WorldWideScience

Sample records for remotec andros mk

  1. Enhanced control and sensing for the REMOTEC ANDROS Mk VI robot. CRADA final report

    International Nuclear Information System (INIS)

    Spelt, P.F.; Harvey, H.W.

    1998-01-01

    This Cooperative Research and Development Agreement (CRADA) between Lockheed Martin Energy Systems, Inc., and REMOTEC, Inc., explored methods of providing operator feedback for various work actions of the ANDROS Mk VI teleoperated robot. In a hazardous environment, an extremely heavy workload seriously degrades the productivity of teleoperated robot operators. This CRADA involved the addition of computer power to the robot along with a variety of sensors and encoders to provide information about the robot's performance in and relationship to its environment. Software was developed to integrate the sensor and encoder information and provide control input to the robot. ANDROS Mk VI robots are presently used by numerous electric utilities to perform tasks in reactors where substantial exposure to radiation exists, as well as in a variety of other hazardous environments. Further, this platform has potential for use in a number of environmental restoration tasks, such as site survey and detection of hazardous waste materials. The addition of sensors and encoders serves to make the robot easier to manage and permits tasks to be done more safely and inexpensively (due to time saved in the completion of complex remote tasks). Prior research on the automation of mobile platforms with manipulators at Oak Ridge National Laboratory's Center for Engineering Systems Advanced Research (CESAR, B ampersand R code KC0401030) Laboratory, a BES-supported facility, indicated that this type of enhancement is effective. This CRADA provided such enhancements to a successful working teleoperated robot for the first time. Performance of this CRADA used the CESAR laboratory facilities and expertise developed under BES funding

  2. Development of a radiation hardened ANDROS robot for environmental restoration and waste management operations

    International Nuclear Information System (INIS)

    Tulenko, J.S.; Youk, G.; Ekdahl, D.; Liu, H.; Zhou, H.; Phillips, K.; Sias, F.; Jones, S.; Cable, T.; Harvey, H.

    1995-01-01

    A radiation hardened and tolerant version of the ANDROS V-A and VI-A system has been developed by a team composed of engineers and scientists from REMOTEC, Inc. and the University of Florida. The final upgrade of the major control components to a hardness level greater than one megarad is detailed. Over twelve hundred parts were reviewed. The project has completed its Phase 1 and Phase 2 SBIR redesign with the upgrade of all control components. The facilities at the University of Florida which include a linear accelerator and multiple cobalt irradiators have provided the capability to perform the extensive testing required. The commercial production of this radiation hardened ANDROS makes available a mobile platform that can serve as a main work and inspection system for hazardous tasks facing the world nuclear industry

  3. CAMEX-4 ANDROS ISLAND RAWINSONDE AND RADIOSONDES V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 Andros Lisland Rawinsonde and Radiosondes dataset was collected by using numerous rawinsondes (radiosondes), which were launched from Andros Island in...

  4. ANDROS: A code for Assessment of Nuclide Doses and Risks with Option Selection

    International Nuclear Information System (INIS)

    Begovich, C.L.; Sjoreen, A.L.; Ohr, S.Y.; Chester, R.O.

    1986-11-01

    ANDROS (Assessment of Nuclide Doses and Risks with Option Selection) is a computer code written to compute doses and health effects from atmospheric releases of radionuclides. ANDROS has been designed as an integral part of the CRRIS (Computerized Radiological Risk Investigation System). ANDROS reads air concentrations and environmental concentrations of radionuclides to produce tables of specified doses and health effects to selected organs via selected pathways (e.g., ingestion or air immersion). The calculation may be done for an individual at a specific location or for the population of the whole assessment grid. The user may request tables of specific effects for every assessment grid location. Along with the radionuclide concentrations, the code requires radionuclide decay data, dose and risk factors, and location-specific data, all of which are available within the CRRIS. This document is a user manual for ANDROS and presents the methodology used in this code

  5. Quality of life for aging men and effects of Andro nutraceuticals

    NARCIS (Netherlands)

    Zhang, H.; Wang, A.R.; Mo, H.Z.; Yang Zhu, Yang

    2007-01-01

    The deterioration of life quality of aging men is mostly associated with metabolic syndrome, based on statistics of the Andros Men's Health Institute in Arnhem, Netherlands. Aging is an inevitable natural process accompanied by several kinds of decline of body function that influences the quality of

  6. Andro Kööp : "Püüan ruumi tunnet maalida" / Gitte Hint

    Index Scriptorium Estoniae

    Hint, Gitte

    2003-01-01

    Andro Kööp (sünd. 1967) sellest, kuidas ta sattus sisearhitektuuriga tegelema, oma eelistustest ja harmooniast sisekujunduses, kodu kujundusest jm. A. Kööbist, tema loomingust, omistatud preemiad, valik A. Kööbi kujundatud ühiskondlikke interjööre. Ill.: värv. foto A. Kööbist

  7. Andro Kööp : villa, mis sai ajaloo / Gitte Hint

    Index Scriptorium Estoniae

    Hint, Gitte

    2003-01-01

    Saaremaal asuva arhitekt Ike Volkovi projekti järgi ehitatud villa sisekujundus. Sisearhitekt Andro Kööp, tema kommentaarid. A. Kööp on kavandanud ka vaibad. Suures osas on villa sisekujunduses kasutatud kataloogimööblit. Ill.: I ja II korruse plaan, 17 värv. vaadet

  8. Habitat Distribution of Birds Wintering in Central Andros, The Bahamas: Implications for Management

    Science.gov (United States)

    DAVE CURRIE; JOSEPH M. WUNDERLE JR.; DAVID N. EWERT; MATTHEW R. ANDERSON; ANCILLENO DAVIS; JASMINE TURNER

    2005-01-01

    We studied winter avian distribution in three representative pine-dominated habitats and three broadleaf habitats in an area recently designated as a National Park on Andros Island, The Bahamas, 1-23 February 2002. During 180 five-minute point counts, 1731 individuals were detected (1427 permanent residents and 304 winter residents) representing 51 species (29...

  9. Temperature profile data collected from the ALE ANDRO DE HUMBOLDT from 19 September 1971 to 26 September 1971 (NODC Accession 7500942)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Temperature profile data were collected using bottle casts from the ALE ANDRO DE HUMBOLDT in the coastal waters of California from 19 September 1971 to 26 September...

  10. PHYTOPLANKTON - WET WEIGHT and Other Data from ALE ANDRO DE HUMBOLDT From North Pacific Ocean from 19780108 to 19780407 (NODC Accession 9700071)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Phytoplankton data were collected from net tows from the Ale Andro De Humboldt in the North Pacific Ocean from 08 January 1978 to 07 April 1978. Chlorophyll A and...

  11. Sigand : une application SIG sous androïd (tablette de la gestion des chantiers

    Directory of Open Access Journals (Sweden)

    CHAKIB SAFAR BATI

    2016-12-01

    Full Text Available L’introduction de données terrain pour les études environnementales ou de gestion de l’espace, régionales ou locales est une nécessité incontournable pour la validation des traitements et des interprétations mais aussi pour fournir des compléments d’informations aux divers travaux. Mais ce retour terrain est également de plus en plus demandé pour les gestionnaires de chantiers et de projets qui ont une exigence de contrôle ou de suivi et donc d’une information temps réel sur l’avancement des travaux, autrement pour introduire de nouvelles informations sur la base de données géoréférencées. Les avancées technologiques en matière de manipulation de l’information géographique (GPS, tablette graphique, téléphone portable, réalité augmentée permettent d’espérer la mise à dispositiondes professionnels, voire d’un plus large public, des outils adéquats pour de tels travaux. Actuellement, les outils d’élaboration, de gestion et d’exploitation des bases de données géographiques (solutions SIG ne sont pas encore complètement opérationnels en version « tablette » ; des applications telles que Qgis ou ArcGis sous Androïd attendent encore des développements. Nous présentons ici la première version d’une application SIG sous Androïd (disponible sur tablette pour la gestion en temps réel des chantiers qui permet de charger des couches vectorielles et de les mettre à jour sur le terrain en fonction de l’observation directe ; les couches (préalablement géoréférencées sont projetées sur des fonds cartographiques fournis par un serveur cartographique Google Maps (Route, Satellite, terrain; dans le cas d’absence de connexion internet, le fond cartographique est ramené d’un cache. Nous utilisons SpatialiteAndroïd pour le stockage et la manipulation des données géographiques. Le contrôleur de cartes Google Maps est employé pour afficher en mode cartographique les données stockées dans

  12. Inferred vs Realized Patterns of Gene Flow: An Analysis of Population Structure in the Andros Island Rock Iguana

    Science.gov (United States)

    Colosimo, Giuliano; Knapp, Charles R.; Wallace, Lisa E.; Welch, Mark E.

    2014-01-01

    Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst =  0.117, p0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes. PMID:25229344

  13. Inferred vs realized patterns of gene flow: an analysis of population structure in the Andros Island Rock Iguana.

    Science.gov (United States)

    Colosimo, Giuliano; Knapp, Charles R; Wallace, Lisa E; Welch, Mark E

    2014-01-01

    Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst =  0.117, p<0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes.

  14. Inferred vs realized patterns of gene flow: an analysis of population structure in the Andros Island Rock Iguana.

    Directory of Open Access Journals (Sweden)

    Giuliano Colosimo

    Full Text Available Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst =  0.117, p<<0.01. These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes.

  15. AndroBird - ein neues GPS-basiertes Erfassungssystem für Vögel, Amphibien und Reptilien für Android-Smartphones

    OpenAIRE

    Braun, Michael; Braun, Andreas; Heine, Georg

    2013-01-01

    AndroBird is a new freeware app (Google Playstore) for logging of birds, amphibians and reptiles. It works with Android Smartphones Vers. 2.1 and beyond. Based on GPS (Global Positioning System), observations in the field are logged and later exported to MiniAvi, a powerful ornithological software for Windows. Major functions of AndroBird include species lists for birds, amphibians and reptiles, GPS tracking (only possible with GPS-Smartphones) using heading and distance (up to 10 km) for pos...

  16. Antidepressant Effects of (+)-MK-801 and (-)-MK-801 in the Social Defeat Stress Model

    Science.gov (United States)

    Yang, Bangkun; Ren, Qian; Ma, Min; Chen, Qian-Xue

    2016-01-01

    Background: Current data on antidepressant action of the N-methyl-D-aspartate receptor antagonist, (+)-MK-801, is inconsistent. This study was conducted to examine the effects of (+)-MK-801 and its less potent stereoisomer, (-)-MK-801, in the social defeat stress model of depression. Methods: The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. Results: In the tail suspension and forced swimming tests, both stereoisomers significantly attenuated increased immobility time in susceptible mice. In the sucrose preference test, (+)-MK-801, but not (-)-MK-801, significantly enhanced reduced sucrose consumption 2 or 4 days after a single dose. However, no antianhedonia effects were detected 7 days after a single dose of either stereoisomer. Conclusions: Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days). PMID:27608811

  17. A 20mK temperature sensor

    International Nuclear Information System (INIS)

    Wang, N.; Sadoulet, B.; Shutt, T.

    1987-11-01

    We are developing a 20mK temperature sensor made of neutron transmutation doped (NTD) germanium for use as a phonon detector in a dark matter search. We find that NTD germanium thermistors around 20mK have resistances which are a strong function of temperature, and have sufficient sensitivity to eventually reach a base line rms energy fluctuation of 6eV at 25mK. Further work is needed to understand the extreme sensitivity of the thermistors to bias power. 13 refs., 18 figs

  18. Rationale, design and methods of the ESPRIT study: Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy, in hypogonadal men.

    Science.gov (United States)

    Behre, Hermann M; Heinemann, Lothar; Morales, Alvaro; Pexman-Fieth, Claire

    2008-06-01

    Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality, and also affect quality of life. The ESPRIT study (Energy, Sexual desire and body PropoRtions wIth AndroGel, Testosterone 1% gel therapy) is a 6-month, multinational, open label, observational study in hypogonadal men being treated with transdermal AndroGel in usual daily clinical practice; 1,700-2,400 patients will be enrolled in Canada, Germany, Central and Eastern Europe, Russia and the Middle East. The main objective will be to evaluate the effect of AndroGel on symptoms of hypogonadism and quality of life as assessed by the Aging Males' Symptoms scale. Further objectives include evaluating the effect and time to onset of improvement in erectile dysfunction and libido/sexual desire (International Index of Erectile Function), fatigue (Multi-dimensional Fatigue Index) and body composition (waist circumference, body mass index). Subgroup analyses will be performed: or = 50 years; absence versus presence of metabolic syndrome. The safety of AndroGel will also be assessed. The study population will consist of newly diagnosed hypogonadal men (age > or = 18 years), in whom testosterone deficiency has been confirmed by clinical features and biochemical tests according to international guidelines, who are currently being prescribed AndroGel (testosterone 1% gel, starting dose 50 mg testosterone per day).

  19. JOYO MK-II core characteristics database

    International Nuclear Information System (INIS)

    Tabuchi, Shiro; Aoyama, Takafumi; Nagasaki, Hideaki; Kato, Yuichi

    1998-12-01

    The experimental fast reactor JOYO served as the MK-II irradiation bed core for testing fuel and material for FBR development for 15 years from 1982 to 1997. During the MK-II operation, extensive data were accumulated from the core characteristics tests conducted in thirty-one duty operations and thirteen special test operations. These core management data and core characteristics data were compiled into a database. The code system MAGI has been developed and used for core management of JOYO MK-II, and the core characteristics and the irradiation test conditions were calculated using MAGI on the basis of three dimensional diffusion theory with seven neutron energy groups. The core management data include extensive data, which were recorded on CD-ROM for user convenience. The data are specifications and configurations of the core, and for about 300 driver fuel subassemblies and about 60 uninstrumented irradiation subassemblies are core composition before and after irradiation, neutron flux, neutron fluences, fuel and control rod burn-up, and temperature and power distributions. MK-II core characteristics and test conditions were stored in the database for post analysis. Core characteristics data include excess reactivities, control rod worths, and reactivity coefficients, e.g., temperature, power and burn-up. Test conditions include both measured and calculated data for irradiation conditions. (author)

  20. JOYO MK-II core characteristics database

    International Nuclear Information System (INIS)

    Ohkawachi, Yasushi; Maeda, Shigetaka; Sekine, Takashi; Aoyama, Takafumi

    2003-04-01

    The 'JOYO' MK-II core characteristics database was compiled and published in 1998. Comments and requests from many users led to the creation of a revised edition. The revisions include changes to the MAGI calculation code system to use the 70 group JFS-3-J3.2 constant set processed from the JENDL-3.2 library. Total control rod worth, reactor kinetic parameters and the MK-II core performance test results were included per user's requests. The core characteristics obtained from the 32 nd to 35 th operational cycles, which were conducted in the MK-III transition core, were newly added in this revised version. The MK-II core management data and core characteristics data were recorded to CD-ROM for user convenience. The Configuration Data' include the core arrangement and refueling record for each operational cycle. The 'Subassembly Library Data' include the atomic number density, neutron fluence, burn-up, integral power of 362 driver fuel subassemblies and 69 irradiation test subassemblies. The 'Output Data' contain the calculated neutron flux, gamma flux, power density, linear heat rate, coolant and fuel temperature distribution of all the fuel subassemblies at the beginning and end of each operational cycle. The 'Core Characteristics Data' include the measured excess reactivity, control rod worth calibration curve, and reactivity coefficients of temperature, power and burn-up. (author)

  1. Reference design (MK-I and MK-II) for experimental multi-purpose VHTR

    International Nuclear Information System (INIS)

    Miyamoto, Yoshiaki; Suzuki, Kunihiko; Sato, Sadao

    1975-10-01

    This report summarizes the results of a study on thermal and mechanical performances of the core, which are obtained in course of reference design (Mk-I and Mk-II) for the experimental multi-purpose VHTR: (1) Design criteria, design methods and design data. These bases are also discussed in order to refer in the case of proceeding a next design work. (2) The results of performance analysis such as the initial core and its prediction for the irradiated core. (auth.)

