pigs treated with ractopamine via their feeding regime. Furthermore, the strategy was found successful when tested on different muscle types (loin, shoulder and thigh), which further expands its applicability. Classification performances were greater than 95% accurate which fully answers requirements of a screening strategy. This research indicates that REIMS implemented in an untargeted-metabolomics workflow can be considered as a high-throughput and accurate strategy for real-time meat classification in relation to ractopamine (and wider β-agonists) treatment in pig production. This approach may subsequently be implemented as a rapid screening test, at the slaughterhouse or at border inspection points, to detect such practice.

  11. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

    International Nuclear Information System (INIS)

    Tsurugizawa, Tomokazu; Mukai, Hideo

    2005-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERα agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERβ agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERα was performed using purified RC-19 antibody. The localization of ERα (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERα and MAP kinase

  12. A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration.

    Science.gov (United States)

    Vaidya, Aditya S; Peterson, Francis C; Yarmolinsky, Dmitry; Merilo, Ebe; Verstraeten, Inge; Park, Sang-Youl; Elzinga, Dezi; Kaundal, Amita; Helander, Jonathan; Lozano-Juste, Jorge; Otani, Masato; Wu, Kevin; Jensen, Davin R; Kollist, Hannes; Volkman, Brian F; Cutler, Sean R

    2017-11-17

    Increasing drought and diminishing freshwater supplies have stimulated interest in developing small molecules that can be used to control transpiration. Receptors for the plant hormone abscisic acid (ABA) have emerged as key targets for this application, because ABA controls the apertures of stomata, which in turn regulate transpiration. Here, we describe the rational design of cyanabactin, an ABA receptor agonist that preferentially activates Pyrabactin Resistance 1 (PYR1) with low nanomolar potency. A 1.63 Å X-ray crystallographic structure of cyanabactin in complex with PYR1 illustrates that cyanabactin's arylnitrile mimics ABA's cyclohexenone oxygen and engages the tryptophan lock, a key component required to stabilize activated receptors. Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA's carboxylate and C6 methyl groups, respectively. Isothermal titration calorimetry measurements show that cyanabactin's compact structure provides ready access to high ligand efficiency on a relatively simple scaffold. Cyanabactin treatments reduce Arabidopsis whole-plant stomatal conductance and activate multiple ABA responses, demonstrating that its in vitro potency translates to ABA-like activity in vivo. Genetic analyses show that the effects of cyanabactin, and the previously identified agonist quinabactin, can be abolished by the genetic removal of PYR1 and PYL1, which form subclade A within the dimeric subfamily III receptors. Thus, cyanabactin is a potent and selective agonist with a wide spectrum of ABA-like activities that defines subfamily IIIA receptors as key target sites for manipulating transpiration.

  13. A new rapid method for quantification of nitrogen in human serum employing the 14N(p,p' γ)14N reaction: application to human pregnancy

    International Nuclear Information System (INIS)

    Nikkenien, P.; Hyvoenen-Dabek, M.; Raeisaenen, J.; Haenninen, R.; Dabek, J.T.

    1985-01-01

    The total nitrogen concentrations in dried serum from 54 pregnant women and 17 newborn babies were determined by a new application of the 14 N(p,p'γ) 14 N reaction resonance at 3.9 MeV. The samples were bombarded in a He atmosphere by 4.1 MeV protons from a tandem Van de Graaff accelerator. The mean dry-weight nitrogen concentration in serum sampled during early pregnancy (6-12 weeks; 13.9 g per 100 g+-5.4%) was significantly higher than that in serum sampled during late pregnancy (38-42 weeks: 13.0 g per 100 g+-3.9%, p<0.001) than that in serum taken from the umbilical cord (13.3 g per 100 g+-4.6%, p<0.01). The nitrogen levels measured using this rapid nuclear technique, applied for the first time to human serum analysis, agree well with parallel Kjeldahl analyses. (author)

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  16. Rapid MR imaging

    International Nuclear Information System (INIS)

    Edelman, R.R.; Buxton, R.B.; Brady, T.J.

    1988-01-01

    Conventional magnetic resonance (MR) imaging methods typically require several minutes to produce an image, but the periods of respiration, cardiac motion and peristalsis are on the order of seconds or less. The need to reduce motion artifact, as well as the need to reduce imaging time for patient comfort and efficiency, have provided a strong impetus for the development of rapid imaging methods. For abdominal imaging, motion artifacts due to respiration can be significantly reduced by collecting the entire image during one breath hold. For other applications, such as following the kinetics of administered contrast agents, rapid imaging is essential to achieve adequate time resolution. A shorter imaging time entails a cost in image signal/noise (S/N), but improvements in recent years in magnet homogeneity, gradient and radiofrequency coil design have led to steady improvements in S/N and consequently in image quality. For many chemical applications the available S/N is greater than needed, and a trade-off of lower S/N for a shorter imaging time is acceptable. In this chapter, the authors consider the underlying principles of rapid imaging as well as clinical applications of these methods. The bulk of this review concentrates on short TR imaging, but methods that provide for a more modest decrease in imaging time as well as or those that dramatically shorten the imaging time to tens of milliseconds are also discussed

  17. Rapid synthesis and characterization of hybrid ZnO@Au core–shell nanorods for high performance, low temperature NO{sub 2} gas sensor applications

    Energy Technology Data Exchange (ETDEWEB)

    Ponnuvelu, Dinesh Veeran [Nanosensor Laboratory, PSG Institute of Advanced Studies, Coimbatore 641 004 (India); Pullithadathil, Biji, E-mail: bijuja123@yahoo.co.in [Nanosensor Laboratory, PSG Institute of Advanced Studies, Coimbatore 641 004 (India); Prasad, Arun K.; Dhara, Sandip [Surface and Nanoscience Division, Indira Gandhi Center for Atomic Research, Kalpakkam (India); Ashok, Anuradha [Nanosensor Laboratory, PSG Institute of Advanced Studies, Coimbatore 641 004 (India); Mohamed, Kamruddin; Tyagi, Ashok Kumar [Surface and Nanoscience Division, Indira Gandhi Center for Atomic Research, Kalpakkam (India); Raj, Baldev [Nanosensor Laboratory, PSG Institute of Advanced Studies, Coimbatore 641 004 (India)

    2015-11-15

    Graphical abstract: - Highlights: • Hybrid ZnO@Au core–shell nanorods were developed using rapid chemical method that can be used as a high performance, low temperature NO{sub 2} gas sensor. • Surface defect analysis (PL and XPS) clearly illustrates the presence of surface oxygen species and Zn interstitials involved in charge transport properties in-turn affecting gas sensing properties. • Hybrid ZnO@Au core–shell nanorods establish enhanced gas sensing performance at 150 °C compared to ZnO (300 °C) with a lower detection limit of 500 ppb using conventional electrodes. • The enhanced performance of ZnO@Au core–shell nanorods based sensor was owing to the presence of Au nanoclusters on the surface of ZnO nanorods which is attributed to the formation of Schottky contacts at the interfaces leading to sensitization effects. • The hybrid material found to be selective toward NO{sub 2} gas and highly stable in nature. - Abstract: A rapid synthesis route for hybrid ZnO@Au core–shell nanorods has been realized for ultrasensitive, trace-level NO{sub 2} gas sensor applications. ZnO nanorods and hybrid ZnO@Au core–shell nanorods are structurally analyzed using X-ray diffraction (XRD), high resolution transmission electron microscopy (HR-TEM) and X-ray photoelectron spectroscopy (XPS). Optical characterization using UV–visible (UV–vis), photoluminescence (PL) and Raman spectroscopies elucidate alteration in the percentage of defect and charge transport properties of ZnO@Au core–shell nanorods. The study reveals the accumulation of electrons at metal–semiconductor junctions leading to upward band bending for ZnO and thus favors direct electron transfer from ZnO to Au nanoclusters, which mitigates charge carrier recombination process. The operating temperature of ZnO@Au core–shell nanorods based sensor significantly decreased to 150 °C compared to alternate NO{sub 2} sensors (300 °C). Moreover, a linear sensor response in the range of 0.5–5

  18. Species detection using HyBeacon(®) probe technology: Working towards rapid onsite testing in non-human forensic and food authentication applications.

    Science.gov (United States)

    Dawnay, Nick; Hughes, Rebecca; Court, Denise Syndercombe; Duxbury, Nicola

    2016-01-01

    Identifying individual species or determining species' composition in an unknown sample is important for a variety of forensic applications. Food authentication, monitoring illegal trade in endangered species, forensic entomology, sexual assault case work and counter terrorism are just some of the fields that can require the detection of the biological species present. Traditional laboratory based approaches employ a wide variety of tools and technologies and exploit a number of different species specific traits including morphology, molecular differences and immuno-chemical analyses. A large number of these approaches require laboratory based apparatus and results can take a number of days to be returned to investigating authorities. Having a presumptive test for rapid identification could lead to savings in terms of cost and time and allow sample prioritisation if confirmatory testing in a laboratory is required later. This model study describes the development of an assay using a single HyBeacon(®) probe and melt curve analyses allowing rapid screening and authentication of food products labelled as Atlantic cod (Gadus morhua). Exploiting melt curve detection of species specific SNP sites on the COI gene the test allows detection of a target species (Atlantic cod) and closely related species which may be used as substitutes. The assay has been designed for use with the Field Portable ParaDNA system, a molecular detection platform for non-expert users. The entire process from sampling to result takes approximately 75min. Validation studies were performed on both single source genomic DNA, mixed genomic DNA and commercial samples. Data suggests the assay has a lower limit of detection of 31 pg DNA. The specificity of the assay to Atlantic cod was measured by testing highly processed food samples including frozen, defrosted and cooked fish fillets as well as fish fingers, battered fish fillet and fish pie. Ninety-six (92.7%) of all Atlantic cod food products

  19. 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.

  20. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

    Science.gov (United States)

    Fay, Jonathan F; Farrens, David L

    2012-09-28

    Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

  1. Long-term optimization of the transport sector to address greenhouse gas reduction targets under rapid growth. Application of an energy system model for Gauteng province, South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Tomaschek, Jan

    2013-12-11

    The transport sector is seen as one of the key factors for driving future energy consumption and greenhouse gas (GHG) emissions. Especially in developing countries, significant growth in transport demand is expected. Gauteng province, as the economic centre of South Africa and transport hub for the whole of southern Africa, is one emerging urban region that faces rapid growth. However, the province is on its way to playing a leading role for supporting ways to adapt to climate change and mitigate GHG emissions. Conversely, there is a lack of scientific research on the promising measures for GHG mitigation in the transport sector. For the rapidly growing transport sector of the province in particular, research is focused primarily on extending and structuring the road infrastructure. Moreover, it is important that the transport sector is considered as part of the whole energy system, as significant contributions to GHG emissions and the associated costs arise from energy supply, provision and conversion. This research is the first application of an integrated energy system model (i.e. the TIMES-GEECO model) for the optimization of the transport sector of Gauteng. Optimizing energy system models allows finding least-cost measures for various scenarios, by considering dependencies and interlinkages in the energy system as well as environmental constraints. To do so, the transport sector and the energy supply sector had to be incorporated into the model application in terms of the characteristics of a developing urban region, which includes all relevant transport modes, vehicle technologies, fuel options, vehicle-to-grid energy storage, the consideration of road types as well as explicit expansions of the public transport system and income-dependent travel demand modelling. Additionally, GHG mitigation options outside the provincial boundaries were incorporated to allow for mitigation at least cost and to consider regional resource availability. Moreover, in TIMES

  2. Application of next-generation sequencing for rapid marker development in molecular plant breeding: a case study on anthracnose disease resistance in Lupinus angustifolius L.

    Directory of Open Access Journals (Sweden)

    Yang Huaan

    2012-07-01

    fingerprinting method for marker-assisted selection in the Australian national lupin breeding program. Conclusions We demonstrated that more than 30 molecular markers linked to a target gene of agronomic trait of interest can be identified from a small portion (1/8 of one sequencing run on HiSeq2000 by applying NGS based RAD sequencing in marker development. The markers developed by the strategy described in this study are all co-dominant SNP markers, which can readily be converted into high throughput multiplex format or low-cost, simple PCR-based markers desirable for large scale marker implementation in plant breeding programs. The high density and closely linked molecular markers associated with a target trait help to overcome a major bottleneck for implementation of molecular markers on a wide range of germplasm in breeding programs. We conclude that application of NGS based RAD sequencing as DNA fingerprinting is a very rapid and cost-effective strategy for marker development in molecular plant breeding. The strategy does not require any prior genome knowledge or molecular information for the species under investigation, and it is applicable to other plant species.

  3. Long-term optimization of the transport sector to address greenhouse gas reduction targets under rapid growth. Application of an energy system model for Gauteng province, South Africa

    International Nuclear Information System (INIS)

    Tomaschek, Jan

    2013-01-01

    The transport sector is seen as one of the key factors for driving future energy consumption and greenhouse gas (GHG) emissions. Especially in developing countries, significant growth in transport demand is expected. Gauteng province, as the economic centre of South Africa and transport hub for the whole of southern Africa, is one emerging urban region that faces rapid growth. However, the province is on its way to playing a leading role for supporting ways to adapt to climate change and mitigate GHG emissions. Conversely, there is a lack of scientific research on the promising measures for GHG mitigation in the transport sector. For the rapidly growing transport sector of the province in particular, research is focused primarily on extending and structuring the road infrastructure. Moreover, it is important that the transport sector is considered as part of the whole energy system, as significant contributions to GHG emissions and the associated costs arise from energy supply, provision and conversion. This research is the first application of an integrated energy system model (i.e. the TIMES-GEECO model) for the optimization of the transport sector of Gauteng. Optimizing energy system models allows finding least-cost measures for various scenarios, by considering dependencies and interlinkages in the energy system as well as environmental constraints. To do so, the transport sector and the energy supply sector had to be incorporated into the model application in terms of the characteristics of a developing urban region, which includes all relevant transport modes, vehicle technologies, fuel options, vehicle-to-grid energy storage, the consideration of road types as well as explicit expansions of the public transport system and income-dependent travel demand modelling. Additionally, GHG mitigation options outside the provincial boundaries were incorporated to allow for mitigation at least cost and to consider regional resource availability. Moreover, in TIMES

  4. 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...

  5. 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.

  6. 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

  7. 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

  8. Rapid jetting status inspection and accurate droplet volume measurement for a piezo drop-on-demand inkjet print head using a scanning mirror for display applications

    Science.gov (United States)

    Shin, Dong-Youn; Kim, Minsung

    2017-02-01

    Despite the inherent fabrication simplicity of piezo drop-on-demand inkjet printing, the non-uniform deposition of colourants or electroluminescent organic materials leads to faulty display products, and hence, the importance of rapid jetting status inspection and accurate droplet volume measurement increases from a process perspective. In this work, various jetting status inspections and droplet volume measurement methods are reviewed by discussing their advantages and disadvantages, and then, the opportunities for the developed prototype with a scanning mirror are explored. This work demonstrates that jetting status inspection of 384 fictitious droplets can be performed within 17 s with maximum and minimum measurement accuracies of 0.2 ± 0.5 μ m for the fictitious droplets of 50 μ m in diameter and -1.2 ± 0.3 μ m for the fictitious droplets of 30 μ m in diameter, respectively. In addition to the new design of an inkjet monitoring instrument with a scanning mirror, two novel methods to accurately measure the droplet volume by amplifying a minute droplet volume difference and then converting to other physical properties are suggested and the droplet volume difference of ±0.3% is demonstrated to be discernible using numerical simulations, even with the low measurement accuracy of 1 μ m . When the fact is considered that the conventional vision-based method with a CCD camera requires the optical measurement accuracy less than 25 nm to measure the volume of an in-flight droplet in the nominal diameter of 50 μ m at the same volume measurement accuracy, the suggested method with the developed prototype offers a whole new opportunity to inkjet printing for display applications.