  2. Crucial roles of the protein kinases MK2 and MK3 in a mouse model of glomerulonephritis.

    Directory of Open Access Journals (Sweden)

    Adam J Guess

    Full Text Available Elevated mitogen-activated protein kinase p38 (p38 MAPK signaling has been implicated in various experimental and human glomerulopathies, and its inhibition has proven beneficial in animal models of these diseases. p38 MAPK signaling is partially mediated through MK2 and MK3, two phylogenetically related protein kinases that are its direct substrates. The current study was designed to determine the specific roles of MK2 and MK3 in a mouse model of acute proliferative glomerulonephritis, using mice with disrupted MK2 and/or MK3 genes. We found that the absence of MK3 alone worsened the disease course and increased mortality slightly compared to wild-type mice, whereas the absence of MK2 alone exhibited no significant effect. However, in an MK3-free background, the disease course depended on the presence of MK2 in a gene dosage-dependent manner, with double knock-out mice being most susceptible to disease induction. Histological and renal functional analyses confirmed kidney damage following disease induction. Because the renal stress response plays a crucial role in kidney physiology and disease, we analyzed the stress response pattern in this disease model. We found that renal cortices of diseased mice exhibited a pronounced and specific pattern of expression and/or phosphorylation of stress proteins and other indicators of the stress response (HSPB1, HSPB6, HSPB8, CHOP, eIF2α, partially in a MK2/MK3 genotype-specific manner, and without induction of a general stress response. Similarly, the expression and activation patterns of other protein kinases downstream of p38 MAPK (MNK1, MSK1 depended partially on the MK2/MK3 genotype in this disease model. In conclusion, MK2 and MK3 together play crucial roles in the regulation of the renal stress response and in the development of glomerulonephritis, which can potentially be exploited to develop novel therapeutic approaches to treat glomerular disease.

  3. MK classification of evolved blue stars in the halo

    International Nuclear Information System (INIS)

    Garrison, R.F.

    1987-01-01

    The problem of the masses and origin of the evolved blue stars is very complex. No single approach can give all the answers unambiguously; it would be naive to suppose otherwise. The MK process and the MK system give a perspective which complements photometric, kinematic, high dispersion and other quantitative data. It is useful to know which stars are similar (or not) in spectral morphology, so that interesting candidates can be selected for further study. In many cases, the gross physical characteristics can be fairly well determined by use of the MK System. 8 references

  4. SAFARI engineering model 50 mK cooler

    Science.gov (United States)

    Duband, L.; Duval, J. M.; Luchier, N.

    2014-11-01

    SAFARI is an infrared instrument developed by a European based consortium to be flown in SPICA, a Japanese led mission. The SAFARI detectors are transition edge sensors (TES) and require temperatures down to 50 mK for their operation. For that purpose we have developed a hybrid architecture based on the combination of a 300 mK sorption stage and a small adiabatic demagnetization stage. An engineering model has been designed to provide net heat lifts of 0.4 and 14 μW respectively at 50 and 300 mK, with an overall cycle duration of 48 h and a duty cycle objective of over 75%. The cooler is self-contained, fits in a volume of 156 × 312 × 182 mm and is expected to weigh 5.1 kg. It has been designed to withstand static loads of 120 g and a random vibration level of 21 g RMS.

  5. Neutral particle retention in the JET MK I divertor

    International Nuclear Information System (INIS)

    Ehrenberg, J.K.; Campbell, D.J.; Harbour, P.J.; Horton, L.D.; Loarte, A.; McCormick, G.K.; Monk, R.D.; Saibene, G.R.; Simonini, R.; Taroni, A.; Stamp, M.F.

    1997-01-01

    Retention of neutral deuterium and nitrogen in the JET MK I divertor has been investigated. Results show that ohmic plasma detachment reduces deuterium retention, that the magnetic divertor configuration has some influence on the achievable deuterium retention, and that nitrogen in nitrogen-seeded steady state detached H-mode discharges accumulates in the divertor. (orig.)

  6. Agitation within Mk-42 insert caused by air sparge

    International Nuclear Information System (INIS)

    Ramsey, C.J.

    1991-01-01

    Dissolution of Rocky Flats Pu alloys and Pu metal using a ''nested insert'' configuration (One Well Insert (S-3352) inside the Mk-42 Insert) will require a Nuclear Safety Study, a major assumption of which will be that the annular dissolver is well-mixed. The ''well-mixed'' assumption was theoretically and experimentally supported for alloy dissolution using the Three Well Insert, but the present situation differs significantly. In the former case, the insert was directly exposed to the agitation induced by air sparging; in the case under consideration, the One Well Insert would be shielded by the Mk-42 Insert. In an effort to determine if the ''nested insert'' approach should be pursued, the past studies and technical literature have been surveyed and an attempt made to predict the extent of mixing and bulk circulation for a ''nested insert'' configuration in the presence of air sparging

  7. MK3 modulation affects BMI1-dependent and independent cell cycle check-points.

    Directory of Open Access Journals (Sweden)

    Peggy Prickaerts

    Full Text Available Although the MK3 gene was originally found deleted in some cancers, it is highly expressed in others. The relevance of MK3 for oncogenesis is currently not clear. We recently reported that MK3 controls ERK activity via a negative feedback mechanism. This prompted us to investigate a potential role for MK3 in cell proliferation. We here show that overexpression of MK3 induces a proliferative arrest in normal diploid human fibroblasts, characterized by enhanced expression of replication stress- and senescence-associated markers. Surprisingly, MK3 depletion evokes similar senescence characteristics in the fibroblast model. We previously identified MK3 as a binding partner of Polycomb Repressive Complex 1 (PRC1 proteins. In the current study we show that MK3 overexpression results in reduced cellular EZH2 levels and concomitant loss of epigenetic H3K27me3-marking and PRC1/chromatin-occupation at the CDKN2A/INK4A locus. In agreement with this, the PRC1 oncoprotein BMI1, but not the PCR2 protein EZH2, bypasses MK3-induced senescence in fibroblasts and suppresses P16INK4A expression. In contrast, BMI1 does not rescue the MK3 loss-of-function phenotype, suggesting the involvement of multiple different checkpoints in gain and loss of MK3 function. Notably, MK3 ablation enhances proliferation in two different cancer cells. Finally, the fibroblast model was used to evaluate the effect of potential tumorigenic MK3 driver-mutations on cell proliferation and M/SAPK signaling imbalance. Taken together, our findings support a role for MK3 in control of proliferation and replicative life-span, in part through concerted action with BMI1, and suggest that the effect of MK3 modulation or mutation on M/SAPK signaling and, ultimately, proliferation, is cell context-dependent.

  8. Manned Certification Tests of the Modernized MK 16 MOD 1

    Science.gov (United States)

    2013-11-01

    three oxygen sensors in the breathing loop and add oxygen via a piezo -electric valve if oxygen partial pressure (PO2) drops below a designated...approved for use in the MK 16 requires that a 6 kΩ resistor be present (no tolerance given) for best 5 function of the sensor’s temperature...external 6.0 kΩ resistor was then inserted between the voltage source and the sensor connector and the secondary reading was noted. RESULTS A

  9. Resurfacing the Jodrell Bank Mk II radio telescope

    Science.gov (United States)

    Spencer, R. E.; Haggis, J. S.; Morrison, I.; Davis, R. J.; Melling, R. J.

    The improvement of the short-wavelength performance of the Jodrell Bank Mk II radio telescope is described. A final rms profile error of 0.6 mm was achieved due to the invention of an inexpensive technique of panel construction and measurement combined with the use of radio-astronomical holographic techniques to measure the telescope under actual operating conditions. Some further improvements to extend the short wavelength performance are suggested.

  10. Radiation-resistant control system

    International Nuclear Information System (INIS)

    Cable, T.C.; Jones, S.

    1995-01-01

    REMOTEC has developed a open-quotes radiation resistanceclose quotes control system under a U.S. Department of Energy Small Business Innovative Research (SBIR) contract with assistance from the University of Florida. The SBIR goal was to develop a radiation resistant mobile robot from the ANDROS family of hazardous duty mobile robots that REMOTEC manufactures. See Refs. 1 and 2 for additional SBIR results. The control system, as well as the entire ANDROS robot, was redesigned, where necessary, to withstand radiation doses in excess of 10 6 rad. Those components of the robot that could not be purchased as open-quotes radiation hardenedclose quotes were tested under standard operating conditions for determination of their open-quotes radiation resistance.close quotes The entire ANDROS robot was then assembled with these new components and tested to > 10 6 rad

  11. Markkinointiviestintäsuunnitelma Case: MK Kivipiha Oy

    OpenAIRE

    Ruohomaa, Sami

    2011-01-01

    Tämän opinnäytetyön tarkoituksena on ollut markkinointiviestintäsuunnitelman laatiminen MK Kivipiha Oy:lle. Opinnäytetyö toteutettiin projektityönä, jonka lisäksi benchmarkkaus osiossa hyödynnettiin kvalitatiivista eli laadullista analyysiä. Lähtökohtana pidettiin suunnitelman realistisuutta ja käytännön toteuttamisen mahdollisuutta. Opinnäytetyö rakentuu kahdesta eri osiosta: teoreettisesta viitekehyksestä sekä empiirisestä osuudesta. Teoriana käytettiin katsausta perinteisen markkinointivie...

  12. Jet Propellant (JP)-8 Fuel Evaluation Test Mk II - Reset (Mk II R) Bridge Erection Boat (BEB)

    Science.gov (United States)

    2008-10-01

    diesel engines (fig. 2 and 3) equipped with Delphi rotary fuel injection pumps. Figure 1. Mk II R BEB pushing a two-bay IRB raft. TR No. WF-E-83 2... nozzles . The new pump (serial No. 08813K7B) and gasket were installed. 24 May 07 51.0 50.4 44.9 103 Port Fuel Pump and Injectors Replaced. At the...part No. 3909356) were installed on the injector nozzles . The new pump (serial No. 59640HZB) and gasket were installed. 31 May 07 51.5 50.5 44.9 104

  13. Development of JOYO MK-II core characteristics database

    International Nuclear Information System (INIS)

    Tabuchi, Shiro; Aoyama, Takafumi

    2000-01-01

    The MK-II core of the experimental fast reactor JOYO served as the irradiation bed for testing fuels and materials for FBR development since 1982 for 15 years. During the MK-II operation, extensive data were accumulated from the core management calculations and characteristics tests conducted in thirty-one duty operations and thirteen special test operations. These core management data and core characteristics data were compiled into a database recorded on CD-ROM for user convenience. The calculated core management data are the text style data. The 'Configuration Data' include the history of the fuel exchange and core arrangement for each cycle. The Subassembly Library Data' include the atomic number density, neutron fluence, burn-up, integral power of about 300 fuel subassemblies, and 60 irradiation subassemblies. The 'Output Data' include the neutron fluxes, gamma fluxes, power density, linear heat rates, coolant and fuel temperature distributions of each core position at the beginning and end of each cycle. The measured core characteristics data, such as the excess reactivity, control rod worths, temperature coefficient, power coefficient, and burn-up coefficient are also included along with the measurement conditions. (J.P.N.)

  14. The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects

    DEFF Research Database (Denmark)

    Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C.

    2015-01-01

    ; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible...... of either MK-7123 (30 mg, po, daily for 28 days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears...

  15. Synthesis and receptor binding studies of (+/-)1-iodo-MK-801

    International Nuclear Information System (INIS)

    Yang, D.J.; Ciliax, B.J.; Van Dort, M.E.; Gildersleeve, D.; Pirat, J.L.; Young, A.B.; Wieland, D.M.

    1989-01-01

    The glutamate analogue N-methyl-D-aspartate (NMDA) binds to a subset of glutamate receptors that are coupled to a voltage-sensitive cation channel. This NMDA-linked channel is the likely binding locus of the potent anticonvulsant MK-801. To develop single-photon emission computed tomography (SPECT) probes of this brain channel, we synthesized (+/)1-iodo-MK-801 and (+/-)1-[ 125 I]iodo-MK-801. The effect of (+/-)1-iodo-MK-801 on ligand binding to the NMDA-linked glutamate receptor site was assessed using a rat brain homogenate assay. (+/-)1-Iodo-MK-801 displaced the dissociative anesthetic ligand [ 3 H]N-[1-(2-thienyl)cyclohexyl]piperidine ([ 3 H]TCP) binding with an IC50 of 1 microM, which is a 10-fold lower binding affinity than that of (+/-)MK-801. In in vivo autoradiographic studies, (+/-)MK-801 failed to block selective uptake of (+/-)1-iodo-MK-801 in rat brain. These results suggest that (+/-)1-iodo-MK-801 may not be a suitable ligand for mapping NMDA-linked glutamate receptor channels

  16. Harmaline competitively inhibits [3H]MK-801 binding to the NMDA receptor in rabbit brain.

    Science.gov (United States)

    Du, W; Aloyo, V J; Harvey, J A

    1997-10-03

    Harmaline, a beta-carboline derivative, is known to produce tremor through a direct activation of cells in the inferior olive. However, the receptor(s) through which harmaline acts remains unknown. It was recently reported that the tremorogenic actions of harmaline could be blocked by the noncompetitive NMDA channel blocker, MK-801. This study examined whether the blockade of harmaline's action, in the rabbit, by MK-801 was due to a pharmacological antagonism at the MK-801 binding site. This was accomplished by measurement of [3H]MK-801 binding in membrane fractions derived from tissue containing the inferior olivary nucleus and from cerebral cortex. Harmaline completely displaced saturable [3H]MK-801 binding in both the inferior olive and cortex with apparent IC50 values of 60 and 170 microM, respectively. These IC50 values are consistent with the high doses of harmaline required to produce tremor, e.g., 10-30 mg/kg. Non-linear curve fitting analysis of [3H]MK-801 saturation experiments indicated that [3H]MK-801 bound to a single site and that harmaline's displacement of [3H]MK-801 binding to the NMDA receptor was competitive as indicated by a shift in Kd but not in Bmax. In addition, a Schild plot gave a slope that was not significantly different from 1 indicating that harmaline was producing a displacement of [3H]MK-801 from its binding site within the NMDA cation channel and not through an action at the glutamate or other allosteric sites on the NMDA receptor. These findings provide in vitro evidence that the competitive blockade of harmaline-induced tremor by MK-801 occurs within the calcium channel coupled to the NMDA receptor. Our hypothesis is that harmaline produces tremor by acting as an inverse agonist at the MK-801 binding site and thus opening the cation channel.

  17. Viscosity of saturated helium-3-helium-4 mixture below 200 mK

    NARCIS (Netherlands)

    Zeegers, J.C.H.; Waele, de A.T.A.M.; Gijsman, H.M.

    1991-01-01

    The shear viscosity of saturated3He-4He mixture has been measured at temperatures between 7 mK and 200 mK using a vibrating-wire viscometer and a calibrated pressure cell. The reliability of the vibrating-wire technique was tested by measuring the viscosity of pure4He. The results are internally

  18. The Effects of Nicotine on MK-801-induced Attentional Deficits: An Animal Model of Schizophrenia

    Science.gov (United States)

    2002-01-01

    purely hedonistic and pleasure-seeking reasons, inclinations that a non-disordered population is better able to control. Finally, the MK-801 model...schizophrenia, and boredom . American Journal of Psychiatry, 153, 583. Smith, J.A., Boyer-Millar, C., & Goudie, A.J. (1999). Does MK-801 discrimination

  19. Spinal Pain and Occupational Disability: A Cohort Study of British Apache AH Mk1 Pilots

    Science.gov (United States)

    2013-09-01

    British RW community. 33 References Apache AH Mk1. 2012. Agusta Westland. http://www.agustawestland.com/ product /apache-ah- mk1-0. Ang, B., and...muscles Physical ex and stretching Continued pt and stretching exercises Use pt session included pumpkin bobs to stretch the neck. No effects noticed

  20. Mr Nissim Dahan, MK, Minister of Health, Israel, at the ATLAS exhibition

    CERN Multimedia

    Laurent Guiraud

    2001-01-01

    Photo 01: L. to r.:Dr Jim Allaby, Dr Peter Jenni, Prof. Bracha Regev, Chief Scientist, Ministry of Health, Mr Nissim Dahan, MK, Minister of Health, Dr Boaz Lev, Director General, Ministry of Health, Dr Hans F. Hoffmann and Dr Georges Mikenberg. Photo 02: Mr Nissim Dahan, MK, Minister of Health, Israel, signing the Guest Book.

  1. NMDA receptor channels: labeling of MK-801 with iodine-125 and fluorine-18

    International Nuclear Information System (INIS)

    Wieland, D.M.; Kilbourn, M.R.; Yang, D.J.; Laborde, E.; Gildersleeve, D.L.; Van Dort, M.E.; Pirat, J.-L.; Ciliax, B.J.; Young, A.B.

    1988-01-01

    Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 ( 125 I) and fluorine-18 ( 18 F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (±)MK-801 by solid-state halogen exchange techniques. Attachment of the [ 18 F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [ 18 F]fluoride with the triflamide alcohol or the novel cyclic sulfamate recently reported by Merck chemists. Radiochemical yields of (±)13-[ 18 F]-fluoromethyl-MK-801 were >72%, EOB; radiochemical purity > 99%. In competitive binding studies using rat brain homogenates, (±)3-bromo-MK-801 showed greater affinity than (±)MK-801 for the glutamate-linked channel. The experimental log P (2.1 ± 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of [ 123 I]iodo-MK-801 and [ 18 F]fluoromethyl-MK-801 as possible agents for in vivo mapping of the glutamate receptor complex. (author)

  2. Pharmacodynamics of Imipenem in Combination with beta-Lactamase Inhibitor MK7655 in a Murine Thigh Model

    NARCIS (Netherlands)

    Mavridou, E.; Melchers, M.J.B.; Mil, A.C. van; Mangin, E.; Motyl, M.R.; Mouton, J.W.

    2015-01-01

    MK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed

  3. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801.

    Directory of Open Access Journals (Sweden)

    Wenjuan Yu

    Full Text Available MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP, a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10 ml/kg body weight for 6 days and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h. Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling.

  4. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801

    Science.gov (United States)

    Wang, Yueming; Li, Guanjun; Wang, Lihua; Li, Huafang

    2015-01-01

    MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP), a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10ml/kg body weight for 6 days) and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h). Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling. PMID:26700309

  5. The effect of high curing temperature on the reaction kinetics in MK/lime and MK-blended cement matrices at 60 deg. C

    International Nuclear Information System (INIS)

    Rojas, Moises Frias; Sanchez de Rojas, M.I.

    2003-01-01

    It is well known that the pozzolanic reaction between metakaolin (MK) and calcium hydroxide produces CSH, C 2 ASH 8 (stratlingite), C 4 AH 13 and C 3 ASH 6 (hydrogarnet). However, the presence or absence of these hydrated phases depends on different parameters, such as curing temperature, matrix used, etc. This paper shows the results of a study in order to know the effect of high curing temperature (60 deg. C) on the kinetics of the pozzolanic reaction in different matrices. MK/lime (calcium hydroxide) and MK-blended cement matrices were studied in samples stored and cured at 60 deg. C and up to 123 days of hydration. The nature, sequence and crystallinity of the hydrated phases were analysed using differential thermal analysis (DTA) and X-ray diffraction (XRD) techniques. Results showed that the sequence and formation of the hydrated phases was different in both matrices cured at 60 deg. C. In an MK/lime matrix, C 2 ASH 8 , C 4 AH 13 and C 3 ASH 6 were the main hydrated phases; while in an MK-blended cement, stratlingite was the sole hydrated phase issued from pozzolanic reaction. The DTA and XRD data also reveal an important fact: there is no evidence of the presence of hydrogarnet in blended cements

  6. Daily intake and serum concentration of menaquinone-4 (MK-4) in haemodialysis patients with chronic kidney disease.

    Science.gov (United States)

    Wyskida, Katarzyna; Żak-Gołąb, Agnieszka; Łabuzek, Krzysztof; Suchy, Dariusz; Ficek, Rafał; Pośpiech, Kornel; Olszanecka-Glinianowicz, Magdalena; Okopień, Bogusław; Więcek, Andrzej; Chudek, Jerzy

    2015-12-01

    Decreased concentration of menaquinone-4 (MK-4) seems to be an important risk factor of vascular calcification in haemodialysis (HD) patients. Optimal dietary intake, as well as serum MK-4 reference range, in HD has not been determined, yet. The aim of the present study was to assess daily vitamin K1 and MK-4 intakes and their relation to serum MK-4 concentration in HD patients. Daily vitamin K1 and MK-4, micro- and macronutrients and energy intakes were assessed using 3-day food diary completed by patients and serum MK-4 concentration was measured by HPLC [limit of quantification (LOQ): 0.055 ng/mL] in 85 HD patients (51 males) and 22 apparently healthy subjects. Daily MK-4 intake was significantly lower (by 29%) among HD, while K1 consumption was similar in both groups. Daily MK-4 intake was associated with fat and protein consumption in HD (r=0.43, pintakes were weaker in HD (r=0.38 and r=0.30 respectively) than in the control group (r=0.47 and r=0.45, respectively). In multiple regression analysis the variability of serum MK-4 concentrations in HD patients was explained by its daily intake. Decreased serum MK-4 concentration in HD patients is caused by lower dietary MK-4 intake, mainly due to diminished meat consumption, and in addition, probably reduced K1 conversion. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. The UK MK III GCR experimental physics programme at AEE Winfrith

    Energy Technology Data Exchange (ETDEWEB)

    Johnstone, I

    1972-06-15

    The UK programme of reactor physics experiments in support of the Mk III GCR project started in 1968/69 and has now reached its third main phase. The overall programme is broadly summarised in this report.

  8. An Aerodynamic Database for the Mk 82 General Purpose Low Drag Bomb

    National Research Council Canada - National Science Library

    Krishnamoorthy, L

    1997-01-01

    The drag database of the Mk 82 General Purpose Low Drag bomb, the primary gravity weapon in the RAAF inventory, has some shortcomings in the quality and traceability of data, and in the variations due...

  9. Berkeley Nuclear Laboratories Reactor Physics Mk. III Experimental Programme. Description of facility and programme for 1971

    Energy Technology Data Exchange (ETDEWEB)

    Nunn, R M; Waterson, R H; Young, J D

    1971-01-15

    Reactor physics experiments have been carried out at Berkeley Nuclear Laboratories during the past few years in support of the Civil Advanced Gas-Cooled Reactors (Mk. II) the Generating Board is building. These experiments are part of an overall programme whose objective is to assess the accuracy of the calculational methods used in the design and operation of these reactors. This report provides a description of the facility for the Mk. III experimental programme and the planned programme for 1971.

  10. Capsicum annuum transcription factor WRKYa positively regulates defense response upon TMV infection and is a substrate of CaMK1 and CaMK2.

    Science.gov (United States)

    Huh, Sung Un; Lee, Gil-Je; Jung, Ji Hoon; Kim, Yunsik; Kim, Young Jin; Paek, Kyung-Hee

    2015-01-23

    Plants are constantly exposed to pathogens and environmental stresses. To minimize damage caused by these potentially harmful factors, plants respond by massive transcriptional reprogramming of various stress-related genes via major transcription factor families. One of the transcription factor families, WRKY, plays an important role in diverse stress response of plants and is often useful to generate genetically engineered crop plants. In this study, we carried out functional characterization of CaWRKYa encoding group I WRKY member, which is induced during hypersensitive response (HR) in hot pepper (Capsicum annuum) upon Tobacco mosaic virus (TMV) infection. CaWRKYa was involved in L-mediated resistance via transcriptional reprogramming of pathogenesis-related (PR) gene expression and affected HR upon TMV-P0 infection. CaWRKYa acts as a positive regulator of this defense system and could bind to the W-box of diverse PR genes promoters. Furthermore, we found Capsicum annuum mitogen-activated protein kinase 1 (CaMK1) and 2 (CaMK2) interacted with CaWRKYa and phosphorylated the SP clusters but not the MAPK docking (D)-domain of CaWRKYa. Thus, these results demonstrated that CaWRKYa was regulated by CaMK1 and CaMK2 at the posttranslational level in hot pepper.

  11. Operator-centered control of a semi-autonomous industrial robot

    International Nuclear Information System (INIS)

    Spelt, P.F.; Jones, S.L.

    1994-01-01

    This paper presents work done by Oak Ridge National Laboratory and Remotec, Inc., to develop a new operator-centered control system for Remotec's Andros telerobot. Andros robots are presently used by numerous electric utilities, the armed forces, and numerous law enforcement agencies to perform tasks which are hazardous for human operators. This project has automated task components and enhanced the video graphics display of the robot's position in the environment to significantly reduce operator workload. The procedure of automating a telerobot requires the addition of computer power to the robot, along with a variety of sensors and encoders to provide information about the robots performance in and relationship to its environment The resulting vehicle serves as a platform for research on strategies to integrate automated tasks with those performed by a human operator. The addition of these capabilities will greatly enhance the safety and efficiency of performance in hazardous environments

  12. MK-2206, an AKT Inhibitor, Promotes Caspase-Independent Cell Death and Inhibits Leiomyoma Growth

    Science.gov (United States)

    Sefton, Elizabeth C.; Qiang, Wenan; Serna, Vanida; Kurita, Takeshi; Wei, Jian-Jun; Chakravarti, Debabrata

    2013-01-01

    Uterine leiomyomas (ULs), benign tumors of the myometrium, are the number one indication for hysterectomies in the United States due to a lack of an effective alternative therapy. ULs show activation of the pro-survival AKT pathway compared with normal myometrium; however, substantial data directly linking AKT to UL cell survival are lacking. We hypothesized that AKT promotes UL cell survival and that it is a viable target for inhibiting UL growth. We used the investigational AKT inhibitor MK-2206, currently in phase II trials, on cultured primary human UL and myometrial cells, immortalized leiomyoma cells, and in leiomyoma grafts grown under the kidney capsule in mice. MK-2206 inhibited AKT and PRAS40 phosphorylation but did not regulate serum- and glucocorticoid-induced kinase and ERK1/2, demonstrating its specificity for AKT. MK-2206 reduced UL cell viability and decreased UL tumor volumes. UL cells exhibited disruption of mitochondrial structures and underwent cell death that was independent of caspases. Additionally, mammalian target of rapamycin and p70S6K phosphorylation were reduced, indicating that mammalian target of rapamycin complex 1 signaling was compromised by AKT inhibition in UL cells. MK-2206 also induced autophagy in UL cells. Pretreatment of primary UL cells with 3-methyladenine enhanced MK-2206-mediated UL cell death, whereas knockdown of ATG5 and/or ATG7 did not significantly influence UL cell viability in the presence of MK-2206. Our data provide molecular evidence for the involvement of AKT in UL cell survival and suggest that AKT inhibition by MK-2206 may be a viable option to consider for the treatment of ULs. PMID:24002033

  13. Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

    Science.gov (United States)

    Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

    2015-01-01

    Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

  14. Analysis of excess reactivity of JOYO MK-III performance test core

    International Nuclear Information System (INIS)

    Maeda, Shigetaka; Yokoyama, Kenji

    2003-10-01

    JOYO is currently being upgraded to the high performance irradiation bed JOYO MK-III core'. The MK-III core is divided into two fuel regions with different plutonium contents. To obtain a higher neutron flux, the active core height was reduced from 55 cm to 50 cm. The reflector subassemblies were replaced by shielding subassemblies in the outer two rows. Twenty of the MK-III outer core fuel subassemblies in the performance test core were partially burned in the transition core. Four irradiation test rigs, which do not contain any fuel material, were loaded in the center of the performance test core. In order to evaluate the excess reactivity of MK-III performance test core accurately, we evaluated it by applying not only the JOYO MK-II core management code system MAGI, but also the MK-III core management code system HESTIA, the JUPITER standard analysis method and the Monte Carlo method with JFS-3-J3.2R content set. The excess reactivity evaluations obtained by the JUPITER standard analysis method were corrected to results based on transport theory with zero mesh-size in space and angle. A bias factor based on the MK-II 35th core, which sensitivity was similar to MK-III performance test core's, was also applied, except in the case where an adjusted nuclear cross-section library was used. Exact three-dimensional, pin-by-pin geometry and continuous-energy cross sections were used in the Monte Carlo calculation. The estimated error components associated with cross-sections, methods correction factors and the bias factor were combined based on Takeda's theory. Those independently calculated values agree well and range from 2.8 to 3.4%Δk/kk'. The calculation result of the MK-III core management code system HESTLA was 3.13% Δk/kk'. The estimated errors for bias method range from 0.1 to 0.2%Δk/kk'. The error in the case using adjusted cross-section was 0.3%Δk/kk'. (author)

  15. Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 {+-} 235% (mean {+-} SEM) of basal level vs. 520 {+-} 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 {+-} 83% of basal level vs. 969 {+-} 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine.

  16. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

    Science.gov (United States)

    Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2015-03-01

    Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The effects of the CXCR2 antagonist, MK-7123, on bone marrow functions in healthy subjects.

    Science.gov (United States)

    Hastrup, Nina; Khalilieh, Sauzanne; Dale, David C; Hanson, Lars G; Magnusson, Peter; Tzontcheva, Anjela; Tseng, Jack; Huyck, Susan; Rosenberg, Elizabeth; Krogsgaard, Kim

    2015-04-01

    The CXCR2 antagonist MK-7123 causes dose-dependent reductions in absolute neutrophil counts (ANC) and decreases neutrophil tissue responses, but its effects on bone marrow functions are not yet known. We conducted a double-blind, randomized study in 18 healthy subjects comparing the effects of either MK-7123 (30mg, po, daily for 28days) or placebo on peripheral blood counts and bone marrow myeloid cell populations. MK-7123 caused a reversible decrease (approximately 50%) in the ANC as demonstrated on days 1 and 28, the first and last days of the treatment period. Bone marrow aspirate smears and biopsy imprints did not differ in the proportion of mature neutrophils in pretreatment, day 28, day 56 or placebo samples. There were no treatment effects on biopsy or aspirate clot cellularity, myeloid to erythroid or myeloid post-mitotic to mitotic ratios; flow-cytometric analyses of aspirate cells; or bone marrow fat to cell balance as assessed by MRI. MK-7123 was generally well tolerated with neutropenia being the most common adverse event; however, there were no clinical symptoms associated with decreased ANCs. These findings indicate that the CXCR2 antagonist MK-7123 causes rapidly reversible decrease in the ANC without measurable myelosuppressive effects. The results support the development of CXCR2 antagonists as potentially useful anti-inflammatory agents, primarily interrupting neutrophil trafficking. Copyright © 2015. Published by Elsevier Ltd.