  9. Rapid colorimetric detection of p53 protein function using DNA-gold nanoconjugates with applications for drug discovery and cancer diagnostics.

    Science.gov (United States)

    Assah, Enock; Goh, Walter; Zheng, Xin Ting; Lim, Ting Xiang; Li, Jun; Lane, David; Ghadessy, Farid; Tan, Yen Nee

    2018-05-05

    The tumor suppressor protein p53 plays a central role in preventing cancer through interaction with DNA response elements (REs) to regulate target gene expression in cells. Due to its significance in cancer biology, relentless efforts have been directed toward understanding p53-DNA interactions for the development of cancer therapeutics and diagnostics. In this paper, we report a rapid, label-free and versatile colorimetric assay to detect wildtype p53 DNA-binding function in complex solutions. The assay design is based on a concept that alters interparticle-distances between RE-AuNPs from a crosslinking effect induced through tetramerization of wildtype p53 protein (p53-WT) upon binding to canonical DNA motifs modified on gold nanoparticles (RE-AuNPs). This leads to a visible solution color change from red to blue, which is quantifiable by the UV- visible absorption spectra with a detection limit of 5 nM. Contrastingly, no color change was observed for the binding-deficient p53 mutants and non-specific proteins due to their inability to crosslink RE-AuNPs. Based on this sensing principle, we further demonstrate its utility for fast detection of drug-induced DNA binding function to cancer-associated Y220C mutant p53 protein using well-established reactivating compounds. By exploiting the dominant-negative property of mutant p53 over p53-WT and interactions with RE-AuNPs, this assay is configurable to detect low numbers of mutant p53 expressing cells in miniscule sample fractions obtained from typical core needle biopsy-sized tissues without signal attrition, alluding to the potential for biopsy sampling in cancer diagnostics or for defining cancer margins. This nanogold enabled colorimetric assay provides a facile yet robust method for studying important parameters influencing p53-DNA interactions with great promises for clinically pertinent applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

    Science.gov (United States)

    Guohua, Hui; Hongyang, Lu; Zhiming, Jiang; Danhua, Zhu; Haifang, Wan

    2017-11-15

    Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. SU-F-303-11: Implementation and Applications of Rapid, SIFT-Based Cine MR Image Binning and Region Tracking

    Energy Technology Data Exchange (ETDEWEB)

    Mazur, T; Wang, Y; Fischer-Valuck, B; Acharya, S; Kashani, R; Li, H; Yang, D; Zoberi, I; Thomas, M; Mutic, S; Li, H [Washington University School of Medicine, St. Louis, MO (United States)

    2015-06-15

    Purpose: To develop a novel and rapid, SIFT-based algorithm for assessing feature motion on cine MR images acquired during MRI-guided radiotherapy treatments. In particular, we apply SIFT descriptors toward both partitioning cine images into respiratory states and tracking regions across frames. Methods: Among a training set of images acquired during a fraction, we densely assign SIFT descriptors to pixels within the images. We cluster these descriptors across all frames in order to produce a dictionary of trackable features. Associating the best-matching descriptors at every frame among the training images to these features, we construct motion traces for the features. We use these traces to define respiratory bins for sorting images in order to facilitate robust pixel-by-pixel tracking. Instead of applying conventional methods for identifying pixel correspondences across frames we utilize a recently-developed algorithm that derives correspondences via a matching objective for SIFT descriptors. Results: We apply these methods to a collection of lung, abdominal, and breast patients. We evaluate the procedure for respiratory binning using target sites exhibiting high-amplitude motion among 20 lung and abdominal patients. In particular, we investigate whether these methods yield minimal variation between images within a bin by perturbing the resulting image distributions among bins. Moreover, we compare the motion between averaged images across respiratory states to 4DCT data for these patients. We evaluate the algorithm for obtaining pixel correspondences between frames by tracking contours among a set of breast patients. As an initial case, we track easily-identifiable edges of lumpectomy cavities that show minimal motion over treatment. Conclusions: These SIFT-based methods reliably extract motion information from cine MR images acquired during patient treatments. While we performed our analysis retrospectively, the algorithm lends itself to prospective motion

  12. Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens.

    Science.gov (United States)

    Moulin, Morgane; Alguacil, Javier; Gu, Siyi; Mehtougui, Asmaa; Adams, Erin J; Peyrottes, Suzanne; Champagne, Eric

    2017-12-01

    Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.

  13. 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.

  14. The effects of a slow release GnRH agonist implant on male rabbits

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

    2015-01-01

    Surgical castration is done in male pet rabbits for reproduction control, to reduce inter-male aggression and to control hyper-sexuality, territory marking and aggression against humans. Alternatives to surgical castration are requested because of a relatively great anaesthetic risk in rabbits....... Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...

  15. Radiolabelled D2 agonists as prolactinoma imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Otto, C.A.

    1989-08-01

    During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB, like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of evaluation of quaternized mAChR ligands in the heart is included. In a limited series of such ligands, we have observed a single binding site and a difference in B{sub max} values: QNB competition studies yield larger B{sub max} values than studies with {sup 3}H-NMS. Progress in the synthesis of D{sub 2} agonists includes solving a synthetic problem and preparation of the cold'' analogue of N-0437 using procedures applicable to eventual synthesis with {sup 11}C-CH{sub 3}I. 2 refs., 5 figs., 1 tab.

  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. Identification of benzothiazole derivatives and polycyclic aromatic hydrocarbons as aryl hydrocarbon receptor agonists present in tire extracts.

    Science.gov (United States)

    He, Guochun; Zhao, Bin; Denison, Michael S

    2011-08-01

    Leachate from rubber tire material contains a complex mixture of chemicals previously shown to produce toxic and biological effects in aquatic organisms. The ability of these leachates to induce Ah receptor (AhR)-dependent cytochrome P4501A1 expression in fish indicated the presence of AhR active chemicals, but the responsible chemicals and their direct interaction with the AhR signaling pathway were not examined. Using a combination of AhR-based bioassays, we have demonstrated the ability of tire extract to stimulate both AhR DNA binding and AhR-dependent gene expression and confirmed that the responsible chemicals were metabolically labile. The application of CALUX (chemical-activated luciferase gene expression) cell bioassay-driven toxicant identification evaluation not only revealed that tire extract contained a variety of known AhR-active polycyclic aromatic hydrocarbons but also identified 2-methylthiobenzothiazole and 2-mercaptobenzothiazole as AhR agonists. Analysis of a structurally diverse series of benzothiazoles identified many that could directly stimulate AhR DNA binding and transiently activate the AhR signaling pathway and identified benzothiazoles as a new class of AhR agonists. In addition to these compounds, the relatively high AhR agonist activity of a large number of fractions strongly suggests that tire extract contains a large number of physiochemically diverse AhR agonists whose identities and toxicological/biological significances are unknown. Copyright © 2011 SETAC.

  19. [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.

  20. 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

  1. Role and development of GLP-1 receptor agonists in the management of diabetes

    Directory of Open Access Journals (Sweden)

    Chee W Chia

    2009-05-01

    Full Text Available Chee W Chia, Josephine M EganNational Institutes of Health, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USAAbstract: Glucagon-like peptide-1 (GLP-1 is a hormone secreted from enteroendocrine L cells of the intestine in response to food. Exogenous GLP-1 administration at pharmacological doses results in many effects that are beneficial for treating type 2 diabetes, these include: (1 an increase in insulin secretion from β cells; (2 a suppression of glucagon secretion from α cells in the presence of hyperglycemia but not hypoglycemia; (3 a delay in gastric emptying and gut motility which in turns delays absorption of ingested nutrients and dampens post-prandial glucose excursion; and (4 an increase in the duration of postprandial satiety therefore suppressing appetite and decreasing food intake which eventually leads to weight loss. However, GLP-1 is subject to rapid enzymatic degradation, and therefore, not suitable for long-term treatment. A synthetic enzyme-resistant GLP-1 receptor agonist that reproduces the biological effects of GLP-1 is in use and more are under development. This review aims at providing a summary of the properties of GLP-1 and the development of GLP-1-based therapies for treatment of diabetes.Keywords: incretin, GLP-1, GLP-1R agonist, diabetes

  2. Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Scherer, N.M.; Nathanson, N.M.

    1990-01-01

    Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

  3. Effect of α7 nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    International Nuclear Information System (INIS)

    Welch, Kevin D.; Pfister, James A.; Lima, Flavia G.; Green, Benedict T.; Gardner, Dale R.

    2013-01-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  4. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on decays of excited strange mesons in the extended NJL model, production of heavy evaporation residues in the reactions induced by an extracted 48 Ca beam on a 208 Pb target, scaling behaviour of tensor analyzing power (A yy ) in the inelastic scattering or relativistic deuterons,two-photon collisions at very low Q 2 from LEP2: forthcoming results, high magnetic field uniformity superconducting magnet for a movable polarized target, multichannel time-to-digital converter for drift detector and wavelet-analysis: application to Gaussian signals

  5. Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

    Science.gov (United States)

    Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

    2012-12-01

    Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

  6. 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...

  7. 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...

  8. 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...

  9. PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.

    Science.gov (United States)

    Di Loreto, S; D'Angelo, B; D'Amico, M A; Benedetti, E; Cristiano, L; Cinque, B; Cifone, M G; Cerù, M P; Festuccia, C; Cimini, A

    2007-06-01

    Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures. Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells. The results obtained demonstrate that many, but not all, oleic acid effects are mediated by PPARbeta and support a role for PPARbeta in neuronal differentiation strongly pointing towards PPAR ligands as new therapeutic strategies against progression and recurrences of neuroblastoma.

  10. 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.

  11. 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.

  12. Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus

    International Nuclear Information System (INIS)

    Murakami, Gen; Tsurugizawa, Tomokazu; Hatanaka, Yusuke; Komatsuzaki, Yoshimasa; Tanabe, Nobuaki; Mukai, Hideo; Hojo, Yasushi; Kominami, Shiro; Yamazaki, Takeshi; Kimoto, Tetsuya; Kawato, Suguru

    2006-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17β-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erk MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ERα agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol

  13. 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.

  14. (-)-N-[(11)C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors.

    Science.gov (United States)

    Hwang, D R; Kegeles, L S; Laruelle, M

    2000-08-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [(11)C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[(11)C]NPA was prepared by reacting norapomorphine with [(11)C]propionyl chloride and a lithium aluminum hydride reduction. [(11)C]Propionyl chloride was prepared by reacting [(11)C]CO(2) with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[(11)C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700+/-1900 mCi/micromol ( N=7; ranged 110-5200 mCi/micromol at EOS). Rodent biodistribution studies showed high uptake of [(11)C](-)-NPA in D(2) receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[(11)C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86+/-0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D(2) receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D(2) agonist. (-)-[(11)C]NPA is a promising new D(2) agonist PET tracer for probing D(2) receptors in vivo using PET.

  15. A rapid and simple determination of A77 1726 in human serum by high-performance liquid chromatography and its application for optimization of leflunomide therapy

    NARCIS (Netherlands)

    van Roon, EN; Yska, JP; Raemaekers, J; Jansen, TLTA; van Wanrooy, M; Brouwers, JRBJ

    2004-01-01

    Leflunomide is a disease-modifying antirheumatic drug, which is bioactivated by fort-nation of A77 1726. In this study a rapid and simple quantitative assay using a reversed phase HPLC-UV method is validated for detection of A77 1726 in human serum. The HPLC-UV method uses a mobile phase consisting

  16. Single and Double Infrared Transitions in Rapid Vapor Deposited Parahydrogen Solids: Application to Sample Thickness Determination and Quantitative Infrared Absorption Spectroscopy

    National Research Council Canada - National Science Library

    Tam, Simon

    2001-01-01

    ...) solid from its infrared (IR) absorption spectrum. Millimeters-thick pH2 solids of exceptional optical clarity can be produced by the rapid vapor deposition method M.E. Fajardo and S. Tam, J. Chem. Phys. 108, 4237 (1998...

  17. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

    Directory of Open Access Journals (Sweden)

    Betul Kul Babur

    Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

  18. Model-Based Discovery of Synthetic Agonists for the Zn2+-Sensing G-Protein-Coupled Receptor 39 (GPR39) Reveals Novel Biological Functions

    DEFF Research Database (Denmark)

    Frimurer, Thomas M.; Mende, Franziska; Graae, Anne-Sofie

    2017-01-01

    binding to other receptors with similar binding pockets to select iterative series of mini-libraries. These libraries were cherry-picked from all com. available synthetic compds. A total of only 520 compds. were tested in vitro, making this method broadly applicable for tool compd. development. The compds....... of the initial library were inactive when tested alone, but lead compds. were identified using Zn2 as an allosteric enhancer. Highly selective, highly potent Zn2-independent GPR39 agonists were found in subsequent mini-libraries. These agonists identified GPR39 as a novel regulator of gastric somatostatin...

  19. How Rapid is Rapid Prototyping? Analysis of ESPADON Programme Results

    Directory of Open Access Journals (Sweden)

    Ian D. Alston

    2003-05-01

    Full Text Available New methodologies, engineering processes, and support environments are beginning to emerge for embedded signal processing systems. The main objectives are to enable defence industry to field state-of-the-art products in less time and with lower costs, including retrofits and upgrades, based predominately on commercial off the shelf (COTS components and the model-year concept. One of the cornerstones of the new methodologies is the concept of rapid prototyping. This is the ability to rapidly and seamlessly move from functional design to the architectural design to the implementation, through automatic code generation tools, onto real-time COTS test beds. In this paper, we try to quantify the term “rapid” and provide results, the metrics, from two independent benchmarks, a radar and sonar beamforming application subset. The metrics show that the rapid prototyping process may be sixteen times faster than a conventional process.

  20. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  1. Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis.

    Science.gov (United States)

    Ouvry, Gilles; Atrux-Tallau, Nicolas; Bihl, Franck; Bondu, Aline; Bouix-Peter, Claire; Carlavan, Isabelle; Christin, Olivier; Cuadrado, Marie-Josée; Defoin-Platel, Claire; Deret, Sophie; Duvert, Denis; Feret, Christophe; Forissier, Mathieu; Fournier, Jean-François; Froude, David; Hacini-Rachinel, Fériel; Harris, Craig Steven; Hervouet, Catherine; Huguet, Hélène; Lafitte, Guillaume; Luzy, Anne-Pascale; Musicki, Branislav; Orfila, Danielle; Ozello, Benjamin; Pascau, Coralie; Pascau, Jonathan; Parnet, Véronique; Peluchon, Guillaume; Pierre, Romain; Piwnica, David; Raffin, Catherine; Rossio, Patricia; Spiesse, Delphine; Taquet, Nathalie; Thoreau, Etienne; Vatinel, Rodolphe; Vial, Emmanuel; Hennequin, Laurent François

    2018-02-20

    With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL-23-induced mouse skin inflammation model. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. 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

  3. Clinical Application of Picodroplet Digital PCR Technology for Rapid Detection of EGFR T790M in Next-Generation Sequencing Libraries and DNA from Limited Tumor Samples.