  18. Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

    Science.gov (United States)

    Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon

    2016-01-01

    Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p801 in mice via the stimulating effects of neurogenesis. PMID:27489382

  19. Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

    Science.gov (United States)

    Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

    2018-01-01

    Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

  20. Effect of MK-801 on the development of nicotine sensitization of nucleus accumbens dopamine release

    International Nuclear Information System (INIS)

    Hong, Soo Kyung; Choung, In Soon; Kim, Sang Eun

    2005-01-01

    We have previously found that MK-801, a noncompetitive NMDA receptor antagonist, prevents behavioral sensitization to nicotine. This study aimed to investigate the effect of MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drug on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague-Dawley rats were pretreated with MK-801 (0.3 mg/kg, i.p.) or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for 7 consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens and DA release was monitored using in vivo microdialysis. In rats pretreated with chronic nicotine, local nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response 969 ± 235% (mean ± SEM) of basal level vs. 520 ± 93%, P < 0.05). Co-administration of MK-801 with nicotine attenuated an increase of DA release elicited by local nicotine challenge, compared with nicotine alone (maximal DA response 427 ± 83% of basal level vs. 969 ± 235%, P < 0.01). These results suggest that MK-801 blocks the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of NMDA receptors in the development of behavioral sensitization to nicotine

  1. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes

    Science.gov (United States)

    Cassoli, Juliana S.; Iwata, Keiko; Steiner, Johann; Guest, Paul C.; Turck, Christoph W.; Nascimento, Juliana M.; Martins-de-Souza, Daniel

    2016-01-01

    Separate lines of evidence have demonstrated the involvement of N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in schizophrenia. Here, we have carried out shotgun mass spectrometry proteome analysis of oligodendrocytes treated with the NMDA receptor antagonist MK-801 to gain potential insights into these effects at the molecular level. The MK-801 treatment led to alterations in the levels of 68 proteins, which are associated with seven distinct biological processes. Most of these proteins are involved in energy metabolism and many have been found to be dysregulated in previous proteomic studies of post-mortem brain tissues from schizophrenia patients. Finally, addition of the antipsychotic clozapine to MK-801-treated oligodendrocyte cultures resulted in changes in the levels of 45 proteins and treatment with clozapine alone altered 122 proteins and many of these showed opposite changes to the MK-801 effects. Therefore, these proteins and the associated energy metabolism pathways should be explored as potential biomarkers of antipsychotic efficacy. In conclusion, MK-801 treatment of oligodendrocytes may provide a useful model for testing the efficacy of novel treatment approaches. PMID:26973466

  2. A continuous dry 300 mK cooler for THz sensing applications

    Energy Technology Data Exchange (ETDEWEB)

    Klemencic, G. M., E-mail: Georgina.Klemencic@astro.cf.ac.uk; Ade, P. A. R.; Sudiwala, R. [School of Physics and Astronomy, Cardiff University, Queen’s Buildings, The Parade, Cardiff CF24 3AA (United Kingdom); Chase, S. [Chase Research Cryogenics Ltd., Uplands, 140 Manchester Road, Sheffield S10 5DL (United Kingdom); Woodcraft, A. L. [QMC Instruments Ltd., School of Physics and Astronomy, Cardiff University, Queen’s Buildings, The Parade, Cardiff CF24 3AA (United Kingdom)

    2016-04-15

    We describe and demonstrate the automated operation of a novel cryostat design that is capable of maintaining an unloaded base temperature of less than 300 mK continuously, without the need to recycle the gases within the final cold head, as is the case for conventional single shot sorption pumped {sup 3}He cooling systems. This closed dry system uses only 5 l of {sup 3}He gas, making this an economical alternative to traditional systems where a long hold time is required. During testing, a temperature of 365 mK was maintained with a constant 20 μW load, simulating the cooling requirement of a far infrared camera.

  3. Macroscopic quantum tunneling in 1 μm Nb junctions below 100mK

    International Nuclear Information System (INIS)

    Voss, R.F.; Webb, R.A.

    1981-01-01

    The transition probabilities out of the superconducting state of low current density 1 μm Nb Josephson junctions with capacitance < 0.15 pF have been measured as a function of temperature T down to 3 mK. Below 100 mK the distribution widths become independent of T. Junctions with critical currents that differ by an order of magnitude have the same dependence of relative width on T. The low T results are interpreted in terms of quantum tunneling of the (macroscopic) junction phase. The observed low temperature widths are smaller than expected indicating the necessity of corrections to the simple WKB tunneling rates. (orig.)

  4. Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

    NARCIS (Netherlands)

    R.J. de Knegt (Robert); J. Kornhuber (Johannes); S.W. Schalm (Solko); K. Rusche (K.); P.F. Riederer (Peter); J. Tan (J.)

    1993-01-01

    textabstractBinding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were

  5. The effect of hippocampal NMDA receptor blockade by MK-801 on cued fear extinction.

    Science.gov (United States)

    Zhang, Bo; Li, Chuan-Yu; Wang, Xiu-Song

    2017-08-14

    Extinction of conditioned fear has been suggested to be a new form of learning instead of erasure of what was originally learned, and the process is NMDA (N-methyl d-aspartate) receptor (NMDAR) dependent. Most of studies have so far revealed the important roles of NMDARs in the amygdala and medial prefrontal cortex (mPFC) in cued fear extinction. Although the ventral hippocampus has intimately reciprocal connections with the amygdala and mPFC, the role of its NMDARs in cued fear extinction remains unclear. The present experiment explored the issue by bilateral pre-extinction microinjection of the noncompetitive NMDAR antagonist MK-801 into the ventral hippocampus. Four groups of rats were given habituation, tone cued fear conditioning, fear extinction training and extinction test. Prior to extinction training, rats received bilateral infusions of either MK-801 (1.5, 3, or 6μg/0.5μl) or saline. Our results showed that MK-801 reduced freezing on the first trial of extinction training with no impact on within-session acquisition of extinction, and that the lower doses of MK-801 resulted in increased freezing on the extinction retrieval test. These findings suggest that ventral hippocampal NMDARs are necessary for the consolidation of tone cued fear extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Preliminary Mark-18A (Mk-18A) Target Material Recovery Program Product Acceptance Criteria

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Sharon M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Patton, Bradley D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-01

    The Mk-18A Target Material Recovery Program (MTMRP) was established in 2015 to preserve the unique materials, e.g. 244Pu, in 65 previously irradiated Mk-18A targets for future use. This program utilizes existing capabilities at SRS and Savannah River National Laboratory (SRNL) to process targets, recover materials from them, and to package the recovered materials for shipping to ORNL. It also utilizes existing capabilities at ORNL to receive and store the recovered materials, and to provide any additional processing of the recovered materials or residuals required to prepare them for future beneficial use. The MTMRP is presently preparing for the processing of these valuable targets which is expected to begin in ~2019. As part of the preparations for operations, this report documents the preliminary acceptance criteria for the plutonium and heavy curium materials to be recovered from the Mk-18A targets at SRNL for transport and storage at ORNL. These acceptance criteria were developed based on preliminary concepts developed for processing, transporting, and storing the recovered Mk-18A materials. They will need to be refined as these concepts are developed in more detail.

  7. Apparatus intended for measuring heat capacity and heat transfer down to mK range

    International Nuclear Information System (INIS)

    Hebral, B.; Frossati, G.; Godfrin, H.; Schumacher, G.; Thoulouze, D.

    1978-01-01

    A cryogenic apparatus to perform heat capacity and heat transfer measurements in the range 1.5 mK-50 mK is described. Measurements are performed in an adiabatic demagnetization cell attached to a dilution refrigerator. Heat capacity measurements were effected on CMN-helium systems; the CMN specific heat was deduced above 1.6 mK when using liquid 3 He or a mixture 1.1% 3 He - 98.9% 4 He. A specific heat anomaly was observed with 4 He below 10 mK. It does not seen possible to interprete it by simple thermal equilibrium considerations. The superfluid 3 He heat capacity was also deduced from the results obtained with liquid 3 He under pressure. In heat transfer measurements at the interface CMN-mixture 3 He- 4 He, the temperature dependence of the thermal boundary resistance is in rather good agreement with other powder results. The measured resistances are larger than those predicted by the classical phonon process [fr

  8. The neuroprotective efficacy of MK-801 in focal cerebral ischemia varies with rat strain and vendor.

    Science.gov (United States)

    Oliff, H S; Marek, P; Miyazaki, B; Weber, E

    1996-08-26

    The present study was designed to evaluate whether the neuroprotective efficacy of MK-801 in focal cerebral ischemia was dependent on strain and/or vendor differences. MK-801 (0.12 mg/kg i.v. bolus followed by 0.108 mg/kg/h infusion or 0.60 mg/kg i.v. bolus followed by 0.540 mg/kg/h infusion) or saline was administered just after intraluminal middle cerebral artery occlusion. Administration of 0.540 mg/kg/h MK-801 provided strain/line-dependent neuroprotection in the following rank order: Simonsen Laboratories Sprague-Dawley rats > Simonsen Laboratories Wistar rats > Taconic Laboratories Sprague-Dawley rats. After 0.108 mg/kg/h MK-801 treatment, Simonsen Laboratories Wistar rats were the only strain/line that were significantly neuroprotected. These results indicate that the neuroprotective effect of an experimental drug may be influenced by rat strain and vendor differences.

  9. Preliminary Mark-18A (Mk-18A) Target Material Recovery Program Product Acceptance Criteria

    International Nuclear Information System (INIS)

    Robinson, Sharon M.; Patton, Bradley D.

    2016-01-01

    The Mk-18A Target Material Recovery Program (MTMRP) was established in 2015 to preserve the unique materials, e.g. 244 Pu, in 65 previously irradiated Mk-18A targets for future use. This program utilizes existing capabilities at SRS and Savannah River National Laboratory (SRNL) to process targets, recover materials from them, and to package the recovered materials for shipping to ORNL. It also utilizes existing capabilities at ORNL to receive and store the recovered materials, and to provide any additional processing of the recovered materials or residuals required to prepare them for future beneficial use. The MTMRP is presently preparing for the processing of these valuable targets which is expected to begin in ~2019. As part of the preparations for operations, this report documents the preliminary acceptance criteria for the plutonium and heavy curium materials to be recovered from the Mk-18A targets at SRNL for transport and storage at ORNL. These acceptance criteria were developed based on preliminary concepts developed for processing, transporting, and storing the recovered Mk-18A materials. They will need to be refined as these concepts are developed in more detail.

  10. Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

    Science.gov (United States)

    Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

    2012-04-01

    Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

  11. MK-801 induced amnesia for the elevated plus-maze in mice

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2002-01-01

    Roč. 131, 1-2 (2002), s. 221-225 ISSN 0166-4328 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : amnesia * elevated plus-maze * MK-801 Subject RIV: FH - Neurology Impact factor: 2.791, year: 2002

  12. Kynurenic acid prevented social recognition deficits induced by MK-801 in rats

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2003-01-01

    Roč. 52, č. 6 (2003), s. 805-808 ISSN 0862-8408 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : amnesia * kynurenic acid * MK-801 Subject RIV: FH - Neurology Impact factor: 0.939, year: 2003

  13. N-methyl-D-aspartate prevented memory deficits induced by MK-801 in mice

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2003-01-01

    Roč. 52, č. 6 (2003), s. 809-812 ISSN 0862-8408 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : N-methyl-D-aspartate * MK-801 * spatial memory Subject RIV: FH - Neurology Impact factor: 0.939, year: 2003

  14. Anticonvulsant Effects of Memantine and MK-801 in Guinea Pig Hippocampal Neurons.

    Science.gov (United States)

    investigation we compared the anticonvulsant properties of Mem to those of MK-801 in guinea pig hippocampal slices. Extracellular recordings were...obtained from area CA1 of guinea pig hippocampal slices in a total submersion chamber at 32 deg C in normal oxygenated artificial cerebrospinal fluid (ACSF

  15. Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group

    Energy Technology Data Exchange (ETDEWEB)

    Bungard, Christopher J.; Williams, Peter D.; Ballard, Jeanine E.; Bennett, David J.; Beaulieu, Christian; Bahnck-Teets, Carolyn; Carroll, Steve S.; Chang, Ronald K.; Dubost, David C.; Fay, John F.; Diamond, Tracy L.; Greshock, Thomas J.; Hao, Li; Holloway, M. Katharine; Felock, Peter J.; Gesell, Jennifer J.; Su, Hua-Poo; Manikowski, Jesse J.; McKay, Daniel J.; Miller, Mike; Min, Xu; Molinaro, Carmela; Moradei, Oscar M.; Nantermet, Philippe G.; Nadeau, Christian; Sanchez, Rosa I.; Satyanarayana, Tummanapalli; Shipe, William D.; Singh, Sanjay K.; Truong, Vouy Linh; Vijayasaradhi, Sivalenka; Wiscount, Catherine M.; Vacca, Joseph P.; Crane, Sheldon N.; McCauley, John A. (Merck); (Albany MR)

    2016-07-14

    A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.

  16. Irradiation performance of experimental fast reactor 'JOYO' MK-1 driver fuel assemblies

    International Nuclear Information System (INIS)

    Itaki, Toshiyuki; Kono, Keiichi; Tachi, Hirokatsu; Yamanouchi, Sadamu; Yuhara, Shunichi; Shibahara, Itaru

    1985-01-01

    The experimental fast reactor ''JOYO'' completed it's breeder core (MK-I) operation in January 1982. The MK-I driver fuel assemblies were removed from the core sequencially in order of burnup increase and have been under postirradiation examination (PIE). The PIE has almost been completed for 30 assemblies including the highest burnup assemblies of 48,000 MWD/MTM. It has been confirmed that all fuel assemblies have exhibited satisfactory performance without detrimental assembly deformation or without any indications of fuel pin breach. The irradiation conditions of the MK-I core were somewhat more moderate than those conditions envisioned for prototypic reactor. However the results of the examination revealed the typical irradiation behavior of LMFBR fuels, although such characteristics were benign as compared with those anticipated in high burnup fuels. Systematic performance data have been accumulated through the fuel fabrication, irradiation and postirradiation examination processes. Based on these data, the MK-I fuel designing and fabrication techniques were totally confirmed. This technical experience and the associated insight into irradiation behavior have established a milestone to the next step of fast reactor fuel development. (author)

  17. The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

    Directory of Open Access Journals (Sweden)

    Nermin Eissa

    2018-02-01

    Full Text Available The role of Histamine H3 receptors (H3Rs in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP and novel object recognition (NOR task in adult male rats, using donepezil (DOZ as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p. significantly ameliorated memory deficits induced with MK801 in PAP (all P < 0.05, n = 7. The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p. was reversed when rats were co-injected with the H3R agonist R-(α-methylhistamine (RAMH, 10 mg/kg, i.p. (p = 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group, n = 6. In the NOR paradigm, DL77 (5 mg/kg, i.p. counteracted long-term memory (LTM deficits induced with MK801 (P < 0.05, n = 6–8, and the DL77-provided effect was similar to that of DOZ (p = 0.788, n = 6–8, and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p. (p = 0.877, n = 6, as compared to the (MK801-amnesic group. However, DL77 (5 mg/kg, i.p. did not alter short-term memory (STM impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801-amnesic group. Moreover, DL77 (5 mg/kg failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6, demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating

  18. Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa.

    Science.gov (United States)

    Livermore, David M; Warner, Marina; Mushtaq, Shazad

    2013-10-01

    MK-7655 is a novel inhibitor of class A and C β-lactamases. We investigated its potential to protect imipenem. Chequerboard MICs were determined by CLSI agar dilution: (i) for Enterobacteriaceae with carbapenemases; (ii) for Enterobacteriaceae with carbapenem resistance contingent on combinations of impermeability together with an extended-spectrum β-lactamase or AmpC enzyme; and (iii) for Pseudomonas aeruginosa and other non-fermenters. At a concentration of 4 mg/L, MK-7655 reduced imipenem MICs for Enterobacteriaceae with KPC carbapenemases from 16-64 mg/L to 0.12-1 mg/L. Synergy also was seen for Enterobacteriaceae with impermeability-mediated carbapenem resistance, with weaker synergy seen for isolates with the OXA-48 enzyme. On the other hand, MK-7655 failed to potentiate imipenem against Enterobacteriaceae with metallo-carbapenemases. In the case of P. aeruginosa, where endogenous AmpC confers slight protection versus imipenem, 4 mg/L MK-7655 reduced the MIC of imipenem for all isolates, except those with metallo-carbapenemases: the MICs of imipenem fell from 1-2 mg/L to 0.25-0.5 mg/L for imipenem-susceptible P. aeruginosa and from 16-64 mg/L to 1-4 mg/L for OprD-deficient strains. No potentiation was seen for chryseobacteria or for Stenotrophomonas maltophilia. MK-7655 potentiated imipenem against Enterobacteriaceae with KPC carbapenemases or combinations of β-lactamase and impermeability, but not those with metallo-carbapenemases. It augmented the activity of imipenem against P. aeruginosa in general and OprD mutants in particular.

  19. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    Science.gov (United States)

    Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

    2015-01-01

    AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

  20. Blockade of voltage-gated K+ currents in rat mesenteric arterial smooth muscle cells by MK801

    Directory of Open Access Journals (Sweden)

    Jeong Min Kim

    2015-01-01

    Full Text Available MK801 (dizocilpine, a phencyclidine (PCP derivative, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr. Another PCP derivative, ketamine, was reported to block voltage-gated K+ (Kv channels, which was independent of NMDAr function. Kv currents are major regulators of the membrane potential (Em and excitability of muscles and neurons. Here, we investigated the effect of MK801 on the Kv channels and Em in rat mesenteric arterial smooth muscle cells (RMASMCs. We used the whole-cell patch clamp technique to analyze the effect of MK801 enantiomers on Kv channels and Em. (+MK801 inhibited Kv channels in a concentration-dependent manner (IC50 of 89.1 ± 13.1 μM, Hill coefficient of 1.05 ± 0.08. The inhibition was voltage- and state- independent. (+MK801 didn't influence steady-state activation and inactivation of Kv channels. (+MK801 treatment depolarized Em in a concentration-dependent manner and concomitantly decreased membrane conductance. (−MK801 also similarly inhibited the Kv channels (IC50 of 134.0 ± 17.5 μM, Hill coefficient of 0.87 ± 0.09. These results indicate that MK801 directly inhibits the Kv channel in a state-independent manner in RMASMCs. This MK801-mediated inhibition of Kv channels should be considered when assessing the various pharmacological effects produced by MK801, such as schizophrenia, neuroprotection, and hypertension.

  1. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

    Science.gov (United States)

    Vainionpää, Mari H; Raekallio, Marja R; Pakkanen, Soile A E; Ranta-Panula, Ville; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2013-05-01

    To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Experimental randomized blinded crossover study. Six healthy horses. Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  2. Systemic dizocilpine (MK-801 facilitates performance in opposition to response bias

    Directory of Open Access Journals (Sweden)

    Lauwereyns Johan

    2007-09-01

    Full Text Available Abstract Previous research has established that dopamine signals are crucial in orienting behavior to reward. Less is known, however, about the psychopharmacology of task performance under small-reward conditions as compared to large-reward conditions. The current study examined the effects of the noncompetitive N-methyl-D-aspartate (NMDA-receptor antagonist dizocilpine (MK-801 on reaction time (RT in a nose-poke task with rats completing an asymmetric reward schedule. In all trials, the rats were required to poke their nose in either the left or the right peripheral hole immediately adjacent to the centre hole when the corresponding light was illuminated. Depending on the stimulus-reward mapping, however, one position was associated with a large reward, while the alternative position was associated with a small reward. Correct performance was required in every trial; if the rat did not make a correct response within 20 s, the trial was aborted, and the same stimulus was presented again on the next trial. In this way, the rat was forced to perform the same visuo-spatial discrimination task under different reward conditions. Reaction times (ms were faster for large-reward trials than for small-reward trials, replicating previous findings. At a dosage of MK-801 (0.04 mg/kg, there was no significant influence of on RT in large-reward trials. In contrast, the same dosage of MK-801 in small-reward trials produced a decrease in RT as compared to the control condition, implying an improvement of performance. Below 0.04 mg/kg of MK-801, a steady decrease of RT in small-trials was seen as a function of dosage. Above 0.04 mg/kg of MK-801, the majority of rats failed to perform the task at all, whereas the rats that did manage to perform the criterion of 80 correct trials in a session showed no difference in RT between large- and small-reward trials. These data indicate that the systemic administration of a relatively small dosage of MK-801 facilitates

  3. Prenatal choline supplementation attenuates MK-801-induced deficits in memory, motor function, and hippocampal plasticity in adult male rats.

    Science.gov (United States)

    Nickerson, Chelsea A; Brown, Alexandra L; Yu, Waylin; Chun, Yoona; Glenn, Melissa J

    2017-10-11

    Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague-Dawley rats were fed a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we found that only prenatal standard-fed rats displayed memory consolidation deficits induced by low-dose MK-801 administered immediately following study of sample objects; all other groups, including prenatal choline supplemented rats given MK-801, showed intact memory. Following high-dose MK-801, prenatal choline supplementation significantly alleviated rats' motor response to MK-801, particularly ataxia. Using doublecortin and Ki67 to mark neurogenesis and cell division, respectively, in the hippocampus, we found that prenatal choline supplementation, in the face of MK-801 toxicity, protected against reduced hippocampal plasticity. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin, MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex.

    Science.gov (United States)

    Wu, Rui; Kausar, Hina; Johnson, Paul; Montoya-Durango, Diego E; Merchant, Michael; Rane, Madhavi J

    2007-07-27

    We have shown previously that Akt exists in a signal complex with p38 MAPK, MAPK-activated protein kinase-2 (MK2), and heat shock protein 27 (Hsp27) and MK2 phosphorylates Akt on Ser-473. Additionally, dissociation of Hsp27 from Akt, prior to Akt activation, induced polymorphonuclear leukocyte (PMN) apoptosis. However, the role of Hsp27 in regulating Akt activation was not examined. This study tested the hypothesis that Hsp27 regulates Akt activation and promotes cell survival by scaffolding MK2 to the Akt signal complex. Here we show that loss of Akt/Hsp27 interaction by anti-Hsp27 antibody treatment resulted in loss of Akt/MK2 interaction, loss of Akt-Ser-473 phosphorylation, and induced PMN apoptosis. Transfection of myristoylated Akt (AktCA) in HK-11 cells induced Akt-Ser-473 phosphorylation, activation, and Hsp27-Ser-82 phosphorylation. Cotransfection of AktCA with Hsp27 short interfering RNA, but not scrambled short interfering RNA, silenced Hsp27 expression, without altering Akt expression in HK-11 cells. Silencing Hsp27 expression inhibited Akt/MK2 interaction, inhibited Akt phosphorylation and Akt activation, and induced HK-11 cell death. Deletion mutagenesis studies identified acidic linker region (amino acids 117-128) on Akt as an Hsp27 binding region. Deletion of amino acids 117-128 on Akt resulted in loss of its interaction with Hsp27 and MK2 but not with Hsp90 as demonstrated by immunoprecipitation and glutathione S-transferase pulldown studies. Co-transfection studies demonstrated that constitutively active MK2 (MK2EE) phosphorylated Aktwt (wild type) on Ser-473 but failed to phosphorylate Akt(Delta117-128) mutant in transfixed cells. These studies collectively define a novel role of Hsp27 in regulating Akt activation and cellular apoptosis by mediating interaction between Akt and its upstream activator MK2.

  5. Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses.

    Science.gov (United States)

    Tapio, Heidi A; Raekallio, Marja R; Mykkänen, Anna; Mama, Khursheed; Mendez-Angulo, Jóse L; Hautajärvi, Heidi; Vainio, Outi M

    2018-04-01

    OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride-induced cardiorespiratory and gastrointestinal changes in horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically. RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK. CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

  6. Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain.

    Science.gov (United States)

    Inta, Ioana; Vogt, Miriam A; Vogel, Anne S; Bettendorf, Markus; Gass, Peter; Inta, Dragos

    2016-10-01

    NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.

  7. Study of an Isospin-Forbidden $0^{+} \\rightarrow 0^{+}$ Transition in $^{38m}$K

    CERN Multimedia

    2002-01-01

    There is at present a discrepancy between the precisely determined value of $V_{ud}^{2}$ obtained from $0^{+} \\rightarrow 0^{+} $ nuclear $\\beta$-decay and the less precisely determined value inferred from neutron decay. One possible explanation for this discrepancy involves the " Coulomb " corrections that must be applied to the nuclear decay rates. We propose to investigate one class of these corrections (for charge-dependent configuration-mixing) by measuring the isospin-forbidden $0^{+} \\rightarrow 0^{+}$ decay rate in $^{38m}$K. $^{38m}$K decay is particularly interesting because it is predicted to have the largest charge-dependent mixing correction of any of the transitions used in the $V_{ud}^{2}$ determination.

  8. AC susceptibility and NQR measurements on CeCu6 below 5 mK

    International Nuclear Information System (INIS)

    Jin, C.; Lee, D.M.; Pollack, L.; Smith, E.N.; Markert, J.T.; Maple, M.B.; Hinks, D.G.

    1994-01-01

    We have measured the zero field ac magnetic susceptibility of single and polycrystalline CeCu 6 samples down to 100 μK. For the single crystal sample, the susceptibility shows pronounced anisotropic behavior with respect to the crystal orientation. At ∼3 mK the susceptibility along two different crystal orientations shows a broad peak, and at 500 μK the susceptibility shows a second peak along one orientation and a plateau along the other. The susceptibility of the polycrystalline sample has a similar peak at 3 mK. NQR measurements are under way to study the Cu nuclear spin system in this compound in order to gain additional information about the nature of the peaks. (orig.)

  9. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, Jens; Kjeldsen, J; Laursen, L S

    1995-01-01

    dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before...... was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p LTE4 was reduced by more than 85% (p

  10. Specialist committee's review reports for experimental fast reactor JOYO' MK-III performance tests

    International Nuclear Information System (INIS)

    Yamashita, Kiyonobu; Okubo, Toshiyuki; Kamide, Hideki

    2004-02-01

    Performance tests (startup-physics tests and power elevation tests) were planed for experimental fast reactor 'JOYO' MK-III where irradiation performances were upgraded by power increase from 100 to 140 MW. The reactor safety committee of O-arai Engineering Center has established a specialist committee for 'JOYO' MK-III Performance Tests at the first meeting of 2003 on 23th. April 2003, to accomplish the tests successfully. Subjects of the specialist committee were reviews of following items covering a wide range. 1) Contents of modification works. 2) Reflections of functional test results to the plant and facilities. 3) Reflections of safety rule modification to instruction and manual for operation. 4) Quality assurances and pre-calculation for performance test. 5) Inspection plan and its results. 6) Adequacy of performance test plan. 7) Confirmation of performance test results. Before test-starts, the specialist committee has confirmed by reviewing the items from 1) to 6) based on explanations and documents of the Division of Experimental Reactor, that the test plan and pre-inspections are adequate. After the tests, the specialist committee had confirmed by reviewing the item 7) in the same way, that the each test result satisfies the corresponding criterion. The specialist committee has concluded from these review's results before and after the tests that the 'JOYO' MK-III Performance Tests were carried out appropriately. Besides, the first criticality of the JOYO MK-III was achieved on 2nd. July 2003, and the continuous full power operation was carried on 20th. Nov. 2003. Finally, all performance tests were completed by the pass of the last governmental pre-serviced inspection (dose rate measurement during the shut down condition). (author)

  11. A 30 mK, 13.5 T scanning tunneling microscope with two independent tips

    Energy Technology Data Exchange (ETDEWEB)

    Roychowdhury, Anita [Laboratory for Physical Sciences, College Park, Maryland 20742 (United States); Center for Nanophysics and Advanced Materials, Department of Physics, University of Maryland, College Park, Maryland 20740 (United States); Gubrud, M. A.; Dana, R.; Dreyer, M. [Laboratory for Physical Sciences, College Park, Maryland 20742 (United States); Anderson, J. R.; Lobb, C. J.; Wellstood, F. C. [Center for Nanophysics and Advanced Materials, Department of Physics, University of Maryland, College Park, Maryland 20740 (United States)

    2014-04-15

    We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of Cu{sub x}Bi{sub 2}Se{sub 3}. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 μeV.

  12. A 30 mK, 13.5 T scanning tunneling microscope with two independent tips.

    Science.gov (United States)

    Roychowdhury, Anita; Gubrud, M A; Dana, R; Anderson, J R; Lobb, C J; Wellstood, F C; Dreyer, M

    2014-04-01

    We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of CuxBi2Se3. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 μeV.

  13. An expert computer program for classifying stars on the MK spectral classification system

    International Nuclear Information System (INIS)

    Gray, R. O.; Corbally, C. J.

    2014-01-01

    This paper describes an expert computer program (MKCLASS) designed to classify stellar spectra on the MK Spectral Classification system in a way similar to humans—by direct comparison with the MK classification standards. Like an expert human classifier, the program first comes up with a rough spectral type, and then refines that spectral type by direct comparison with MK standards drawn from a standards library. A number of spectral peculiarities, including barium stars, Ap and Am stars, λ Bootis stars, carbon-rich giants, etc., can be detected and classified by the program. The program also evaluates the quality of the delivered spectral type. The program currently is capable of classifying spectra in the violet-green region in either the rectified or flux-calibrated format, although the accuracy of the flux calibration is not important. We report on tests of MKCLASS on spectra classified by human classifiers; those tests suggest that over the entire HR diagram, MKCLASS will classify in the temperature dimension with a precision of 0.6 spectral subclass, and in the luminosity dimension with a precision of about one half of a luminosity class. These results compare well with human classifiers.

  14. Use of ELOCA.Mk5 to calculate transient fission product release from CANDU fuel elements

    International Nuclear Information System (INIS)

    Walker, J.R.; de Vaal, J.W.; Arimescu, V.I.; McGrady, T.G.; Wong, C.