    Science.gov (United States)

    Borsu, Laetitia; Intrieri, Julie; Thampi, Linta; Yu, Helena; Riely, Gregory; Nafa, Khedoudja; Chandramohan, Raghu; Ladanyi, Marc; Arcila, Maria E

    2016-11-01

    Although next-generation sequencing (NGS) is a robust technology for comprehensive assessment of EGFR-mutant lung adenocarcinomas with acquired resistance to tyrosine kinase inhibitors, it may not provide sufficiently rapid and sensitive detection of the EGFR T790M mutation, the most clinically relevant resistance biomarker. Here, we describe a digital PCR (dPCR) assay for rapid T790M detection on aliquots of NGS libraries prepared for comprehensive profiling, fully maximizing broad genomic analysis on limited samples. Tumor DNAs from patients with EGFR-mutant lung adenocarcinomas and acquired resistance to epidermal growth factor receptor inhibitors were prepared for Memorial Sloan-Kettering-Integrated Mutation Profiling of Actionable Cancer Targets sequencing, a hybrid capture-based assay interrogating 410 cancer-related genes. Precapture library aliquots were used for rapid EGFR T790M testing by dPCR, and results were compared with NGS and locked nucleic acid-PCR Sanger sequencing (reference high sensitivity method). Seventy resistance samples showed 99% concordance with the reference high sensitivity method in accuracy studies. Input as low as 2.5 ng provided a sensitivity of 1% and improved further with increasing DNA input. dPCR on libraries required less DNA and showed better performance than direct genomic DNA. dPCR on NGS libraries is a robust and rapid approach to EGFR T790M testing, allowing most economical utilization of limited material for comprehensive assessment. The same assay can also be performed directly on any limited DNA source and cell-free DNA. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  4. Dependence of mitochondrial and cytosolic adenine nucleotides on oxygen partial pressure in isolated hepatocytes. Application of a new rapid high pressure filtration technique for fractionation.

    OpenAIRE

    Hummerich, H; de Groot, H; Noll, T; Soboll, S

    1988-01-01

    By using a new rapid high pressure filtration technique, mitochondrial and cytosolic ATP and ADP contents were determined in isolated hepatocytes at different oxygen partial pressures. At 670 mmHg, subcellular adenine nucleotide contents and ATP/ADP ratios were comparable with values obtained with the digitonin fractionation technique. However at lower oxygen partial pressure ADP appears to be rephosphorylated during digitonin fractionation whereas with high pressure filtration fractionation ...

  5. Rapid data analysis in manifold ranges of application. IT solutions for the energy data management; Schnelle Datenanalyse in vielfaeltigen Einsatzbereichen. IT-Loesung fuer das Energiedatenmanagement

    Energy Technology Data Exchange (ETDEWEB)

    Bock, Joachim [Stadtwerke Niebuell-Netz GmbH, Niebuell (Germany)

    2013-03-11

    Data management is a challenge for all energy suppliers. Whether master data, device management, malfunction analysis, network planning, customer management or billings - quite often, huge amounts of data have to be controlled and evaluated flexibly. The industry systems are not suitable for all tasks. Microsoft Excel is overstrained with the flood of data. Thus, the public utility Niebuell (Federal Republic of Germany) applies an easy to handle analysis tool which is designed for a rapid and easy analysis of huge amounts of data.

  6. 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

  7. Rapid deployment intrusion detection system

    International Nuclear Information System (INIS)

    Graham, R.H.

    1997-01-01

    A rapidly deployable security system is one that provides intrusion detection, assessment, communications, and annunciation capabilities; is easy to install and configure; can be rapidly deployed, and is reusable. A rapidly deployable intrusion detection system (RADIDS) has many potential applications within the DOE Complex: back-up protection for failed zones in a perimeter intrusion detection and assessment system, intrusion detection and assessment capabilities in temporary locations, protection of assets during Complex reconfiguration, and protection in hazardous locations, protection of assets during Complex reconfiguration, and protection in hazardous locations. Many DOE user-need documents have indicated an interest in a rapidly deployable intrusion detection system. The purpose of the RADIDS project is to design, develop, and implement such a system. 2 figs

  8. A completely automatic operation type super-safe fast reactor, RAPID. Its application to dispersion source on lunar and earth surfaces

    International Nuclear Information System (INIS)

    Kanbe, Mitsuru; Tsunoda, Hirokazu; Mishima, Kaichiro; Kawasaki, Akira; Iwamura, Takamichi

    2002-01-01

    At a viewpoint of flexible measures to future electric power demands, expectation onto a small-scale reactor for dispersion source is increasing gradually. This is thought to increase its importance not only for a source at proximity of its market in advanced nations but also for the one in developing nations. A study on development of the completely automatic operation type super-safe fast reactor, RAPID (refueling by all pins integrated design) has been carried out as a part of the nuclear energy basic research promoting system under three years project since 1999 by a trust of the Japan Atomic Energy Research Institute to a group of the Central Research Institute of Electric Power Industry (CRIEPI) and so on. As the reactor is a lithium cooled fast reactor with 200 Kw of electric output supposing to use at lunar surface, it can be applied to a super-small scale nuclear reactor on the earth, and has feasibility to become a new option of future nuclear power generation. On the other hand, CRIEPI has investigated on various types of fast reactors (RAPID series) for fast reactor for dispersion source on the earth. Here was introduced on such super-safe fast reactors at a center of RAPID-L. (G.K.)

  9. Rapid localized deactivation of self-assembled monolayers by propagation-controlled laser-induced plasma and its application to self-patterning of electronics and biosensors

    Science.gov (United States)

    Kim, Jongsu; Kwon, Seung-Gab; Back, Seunghyun; Kang, Bongchul

    2018-03-01

    We present a novel laser-induced surface treatment process to rapidly control the spatial wettabilities of various functional solutions with submicron to micron resolutions. Ultrathin hydrophobic self-assembled monolayers (SAMs) that little absorb typical laser lights due to short penetration depth were selectively deactivated by instantaneous interaction with laser-induced metallic plasmas. The spatial region of the deactivated SAM, which corresponds to process resolution, is adjustable by controlling the spatial propagation of the plasma. This method leads to the parallel formation of hydrophilic functional solutions on glass substrates with a minimum resolution on the submicron scale. To show its feasibility in device engineering fields, this method was applied to the cost-effective fabrication of electronics and biosensors. Rapid self-patterning of electronic and biological functional solutions (silver nanoparticle solution and streptavidin protein solution) was successfully realized by selective deactivation of two different SAMs (tridecafluoro-1,1,2,2-tetrahydrooctyltrichlorosilane (FOTS) for electronics and the hetero-hybrid SAM (octadecyltrichlorosilane (OTS)/2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG)) for biosensors). As a result, this method can be exploited for the rapid and low-cost fabrication of various thin film devices such as electronics, biosensors, energy, displays, and photonics.

  10. Application of analytical capability to predict rapid cladding cooling and quench during the blowdown phase of a large break loss-of-coolant accident

    International Nuclear Information System (INIS)

    Aksan, S.N.; Tolman, E.L.; Nelson, R.A.

    1983-01-01

    Large-break Experiments L2-2 and L2-3 conducted in the Loss-of-Fluid Test (LOFT) facility experienced core-wide rapid quenches early in the blowdown transients. To further investigate rapid cladding quenches, separate effects experiments using Semiscale solid-type electric heater rods were conducted in the LOFT Test Support Facility (LTSF) over a wide range of inlet coolant conditions. The analytical capability to predict the cladding temperature response from selected LTSF experiments estimated to bound the hydraulic conditions causing the LOFT early blowdown quenches was investigated using the RELAP4 computer code and was shown to be acceptable over the film boiling cooldown phase. This analytical capability was then used to investigate the behavior of nuclear fuel rods under the same hydraulic conditions. The calculations show that, under rapid cooling conditions, the behaviors of nuclear and electrical heater rods are significantly different because the nuclear rods are conduction limited, while the electrical rods are convection limited

  11. The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

    Science.gov (United States)

    Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

    2015-01-01

    We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. Dopamine D2 receptor radiotracers [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, Patrick N. [Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada)], E-mail: patrick.mccormick@camhpet.ca; Kapur, Shitij [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada)

    2008-01-15

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [{sup 11}C](+)-PHNO ([{sup 11}C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [{sup 3}H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for {sup 11}C and {sup 3}H. The specific binding ratio {l_brace}SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum){r_brace} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs responded indistinguishably in terms of both ED{sub 50} and Hill slope (e.g., (-)-NPA ED{sub 50} values are 0.027 and 0.023 mg/kg for [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride, respectively). In response to AMPH challenge, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [{sup 11}C](+)-PHNO- and [{sup 3}H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo

  17. Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    International Nuclear Information System (INIS)

    McCormick, Patrick N.; Kapur, Shitij; Seeman, Philip; Wilson, Alan A.

    2008-01-01

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [ 11 C](+)-PHNO ([ 11 C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [ 3 H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [ 11 C](+)-PHNO and [ 3 H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for 11 C and 3 H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs responded indistinguishably in terms of both ED 50 and Hill slope (e.g., (-)-NPA ED 50 values are 0.027 and 0.023 mg/kg for [ 11 C](+)-PHNO and [ 3 H]raclopride, respectively). In response to AMPH challenge, [ 11 C](+)-PHNO and [ 3 H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [ 11 C](+)-PHNO- and [ 3 H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments

  18. 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...

  19. 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.

  20. 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....

  1. 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...

  2. 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.

  3. 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.

  4. 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)

  5. 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.

  6. 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

  7. JINR Rapid Communications. Collection

    International Nuclear Information System (INIS)

    1994-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on quasi-classical description of one-nucleon transfer reactions with heavy ions, elastic and inelastic scattering in the high energy approximation, experimental study of fission and evaporation cross sections for 6 He + 209 Bi reaction, d ↑ + 12 C → p + X at Θ p = 0 o in the region of high internal momenta in the deuteron, the Nuclotron internal targets, actively screened superconducting magnets, using of polarized target in backward elastic dp scattering, application of transputers in the data acquisition system of the INESS-ALPHA spectrometer, narrow dibaryon resonances with isotopic spin I=2. 93 refs., 27 figs., 4 tabs

  8. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  9. Application of NIRS coupled with PLS regression as a rapid, non-destructive alternative method for quantification of KBA in Boswellia sacra

    Science.gov (United States)

    Al-Harrasi, Ahmed; Rehman, Najeeb Ur; Mabood, Fazal; Albroumi, Muhammaed; Ali, Liaqat; Hussain, Javid; Hussain, Hidayat; Csuk, René; Khan, Abdul Latif; Alam, Tanveer; Alameri, Saif

    2017-09-01

    In the present study, for the first time, NIR spectroscopy coupled with PLS regression as a rapid and alternative method was developed to quantify the amount of Keto-β-Boswellic Acid (KBA) in different plant parts of Boswellia sacra and the resin exudates of the trunk. NIR spectroscopy was used for the measurement of KBA standards and B. sacra samples in absorption mode in the wavelength range from 700-2500 nm. PLS regression model was built from the obtained spectral data using 70% of KBA standards (training set) in the range from 0.1 ppm to 100 ppm. The PLS regression model obtained was having R-square value of 98% with 0.99 corelationship value and having good prediction with RMSEP value 3.2 and correlation of 0.99. It was then used to quantify the amount of KBA in the samples of B. sacra. The results indicated that the MeOH extract of resin has the highest concentration of KBA (0.6%) followed by essential oil (0.1%). However, no KBA was found in the aqueous extract. The MeOH extract of the resin was subjected to column chromatography to get various sub-fractions at different polarity of organic solvents. The sub-fraction at 4% MeOH/CHCl3 (4.1% of KBA) was found to contain the highest percentage of KBA followed by another sub-fraction at 2% MeOH/CHCl3 (2.2% of KBA). The present results also indicated that KBA is only present in the gum-resin of the trunk and not in all parts of the plant. These results were further confirmed through HPLC analysis and therefore it is concluded that NIRS coupled with PLS regression is a rapid and alternate method for quantification of KBA in Boswellia sacra. It is non-destructive, rapid, sensitive and uses simple methods of sample preparation.

  10. Mechanical stability of a salt cavern submitted to rapid pressure variations: Application to the underground storage of natural gas, compressed air and hydrogen

    International Nuclear Information System (INIS)

    Djizanne-Djakeun, Hippolyte

    2014-01-01

    Salt caverns used for the underground storage of large volumes of natural gas are in high demand given the ever-increasing energy needs. The storage of renewable energy is also envisaged in these salt caverns for example, storage of compressed air and hydrogen mass storage. In both cases, salt caverns are more solicited than before because they are subject to rapid injection and withdrawal rates. These new operating modes raise new mechanical problems, illustrated in particular by sloughing, and falling of overhanging blocks at cavern wall. Indeed, to the purely mechanical stress related to changes in gas pressure variations, repeated dozens of degrees Celsius of temperature variation are superimposed; causes in particular during withdrawal, additional tensile stresses whom may lead to fractures at cavern wall; whose evolution could be dangerous. The mechanical behavior of rock salt is known: it is elasto-viscoplastic, nonlinear and highly thermo sensitive. The existing rock salt constitutive laws and failures and damages criteria have been used to analyze the behavior of caverns under the effects of these new loading. The study deals with the thermo mechanics of rocks and helps to analyze the effects of these new operations modes on the structural stability of salt caverns. The approach was to firstly design and validate a thermodynamic model of the behavior of gas in the cavern. This model was used to analyze blowout in gas salt cavern. Then, with the thermo mechanical coupling, to analyze the effects of rapid withdrawal, rapid injection and daily cycles on the structural stability of caverns. At the experimental level, we sought the optimal conditions to the occurrence and the development of cracks on a pastille and a block of rock salt. The creep behavior of rock salt specimens in triaxial extension also was analyzed. (author)

  11. Rapid determination of telmisartan in human plasma by HPLC using a monolithic column with fluorescence detection and its application to a bioequivalence study.

    Science.gov (United States)

    Zhang, He; Jiang, Yunyun; Wen, Jun; Zhou, Tingting; Fan, Guorong; Wu, Yutian

    2009-11-01

    A rapid HPLC method using a monolithic column with fluorescence detection has been developed for determination of telmisartan in human plasma. Sample preparation was done by protein precipitation with acetonitrile and naproxen was used as IS. The compounds were detected by fluorescence detection, using an excitation wavelength of 300 nm and emission wavelength of 385 nm. Calibration curves of telmisartan were linear in the range of 1-200 ng/mL. The assay was high throughput, sensitive and precise, and it was successfully applied to a bioequivalence study of two formulations of telmisartan.

  12. Fabrication of a novel transparent SERS substrate comprised of Ag-nanoparticle arrays and its application in rapid detection of ractopamine on meat

    Science.gov (United States)

    Surface-enhanced Raman spectroscopy (SERS) is an emerging analytical tool that boasts the feature of high detection sensitivity and molecular fingerprint specificity attracting increased attention and showing promise in applications including detecting residues of veterinary drugs. In practice, spec...

  13. Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.

    Science.gov (United States)

    Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet; Moynihan, Kelly D; Szeto, Gregory L; Chen, Stephanie H; Melo, Mariane B; Mueller, Stefanie; Irvine, Darrell J

    2015-06-01

    Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

  14. 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

  15. Rapid preparation of α-FeOOH and α-Fe2O3 nanostructures by microwave heating and their application in electrochemical sensors

    International Nuclear Information System (INIS)

    Marinho, J.Z.; Montes, R.H.O.; Moura, A.P. de; Longo, E.; Varela, J.A.; Munoz, R.A.A.; Lima, R.C.