    1992-04-01

    A change in fuel element power output, or a change in heat transfer conditions, will result in an immediate change in the temperature distribution in a fuel element. The temperature distribution change will be accompanied by concomitant changes in fuel stress distribution that lead, in turn, to a release of fission products to the fuel-to-sheath gap. It is important to know the inventory of fission products in the fuel-to-sheath gap, because this inventory is a major component of the source term for many postulated reactor accidents. ELOCA.Mk5 is a FORTRAN-77 computer code that has been developed to estimate transient releases to the fuel-to-sheath gap in CANDU reactors. ELOCA.Mk5 is an integration of the FREEDOM fission product release model into the ELOCA fuel element thermo-mechanical code. The integration of FREEDOM into ELOCA allows ELOCA.Mk5 to model the feedback mechanisms between the fission product release and the thermo-mechanical response of the fuel element. This paper describes the physical model, gives details of the ELOCA.Mkt code, and describes the validation of the model. We demonstrate that the model gives good agreement with experimental results for both steady state and transient conditions

  15. An expert computer program for classifying stars on the MK spectral classification system

    Energy Technology Data Exchange (ETDEWEB)

    Gray, R. O. [Department of Physics and Astronomy, Appalachian State University, Boone, NC 26808 (United States); Corbally, C. J. [Vatican Observatory Research Group, Tucson, AZ 85721-0065 (United States)

    2014-04-01

    This paper describes an expert computer program (MKCLASS) designed to classify stellar spectra on the MK Spectral Classification system in a way similar to humans—by direct comparison with the MK classification standards. Like an expert human classifier, the program first comes up with a rough spectral type, and then refines that spectral type by direct comparison with MK standards drawn from a standards library. A number of spectral peculiarities, including barium stars, Ap and Am stars, λ Bootis stars, carbon-rich giants, etc., can be detected and classified by the program. The program also evaluates the quality of the delivered spectral type. The program currently is capable of classifying spectra in the violet-green region in either the rectified or flux-calibrated format, although the accuracy of the flux calibration is not important. We report on tests of MKCLASS on spectra classified by human classifiers; those tests suggest that over the entire HR diagram, MKCLASS will classify in the temperature dimension with a precision of 0.6 spectral subclass, and in the luminosity dimension with a precision of about one half of a luminosity class. These results compare well with human classifiers.

  16. IMPLIKASI YURIDIS PUTUSAN MK NOMOR 46/PUU- VIII/ 2010 TERHADAP AKTA KELAHIRAN ANAK LUAR KAWIN

    Directory of Open Access Journals (Sweden)

    Djumikasih Djumikasih

    2014-08-01

    Full Text Available Abstract This paper aims to identify and analyze what the juridical implications of the publication of the decision of the Constitutional Court No. 46/PUU-VIII / 2010 on Child Outside Marriage Deed which has been published by the Department of Population and Civil Registration prior to the establishment of the Constitutional Court's decision . The method used in this study is a normative juridical approach legislation. From the discussion, it can be concluded that the Constitutional Court 46/PUU-VIII/2010 Number of Tests on Article 43 paragraph ( 1 Marriage Act ( Act No. 1 of 1974 when viewed from the angle of legal certainty it will lead to legal certainty . But the decision will not have any juridical implications of the child's birth certificate that has been published outside of marriage and illegitimate child who was born before the date of February 17, 2012, as if enacted would be contrary to the principle of legality is interpreted Article 47 of the Law on the Constitutional Court and Article 28 ( i of the 1945 Constitution . Likewise, if the terms of the fairness and usefulness , especially for justice seekers / applicant , the timing of this decision is not fair and not useful , because although the Court granted the petition but the Constitutional Court can not be applied to her .   Key words: yuridical implication, birth certificate, children who are born outside of marriage   Abstrak   Tulisan ini bertujuan untuk mengetahui dan menganalisis apa implikasi yuridis dari terbitnya putusan MK Nomor 46/PUU-VIII/ 2010 terhadap Akta Anak Luar Kawin yang sudah diterbitkan oleh Dinas Kependudukan dan Catatan Sipil sebelum lahirnya putusan MK tersebut. Metode yang digunakan dalam penelitian ini adalah yuridis normative dengan pendekatan perundang-undangan. Dari pembahasan dapat disimpulkan bahwa Putusan MK Nomer 46/PUU-VIII/2010 tentang Pengujian terhadap Pasal 43 ayat (1 UU Perkawinan (UU NO 1 Tahun 1974 jika dilihat dari sudut kepastian

  17. Psychotomimetic effects of different doses of MK-801 and the underlying mechanisms in a selective memory impairment model.

    Science.gov (United States)

    Liu, Weiqing; Wang, Dong; Hong, Wenjuan; Yu, Yi; Tang, Jinsong; Wang, Jicai; Liu, Fang; Xu, Xiufeng; Tan, Liwen; Chen, Xiaogang

    2017-03-01

    Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC. Copyright © 2016. Published by Elsevier B.V.

  18. Effects of MK-801 upon local cerebral glucose utilization in conscious rats and in rats anaesthetised with halothane

    International Nuclear Information System (INIS)

    Kurumaji, A.; McCulloch, J.

    1989-01-01

    The effects of MK-801 (0.5 mg/kg i.v.), a non-competitive N-methyl-D-aspartate (NMDA) antagonist, upon local cerebral glucose utilization were examined in conscious, lightly restrained rats and in rats anaesthetised with halothane in nitrous oxide by means of the quantitative autoradiographic [14C]-2-deoxyglucose technique. In the conscious rats, MK-801 produced a heterogenous pattern of altered cerebral glucose utilization with significant increases being observed in 12 of the 28 regions of gray matter examined and significant decreases in 6 of the 28 regions. Pronounced increases in glucose use were observed after MK-801 in the olfactory areas and in a number of brain areas in the limbic system (e.g., hippocampus molecular layer, dentate gyrus, subicular complex, posterior cingulate cortex, and mammillary body). In the cerebral cortices, large reductions in glucose use were observed after administration of MK-801, whereas in the extrapyramidal and sensory-motor areas, glucose use remained unchanged after MK-801 administration in conscious rats. In the halothane-anaesthetised rats, the pattern of altered glucose use after MK-801 differed qualitatively and quantitatively from that observed in conscious rats. In anaesthetised rats, significant reductions in glucose use were noted after MK-801 in 10 of the 28 regions examined, with no area displaying significantly increased glucose use after administration of the drug. In halothane-anaesthetised rats, MK-801 failed to change the rates of glucose use in the olfactory areas, the hippocampus molecular layer, and the dentate gyrus

  19. Effect of MK-801 on methamphetamine-induced dopaminergic neurotoxicity: long-term attenuation of methamphetamine-induced dopamine release

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Eun; Kim, Yu Ri; Hwang, Se Hwan [Sungkyunkwan Univ., School of Medicine, Seoul (Korea, Republic of)

    2001-08-01

    Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum using [{sup 3}H] WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 g/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli.

  20. Effect of MK-801 on methamphetamine-induced dopaminergic neurotoxicity: long-term attenuation of methamphetamine-induced dopamine release

    International Nuclear Information System (INIS)

    Kim, Sang Eun; Kim, Yu Ri; Hwang, Se Hwan

    2001-01-01

    Repeated administration of methamphetamine (METH) produces high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. The effect of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, on METH-induced changes in DA transporter (DAT) and DA release evoked by an acute METH challenge was evaluated in rodent striatum using [ 3 H] WIN 38,428 ex vivo auto-radiography and in vivo microdialysis. Four injections of METH (10 mg/kg, i.p.), each given 2 h apart, produced 71% decrease in DAT levels in mouse striatum 3 d after administration. Pretreatment with MK-801 (2.5 g/kg, i.p.) 15 min before each of the four METH injections protected completely against striatal DAT depletions. Four injections of MK-801 alone did not significantly change striatal DAT levels. Striatal DA release evoked by an acute METH challenge (4mg/kg, i.p.) at 3 d after repeated administration of METH in rats was decreased but significant compared with controls, which was attenuated by repeated pretreatment with MK-801. Also, repeated injections of MK-801 alone attenuated acute METH-induced striatal DA release 3 d after administration. These results suggest that repeated administration of MK-801 may exert a preventive effect against METH-induced DA terminal injury through long-term attenuation of DA release induced by METH and other stimuli

  1. The excitatory amino acid receptor antagonist MK-801 prevents the hypersensitivity induced by spinal cord ischemia in the rat

    International Nuclear Information System (INIS)

    Hao, J.X.; Xu, X.J.; Aldskogius, H.; Seiger, A.; Wiesenfeld-Hallin, Z.

    1991-01-01

    Protection by the NMDA receptor antagonist MK-801 against transient spinal cord ischemia-induced hypersensitivity was studied in rats. The spinal ischemia was initiated by vascular occlusion resulting from the interaction between the photosensitizing dye Erythrosin B and an argon laser beam. The hypersensitivity, termed allodynia, where the animals reacted by vocalization to nonnoxious mechanical stimuli in the flank area, was consistently observed during several days after induction of the ischemia. Pretreatment with MK-801 (0.1-0.5 mg/kg, iv) 10 min before laser irradiation dose dependently prevented the occurrence of allodynia. The neuroprotective effect of MK-801 was not reduced by maintaining normal body temperature during and after irradiation. There was a significant negative correlation between the delay in the administration of MK-801 after irradiation and the protective effect of the drug. Histological examination revealed slight morphological damage in the spinal cord in 38% of control rats after 1 min of laser irradiation without pretreatment with MK-801. No morphological abnormalities were observed in rats after pretreatment with MK-801 (0.5 mg/kg). The present results provide further evidence for the involvement of excitatory amino acids, through activation of the NMDA receptor, in the development of dysfunction following ischemic trauma to the spinal cord

  2. Pharmacodynamics of Imipenem in Combination with β-Lactamase Inhibitor MK7655 in a Murine Thigh Model

    Science.gov (United States)

    Mavridou, Eleftheria; Melchers, Ria J. B.; van Mil, Anita C. H. A. M.; Mangin, E.; Motyl, Mary R.

    2014-01-01

    MK7655 is a newly developed beta-lactamase inhibitor of class A and class C carbapenemases. Pharmacokinetics (PK) of imipenem-cilastatin (IMP/C) and MK7655 were determined for intraperitoneal doses of 4 mg/kg to 128 mg/kg of body weight. MIC and pharmacodynamics (PD) studies of MK7655 were performed against several beta-lactamase producing Pseudomonas aeruginosa and Klebsiella pneumoniae strains to determine its effect in vitro and in vivo. Neutropenic mice were infected in each thigh 2 h before treatment with an inoculum of approximately 5 × 106 CFU. They were treated with IMP/C alone (every 2 hours [q2h], various doses) or in combination with MK7655 in either a dose fractionation study or q2h for 24 h and sacrificed for CFU determinations. IMP/MK7655 decreased MICs regarding IMP MIC. The PK profiles of IMP/C and MK7655 were linear over the dosing range studied and comparable with volumes of distribution (V) of 0.434 and 0.544 liter/kg and half-lives (t1/2) of 0.24 and 0.25 h, respectively. Protein binding of MK7655 was 20%. A sigmoidal maximum effect (Emax) model was fit to the PK/PD index responses. The effect of the inhibitor was not related to the maximum concentration of drug in serum (Cmax)/MIC, and model fits for T>MIC and area under the concentration-time curve (AUC)/MIC were comparable (R2 of 0.7 and 0.75), but there appeared to be no significant relationship of effect with dose frequency. Escalating doses of MK7655 and IMP/C showed that the AUC of MK7655 required for a static effect was dependent on the dose of IMP/C and the MIC of the strain, with a mean area under the concentration-time curve for the free, unbound fraction of the drug (fAUC) of 26.0 mg · h/liter. MK7655 shows significant activity in vivo and results in efficacy of IMP/C in otherwise resistant strains. The exposure-response relationships found can serve as a basis for establishing dosing regimens in humans. PMID:25403667

  3. Pharmacological or genetic orexin 1 receptor inhibition attenuates MK-801 induced glutamate release in mouse cortex

    Directory of Open Access Journals (Sweden)

    Leah eAluisio

    2014-05-01

    Full Text Available The orexin/hypocretin neuropeptides are produced by a cluster of neurons within the lateral posterior hypothalamus and participate in neuronal regulation by activating their receptors (OX1 and OX2 receptors. The orexin system projects widely through the brain and functions as an interface between multiple regulatory systems including wakefulness, energy balance, stress, reward and emotion. Recent studies have demonstrated that orexins and glutamate interact at the synaptic level and that orexins facilitate glutamate actions. We tested the hypothesis that orexins modulate glutamate signaling via OX1 receptors by monitoring levels of glutamate in frontal cortex of freely moving mice using enzyme coated biosensors under inhibited OX1 receptor conditions. MK-801, an NMDA receptor antagonist, was administered subcutaneously (0.178 mg/kg to indirectly disinhibit pyramidal neurons and therefore increase cortical glutamate release. In wild-type mice, pretreatment with the OX1 receptor antagonist GSK-1059865 (10 mg/kg S.C. which had no effect by itself, significantly attenuated the cortical glutamate release elicited by MK-801. OX1 receptor knockout mice had a blunted glutamate release response to MK-801 and exhibited about half of the glutamate release observed in wild-type mice in agreement with the data obtained with transient blockade of OX1 receptors. These results indicate that pharmacological (transient or genetic (permanent inhibition of the OX1 receptor similarly interfere with glutamatergic function in the cortex. Selectively targeting the OX1 receptor with an antagonist may normalize hyperglutamatergic states and thus may represent a novel therapeutic strategy for the treatment of various psychiatric disorders associated with hyperactive states.

  4. Hippocampal serotonin depletion unmasks differences in the hyperlocomotor effects of phencyclidine and MK-801: quantitative versus qualitative analyses

    Directory of Open Access Journals (Sweden)

    Wendy K Adams

    2013-08-01

    Full Text Available Antagonism of N-methyl-D-aspartate (NMDA receptors by phencyclidine is thought to underlie its ability to induce a schizophrenia-like syndrome in humans, yet evidence indicates it has a broader pharmacological profile. Our previous lesion studies highlighted a role for serotonergic projections from the median, but not dorsal, raphe nucleus in mediating the hyperlocomotor effects of phencyclidine, without changing the action of the more selective NMDA receptor antagonist, MK-801. Here we compared locomotor responses to phencyclidine and MK 801 in rats that were administered 5,7 dihydroxytryptamine (5,7-DHT into either the dorsal or ventral hippocampus, which are preferentially innervated by median and dorsal raphe, respectively. Dorsal hippocampus lesions potentiated phencyclidine-induced hyperlocomotion (0.5, 2.5 mg/kg, but not the effect of MK-801 (0.1 mg/kg. Ventral hippocampus lesions did not alter the hyperlocomotion elicited by either compound. Given that phencyclidine and MK-801 may induce different spatiotemporal patterns of locomotor behavior, together with the known role of the dorsal hippocampus in spatial processing, we also assessed whether the 5,7-DHT-lesions caused any qualitative differences in locomotor responses. Treatment with phencyclidine or MK-801 increased the smoothness of the path travelled (reduced spatial d and decreased the predictability of locomotor patterns within the chambers (increased entropy. 5,7-DHT-lesions of the dorsal hippocampus did not alter the effects of phencyclidine on spatial d or entropy—despite potentiating total distance moved—but caused a slight reduction in levels of MK-801-induced entropy. Taken together, serotonergic lesions targeting the dorsal hippocampus unmask a functional differentiation of the hyperlocomotor effects of phencyclidine and MK 801. These findings have implications for studies utilising NMDA receptor antagonists in modeling glutamatergic dysfunction in schizophrenia.

  5. Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas.

    Directory of Open Access Journals (Sweden)

    Jenny M Kreahling

    Full Text Available Sarcomas are rare and heterogeneous mesenchymal tumors affecting both pediatric and adult populations with more than 70 recognized histologies. Doxorubicin and ifosfamide have been the main course of therapy for treatment of sarcomas; however, the response rate to these therapies is about 10-20% in metastatic setting. Toxicity with the drug combination is high, response rates remain low, and improvement in overall survival, especially in the metastatic disease, remains negligible and new agents are needed. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by MK1775 has been reported to enhance the cytotoxic effect of DNA damaging agents in different types of carcinomas. In this study we investigated the therapeutic efficacy of MK1775 in various sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo both alone and in combination with gemcitabine, which is frequently used in the treatment of sarcomas. Our data demonstrate that MK1775 treatment as a single agent at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. Additionally, MK1775 significantly enhances the cytotoxic effect of gemcitabine in sarcoma cells lines with different p53 mutational status. In patient-derived bone and soft tissue sarcoma samples we showed that MK1775 alone and in combination with gemcitabine causes significant apoptotic cell death. Magnetic resonance imaging (MRI and histopathologic studies showed that MK1775 induces significant cell death and terminal differentiation in a patient-derived xenograft mouse model of osteosarcoma in vivo. Our results together with the high safety profile of MK1775 strongly suggest that this drug can be used as a potential therapeutic agent in the treatment of both adult as well as pediatric sarcoma patients.

  6. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum

    Directory of Open Access Journals (Sweden)

    Huai Guan

    2016-01-01

    Full Text Available We previously reported that arsenic (As impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR/retinoid X receptor (RXR heterodimer and thyroid hormone (TH may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3’-triiodothyronine (T3 and thyroxin (T4 levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  7. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.

    Science.gov (United States)

    Guan, Huai; Li, Shuangyue; Guo, Yanjie; Liu, Xiaofeng; Yang, Yi; Guo, Jinqiu; Li, Sheng; Zhang, Cong; Shang, Lixin; Piao, Fengyuan

    2016-01-26

    We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  8. MK-III function tests in JOYO. Primary main cooling pump

    International Nuclear Information System (INIS)

    Isozaki, Kazunori; Saito, Takakazu; Sumino, Kouzo; Karube, Kouji; Terano, Toshihiro; Sakaba, Hideo; Nakai, Satoru

    2004-06-01

    MK-III function test (SKS-1) that was carried out from October 17, 2001 through October 23, 2001 using MK-III transition core configuration and MK-III function tests (SKS-2) was carried out from January 27, 2003 through February 13, 2003 using MK-III core configuration. The major function tests results of primary cooling system were shown as follows; (1) The stability of the primary main pump flow control system was confirmed on both CAS (cascade) mode and Man (manual) mode. Also no divergence of flow and revolution of the pump were observed at step flow change disturbance. (2) The main motor was shifted to run-back flow control operation in about 54 seconds after scram. The flow rate and pump revolution at run-back operation of A and B cooling system were 167 m 3 /h and 117 rpm, 185m 3 /h and 118 rpm respectively. The pump revolution was within the design target revolution 122 rpm ± 8 rpm and the flow was over the 10% of the rated flow. (3) The pony motor was engaged in operation in about 39 seconds after the primary main pump trip. The flow rate and pump revolution at the pony motor operation of A and B cooling system were 180 m 3 /h and 124 rpm, 190 m 3 /h and 123 rpm respectively. These values were satisfied the design low limit of 93 rpm and 10% of the rated flow. (4) Free flow coast down time constant was longer than 10 seconds that was design shortest time at both the primary pump trip and run-back operation. (5) Pump over flow column sodium levels of both A and B cooling system at rated operating condition were NL-1550 mm and, NL-1468 mm respectively and were lower than NL-1581 mm of the design value. This result shows the new IHX pressure loss estimation was conservative. (6) It was confirmed that the primary main pump could operate with out scram for up to 0.6 seconds of external power supply loss. (author)

  9. Combined administration of MK-801 and cycloheximide produces a delayed potentiation of fear discrimination memory extinction.

    Science.gov (United States)

    Kochli, Daniel E; Campbell, Tiffany L; Hollingsworth, Ethan W; Lab, Rain S; Postle, Abagail F; Perry, Megan M; Mordzinski, Victoria M; Quinn, Jennifer J

    2018-04-01

    Mixed evidence exists regarding the role of N-methyl-D-aspartate (NMDA) receptors in memory reconsolidation. We provide no evidence that NMDA receptors are involved with memory reconsolidation, but instead demonstrate that prereactivation systemic MK-801 injection, combined with postreactivation intrabasolateral amygdala (BLA) cycloheximide infusion, produces a delayed potentiation of extinction learning. These data suggest that an interaction between NMDA antagonism and protein synthesis inhibition may enhance extinction by exerting effects outside of the intended reconsolidation manipulation window. The present work demonstrates a novel pharmacological enhancement of extinction, and underscores the importance of employing proper control procedures in reconsolidation research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  10. On the mechanism of boron transfer through the cation-exchange membrane MK-40

    International Nuclear Information System (INIS)

    Pilipenko, A.T.; Varvaruk, L.A.; Grebenyuk, V.D.; Trachevskij, V.V.

    1985-01-01

    Proceses of boron electromigration in solutions with different pH values are investigated. It is shown, that boron transfer through ion-exchange membranes is determined by pH of solution. Phenomenon of boron transfer (existing in the solution in the form of boric acid) through cation-exchange membrane MK-40 has been detected and described for the first time. The process of boron (3) complexing with sulfate groups of the membrane by means of competing reversible substitution of hydroxoligands is the basis of the phenomenon

  11. Qualitative assessment of the fission product release capability of ELOCA.Mk5

    International Nuclear Information System (INIS)

    Klein, M.E.; Carlucci, L.N.; Arimescu, V.I.

    1995-01-01

    A qualitative assessment of the fission product release capability of the ELOCA.Mk5 computer code was performed by simulating two transients from the sweep-gas experiment, FIO-133. Improved agreement between calculated and experimental trends in release was obtained by applying an interface pressure stress component to the pellet center. As well, results show that the current system for defining the reference temperature distribution for the thermal stress component is not always realistic. These results are being used in the development of a new, mechanistic pellet stress model. (author)

  12. Computer analysis, design and construction of the BNL Mk V magnetron

    International Nuclear Information System (INIS)

    McKenzie-Wilson, R.B.; Kovarik, V.J.

    1981-01-01

    As part of a program to develop a high energy neutral beam injector for fusion reactor applications, the BNL Neutral Beam Group is studying, among other options, a surface plasma source of the magnetron type. This source has been developed to the point at which a large compact model, known as the Mk V magnetron, has been designed and constructed. The source is designed to operate in the steady state mode and to produce 1-2A of H - (D - ) ions at 25 kV. Under these conditions, 18 KW of heat are removed from the source by the cooling system

  13. MOTHER MK II: An advanced direct cycle high temperature gas reactor

    International Nuclear Information System (INIS)

    Hart, R.S.; Kendall, J.M.; Marsden, B.J.

    2003-01-01

    The MOTHER (MOdular Thermal HElium Reactor) power plant concepts employ high temperature gas reactors utilizing TRISO fuel, graphite moderator, and helium coolant, in combination with a direct Brayton cycle for electricity generation. The helium coolant from the reactor vessel passes through a Power Conversion Unit (PCU), which includes a turbine-generator, recuperator, precooler, intercooler and turbine-compressors, before being returned to the reactor vessel. The PCU substitutes for the reactor coolant system pumps and steam generators and most of the Balance Of Plant (BOP), including the steam turbines and condensers, employed by conventional nuclear power plants utilizing water cooled reactors. This provides a compact, efficient, and relatively simple plant configuration. The MOTHER MK I conceptual design, completed in the 1987 - 1989 time frame, was developed to economically meet the energy demands for extracting and processing heavy oil from the tar sands of western Canada. However, considerable effort was made to maximize the market potential beyond this application. Consistent with the remote and very high labour rate environment in the tar sands region, simplification of maintenance procedures and facilitation of 'change-out' in lieu of in situ repair was a design focus. MOTHER MK I had a thermal output of 288 MW and produced 120 MW electrical when operated in the electricity only production mode. An annular Prismatic reactor core was utilized, largely to minimize day-to-day operations activities. Key features of the power conversion system included two Power Conversion Units (144 MW th each), the horizontal orientation of all rotating machinery and major heat exchangers axes, high speed rotating machinery (17,030 rpm for the turbine-compressors and 10,200 rpm for the power turbine-generator), gas (helium) bearings for all rotating machinery, and solid state frequency conversion from 170 cps (at full power) to the grid frequency. Recognizing that the on

  14. Experimental fast reactor JOYO MK-III functional test. Primary auxiliary cooling system test

    International Nuclear Information System (INIS)

    Karube, Koji; Akagi, Shinji; Terano, Toshihiro; Onuki, Osamu; Ito, Hideaki; Aoki, Hiroshi; Odo, Toshihiro

    2004-03-01

    This paper describes the results of primary auxiliary cooling system, which were done as a part of JOYO MK-III function test. The aim of the tests was to confirm the operational performance of primary auxiliary EMP and the protection system including siphon breaker of primary auxiliary cooling system. The items of the tests were: (Test No.): (Test item). 1) SKS-117: EMP start up test. 2) SKS-118-1: EMP start up test when pony motor running. 3) SKS-121: Function test of siphon breaker. The results of the tests satisfied the required performance, and demonstrated successful operation of primary auxiliary cooling system. (author)

  15. Development of pop-up Langmuir probe system for the JET MkIIa divertor

    International Nuclear Information System (INIS)

    Davies, S.J.; Tellier, X.; Matthews, G.F.; Wilson, C.H.

    1999-01-01

    The successful operation of a pop-up Langmuir probe system, which was installed in the JET MkIIa divertor, is described. The system utilises the ambient magnetic field in tokamak plasmas to act on a current carrying coil and pop up a rail containing Langmuir probes. Measurements were made using pin-plate probes which, owing to their relatively large exposed area, are ideally suited for use with such a system. Details of the design, testing, measurements and potential applications of JET's pop-up system are given. (orig.)

  16. Development of 'popup' Langmuir probe system for the JET MkIIa divertor

    International Nuclear Information System (INIS)

    Davies, S.; Tellier, X.; Matthews, G.

    1999-01-01

    The successful operation of a 'popup' Langmuir probe system, which was installed in the JET MkIIa divertor, is described. The system utilises the ambient magnetic field in tokamak plasmas to act on a current carrying coil and pop up a rail containing Langmuir probes. Measurements were made using 'Pin-Plate' probes which, owing to their relatively large exposed area, are ideally suited for use with such a system. Details of the design, testing, measurements and potential applications of JET's 'popup' system are given. (author)

  17. A compact dilution refrigerator with vertical heat exchangers for operation to 2 mK

    International Nuclear Information System (INIS)

    Bunkov, Yu.M.; Guenault, A.M.; Hayward, D.J.; Jackson, D.A.; Kennedy, C.J.; Nichols, T.R.; Miller, I.E.; Pickett, G.R.; Ward, M.G.

    1991-01-01

    A compactly designed dilution refrigerator with closely packed, vertical heat exchangers is described. The refrigerator reaches a temperature of 2 mK and is easily constructed, since the sintered heat exchangers are straight units. Vibrating wire resonators are employed in the mixing chamber as diagnostic tools, which may act as both thermometers and phase-boundary level indicators. There is a design problem in the vertical arrangement, namely, the sumps on the concentrated phase side that can slowly fill with dilute phase and degrade the performance. The problem is solved by draining the superfluid 4 He component in any collected dilute phase through superleaks into the mixing chamber

  18. Operating experience of TRIGA MK-II Research Reactor in Bangladesh

    International Nuclear Information System (INIS)

    Mannan, M.A.; Ahmed, K.

    1992-01-01

    A 3 MW TRIGA MK II Research Reactor was installed in Bangladesh in 1986. The reactor is being utilized for research, training and for production of radioisotopes. Recently two faults were detected, one in the Emergency Core Cooling System and the other in the Primary Coolant Loop, which hindered the operation of the reactor partially. The faults were investigated by a team of local experts. Results of analyses of possible initiating events of the faults and the remedial steps are briefly discussed in the paper. (author)

  19. Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

    Science.gov (United States)

    Torrisi, Sebastiano Alfio; Salomone, Salvatore; Geraci, Federica; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Leggio, Gian Marco

    2017-01-01

    Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be

  20. MK-III function tests in JOYO. Dump heat exchanger (DHX)

    International Nuclear Information System (INIS)

    Kawahara, Hirotaka; Isozaki, Kazunori; Ishii, Takayuki; Ichige, Satoshi; Sakaba, Hideo; Nakai, Satoru; Nose, Shouiti

    2004-06-01

    A key part of the upgrade of the experimental fast reactor JOYO to the MK-III design was the replacement of the dump heat exchangers. MK-III function tests (SKS-1) of the new dump heat exchangers were carried out from August 27, 2001 through September 13, 2001. The major results of the function tests of the dump heat exchangers were as follows: (1) Air flow of the main blower with an inlet vane opening of 50% was confirmed to exceed the design rated flow of 7,700 m 3 /min. It was also demonstrated that an inlet vane opening of 100% provides about 130% of the design rated flow. This is because the new DHX flow route has more low pressure loss than the design value. (2) Tests of the air flow of the main blower demonstrated that with a fully opened inlet damper, a full opened outlet damper and an inlet vane opening of 0% provides about 5% of the design rated flow. (3) Free flow coast down characteristics of the main blower achieved an inlet vane 0% opening in an average of 7.9 seconds. Revolutions per minute of the main blower reached zero in an average of 8.7 seconds. The delay time from the opening of the vacuum contact breaker to the air flow decrease was approximately 1 second. This was a more conservative value than the 5 seconds assumed in design thermal transient analyses. (4) The loudest noise occurred with the main blower operating with a 25% inlet vane opening. At that time, the noise around the main blower was approximately 100 dB, and in the surrounding monitoring area boundary, the noise was 50 dB. This was confirmed to be within the standard of the Ibaraki prefectural ordinance. (5) Although the MK-III inlet vane and inlet damper drive unit was bigger than the MK-II unit, the accumulator tank was confirmed to provide sufficient volume during a compression air loss event. (author)

  1. Qualification campaign of the 50 mK hybrid sorption-ADR cooler for SPICA/SAFARI

    International Nuclear Information System (INIS)

    Duval, J-M; Duband, L; Attard, A

    2015-01-01

    SAFARI (SpicA FAR-infrared Instrument) is an infrared instrument planned to be part of the SPICA (SPace Infrared telescope for Cosmology and Astrophysics) Satellite. It will offer high spectral resolution in the 30 - 210 μm frequency range. SAFARI will benefit from the cold telescope of SPICA and to obtain the required detectors sensitivity, a temperature of 50 mK is required. This temperature is reached thanks to the use of a hybrid sorption - ADR (Adiabatic Demagnetization Refrigerator) cooler presented here. This cooler provides respectively 14 μW and 0.4 μW of cooling power at 300 mK and 50 mK. The cooler is planned to advantageously use two thermal interfaces of the instrument at 1.8 and 4.9 K. One of the challenges discussed in this paper is the low power available at each intercept. A dedicated laboratory electronic is being designed based on previous development with a particular focus on the 50 mK readout. Temperature regulation at 50 mK is also discussed. This cooler has been designed following flight constraints and will reach a high TRL, including mechanical and environmental tests at the end of the on-going qualification campaign. (paper)

  2. Qualification campaign of the 50 mK hybrid sorption-ADR cooler for SPICA/SAFARI

    Science.gov (United States)

    Duval, J.-M.; Duband, L.; Attard, A.

    2015-12-01

    SAFARI (SpicA FAR-infrared Instrument) is an infrared instrument planned to be part of the SPICA (SPace Infrared telescope for Cosmology and Astrophysics) Satellite. It will offer high spectral resolution in the 30 - 210 μm frequency range. SAFARI will benefit from the cold telescope of SPICA and to obtain the required detectors sensitivity, a temperature of 50 mK is required. This temperature is reached thanks to the use of a hybrid sorption - ADR (Adiabatic Demagnetization Refrigerator) cooler presented here. This cooler provides respectively 14 μW and 0.4 μW of cooling power at 300 mK and 50 mK. The cooler is planned to advantageously use two thermal interfaces of the instrument at 1.8 and 4.9 K. One of the challenges discussed in this paper is the low power available at each intercept. A dedicated laboratory electronic is being designed based on previous development with a particular focus on the 50 mK readout. Temperature regulation at 50 mK is also discussed. This cooler has been designed following flight constraints and will reach a high TRL, including mechanical and environmental tests at the end of the on-going qualification campaign.