    2014-01-01

    Graphical abstract: - Highlights: • Simple microwave method leads to the rapid formation of the goethite and hematite. • Homogenous nucleation and growth of particles are controlled by synthesis time. • Modified electrode with α-FeOOH nanoplates improved the electrochemical response. • The sample is directly heated by microwaves and its crystallization is accelerated. • Fe 3+ nanostructures are promising for development of electrochemical sensors. - Abstract: α-FeOOH (goethite) and α-Fe 2 O 3 (hematite) nanostructures have been successfully synthesized using the microwave-assisted hydrothermal (MAH) method and by the rapid burning in a microwave oven of the as-prepared goethite, respectively. The orthorhombic α-FeOOH to rhombohedralα-Fe 2 O 3 structural transformation was observed by X-ray diffraction (XRD) and Raman spectroscopy results. Plates-like α-FeOOH prepared in 2 min and rounded and quasi-octahedral shaped α-Fe 2 O 3 particles obtained in 10 min were observed using field emission gun scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The use of microwave heating allowed iron oxides to be prepared with shorter reaction times when compared to other synthesis methods. α-FeOOH nanoplates were incorporated into graphite-composite electrodes, which presented electrocatalytic properties towards the electrochemical oxidation of ascorbic acid in comparison with unmodified electrodes. This result demonstrates that such α-FeOOH nanostructures are very promising chemical modifiers for the development of improved electrochemical sensors

  16. Alkaliphilic Bacillus species show potential application in concrete crack repair by virtue of rapid spore production and germination then extracellular calcite formation.

    Science.gov (United States)

    Sharma, T K; Alazhari, M; Heath, A; Paine, K; Cooper, R M

    2017-05-01

    Characterization of alkaliphilic Bacillus species for spore production and germination and calcite formation as a prelude to investigate their potential in microcrack remediation in concrete. Conditions, extent and timing of endospore production was determined by dark-field light microscopy; germination induction and kinetics were assessed by combining reduction in optical density with formation of refractile bodies by phase-contrast microscopy. Bacillus pseudofirmus was selected from several species as the most suitable isolate. Levels and timing of calcium carbonate precipitated in vitro by B. pseudofirmus were evaluated by atomic absorption spectroscopy and structural identity confirmed as calcite and aragonite by Raman spectroscopy and FTIR. The isolate produced copious spores that germinated rapidly in the presence of germinants l-alanine, inosine and NaCl. Bacterial cells produced CaCO 3 crystals in microcracks and the resulting occlusion markedly restricted water ingress. By virtue of rapid spore production and germination, calcium carbonate formation in vitro and in situ, leading to sealing of microcracks, B. pseudofirmus shows clear potential for remediation of concrete on a commercial scale. Microbial sealing of microcracks should become a practicable and sustainable means of increasing concrete durability. © 2017 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

  17. 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.

  18. PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

    Science.gov (United States)

    Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

    2017-08-01

    Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form

  19. Application of Fourier transform near-infrared spectroscopy combined with high-performance liquid chromatography in rapid and simultaneous determination of essential components in crude Radix Scrophulariae.

    Science.gov (United States)

    Li, Xiaomeng; Fang, Dansi; Cong, Xiaodong; Cao, Gang; Cai, Hao; Cai, Baochang

    2012-12-01

    A method is described using rapid and sensitive Fourier transform near-infrared spectroscopy combined with high-performance liquid chromatography-diode array detection for the simultaneous identification and determination of four bioactive compounds in crude Radix Scrophulariae samples. Partial least squares regression is selected as the analysis type and multiplicative scatter correction, second derivative, and Savitzky-Golay filter were adopted for the spectral pretreatment. The correlation coefficients (R) of the calibration models were above 0.96 and the root mean square error of predictions were under 0.028. The developed models were applied to unknown samples with satisfactory results. The established method was validated and can be applied to the intrinsic quality control of crude Radix Scrophulariae.

  20. A simple and rapid micromethod for genomic DNA extraction from jugal epithelial cells. Application to human lymphocyte antigen typing in one large family of atopic/asthmatic probands.

    Science.gov (United States)

    Aron, Y; Swierczewski, E; Lockhart, A

    1994-10-01

    We describe a rapid and reliable micromethod for DNA isolation from buccal epithelial cells from the interior mouth mucosa. This convenient, noninvasive method could be applied to genetic typing in a small number of cells (about 2000 cells per cheek). We have shown that DNA released by this method is suitable for further amplification by polymerase chain reaction (PCR). Using this protocol, coupled with the PCR-RFLP (restriction fragment length polymorphism) method, we analyzed the allelic sequence diversity of the human lymphocyte antigen (HLA) class II genes in an extended family of 33 persons containing 14 asthmatic or atopic members. Six of eight DQA1 alleles, and 11 DQB1, 20 DPB1, and 10 DR haplotypes could be identified in a single DNA sample. Our results suggest that the DR53 group haplotype is frequently associated with allergic asthma and atopy. The micromethod described here may be useful in genetic epidemiology, especially in family studies involving small children.

  1. Rapid reagent-less on-line H2O2 quantification in alkaline semiconductor etching solution, Part 2: Nephelometry application.

    Science.gov (United States)

    Zlatev, Roumen; Stoytcheva, Margarita; Valdez, Benjamin

    2018-03-01

    A simple and rapid reagent less nephelometric method for on-line H 2 O 2 quantification in semiconductors etching solutions was developed, optimized, characterized and validated. The intensity of the light scattered by the oxygen gas suspension resulted from H 2 O 2 catalytic decomposition by immobilized MnO 2 was registered as analytical response. The influences of the light wave length, the agitation rate, the temperature and the catalyst surface area on the response amplitude were studied and optimization was done. The achieved linear concentration range from 10 to 150mmolL -1 at 0.9835 calibration curve correlation coefficient, precision from 3.65% to 0.95% and response time from 35 to 20s respectively, at sensitivity of 8.01µAmmol -1 L and LOD of 2.9mmolL -1 completely satisfy the semiconductor industry requirements. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Rapid in situ synthesis of spherical microflower Pt/C catalyst via spray-drying for high performance fuel cell application

    Energy Technology Data Exchange (ETDEWEB)

    Balgis, R.; Ogi, T.; Okuyama, K. [Department of Chemical Engineering, Graduate School of Engineering, Hiroshima University, Higashi Hiroshima, Hiroshima (Japan); Anilkumar, G.M.; Sago, S. [Research and Development Centre, Noritake Co., Ltd., Higashiyama, Miyoshi, Aichi (Japan)

    2012-08-15

    A facile route for the rapid in situ synthesis of platinum nanoparticles on spherical microflower carbon has been developed. An aqueous precursor slurry containing carbon black, polystyrene latex (PSL), polyvinyl alcohol, and platinum salt was spray-dried, followed by calcination to simultaneously reduce platinum salt and to decompose PSL particles. Prepared Pt/C catalyst showed high-performance electrocatalytic activity with excellent durability. The mass activity and specific activity values were 132.26 mA mg{sup -1} Pt and 207.62 {mu}A cm{sup -2} Pt, respectively. This work presents a future direction for the production of high-performance Pt/C catalyst in an industrial scale. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. 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...

  4. Rapid preparation of α-FeOOH and α-Fe{sub 2}O{sub 3} nanostructures by microwave heating and their application in electrochemical sensors

    Energy Technology Data Exchange (ETDEWEB)

    Marinho, J.Z.; Montes, R.H.O. [Universidade Federal de Uberlândia, Instituto de Química, 38400-902 Uberlândia, MG (Brazil); Moura, A.P. de; Longo, E.; Varela, J.A. [Universidade Estadual Paulista, Instituto de Química, 14800-900 Araraquara, SP (Brazil); Munoz, R.A.A. [Universidade Federal de Uberlândia, Instituto de Química, 38400-902 Uberlândia, MG (Brazil); Lima, R.C., E-mail: rclima@iqufu.ufu.br [Universidade Federal de Uberlândia, Instituto de Química, 38400-902 Uberlândia, MG (Brazil)

    2014-01-01

    Graphical abstract: - Highlights: • Simple microwave method leads to the rapid formation of the goethite and hematite. • Homogenous nucleation and growth of particles are controlled by synthesis time. • Modified electrode with α-FeOOH nanoplates improved the electrochemical response. • The sample is directly heated by microwaves and its crystallization is accelerated. • Fe{sup 3+} nanostructures are promising for development of electrochemical sensors. - Abstract: α-FeOOH (goethite) and α-Fe{sub 2}O{sub 3} (hematite) nanostructures have been successfully synthesized using the microwave-assisted hydrothermal (MAH) method and by the rapid burning in a microwave oven of the as-prepared goethite, respectively. The orthorhombic α-FeOOH to rhombohedralα-Fe{sub 2}O{sub 3} structural transformation was observed by X-ray diffraction (XRD) and Raman spectroscopy results. Plates-like α-FeOOH prepared in 2 min and rounded and quasi-octahedral shaped α-Fe{sub 2}O{sub 3} particles obtained in 10 min were observed using field emission gun scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The use of microwave heating allowed iron oxides to be prepared with shorter reaction times when compared to other synthesis methods. α-FeOOH nanoplates were incorporated into graphite-composite electrodes, which presented electrocatalytic properties towards the electrochemical oxidation of ascorbic acid in comparison with unmodified electrodes. This result demonstrates that such α-FeOOH nanostructures are very promising chemical modifiers for the development of improved electrochemical sensors.

  5. Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

    Directory of Open Access Journals (Sweden)

    Maxime Belondrade

    Full Text Available The prevalence of variant Creutzfeldt-Jakob disease (vCJD in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA. This assay allowed the specific detection of minute quantities (10-8 brain dilution of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

  6. Development and Application of Loop-Mediated Isothermal Amplification Assays for Rapid Visual Detection of cry2Ab and cry3A Genes in Genetically-Modified Crops

    Directory of Open Access Journals (Sweden)

    Feiwu Li

    2014-08-01

    Full Text Available The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

  7. Development and application of loop-mediated isothermal amplification assays for rapid visual detection of cry2Ab and cry3A genes in genetically-modified crops.

    Science.gov (United States)

    Li, Feiwu; Yan, Wei; Long, Likun; Qi, Xing; Li, Congcong; Zhang, Shihong

    2014-08-27

    The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs) containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP) method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM) crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

  8. 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.

  9. 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...

  10. 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....

  11. 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...

  12. Rapid adjustment in chrysanthemum carbohydrate turnover and growth activity to a change in time-of-day application of light and daylength

    DEFF Research Database (Denmark)

    Kjær, Katrine Heinsvig; Poiré, Richard; Ottosen, Carl-Otto

    2012-01-01

    diurnally-regulated parameters related to growth. In this study, chrysanthemum plants were exposed to a change in the time-of-day application of light followed by short days or long days with a night interruption of light. We observed a clear shift in the diel cycle of sucrose turnover and relative leaf......Abstract. Diel (24 h) rhythms are believed to be of great importance to plant growth and carbohydrate metabolism in fluctuating environments. However, it is unclear how plants that have evolved to experience regular day–night patterns will respond to irregular light environments that disturb...... expansion, indicating a resetting of these activities with a temporal trigger in the early morning. The starch pool was relatively stable in long-day plants and marginally affected by the change in the time-of-day application in light followed by long days with a night interruption. This was in contrast...

  13. Rapid dopaminergic modulation of the fish hypothalamic transcriptome and proteome.

    Directory of Open Access Journals (Sweden)

    Jason T Popesku

    2010-08-01

    Full Text Available Dopamine (DA is a major neurotransmitter playing an important role in the regulation of vertebrate reproduction. We developed a novel method for the comparison of transcriptomic and proteomic data obtained from in vivo experiments designed to study the neuroendocrine actions of DA.Female goldfish were injected (i.p. with DA agonists (D1-specific; SKF 38393, or D2-specific; LY 171555 and sacrificed after 5 h. Serum LH levels were reduced by 57% and 75% by SKF 38393 and LY 171555, respectively, indicating that the treatments produced physiologically relevant responses in vivo. Bioinformatic strategies and a ray-finned fish database were established for microarray and iTRAQ proteomic analysis of the hypothalamus, revealing a total of 3088 mRNAs and 42 proteins as being differentially regulated by the treatments. Twenty one proteins and mRNAs corresponding to these proteins appeared on both lists. Many of the mRNAs and proteins affected by the treatments were grouped into the Gene Ontology categorizations of protein complex, signal transduction, response to stimulus, and regulation of cellular processes. There was a 57% and 14% directional agreement between the differentially-regulated mRNAs and proteins for SKF 38393 and LY 171555, respectively.The results demonstrate the applicability of advanced high-throughput genomic and proteomic analyses in an amendable well-studied teleost model species whose genome has yet to be sequenced. We demonstrate that DA rapidly regulates multiple hypothalamic pathways and processes that are also known to be involved in pathologies of the central nervous system.

  14. Rapid, Sensitive and Validated Ultra-Performance Liquid Chromatography/Mass Spectrometric Method for the Determination of Fenofibric Acid and its Application to Human Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Sunil K. Dubey

    2010-01-01

    Full Text Available The first, rapid and sensitive ultra performance liquid chromatography mass spectrometric method for the determination of fenofibric acid, the active metabolite of fenofibrate, a lipid regulating agent, in human EDTA plasma has been developed and validated using fenofibric d6 acid as internal standard and Waters LC-MS/MS. Negative ions of fenofibric acid and fenofibric d6 acid were detected in multiple reaction-monitoring (MRM mode. The method was validated over a concentration range of 0.176 μg/mL to 19.837 μg/mL (r ≥ 0.99. It took only 1.5 minute to analyse a sample. Intra- and inter-run precision of fenofibric acid assay at four concentrations ranged from 0.5% to 4.3% with accuracy varied from 93.1 to 108.1% indicating good precision and accuracy. Analytical recoveries of fenofibric acid and internal standard in plasma were less than 90%. This method was successfully applied for evaluation of pharmacokinetics of fenofibric acid after a single oral dose of 145 mg fenofibrate to 10 Indian healthy volunteers

  15. Application of computer-aided three-dimensional skull model with rapid prototyping technique in repair of zygomatico-orbito-maxillary complex fracture.

    Science.gov (United States)

    Li, Wei Zhong; Zhang, Mei Chao; Li, Shao Ping; Zhang, Lei Tao; Huang, Yu

    2009-06-01

    With the advent of CAD/CAM and rapid prototyping (RP), a technical revolution in oral and maxillofacial trauma was promoted to benefit treatment, repair of maxillofacial fractures and reconstruction of maxillofacial defects. For a patient with zygomatico-facial collapse deformity resulting from a zygomatico-orbito-maxillary complex (ZOMC) fracture, CT scan data were processed by using Mimics 10.0 for three-dimensional (3D) reconstruction. The reduction design was aided by 3D virtual imaging and the 3D skull model was reproduced using the RP technique. In line with the design by Mimics, presurgery was performed on the 3D skull model and the semi-coronal incision was taken for reduction of ZOMC fracture, based on the outcome from the presurgery. Postoperative CT and images revealed significantly modified zygomatic collapse and zygomatic arch rise and well-modified facial symmetry. The CAD/CAM and RP technique is a relatively useful tool that can assist surgeons with reconstruction of the maxillofacial skeleton, especially in repairs of ZOMC fracture.

  16. Rapid thermal melted TiO2 nano-particles into ZnO nano-rod and its application for dye sensitized solar cells

    International Nuclear Information System (INIS)

    Chao, Ching-Hsun; Chang, Chi-Lung; Chan, Chien-Hung; Lien, Shui-Yang; Weng, Ko-Wei; Yao, Kuo-Shan

    2010-01-01

    TiO 2 nano-particles with an anchored ZnO nano-rod structure were synthesized using the hydrothermal method to grow ZnO nano-rods and coated TiO 2 nano-particles on ZnO nano-rods using the rapid thermal annealing method on ITO conducting glass pre-coated with nano porous TiO 2 film. The XRD study showed that there was little difference in crystal composition for various types of TiO 2 nano-particles anchored to ZnO nano-rods. The as-prepared architecture was characterized using field-emission scanning electron microscopy (FE-SEM). Films with TiO 2 nano-particles anchored to ZnO nano-rods were used as electrode materials to fabricate dye sensitized solar cells (DSSCs). The best solar energy conversion efficiency of 2.397% was obtained by modified electrode material, under AM 1.5 illumination, achieved up to J sc = 15.382 mA/cm 2 , V oc = 0.479 V and fill factor = 32.8%.

  17. [Application of precursor ion scanning method in rapid screening of illegally added phosphodiesterase-5 inhibitors and their unknown derivatives in Chinese traditional patent medicines and health foods].

    Science.gov (United States)

    Sun, Jing; Cao, Ling; Feng, Youlong; Tan, Li

    2014-11-01

    The compounds with similar structure often have similar pharmacological activities. So it is a trend for illegal addition that new derivatives of effective drugs are synthesized to avoid the statutory test. This bring challenges to crack down on illegal addition behavior, however, modified derivatives usually have similar product ions, which allow for precursor ion scanning. In this work, precursor ion scanning mode of a triple quadrupole mass spectrometer was first applied to screen illegally added drugs in complex matrix such as Chinese traditional patent medicines and healthy foods. Phosphodiesterase-5 inhibitors were used as experimental examples. Through the analysis of the structure and mass spectrum characteristics of the compounds, phosphodiesterase-5 inhibitors were classified, and their common product ions were screened by full scan of product ions of typical compounds. Then high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with precursor ion scanning mode was established based on the optimization of MS parameters. The effect of mass parameters and the choice of fragment ions were also studied. The method was applied to determine actual samples and further refined. The results demonstrated that this method can meet the need of rapid screening of unknown derivatives of phosphodiesterase-5 inhibitors in complex matrix, and prevent unknown derivatives undetected. This method shows advantages in sensitivity, specificity and efficiency, and is worth to be further investigated.

  18. Application of response surface methodology for rapid chrysene biodegradation by newly isolated marine-derived fungus Cochliobolus lunatus strain CHR4D.

    Science.gov (United States)

    Bhatt, Jwalant K; Ghevariya, Chirag M; Dudhagara, Dushyant R; Rajpara, Rahul K; Dave, Bharti P

    2014-11-01

    For the first time, Cochliobolus lunatus strain CHR4D, a marine-derived ascomycete fungus isolated from historically contaminated crude oil polluted shoreline of Alang-Sosiya ship-breaking yard, at Bhavnagar coast, Gujarat has been reported showing the rapid and enhanced biodegradation of chrysene, a four ringed high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH). Mineral Salt Broth (MSB) components such as ammonium tartrate and glucose along with chrysene, pH and trace metal solution have been successfully optimized by Response Surface Methodology (RSM) using central composite design (CCD). A validated, two-step optimization protocol has yielded a substantial 93.10% chrysene degradation on the 4(th) day, against unoptimized 56.37% degradation on the 14(th) day. The results depict 1.65 fold increase in chrysene degradation and 1.40 fold increase in biomass with a considerable decrement in time. Based on the successful laboratory experiments, C. lunatus strain CHR4D can thus be predicted as a potential candidate for mycoremediation of HMW PAHs impacted environments.

  19. Application of rapid solidification powder metallurgy processing to prepare Cu–Al–Ni high temperature shape memory alloy strips with high strength and high ductility

    Energy Technology Data Exchange (ETDEWEB)

    Vajpai, S.K., E-mail: vajpaisk@gmail.com [Department of Materials Science and Engineering, Indian Institute of Technology, Kanpur 208016, Uttar Pradesh (India); Dube, R.K., E-mail: rkd@iitk.ac.in [Department of Materials Science and Engineering, Indian Institute of Technology, Kanpur 208016, Uttar Pradesh (India); Sangal, S., E-mail: sangals@iitk.ac.in [Department of Materials Science and Engineering, Indian Institute of Technology, Kanpur 208016, Uttar Pradesh (India)

    2013-05-15

    Cu–Al–Ni high temperature shape memory alloy (HTSMA) strips were successfully prepared from rapid solidified water atomized Cu–Al–Ni pre-alloyed powders via hot densification rolling of unsheathed sintered powder preforms. Finished heat-treated Cu–Al–Ni alloy strips had fine-grained structure, average grain size approximately 16 μm, and exhibited a combination of high strength and high ductility. It has been demonstrated that the redistribution of nano-sized alumina particles, present on the surface as well as inside the starting water atomized Cu–Al–Ni pre-alloyed powder particles, due to plastic deformation of starting powder particles during hot densification rolling resulted in the fine grained microstructure in the finished SMA strips. The finished SMA strips were almost fully martensitic in nature, consisting of a mixture of β{sub 1}{sup ′} and γ{sub 1}{sup ′} martensite. The average fracture strength and fracture strain of the finished SMA strips were 810 MPa and 12%, respectively, and the fractured specimens exhibited primarily micro-void coalescence type ductile nature of fracture. Finished Cu–Al–Ni SMA strips exhibited high characteristic transformation temperatures and an almost 100% one-way shape recovery was obtained in the specimens up to 4% applied deformation pre-strain. The retained two-way shape memory recovery increased with increasing applied training pre-strain, achieving a maximum value of 16.25% at 5% applied training pre-strain.

  20. Rapid ultrasound-induced transient-liquid-phase bonding of Al-50Si alloys with Zn interlayer in air for electrical packaging application.

    Science.gov (United States)

    Wang, Qian; Chen, Xiaoguang; Zhu, Lin; Yan, Jiuchun; Lai, Zhiwei; Zhao, Pizhi; Bao, Juncheng; Lv, Guicai; You, Chen; Zhou, Xiaoyu; Zhang, Jian; Li, Yuntao

    2017-01-01

    Al-50Si alloys were joined by rapid ultrasound-induced transient-liquid-phase bonding method using Zn foil as interlayer at 390°C in air, below the melt point of interlayer. The fracture of oxide films along the edge of Si particles led to contact and inter-diffusion between aluminum substrate and Zn interlayer, and liquefied Zn-Al alloys were developed. The width of Zn-Al alloys gradually decreased with increasing the ultrasonic vibration time due to liquid squeezing out and accelerated diffusion. A stage of isothermal solidification existed, and the completion time was significantly shortened. In the liquid metal, the acoustic streaming and ultrasonic cavitations were induced. As the process developed, much more Si particles, which were particulate-reinforced phases of Al-50Si, gradually migrated to the center of soldering seam. The highest average shear strength of joints reached to 94.2MPa, and the fracture mainly occurred at the base metal. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. New Statistical Method to Analyze Three-Dimensional Landmark Configurations Obtained with Cone-Beam CT: Basic Features and Clinical Application for Rapid Maxillary Expansion

    Energy Technology Data Exchange (ETDEWEB)

    Gamble, Jennifer; Lagravere, Manuel O.; Major, Paul W.; Heo, Giseon [University of Alberta, Edmonton (Canada)

    2012-03-15

    To describe a statistical method of three-dimensional landmark configuration data and apply it to an orthodontic data set comparing two types of rapid maxillary expansion (RME) treatments. Landmark configurations obtained from cone beam CT scans were used to represent patients in two types (please describe what were two types) of RME groups and a control group over four time points. A method using tools from persistent homology and dimensionality reduction is presented and used to identify variability between the subjects. The analysis was in agreement with previous results using conventional methods, which found significant differences between treatment groups and the control, but no distinction between the types of treatment. Additionally, it was found that second molar eruption varied considerably between the subjects, and this has not been evaluated in previous analyses. This method of analysis allows entire configurations to be considered as a whole, and does not require specific inter-landmark distances or angles to be selected. Sources of variability present themselves, without having to be individually sought after. This method is suggested as an additional tool for the analysis of landmark configuration data.

  2. 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...

  3. 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

  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. 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

  6. 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....

  7. 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...

  8. 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.

  9. A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity.

    Directory of Open Access Journals (Sweden)

    Nicholas D Leigh

    Full Text Available Toll-like receptor (TLR mediated recognition of pathogen associated molecular patterns allows the immune system to rapidly respond to a pathogenic insult. The "danger context" elicited by TLR agonists allows an initially non-immunogenic antigen to become immunogenic. This ability to alter environment is highly relevant in tumor immunity, since it is inherently difficult for the immune system to recognize host-derived tumors as immunogenic. However, immune cells may have encountered certain TLR ligands associated with tumor development, yet the endogenous stimulation is typically not sufficient to induce spontaneous tumor rejection. Of special interest are TLR5 agonists, because there are no endogenous ligands that bind TLR5. CBLB502 is a pharmacologically optimized TLR5 agonist derived from Salmonella enterica flagellin. We examined the effect of CBLB502 on tumor immunity using two syngeneic lymphoma models, both of which do not express TLR5, and thus do not directly respond to CBLB502. Upon challenge with the T-cell lymphoma RMAS, CBLB502 treatment after tumor inoculation protects C57BL/6 mice from death caused by tumor growth. This protective effect is both natural killer (NK cell- and perforin-dependent. In addition, CBLB502 stimulates clearance of the B-cell lymphoma A20 in BALB/c mice in a CD8(+ T cell-dependent fashion. Analysis on the cellular level via ImageStream flow cytometry reveals that CD11b(+ and CD11c(+ cells, but neither NK nor T cells, directly respond to CBLB502 as determined by NFκB nuclear translocation. Our findings demonstrate that CBLB502 stimulates a robust antitumor response by directly activating TLR5-expressing accessory immune cells, which in turn activate cytotoxic lymphocytes.

  10. Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Ponnusamy, Suriyan; Sullivan, Ryan D; You, Dahui; Zafar, Nadeem; He Yang, Chuan; Thiyagarajan, Thirumagal; Johnson, Daniel L; Barrett, Maron L; Koehler, Nikki J; Star, Mayra; Stephenson, Erin J; Bridges, Dave; Cormier, Stephania A; Pfeffer, Lawrence M; Narayanan, Ramesh

    2017-07-01

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Benefits and challenges of a QSP approach through case study: Evaluation of a hypothetical GLP-1/GIP dual agonist therapy.

    Science.gov (United States)

    Rieger, Theodore R; Musante, Cynthia J

    2016-10-30

    Quantitative Systems Pharmacology (QSP) is an emerging science with increasing application to pharmaceutical research and development paradigms. Through case study we provide an overview of the benefits and challenges of applying QSP approaches to inform program decisions in the early stages of drug discovery and development. Specifically, we describe the use of a type 2 diabetes systems model to inform a No-Go decision prior to lead development for a potential GLP-1/GIP dual agonist program, enabling prioritization of exploratory programs with higher probability of clinical success. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Application of a rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of bumetanide in human plasma for a bioequivalence study.

    Science.gov (United States)

    Patel, Dinesh S; Sharma, Naveen; Patel, Mukesh C; Patel, Bhavin N; Shrivastav, Pranav S; Sanyal, Mallika

    2012-07-01

    A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of bumetanide in human plasma using tamsulosin as internal standard (IS). The analyte and IS were extracted from 200 μL of human plasma via solid phase extraction and the chromatographic separation was achieved on Peerless Basic C18 (100 mm × 4.6 mm, 3 μm) column under isocratic conditions. Detection of bumetanide and IS was done by tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for bumetanide and IS were m/z 365.2→240.2 and 409.2→228.2 respectively. The method was fully validated as per the US FDA guidelines. The limit of detection and lower limit of quantitation of the method were 0.03 and 0.30 ng/mL respectively with a linear dynamic range of 0.30-200.0 ng/mL for bumetanide. The intra-batch and inter-batch precision (% CV) was ≤6.9% while the mean extraction recovery was >90% across quality control levels. The method is selective in presence of four diuretic drugs and some commonly used medications by healthy volunteers. It was successfully applied to a bioequivalence study of 2mg bumetanide tablet formulation in 10 healthy Indian male subjects under fasting condition. The reproducibility in the measurement of study data was demonstrated by reanalysis of 42 incurred samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Establishment of a simple and rapid identification method for Listeria spp. by using high-resolution melting analysis, and its application in food industry.

    Science.gov (United States)

    Ohshima, Chihiro; Takahashi, Hajime; Phraephaisarn, Chirapiphat; Vesaratchavest, Mongkol; Keeratipibul, Suwimon; Kuda, Takashi; Kimura, Bon

    2014-01-01

    Listeria monocytogenes is the causative bacteria of listeriosis, which has a higher mortality rate than that of other causes of food poisoning. Listeria spp., of which L. monocytogenes is a member, have been isolated from food and manufacturing environments. Several methods have been published for identifying Listeria spp.; however, many of the methods cannot identify newly categorized Listeria spp. Additionally, they are often not suitable for the food industry, owing to their complexity, cost, or time consumption. Recently, high-resolution melting analysis (HRMA), which exploits DNA-sequence differences, has received attention as a simple and quick genomic typing method. In the present study, a new method for the simple, rapid, and low-cost identification of Listeria spp. has been presented using the genes rarA and ldh as targets for HRMA. DNA sequences of 9 Listeria species were first compared, and polymorphisms were identified for each species for primer design. Species specificity of each HRM curve pattern was estimated using type strains of all the species. Among the 9 species, 7 were identified by HRMA using rarA gene, including 3 new species. The remaining 2 species were identified by HRMA of ldh gene. The newly developed HRMA method was then used to assess Listeria isolates from the food industry, and the method efficiency was compared to that of identification by 16S rDNA sequence analysis. The 2 methods were in coherence for 92.6% of the samples, demonstrating the high accuracy of HRMA. The time required for identifying Listeria spp. was substantially low, and the process was considerably simplified, providing a useful and precise method for processing multiple samples per day. Our newly developed method for identifying Listeria spp. is highly valuable; its use is not limited to the food industry, and it can be used for the isolates from the natural environment.

  14. High-throughput and rapid quantification of lipids by nanoflow UPLC-ESI-MS/MS: application to the hepatic lipids of rabbits with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Byeon, Seul Kee; Lee, Jong Cheol; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

    2016-07-01

    A rapid and high-throughput quantification method (approximately 300 lipids within 20 min) was established using nanoflow ultrahigh-pressure liquid chromatography-tandem mass spectrometry (nUPLC-ESI-MS/MS) with selective reaction monitoring (SRM) and applied to the quantitative profiling of the hepatic lipids of rabbits with different metabolic conditions that stimulate the development of nonalcoholic fatty liver disease (NAFLD). Among the metabolic conditions of rabbits in this study [inflammation (I), high-cholesterol diet (HC), and high-cholesterol diet combined with inflammation (HCI)], significant perturbation in hepatic lipidome (>3-fold and p groups, while no single lipid showed a significant change in group I. In addition, this study revealed a dramatic increase (>2-fold) in relatively high-abundant monohexosylceramides (MHCs), sphingomyelins (SMs), and triacylglycerols (TGs) in both the HC and HCI groups, especially in MHCs as all 11 MHCs increased by larger than 3- to 12-fold. As the levels of the relatively high-abundant lipids in the above classes increased, the total lipidome level of each class increased significantly by approximately 2-fold to 5-fold. Other classes of lipids also generally increased, which was likely induced by the increase in mitogenic and nonapoptotic MHCs and SMs, as they promote cell proliferation. On the other hand, a slight decrease in the level of apoptotic ceramides (Cers) was observed, which agreed with the general increase in total lipid level. As distinct changes in hepatic lipidome were observed from HC groups, this suggests that HC or HCI is highly associated with NAFLD but not inflammation alone itself. Graphical Abstract Schematic of lipidomic analysis from hepatic tissue using nanoflow LC-ESI-MS/MS and nUPLC-ESI-MS/MS.

  15. Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

    Directory of Open Access Journals (Sweden)

    Aihua Hong

    2012-03-01

    Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

  16. Development of a new rapid isolation device for circulating tumor cells (CTCs using 3D palladium filter and its application for genetic analysis.

    Directory of Open Access Journals (Sweden)

    Akiko Yusa

    Full Text Available Circulating tumor cells (CTCs in the blood of patients with epithelial malignancies provide a promising and minimally invasive source for early detection of metastasis, monitoring of therapeutic effects and basic research addressing the mechanism of metastasis. In this study, we developed a new filtration-based, sensitive CTC isolation device. This device consists of a 3-dimensional (3D palladium (Pd filter with an 8 µm-sized pore in the lower layer and a 30 µm-sized pocket in the upper layer to trap CTCs on a filter micro-fabricated by precise lithography plus electroforming process. This is a simple pump-less device driven by gravity flow and can enrich CTCs from whole blood within 20 min. After on-device staining of CTCs for 30 min, the filter cassette was removed from the device, fixed in a cassette holder and set up on the upright fluorescence microscope. Enumeration and isolation of CTCs for subsequent genetic analysis from the beginning were completed within 1.5 hr and 2 hr, respectively. Cell spike experiments demonstrated that the recovery rate of tumor cells from blood by this Pd filter device was more than 85%. Single living tumor cells were efficiently isolated from these spiked tumor cells by a micromanipulator, and KRAS mutation, HER2 gene amplification and overexpression, for example, were successfully detected from such isolated single tumor cells. Sequential analysis of blood from mice bearing metastasis revealed that CTC increased with progression of metastasis. Furthermore, a significant increase in the number of CTCs from the blood of patients with metastatic breast cancer was observed compared with patients without metastasis and healthy volunteers. These results suggest that this new 3D Pd filter-based device would be a useful tool for the rapid, cost effective and sensitive detection, enumeration, isolation and genetic analysis of CTCs from peripheral blood in both preclinical and clinical settings.

  17. A hybrid peptide PTS that facilitates transmembrane delivery and its application for the rapid in vivo imaging via near-infrared fluorescence imaging

    Directory of Open Access Journals (Sweden)

    Xuejiao eYan

    2016-03-01

    Full Text Available Background and purpose: Intravital imaging provides invaluable readouts for clinical diagnoses and therapies and shows great potential in the design of individualized drug dosage regimes. Ts is a mammalian free cell membrane-penetrating peptide. This study aimed to introduce a novel approach to the design of a cancer-selective peptide on the basis of a membrane-penetrating peptide and to explore its potential as a carrier of medical substances. Experimental approach: Ts was linked with a αvβ3-binding peptide P1c to create a hybrid referred to as PTS. The hybrid was labeled with an FITC or Cy5.5 as an imaging indicator to evaluate its in vitro and in vivo bioactivity. Key results: Hemolysis tests proved that in comparison with Ts, PTS caused similar or even less leakage of human erythrocytes at concentrations of up to 1 mmol/L. Flow cytometry assay and confocal microscopy demonstrated the following. 1 P1c alone could target and mostly halt at the cancer cell membrane. 2 Ts alone could not bind to the membrane sufficiently. 3 P1c greatly enhanced the binding affinity of PTS with MDA-MB-231 breast cancer cells that upregulated αvβ3. 4 Ts conferred PTS with the ability to traverse a cell membrane and thus facilitate the transmembrane delivery of imaging probes. In vivo near-infrared fluorescence (NIRF imaging demonstrated that the imaging probes were rapidly concentrated in a MDA-MB-231 tumor tissue within 1 h after intravenous injection. Conclusions and implications: PTS exhibited the capability of targeting specific tumors and greatly facilitating the transmembrane delivery of imaging probes.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Applications of copolymer for rapid identification of bacteria in blood culture broths using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Ashizawa, Kazuho; Murata, Syota; Terada, Takashi; Ito, Daisuke; Bunya, Masaru; Watanabe, Koji; Teruuchi, Yoko; Tsuchida, Sachio; Satoh, Mamoru; Nishimura, Motoi; Matsushita, Kazuyuki; Sugama, Yuji; Nomura, Fumio

    2017-08-01

    Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) can be used to identify pathogens in blood culture samples. However, sample pretreatment is needed for direct identification of microbes in blood culture bottles. Conventional protocols are complex and time-consuming. Therefore, in this study, we developed a method for collecting bacteria using polyallylamine-polystyrene copolymer for application in wastewater treatment technology. Using representative bacterial species Escherichia coli and Staphylococcus capitis, we found that polyallylamine-polystyrene can form visible aggregates with bacteria, which can be identified using MALDI-TOF MS. The processing time of our protocol was as short as 15min. Hemoglobin interference in MALDI spectra analysis was significantly decreased in our method compared with the conventional method. In a preliminary experiment, we evaluated the use of our protocol to identify clinical isolates from blood culture bottles. MALDI-TOF MS-based identification of 17 strains from five bacterial species (E. coli, Klebsiella pneumoniae, Enterococcus faecalis, S. aureus, and S. capitis) collected by our protocol was satisfactory. Prospective large-scale studies are needed to further evaluate the clinical application of this novel and simple method of collecting bacteria in blood culture bottles. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction.

    Science.gov (United States)

    Serra, Aida; Rubió, Laura; Macià, Alba; Valls, Rosa-M; Catalán, Úrsula; de la Torre, Rafael; Motilva, Maria-José

    2013-11-01

    Two different rapid sample pretreatment strategies, dried spot cards, and microelution solid-phase extraction plates (μSPE), with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been developed and validated for the determination of hydroxytyrosol and its metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3'-O-glucuronide, hydroxytyrosol-4'-O-glucuronide, hydroxytyrosol-3-O-sulphate, and homovanillic alcohol-4'-O-glucuronide were used as the target compounds. Using the FTA DMPK-A dried urine spot card under optimum conditions, with 5 μL of preconcentrated urine volume and 100 μL of methanol/water (50/50, v/v) as the elution solvent, the extraction recovery (%R) of the compounds studied was higher than 80%, and the matrix effect (%ME) was less than 8%. The stability of these cards and punching at the centre or side of the card were also studied, obtaining an excellent stability after 7 days of storage and complete homogeneity across the surface of the dried drop. The different μSPE parameters that affect the efficiency were also studied, and under optimum conditions, the %R and the %ME were higher than 70% and lower than 17%, respectively. The linearity range in dried urine spot cards was 2.5-20 μM for all the metabolites, with the exception of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 μM and 2.5-50 μM respectively. With regards to μSPE, the linearity range was 0.5-5 μM for all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08-5 μM. The quantification limits (LOQs) were 0.3-2.5 μM and 0.08-0.5 μM in dried spot cards and in μSPE, respectively. The two developed methods were then applied and compared for determining hydroxytyrosol and its metabolites in human 24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched virgin olive oil. The metabolites identified were hydroxytyrosol in its glucuronide and sulphate

  6. A rapid, LC-MS/MS assay for quantification of piperacillin and tazobactam in human plasma and pleural fluid; application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Popowicz, Natalia D; O'Halloran, Sean J; Fitzgerald, Deirdre; Lee, Y C Gary; Joyce, David A

    2018-04-01

    Piperacillin, in combination with tazobactam is a common first-line antibiotic used for the treatment of pleural infection, however its pleural pharmacokinetics and penetration has not previously been reported. The objective of this work was to develop and validate a rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay for quantification of piperacillin (PIP) and tazobactam (TAZ). PIP and TAZ were extracted from both human plasma and pleural fluid samples by protein precipitation in methanol containing the internal standards (IS) piperacillin-d 5 (PIP-d 5 ) and sulbactam (SUL). Briefly, 5 μL of sample was mixed with 125 μL of methanol containing IS, vortexed and centrifuged. Supernatant (50 μL) was diluted into 500 μL of mobile phase containing 10 mM of ammonium bicarbonate in LCMS grade water and transferred to the autosampler tray. Electrospray ionization in positive mode and multiple reaction monitoring (MRM) were used for PIP and PIP-d 5 at the transitions m/z 518.2 → 143.2 and m/z 523.2 → 148.2 respectively, and electrospray ionization in negative mode and MRM were used for TAZ and SUL at the transitions m/z 299.1 → 138.1 and m/z 232.4 → 140.1. The chromatographic separation was achieved using an Acquity BEH C-18 column with gradient elution of mobile phase containing 10 mmol/L ammonium bicarbonate in water and methanol. A linear range was observed over the concentration range of 0.25-352 mg/L and 0.25-50.5 mg/L for PIP and TAZ respectively. Complete method validation was performed according to US FDA guidelines for selectivity, specificity, precision and accuracy, LLOQ, matrix effects, recovery and stability, with all results within acceptable limits. This method was successfully applied to two patients with pleural infection and is suitable for further pharmacokinetic studies and therapeutic drug monitoring. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  7. Rapid, reliable, and sensitive detection of adenosine deaminase activity by UHPLC-Q-Orbitrap HRMS and its application to inhibitory activity evaluation of traditional Chinese medicines.

    Science.gov (United States)

    Qi, Shenglan; Guan, Huida; Deng, Gang; Yang, Tao; Cheng, Xuemei; Liu, Wei; Liu, Ping; Wang, Changhong

    2018-05-10

    Adenosine deaminase (ADA), which is a key enzyme in the metabolism of purine nucleosides, plays important roles in diverse disorders, such as tuberculosis, diabetes, liver disorders, and cancer. Determination of the activities of ADA and its isoenzymes in body fluids has received considerable attention in the diagnosis and treatment of relative diseases. Ultraviolet spectroscopy with adenosine (AD) as a substrate is a classical approach for screening potential ADA inhibitors by measuring the decrease in substrate (AD) at 265 nm or increase in the product (inosine) at 248 nm. However, AD and inosine share a very close maximum absorption wavelength, and the reaction is uncertain and is frequently interfered by the background color of matrix compounds or plant extracts. Thus, the method usually yields false positive or negative results. In this study, a novel, rapid, sensitive, and accurate ultra-high-performance liquid chromatography-Q exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometric (UHPLC-Q-Orbitrap HRMS) method was developed for determining and screening ADA inhibitors by directly determining the deamination product of AD, inosine. A proper separation was achieved for inosine and chlormequat (internal standard) within 2 min via isocratic elution (0.1% formic acid:methanol = 85:15, v/v) at a flow rate of 0.3 mL min -1 on a Waters ACQUITY HSS T3 column (2.1 mm × 100 mm, 1.8 μm) following a simple precipitation of proteins. The intra- and inter-day precisions of the developed method were below 7.17% and 8.99%, respectively. The method exhibited advantages of small total reaction volume (60 μL), short running time (2 min), high sensitivity (lowest limit of quantification of 0.02 μM for inosine), and low cost (small enzyme consumption of 0.007 unit mL -1 for ADA and substrate of 3.74 μM for AD in individual inhibition), and no matrix effects (101.64%-107.12%). Stability results showed that all

  8. Rapid synthesis of flower shaped Cu{sub 2}ZnSnS{sub 4} nanoparticles by microwave irradiation for solar cell application

    Energy Technology Data Exchange (ETDEWEB)

    Ansari, Mohd Zubair, E-mail: mhd.zubair1@gmail.com; Khare, Neeraj [Department of Physics, Indian Institute of Technology Delhi, New Delhi (India)

    2016-05-06

    Single phase Cu{sub 2}ZnSnS{sub 4} (CZTS) nanoparticles have been synthesized by the microwave-assisted solution method in a one step process. Structural, morphological and optical characterizations of the CZTS nanoparticles have been carried out. X-ray diffraction confirms the single phase formation of CZTS nanoparticles with kesterite structure. SEM confirms the homogenous distribution of CZTS nanoparticles flower like assemblies. High resolution TEM image confirms the good crystallinity of the CZTS nanoparticles with the average grain size ~20 nm. The CZTS nanoparticles have strong optical absorption in the visible region with direct band gap as ~1.6 eV which is optimal for photovoltaic application.

  9. The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration.

    Science.gov (United States)

    Vaczy, A; Reglodi, D; Somoskeoy, T; Kovacs, K; Lokos, E; Szabo, E; Tamas, A; Atlasz, T

    2016-10-01

    A number of studies have proven that pituitary adenylate cyclase activating polypeptide (PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous studies, protective effects were observed with PACAP1-38, PACAP1-27, and VIP but not with their related peptides, glucagon, or secretin in BCCAO. All three PACAP receptors (PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis demonstrated that the retinoprotective effects are most probably mainly mediated by the PAC1 receptor. The aim of the present study was to investigate the retinoprotective effects of a selective PAC1-receptor agonist maxadilan in BCCAO-induced retinopathy. Wistar rats were used in the experiment. After performing BCCAO, the right eye was treated with intravitreal maxadilan (0.1 or 1 μM), while the left eye was injected with vehicle. Sham-operated rats received the same treatment. Two weeks after the operation, retinas were processed for standard morphometric and molecular analysis. Intravitreal injection of 0.1 or 1 μM maxadilan caused significant protection in the thickness of most retinal layers and the number of cells in the GCL compared to the BCCAO-operated eyes. In addition, 1 μM maxadilan application was more effective than 0.1 μM maxadilan treatment in the ONL, INL, IPL, and the entire retina (OLM-ILM). Maxadilan treatment significantly decreased cytokine expression (CINC-1, IL-1α, and L-selectin) in ischemia. In summary, our histological and molecular analysis showed that maxadilan, a selective PAC1 receptor agonist, has a protective role in BCCAO-induced retinal degeneration, further supporting the role of PAC1 receptor conveying the retinoprotective effects of PACAP.

  10. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains twelve separate reports on an estimation of the possibility of fusion reactions in water molecules, an analysis of pion spectra of the charge-exchange reaction Mg(t, 3 He), the results of simulation of e + e - pair production and detection in the ALICE experiment, the data on the edge effects in multiwire proportional chambers, standard and nonstandard applications of wavelet analysis, the design and study of light readout system for scintillator shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, a study of multiparticle azimuthal correlations in high energy interactions, coherent multifragmentation of relativistic nuclei, superposition of neutrino eigenstates and neutrino oscillation, simulation results and suggestions for possible design of gaseous shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, determination of the sizes of the pion emission region in np-interactions at P n =(5.2±0.16)GeV/c using the interference correlation method for identical particles, inelasticity of nucleus-nucleus collisions in the CMS experiment. 65 figs., 19 tabs

  11. Effect of phenolic compounds on the rapid direct enzymatic ...

    African Journals Online (AJOL)

    2009-05-15

    May 15, 2009 ... A range of bioprobes and biosensors have recently been developed for the rapid, direct and in situ .... maximum absorbance of 4 mOD (milli optical density). ..... FIKSDAL L and TRYLAND I (2008) Application of rapid enzyme.

  12. 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.

  13. Redox-active thionine-graphene oxide hybrid nanosheet: One-pot, rapid synthesis, and application as a sensing platform for uric acid

    Energy Technology Data Exchange (ETDEWEB)

    Sun Zhoumin; Fu Haiying [Key Laboratory of Resources Chemistry of Nonferrous Metals, Ministry of Education, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan (China); Deng Liu, E-mail: dengliu@csu.edu.cn [Key Laboratory of Resources Chemistry of Nonferrous Metals, Ministry of Education, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan (China); Wang Jianxiu [Key Laboratory of Resources Chemistry of Nonferrous Metals, Ministry of Education, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan (China)

    2013-01-25

    Highlights: Black-Right-Pointing-Pointer A simple wet-chemical strategy for synthesis of thionine-graphene oxide hybrid nanosheets (T-GOs). Black-Right-Pointing-Pointer T-GOs serve as a biocompatible matrix for enzyme assembly and a mediator. Black-Right-Pointing-Pointer A simple and effective sensor for assay of uric acid at physiological levels. Black-Right-Pointing-Pointer Demonstrate further application of GOs for biosensors and other fields. - Abstract: In this paper, we fabricate a sensitive and stable amperometric UA amperometric biosensor using nanobiocomposite derived from thionine modified graphene oxide in this study. A simple wet-chemical strategy for synthesis of thionine-graphene oxide hybrid nanosheets (T-GOs) through {pi}-{pi} stacking has been demonstrated. Various techniques, such as UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), atomic force microscopy (AFM) and electrochemistry have been utilized to characterize the formation of the T-GOs. Due to the synergistic effect between thionine and graphene oxide, the nanosheets exhibited excellent performance toward H{sub 2}O{sub 2} reduction. The incorporation of thionine onto graphene oxide surface resulted in more than a twice increase in the amperometric response to H{sub 2}O{sub 2} of the thionine modified electrode. The as-formed T-GOs also served as a biocompatible matrix for enzyme assembly and a mediator to facilitate the electron transfer between the enzyme and the electrode. Using UOx as a model system, we have developed a simple and effective sensing platform for assay of uric acid at physiological levels. UA has been successfully detected at -0.1 V without any interference due to other electroactive compounds at physiological levels of glucose (5 mM), ascorbic acid (0.1 mM), noradrenalin (0.1 mM), and dopamine (0.1 mM). The response displays a good linear range from 0.02 to 4.5 mM with detection limit 7 {mu}M. The application

  14. Rapid efficient synthesis and characterization of silver, gold, and bimetallic nanoparticles from the medicinal plant Plumbago zeylanica and their application in biofilm control

    Directory of Open Access Journals (Sweden)

    Salunke GR

    2014-05-01

     nm (AgAuNPs, respectively. The maximum rate of synthesis at 50°C was achieved with 5 mM AgNO3 within 4.5 hours for AgNPs; and with 0.7 mM HAuCl4 within 5 hours for AuNPs. The synthesis of AgAuNPs, which completed within 90 minutes with 0.7 mM AgNO3 and HAuCl4, was found to be the fastest. Fourier-transform infrared spectroscopy confirmed bioreduction, while EDS and XRD patterns confirmed purity and the crystalline nature of the NPs, respectively. TEM micrographs and DLS showed about 60 nm monodispersed Ag nanospheres, 20–30 nm Au nanospheres adhering to form Au nanotriangles, and about 90 nm hexagonal blunt-ended AgAuNPs. These NPs also showed antimicrobial and antibiofilm activity against E. coli, A. baumannii, S. aureus, and a mixed culture of A. baumannii and S. aureus. AgNPs inhibited biofilm in the range of 96%–99% and AgAuNPs from 93% to 98% in single-culture biofilms. AuNPs also showed biofilm inhibition, with the highest of 98% in S. aureus. AgNPs also showed good biofilm disruption, with the highest of 88% in A. baumannii. Conclusion: This is the first report on rapid and efficient synthesis of AgNPs, AuNPs and AgAuNPs from P. zeylanica and their effect on quantitative inhibition and disruption of bacterial biofilms. Keywords: P. zeylanica, AgNPs, AuNPs, AgAuNPs, biofilm inhibition and disruption, GC-TOF-MS

  15. 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

  16. The rapid and direct determination of ATPase activity by ion exchange chromatography and the application to the activity of heat shock protein-90.

    Science.gov (United States)

    Bartolini, Manuela; Wainer, Irving W; Bertucci, Carlo; Andrisano, Vincenza

    2013-01-25

    Adenosine nucleotides are involved as substrates or co-factors in several biochemical reactions, catalyzed by enzymes, which modulate energy production, signal transduction and cell proliferation. We here report the development and optimization of an ion exchange liquid chromatography (LC) method for the determination of ATP, ADP and AMP. This method is specifically aimed at the determination of the ATP-ase activity of human heat shock protein 90 (Hsp90), a molecular chaperone that has emerged as target enzyme in cancer therapy. Separation of the three nucleotides was achieved in a 15-min run by using a disk shaped monolithic ethylene diamine stationary phase of small dimensions (2mm×6mm i.d.), under a three-solvent gradient elution mode and UV detection at 256nm. The described direct LC method resulted highly specific as a consequence of the baseline separation of the three adenosine nucleotides and could be applied to the determination of the enzymatic activity of ADP/ATP generating or consuming enzymes (such as kinases). Furthermore, comparison of the LOD and LOQ values of the LC method with those obtained with the malachite green assay, which is one of the most used indirect screening methodologies for ATP-ase activity, showed that the LC method has a similar range of application without presenting the drawbacks related to contamination by inorganic phosphate ions and glycerol, which are present in Hsp90 commercial samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Dispersible crystalline nanobundles of YPO{sub 4} and Ln (Eu, Tb)-doped YPO{sub 4}: rapid synthesis, optical properties and bio-probe applications

    Energy Technology Data Exchange (ETDEWEB)

    Majeed, Shafquat, E-mail: shafquatmajeed@gmail.com [Indian Institute of Science, Materials Research Centre (India); Bashir, Mohsin [Indian Institute of Science, Department of Molecular Reproduction, Development and Genetics (MRDG) (India); Shivashankar, S. A. [Indian Institute of Science, Materials Research Centre (India)

    2015-07-15

    Undoped and Ln{sup 3+} (Eu and Tb)-doped crystalline nanobundles of YPO{sub 4} were prepared by a facile microwave-assisted route with water as a solvent and without using any surfactant. TEM investigations reveal that the as-prepared powder consists of lenticular-shaped nanobundles (∼100 nm in diameter) made of very small nanorods with diameter less than 10 nm and length varying from 20 to 50 nm. Each nanorod in turn is single crystalline, as revealed by HRTEM imaging. The as-prepared nanobundles are easily dispersible in various solvents, especially water, without any surface functionalization, which is critical for various bio-probe applications like cell and tissue imaging. The Eu- and Tb-doped YPO{sub 4} nanobundles show good photoluminescence properties and were further evaluated for their use as fluorescent biolabels. Our results show that HeLa cells labelled with Eu- and Tb-doped YPO{sub 4} nanobundles show bright red (Eu) and green (Tb) intracellular luminescence under a confocal microscope. Concentration- and time-dependent MTT cell viability assays show that the nanobundles show low toxicity towards cells which makes them promising in bioimaging field.

  18. (-)-N-[11C]propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D2 receptors

    International Nuclear Information System (INIS)

    Hwang, Dah-Ren; Kegeles, Lawrence S.; Laruelle, Marc

    2000-01-01

    Imaging neuroreceptors with radiolabeled agonists might provide valuable information on the in vivo agonist affinity states of receptors of interest. We report here the radiosynthesis, biodistribution in rodents, and imaging studies in baboons of [ 11 C]-labeled (-)-N-propyl-norapomorphine [(-)-NPA]. (-)-[ 11 C]NPA was prepared by reacting norapomorphine with [ 11 C]propionyl chloride and a lithium aluminum hydride reduction. [ 11 C]Propionyl chloride was prepared by reacting [ 11 C]CO 2 with ethylmagnesium bromide, followed by reacting with phthaloyl chloride. The radiochemical yield of (-)-[ 11 C]NPA was 2.5% at end of synthesis (EOS), and the synthesis time was 60 min. The specific activity was 1700±1900 mCi/μmol ( N=7; ranged 110-5200 mCi/μmol at EOS). Rodent biodistribution studies showed high uptake of [ 11 C](-)-NPA in D 2 receptor-rich areas, and the striatum/cerebellum ratios were 1.7, 3.4, and 4.4 at 5 min, 30 min, and 60 min postinjection, respectively. Pretreating the animals with haloperidol (1 mg/kg) decreased the striatum/cerebellum ratio at 30 min postinjection to 1.3. (-)-[ 11 C]NPA was also evaluated via baboon positron emission tomography (PET) studies. Under control conditions ( N=4), rapid uptake of the tracer was observed and the striatum/cerebellum ratio reached 2.86±0.15 at 45 min postinjection. Following haloperidol pretreatment (0.2 mg/kg IV), the striatum/cerebellum ratio was 1.29 at 45 min postinjection. The result demonstrated the existence of specific binding of this new tracer to the D 2 receptor. To our knowledge, the current finding of a striatum/cerebellum ratio of 2.8 in baboon was the highest reported with a radiolabeled D 2 agonist. (-)-[ 11 C]NPA is a promising new D 2 agonist PET tracer for probing D 2 receptors in vivo using PET

  19. Effect of α{sub 7} nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

    Energy Technology Data Exchange (ETDEWEB)

    Welch, Kevin D., E-mail: kevin.welch@ars.usda.gov [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Pfister, James A. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States); Lima, Flavia G. [Federal University of Goías, School of Veterinary Medicine, Goiânia, Goías (Brazil); Green, Benedict T.; Gardner, Dale R. [USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341 (United States)

    2013-02-01

    Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline. -- Highlights: ► Mice treated with nAChR agonists and antagonists have a loss in motor function. ► These deficits are temporary as near normal motor function returns within 10 min. ► There are compound-specific differences in the effects on motor function.

  20. Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist.

    Science.gov (United States)

    Ogilvie, Brian W; Torres, Rosarelis; Dressman, Marlene A; Kramer, William G; Baroldi, Paolo

    2015-09-01

    Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans. Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin pretreatment resulted in a decrease in tasimelteon's exposure of approximately 89%. © 2015 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  1. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  2. Two new DOSXYZnrc sources for 4D Monte Carlo simulations of continuously variable beam configurations, with applications to RapidArc, VMAT, TomoTherapy and CyberKnife

    International Nuclear Information System (INIS)

    Lobo, Julio; Popescu, I Antoniu

    2010-01-01

    We present two new Monte Carlo sources for the DOSXYZnrc code, which can be used to compute dose distributions due to continuously variable beam configurations. These sources support a continuously rotating gantry and collimator, dynamic multileaf collimator (MLC) motion, variable monitor unit (MU) rate, couch rotation and translation in any direction, arbitrary isocentre motion with respect to the patient and variable source-to-axis distance (SAD). These features make them applicable to Monte Carlo simulations for RapidArc(TM), Elekta VMAT, TomoTherapy(TM) and CyberKnife(TM). Unique to these sources is the synchronization between the motion in the DOSXYZnrc geometry and the motion within the linac head, represented by a shared library (either a BEAMnrc accelerator with dynamic component modules, or an external library). The simulations are achieved in single runs, with no intermediate phase space files.

  3. Redox-active thionine-graphene oxide hybrid nanosheet: one-pot, rapid synthesis, and application as a sensing platform for uric acid.

    Science.gov (United States)

    Sun, Zhoumin; Fu, Haiying; Deng, Liu; Wang, Jianxiu

    2013-01-25

    In this paper, we fabricate a sensitive and stable amperometric UA amperometric biosensor using nanobiocomposite derived from thionine modified graphene oxide in this study. A simple wet-chemical strategy for synthesis of thionine-graphene oxide hybrid nanosheets (T-GOs) through π-π stacking has been demonstrated. Various techniques, such as UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), atomic force microscopy (AFM) and electrochemistry have been utilized to characterize the formation of the T-GOs. Due to the synergistic effect between thionine and graphene oxide, the nanosheets exhibited excellent performance toward H(2)O(2) reduction. The incorporation of thionine onto graphene oxide surface resulted in more than a twice increase in the amperometric response to H(2)O(2) of the thionine modified electrode. The as-formed T-GOs also served as a biocompatible matrix for enzyme assembly and a mediator to facilitate the electron transfer between the enzyme and the electrode. Using UOx as a model system, we have developed a simple and effective sensing platform for assay of uric acid at physiological levels. UA has been successfully detected at -0.1 V without any interference due to other electroactive compounds at physiological levels of glucose (5 mM), ascorbic acid (0.1 mM), noradrenalin (0.1 mM), and dopamine (0.1 mM). The response displays a good linear range from 0.02 to 4.5 mM with detection limit 7 μM. The application of this modified electrode in blood and urine UA exhibited a good performance. The robust and advanced hybrid materials might hold great promise in biosensing, energy conversion, and biomedical and electronic systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Preparation of immunomagnetic iron-dextran nanoparticles and application in rapid isolation of E.coli O157:H7 from foods

    Science.gov (United States)

    Duan, Hui-Li; Shen, Zhi-Qiang; Wang, Xin-Wei; Chao, Fu-Huan; Li, Jun-Wen

    2005-01-01

    AIM: To prepare a kind of magnetic iron-dextran nanoparticles that was coated with anti-E.coli O157:H7 IgG, analyze its application conditions, and try to use it to isolate E.coli O157:H7 from foods. METHODS: Magnetic iron-dextran nanoparticles were prepared by the reaction of a mixture of ferric and ferrous ions with dextran polymers under alkaline conditions. The particles were coated with antiserum against E.coli O157:H7 by the periodate oxidation-borohydride reduction procedure. The oxidation time, amount of antibody coating the particles, amount of nanoparticles, incubation time and isolation time were varied to determine their effects on recovery of the organisms. Finally, the optimum conditions for isolating E.coli O157:H7 from food samples were established. RESULTS: E.coli O157:H7 can be isolated from samples within 15 min with the sensitivity of 101 CFU/mL or even less. In the presence of 108 CFU/mL of other organisms, the sensitivity is 101-102 CFU/mL. Nonspecific binding of other bacteria to the particles was not observed. Two and a half hours of enrichment is enough for the particles to detect the target from the food samples inoculated with 1 CFU/g. CONCLUSION: Isolation of target bacteria by immuno-magnetic nanoparticles is an efficient method with high sensitivity and specificity. The technique is so simple that it can be operated in lab and field even by untrained personnel. PMID:15968716

  5. A rapid method to map the crustal and lithospheric thickness using elevation, geoid anomaly and thermal analysis. Application to the Gibraltar Arc System, Atlas Mountains and adjacent zones

    Science.gov (United States)

    Fullea, J.; Fernàndez, M.; Zeyen, H.; Vergés, J.

    2007-02-01

    We present a method based on the combination of elevation and geoid anomaly data together with thermal field to map crustal and lithospheric thickness. The main assumptions are local isostasy and a four-layered model composed of crust, lithospheric mantle, sea water and the asthenosphere. We consider a linear density gradient for the crust and a temperature dependent density for the lithospheric mantle. We perform sensitivity tests to evaluate the effect of the variation of the model parameters and the influence of RMS error of elevation and geoid anomaly databases. The application of this method to the Gibraltar Arc System, Atlas Mountains and adjacent zones reveals the presence of a lithospheric thinning zone, SW-NE oriented. This zone affects the High and Middle Atlas and extends from the Canary Islands to the eastern Alboran Basin and is probably linked with a similarly trending zone of thick lithosphere constituting the western Betics, eastern Rif, Rharb Basin, and Gulf of Cadiz. A number of different, even mutually opposite, geodynamic models have been proposed to explain the origin and evolution of the study area. Our results suggest that a plausible slab-retreating model should incorporate tear and asymmetric roll-back of the subducting slab to fit the present-day observed lithosphere geometry. In this context, the lithospheric thinning would be caused by lateral asthenospheric flow. An alternative mechanism responsible for lithospheric thinning is the presence of a hot magmatic reservoir derived from a deep ancient plume centred in the Canary Island, and extending as far as Central Europe.

  6. Simple and rapid quantification of vancomycin in serum, urine and peritoneal/pleural effusion via UHPLC-MS/MS applicable to personalized antibiotic dosing research.

    Science.gov (United States)

    Javorska, Lenka; Krcmova, Lenka Kujovska; Solich, Petr; Kaska, Milan

    2017-08-05

    Management of the therapy of life-threatening bacterial infection is extremely based on an optimal antibiotic treatment. Achieving the correct vancomycin dosage in blood and target tissues can be complicated in special situations, e.g., where large fluid sequestration and/or acute renal failure occur. A UHPLC-MS/MS method operating in electrospray (ESI) positive ion mode was applied for the determination of vancomycin in serum, urine and peritoneal/pleural effusion. Sample pretreatment was composed of dilution and simple protein precipitation where only a small volume (50μL) of serum, urine or peritoneal/pleural effusion was required. The separation of vancomycin was performed on a Meteoric Core C18 BIO column (100×4.6mm, 2.7μm) by gradient elution with 0.1% formic acid in water and acetonitrile. The total time of analysis was 4.5min. The method was found to be linear in the range of 2-60μM (or 0.5-10μM) for serum, 0.27-10μM (or 2-60μM) for peritoneal/pleural effusion and 25-300μM for urine, which was adequate for the determination of vancomycin in patient samples. The intra- and inter-day precision was below 8% RSD, and accuracy was from 89 to 104%. The UHPLC/MS-MS method offers a fast and reliable approach to determine vancomycin concentrations in three different human body fluid samples (serum, urine and peritoneal/pleural effusion) with a simple sample pretreatment that was the same for all selected specimens. This method should be applicable to large sample series in clinical (pharmacokinetic/pharmacodynamic) studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Using mobile devices for inpatient rounding and handoffs: an innovative application developed and rapidly adopted by clinicians in a pediatric hospital.

    Science.gov (United States)

    Motulsky, Aude; Wong, Jenna; Cordeau, Jean-Pierre; Pomalaza, Jorge; Barkun, Jeffrey; Tamblyn, Robyn

    2017-04-01

    To describe the usage of a novel application (The FLOW) that allows mobile devices to be used for rounding and handoffs. The FLOW provides a view of patient data and the capacity to enter short notes via personal mobile devices. It was deployed using a "bring-your-own-device" model in 4 pilot units. Social network analysis (SNA) was applied to audit trails in order to visualize usage patterns. A questionnaire was used to describe user experience. Overall, 253 health professionals used The FLOW with their personal mobile devices from October 2013 to March 2015. In pediatric and neonatal intensive care units (ICUs), a median of 26-26.5 notes were entered per user per day. Visual network representation of app entries showed that usage patterns were different between the ICUs. In 127 questionnaires (50%), respondents reported using The FLOW most often to enter notes and for handoffs. The FLOW was perceived as having improved patient care by 57% of respondents, compared to usual care. Most respondents (86%) wished to continue using The FLOW. This study shows how a handoff and rounding tool was quickly adopted in pediatric and neonatal ICUs in a hospital setting where patient charts were still paper-based. Originally developed as a tool to support informal documentation using smartphones, it was adapted to local practices and expanded to print sign-out documents and import notes within the medicolegal record with desktop computers. Interestingly, even if not supported by the nursing administrative authorities, the level of use for data entry among nurses and doctors was similar in all units, indicating close collaboration in documentation practices in these ICUs. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  8. 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...

  9. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based 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; Jones, Stacey A; Kaldor, Istvan; Liu, Yaping; 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; Wisely, G Bruce

    2008-08-01

    Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.

  10. 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

  11. Low-dose add-back therapy during postoperative GnRH agonist treatment

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Tsai

    2016-02-01

    Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

  12. Small-molecule agonists for the glucagon-like peptide 1 receptor

    DEFF Research Database (Denmark)

    Knudsen, Lotte Bjerre; Kiel, Dan; Teng, Min

    2007-01-01

    and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also...

  13. Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

    DEFF Research Database (Denmark)

    Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

    2017-01-01

    The melanocortin receptor 4 (MC4R) subtype of the melanocortin receptor family is a target for therapeutics to ameliorate metabolic dysfunction. Endogenous MC4R agonists possess a critical pharmacophore (HFRW), and cyclization of peptide agonists often enhances potency. Thus, 17 cyclized peptides...

  14. Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

    NARCIS (Netherlands)

    Michel-Reher, Martina B.; Michel, Martin C.

    2013-01-01

    β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

  15. Long-acting beta 2-agonists in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Llewellyn-Jones, Carol

    2002-01-01

    Until recently, the use of long-acting beta 2-agonists in chronic obstructive pulmonary disease has been understated. There is now evidence that they may offer benefits beyond bronchodilation. This article reviews the management of chronic obstructive pulmonary disease and looks at the place of long-acting beta 2-agonists as a first-line treatment option.

  16. Long-term outcome of patients with macroprolactinomas initially treated with dopamine agonists

    NARCIS (Netherlands)

    Kars, Marleen; Pereira, Alberto M.; Smit, Johannes W.; Romijn, Johannes A.

    2009-01-01

    Dopamine agonists are the first line therapy for the treatment of prolactinomas. The aim of this study was to assess the outcome of macroprolactinomas during long-term follow-up after initial treatment with dopamine agonists. Retrospective follow-up study. We included 72 consecutive patients (age

  17. Helminthosporic acid functions as an agonist for gibberellin receptor.

    Science.gov (United States)

    Miyazaki, Sho; Jiang, Kai; Kobayashi, Masatomo; Asami, Tadao; Nakajima, Masatoshi

    2017-11-01

    Helminthosporol was isolated from a fungus, Helminthosporium sativum, as a natural plant growth regulator in 1963. It showed gibberellin-like bioactivity that stimulated the growth of the second leaf sheath of rice. After studying the structure-activity relationship between the compound and some synthesized analogs, it was found that helminthosporic acid (H-acid) has higher gibberellin-like activity and chemical stability than helminthosporol. In this study, we showed that (1) H-acid displays gibberellin-like activities not only in rice but also in Arabidopsis, (2) it regulates the expression of gibberellin-related genes, (3) it induces DELLA degradation through binding with a gibberellin receptor (GID1), and (4) it forms the GID1-(H-acid)-DELLA complex to transduce the gibberellin signal in the same manner as gibberellin. This work shows that the H-acid mode of action acts as an agonist for gibberellin receptor.

  18. 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.

  19. Climate Change Journalism: From Agony to Agonistic Debate

    Directory of Open Access Journals (Sweden)

    Yves Pepermans

    2017-04-01

    Full Text Available Starting from a politicized outlook on climate change, this essay criticizes mainstream journalistic norms for failing to enable an agonistic, democratic debate about how to move forward. Based on a targeted search for examples from the reporting (and reflection thereof of two Dutch-speaking alternative news sites (DeWereldMorgen and De Correspondent, we seek to illustrate how their respective (climate journalists look for truth, generate democratic debate and hold power accountable by combining practices from constructive journalism, slow journalism and advocacy journalism. We find these journalists to focus on patterns, root causes and underlying values, rather than on novelty or exceptional events. Furthermore, an impartial and detached style of reporting is explicitly denounced in favor of an open and reflexive choice of news-making based on advocacy.

  20. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

    Science.gov (United States)

    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 thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range. PMID:23365787

  1. TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

    Directory of Open Access Journals (Sweden)

    Johannes W. Dietrich

    2012-01-01

    Full Text Available 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 thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range.

  2. INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.

    Science.gov (United States)

    Mahon, Eugene J

    2015-07-01

    In this reading of Sophocles's Oedipus the King, the author suggests that insight can be thought of as the main protagonist of the tragedy. He personifies this depiction of insight, calling it Insight Agonistes, as if it were the sole conflicted character on the stage, albeit masquerading at times as several other characters, including gods, sphinxes, and oracles. This psychoanalytic reading of the text lends itself to an analogy between psychoanalytic process and Sophocles's tragic hero. The author views insight as always transgressing against, always at war with a conservative, societal, or intrapsychic chorus of structured elements. A clinical vignette is presented to illustrate this view of insight. © 2015 The Psychoanalytic Quarterly, Inc.

  3. N-methyl-D-aspartic acid receptor agonists

    DEFF Research Database (Denmark)

    Madsen, U; Frydenvang, Karla Andrea; Ebert, B

    1996-01-01

    (R,S)-2-Amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid [(R,S)-AMAA, 4] is a potent and selective agonist at the N-methyl-D-aspartic acid (NMDA) subtype of excitatory amino acid receptors. Using the Ugi "four-component condensation" method, the two diastereomers (2R)- and (2S)-2-[3-(benzyloxy......) showed peak affinity for [3H]AMPA receptor sites (IC50 = 72 +/- 13 microM) and was shown to be a more potent inhibitor of [3H]CPP binding (IC50 = 3.7 +/- 1.5 microM) than (S)-AMAA (9) (IC50 = 61 +/- 6.4 microM). Neither enantiomer of AMAA affected [3H]kainic acid receptor binding significantly...

  4. [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.

  5. 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.

    2012-01-01

    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 A1 receptor (A1R). In contrast, AMP only activated the adenosine A2B receptor (A2BR) after hydrolysis to adenosine by ecto-5′-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A1R 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 A1R. 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 A1R 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 A1R. 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. PMID:22215671

  6. 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...

  7. An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.

    Science.gov (United States)

    Uchiyama, Masaaki; Shimizu, Akira; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

    2013-01-01

    We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.

  8. An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model

    Science.gov (United States)

    Uchiyama, Masaaki; Masuda, Yukinari; Nagasaka, Shinya; Fukuda, Yuh; Takahashi, Hiroshi

    2013-01-01

    Purpose We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats. Methods After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed. Results After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation. Conclusions The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing. PMID:24194635

  9. Rapid improvement teams.

    Science.gov (United States)

    Alemi, F; Moore, S; Headrick, L; Neuhauser, D; Hekelman, F; Kizys, N

    1998-03-01

    Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

  10. Rapid mask prototyping for microfluidics.

    Science.gov (United States)

    Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

    2016-03-01

    With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

  11. Promotion of Wound Healing by an Agonist of Adenosine A2A Receptor Is Dependent on Tissue Plasminogen Activator.

    Science.gov (United States)

    Montesinos, M Carmen; Desai-Merchant, Avani; Cronstein, Bruce N

    2015-12-01

    Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid treatment, is commonly associated with disability, diminished quality of life, and high economic costs. Selective agonists of the A2A receptor subtype of adenosine, an endogenous regulator of inflammation, promote tissue repair in animal models, both healthy and with impaired healing. Plasmin-mediated proteolysis of fibrin and other matrix proteins is essential for cell migration at sites of injury. Since adenosine A2A receptor activation increases plasminogen activator release from macrophages and mast cells, we studied the effect of a selective agonist, CGS-21680, on full-thickness excisional wound closure in wild-type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen activator (tPA)-deficient mice. Wound closure was impaired in tPA- and uPA-deficient mice as compared with wild-type mice, and topical application of CGS-21680 significantly increased the rate at which wounds closed in wild-type mice and uPA-deficient mice, but not in tPA-deficient mice. Immunostaining of tissue sections showed that tPA was present in endothelial cells and histiocytes by day 3 post-wound and also by day 6. In contrast, uPA was more prominent in these cell types only by day 6 post-wound. Our results confirm that plasminogen activation contributes to wound repair and are consistent with the hypothesis that adenosine A2A receptor activation promotes wound closure by a mechanism that depends upon tPA, but not uPA. Moreover, our results suggest that topical adenosine A2A receptor agonists may be useful in promotion of wound closure in patients with impaired wound healing.

  12. Rapid-scan EPR imaging.

    Science.gov (United States)

    Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas; Buchanan, Laura A; McPeak, Joseph; Quine, Richard W; Rinard, George A; Epel, Boris; Halpern, Howard J; Eaton, Gareth R

    2017-07-01

    In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Rapid response systems.

    Science.gov (United States)

    Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

    2018-07-01

    Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells.

    Science.gov (United States)

    Ning, R B; Zhu, J; Chai, D J; Xu, C S; Xie, H; Lin, X Y; Zeng, J Z; Lin, J X

    2013-12-13

    An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.

  15. 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.

  16. Ascorbic acid enables reversible dopamine receptor 3H-agonist binding

    International Nuclear Information System (INIS)

    Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

    1981-01-01

    The effects of ascorbic acid on dopaminergic 3 H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the 3 H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total 3 H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable 3 H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable 3 H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of 3 H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific 3 H-agonist binding to dopamine receptors

  17. Hydroxyapatite hierarchically nanostructured porous hollow microspheres: rapid, sustainable microwave-hydrothermal synthesis by using creatine phosphate as an organic phosphorus source and application in drug delivery and protein adsorption.

    Science.gov (United States)

    Qi, Chao; Zhu, Ying-Jie; Lu, Bing-Qiang; Zhao, Xin-Yu; Zhao, Jing; Chen, Feng; Wu, Jin

    2013-04-22

    Hierarchically nanostructured porous hollow microspheres of hydroxyapatite (HAP) are a promising biomaterial, owing to their excellent biocompatibility and porous hollow structure. Traditionally, synthetic hydroxyapatite is prepared by using an inorganic phosphorus source. Herein, we report a new strategy for the rapid, sustainable synthesis of HAP hierarchically nanostructured porous hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through a microwave-assisted hydrothermal method. The as-obtained products are characterized by powder X-ray diffraction (XRD), Fourier-transform IR (FTIR) spectroscopy, SEM, TEM, Brunauer-Emmett-Teller (BET) nitrogen sorptometry, dynamic light scattering (DLS), and thermogravimetric analysis (TGA). SEM and TEM micrographs show that HAP hierarchically nanostructured porous hollow microspheres consist of HAP nanosheets or nanorods as the building blocks and DLS measurements show that the diameters of HAP hollow microspheres are within the range 0.8-1.5 μm. The specific surface area and average pore size of the HAP porous hollow microspheres are 87.3 m(2) g(-1) and 20.6 nm, respectively. The important role of creatine phosphate disodium salt and the influence of the experimental conditions on the products were systematically investigated. This method is facile, rapid, surfactant-free and environmentally friendly. The as-prepared HAP porous hollow microspheres show a relatively high drug-loading capacity and protein-adsorption ability, as well as sustained drug and protein release, by using ibuprofen as a model drug and hemoglobin (Hb) as a model protein, respectively. These experiments indicate that the as-prepared HAP porous hollow microspheres are promising for applications in biomedical fields, such as drug delivery and protein adsorption. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Binding Mode of Insulin Receptor and Agonist Peptide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two α subunits with a molecular weight of 135 kD and twoβ subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular α subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the α subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide.We employed the extracellular domain (PDBID: 1IGR) of the insulin-like growth factor-1 receptor (IGF-1 R ) as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides.Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small

  19. 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.

  20. Rapid molecular biosensing for medical applications

    NARCIS (Netherlands)

    Prins, M.W.J.

    2015-01-01

    An important challenge in today’s societies is that life expectancy and the prevalence of chronic conditions are increasing. This puts pressure on the healthcare system and raises a demand for easy to use and cost-effective medical technologies in order to manage chronic conditions outside large

  1. 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...

  2. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Brink, Willem van den; Emerenciana, Annette [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands); Bellanti, Francesco [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Della Pasqua, Oscar [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, Uxbridge (United Kingdom); Clinical Pharmacology & Therapeutics, UCL, School of Life and Medical Sciences, London (United Kingdom); Laan, Jan Willem van der, E-mail: jw.vd.laan@cbg-meb.nl [Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands)

    2017-04-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

  3. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

    International Nuclear Information System (INIS)

    Brink, Willem van den; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; Laan, Jan Willem van der

    2017-01-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

  4. Cognitive-Behavioral Therapy for Rapid Cycling Bipolar Disorder

    Science.gov (United States)

    Reilly-Harrington, Noreen A.; Knauz, Robert O.

    2005-01-01

    This article describes the application of cognitive-behavioral therapy (CBT) to the treatment of rapid cycling bipolar disorder. Between 10% and 24% of bipol