  3. Thermometry using 1/8 W carbon resistors in a temperature region around 10 mK

    International Nuclear Information System (INIS)

    Kobayasi, S.; Shinohara, M.; Ono, K.

    1976-01-01

    The resistance-temperature characteristics of 1/8 W carbon resistors of grade ERC-18SG, manufactured by Matsushita, with the nominal values of 48, 82, 100, 220 and 330 Ω have been measured in the region 4.2 K to 25 mK and their application as thermometers in this region is confirmed. For the 82 Ω resistor, measurements were taken at temperatures below 10mK. The temperature dependence of the resistance was found to be linear on the log-log plot over a wide range below 50 mK. The sensitivity remains finite even at 6 mK, but below 10 mK rapid measurements were prevented by a considerable increase in the thermal relaxation time. Measurement of the characteristics of several 100 Ω resistors from two different sets showed that resistors from the same set separate into two groups with different characteristics. This become appreciable at temperatures below 4.2 K, so it is difficult to predict the behaviour of Matsushite resistors below 4.2 K from the characteristics at higher temperatures. (author)

  4. AC-3933, a benzodiazepine partial inverse agonist, improves memory performance in MK-801-induced amnesia mouse model.

    Science.gov (United States)

    Hashimoto, Takashi; Iwamura, Yoshihiro

    2016-05-01

    AC-3933, a novel benzodiazepine receptor partial inverse agonist, is a drug candidate for cognitive disorders including Alzheimer's disease. We have previously reported that AC-3933 enhances acetylcholine release in the rat hippocampus and ameliorates scopolamine-induced memory impairment and age-related cognitive decline in both rats and mice. In this study, we further evaluated the procognitive effect of AC-3933 on memory impairment induced by MK-801, an N-methyl-d-aspartate receptor antagonist, in mice. Unlike the acetylcholinesterase inhibitor donepezil and the benzodiazepine receptor inverse agonist FG-7142, oral administration of AC-3933 significantly ameliorated MK-801-induced memory impairment in the Y-maze test and in the object location test. Interestingly, the procognitive effects of AC-3933 on MK-801-induced memory impairment were not affected by the benzodiazepine receptor antagonist flumazenil, although this was not the case for the beneficial effects of AC-3933 on scopolamine-induced memory deficit. Moreover, the onset of AC-3933 ameliorating effect on scopolamine- or MK-801-induced memory impairment was different in the Y-maze test. Taken together, these results indicate that AC-3933 improves memory deficits caused by both cholinergic and glutamatergic hypofunction and suggest that the ameliorating effect of AC-3933 on MK-801-induced memory impairment is mediated by a mechanism other than inverse activation of the benzodiazepine receptor. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Superior effects of quetiapine compared with aripiprazole and iloperidone on MK-801-induced olfactory memory impairment in female mice.

    Science.gov (United States)

    Mutlu, Ahmet; Mutlu, Oguz; Ulak, Guner; Akar, Furuzan; Kaya, Havva; Erden, Faruk; Tanyeri, Pelin

    2017-05-01

    Cognitive dysfunction is commonly observed in schizophrenic patients and the administration of antipsychotic treatments results in different outcomes. Although the typical antipsychotic treatments, such as haloperidol, appear to be unable to improve cognition dysfunction, the atypical antipsychotic drugs (quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose of the current study was to investigate the effects of atypical antipsychotics on olfactory memory in mice, utilizing the social transmission of food preference (STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg), aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg) alone or concurrently prior to retention sessions of STFP tests. In the STFP tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001, respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten (%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced decreases in cued/total food eaten (%), while aripiprazole and iloperidone demonstrated no significant effects. The results revealed that all of the drugs disturbed olfactory memory in the naive mice; however, only quetiapine reversed MK-801-induced memory impairment in the STFP test.

  6. A scanning Hall probe microscope for high resolution magnetic imaging down to 300 mK

    International Nuclear Information System (INIS)

    Khotkevych, V. V.; Bending, S. J.; Milosevic, M. V.

    2008-01-01

    We present the design, construction, and performance of a low-temperature scanning Hall probe microscope with submicron lateral resolution and a large scanning range. The detachable microscope head is mounted on the cold flange of a commercial 3 He-refrigerator (Oxford Instruments, Heliox VT-50) and operates between room temperature and 300 mK. It is fitted with a three-axis slip-stick nanopositioner that enables precise in situ adjustment of the probe location within a 6x6x7 mm 3 space. The local magnetic induction at the sample surface is mapped with an easily changeable microfabricated Hall probe [typically GsAs/AlGaAs or AlGaAs/InGaAs/GaAs Hall sensors with integrated scanning tunnel microscopy (STM) tunneling tips] and can achieve minimum detectable fields ≥10 mG/Hz 1/2 . The Hall probe is brought into very close proximity to the sample surface by sensing and controlling tunnel currents at the integrated STM tip. The instrument is capable of simultaneous tunneling and Hall signal acquisition in surface-tracking mode. We illustrate the potential of the system with images of superconducting vortices at the surface of a Nb thin film down to 372 mK, and also of labyrinth magnetic-domain patterns of an yttrium iron garnet film captured at room temperature.

  7. Biotransformation of menadione to its prenylated derivative MK-3 using recombinant Pichia pastoris.

    Science.gov (United States)

    Li, Zhemin; Zhao, Genhai; Liu, Hui; Guo, Yugang; Wu, Hefang; Sun, Xiaowen; Wu, Xihua; Zheng, Zhiming

    2017-07-01

    Prenylated quinones, especially menaquinones, have significant physiological activities, but are arduous to synthesize efficiently. Due to the relaxed aromatic substrate specificity and prenylation regiospecificity at the ortho- site of the phenolic hydroxyl group, the aromatic prenyltransferase NovQ from Streptomyces may be useful in menaquinone synthesis from menadione. In this study, NovQ was overexpressed in Pichia pastoris. After fermentation optimization, NovQ production increased by 1617%. Then the different effects of metal ions, detergents and pH on the activity of purified NovQ were investigated to optimize the prenylation reaction. Finally, purified NovQ and cells containing NovQ were used for menadione prenylation in vitro and in vivo, respectively. Menaquinone-1 (MK-1) was detected as the only product in vitro with γ,γ-dimethylallyl pyrophosphate and menadione hydroquinol substrates. MK-3 at a concentration of 90.53 mg/L was detected as the major product of whole cell catalysis with 3-methyl-2-buten-1-ol and menadione hydroquinol substrates. This study realized whole cell catalysis converting menadione to menaquinones.

  8. JOYO coolant sodium and cover gas purity control database (MK-II core)

    International Nuclear Information System (INIS)

    Ito, Kazuhiro; Nemoto, Masaaki

    2000-03-01

    The experimental fast reactor 'JOYO' served as the MK-II irradiation bed core for testing fuel and material for FBR development for 15 years from 1982 to 1997. During the MK-II operation, impurities concentrations in the sodium and the argon gas were determined by 67 samples of primary sodium, 81 samples of secondary sodium, 75 samples of primary argon gas, 89 samples of secondary argon gas (the overflow tank) and 89 samples of secondary argon gas (the dump tank). The sodium and the argon gas purity control data were accumulated from in thirty-one duty operations, thirteen special test operations and eight annual inspections. These purity control results and related plant data were compiled into database, which were recorded on CD-ROM for user convenience. Purity control data include concentration of oxygen, carbon, hydrogen, nitrogen, chlorine, iron, nickel and chromium in sodium, concentration of oxygen, hydrogen, nitrogen, carbon dioxide, methane and helium in argon gas with the reactor condition. (author)

  9. Design and performance of a 50mK rapid turnaround detector characterization system

    International Nuclear Information System (INIS)

    Benford, Dominic J.; Dipirro, Michael J.; Forgione, Joshua B.; Jackson, Michael L.; Harvey Moseley, S.; Panek, John; Shirron, Peter J.; Staguhn, Johannes G.

    2006-01-01

    Upcoming major NASA missions such as the Einstein Inflation Probe and the Single Aperture Far-Infrared Observatory will require arrays of detectors with thousands of background-limited elements sensitive to wavelengths from ∼50μm to ∼3mm. Because of the low power levels present in space with cryogenic telescopes, these detectors will likely operate at temperatures below 100mK. In order to make rapid progress on detector development, the cryogenic testing cycle must be made convenient and quick. We have developed a cryogenic detector characterization system capable of testing superconducting detector arrays in formats up to 8x32, read out by SQUID multiplexers. The system relies on the cooling of a two-stage adiabatic demagnetization refrigerator immersed in a liquid helium bath. This approach permits a detector to be cooled from 300K to 50mK in under 6h, so that a test cycle begun in the morning will be over by the end of the day. The system is modular, with two identical immersible units, so that while one unit is cooling, the second can be reconfigured for the next battery of tests

  10. Altered 13C glucose metabolism in the cortico-striato-thalamo-cortical loop in the MK-801 rat model of schizophrenia

    DEFF Research Database (Denmark)

    Eyjolfsson, Elvar M; Nilsen, Linn Hege; Kondziella, Daniel

    2011-01-01

    Using a modified MK-801 (dizocilpine) N-methyl-D-aspartic acid (NMDA) receptor hypofunction model for schizophrenia, we analyzed glycolysis, as well as glutamatergic, GABAergic, and monoaminergic neurotransmitter synthesis and degradation. Rats received an injection of MK-801 daily for 6 days...... in all regions. In conclusion, neurotransmitter metabolism in the cortico-striato-thalamo-cortical loop is severely impaired in the MK-801 (dizocilpine) NMDA receptor hypofunction animal model for schizophrenia....

  11. Cooling of electrically insulated high voltage electrodes down to 30 mK Kühlung von elektrisch isolierten Hochspannungselektroden bis 30 mK

    CERN Document Server

    Eisel, Thomas; Bremer, J

    2011-01-01

    The Antimatter Experiment: Gravity, Interferometry, Spectroscopy (AEGIS) at the European Organization for Nuclear Research (CERN) is an experiment investigating the influence of earth’s gravitational force upon antimatter. To perform precise measurements the antimatter needs to be cooled to a temperature of 100 mK. This will be done in a Penning trap, formed by several electrodes, which are charged with several kV and have to be individually electrically insulated. The trap is thermally linked to a mixing chamber of a 3He-4He dilution refrigerator. Two link designs are examined, the Rod design and the Sandwich design. The Rod design electrically connects a single electrode with a heat exchanger, immersed in the helium of the mixing chamber, by a copper pin. An alumina ring and the helium electrically insulate the Rod design. The Sandwich uses an electrically insulating sapphire plate sandwiched between the electrode and the mixing chamber. Indium layers on the sapphire plate are applied to improve the ther...

  12. New concept of combustion technology in small DI diesel engines. 4th Report. Effects of fuel injection rates on MK combustion; Kogata chokufun diesel kikan no shinnensho concept. 4. Funsharitsu no MK nensho eno eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, S; Matsui, Y; Kamihara, T [Nissan Motor Co. Ltd., Tokyo (Japan)

    1997-10-01

    A previous paper showed that EGR cooling and a low compression ratio which prolongs the ignition delay can expand the area of the new combustion concept. Experimental investigations were conducted in this research to examine the effects of the fuel injection rates, the injection pressure and the injection duration, on the exhaust emissions of an engine incorporating the MK concept The results showed that a higher injection pressure was effective in reducing NOx and particulate matter (PM) under MK combustion conditions. 10 refs., 9 figs., 1 tab.

  13. Effect of subchronic caffeine treatment on MK-801-induced changes in locomotion, cognition and ataxia in mice.

    Science.gov (United States)

    de Oliveira, R V; Dall'Igna, O P; Tort, A B L; Schuh, J F; Neto, P F; Santos Gomes, M W; Souza, D O; Lara, D R

    2005-03-01

    N-Methyl-D-aspartate (NMDA) receptor antagonists cause hyperlocomotion and cognitive deficits in rodents, and caffeine-tolerant mice show diminished locomotor response to NMDA receptor antagonists. The aim of this study was to evaluate the effect of subchronic caffeine treatment on MK-801-induced hyperlocomotion, ataxia and cognitive deficits, as well as amphetamine-induced hyperlocomotion in mice. Mice were treated subchronically with caffeine (0, 0.1, 0.3 and 1 mg/ml and 1, 3 and 7 days) and evaluated for locomotor activity, working memory (delayed alternation test), long-term memory (inhibitory avoidance task) and ataxia. Hyperlocomotion induced by MK-801 (0.25 mg/kg i.p.) was diminished after 3 days and almost abolished after 7 days of caffeine treatment at the 1 mg/ml dose, and this effect was also dose-dependent. Ataxia induced by 0.5 mg/kg MK-801 was not affected by caffeine treatment, but a short-lived hyperlocomotor effect was observed. Performance deficit in the inhibitory avoidance task induced by MK-801 (0.01 mg/kg) was prevented in mice treated with caffeine for 7 days at 1 mg/ml, and perseverative errors in the T-maze by MK-801 (0.4 mg/kg) were attenuated. The locomotor effect of amphetamine (5 mg/kg) was unaffected by subchronic caffeine treatment. The findings that hyperlocomotion and cognitive effects induced by MK-801 can be specifically influenced by reduced adenosinergic activity agree with a model of adenosine hypofunction in schizophrenia, since NMDA receptor antagonists are pharmacological models for this disorder.

  14. Competitive (AP7) and non-competitive (MK-801) NMDA receptor antagonists differentially alter glucose utilization in rat cortex

    International Nuclear Information System (INIS)

    Clow, D.W.; Lee, S.J.; Hammer, R.P. Jr.

    1991-01-01

    The effects of D,L-2-amino-7-phosphonoheptanoic acid (AP7), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and MK-801, a non-competitive NMDA receptor antagonist, on regional brain metabolism were studied in unanesthetized, freely moving rats by using the quantitative 14 C2-deoxyglucose autoradiographic procedure. AP7 (338 or 901 mg/kg) produced a dose-dependent decrease of metabolic activity throughout most of the regions studied including sensory, motor, and limbic cortices. In contrast, MK-801 (0.1 or 1.0 mg/kg) resulted in a dose-dependent decrease of metabolic activity in sensory cortices, and an increase in limbic regions such as the hippocampal stratum lacunosum moleculare and entorhinal cortex. MK-801 also produced a biphasic response in agranular motor cortex, whereby the low dose increased while the high dose decreased labeling. In addition, MK-801 produced heterogeneous effects on regional cerebral metabolism in sensory cortices. Metabolic activity decreased in layer IV relative to layer Va following MK-801 treatment in primary somatosensory (SI) and visual (VI) cortices, suggesting a shift in activity from afferent fibers innervating layer IV to those innervating layer Va. MK-801 administration also decreased metabolic activity in granular SI relative to dysgranular SI, and in VI relative to secondary visual cortex (VII), thus providing a relative sparing of activity in dysgranular SI and VII. Thus, the non-competitive NMDA receptor antagonist suppressed activity from extrinsic neocortical sources, enhancing relative intracortical activity and stimulating limbic regions, while the competitive NMDA antagonist depressed metabolic activity in all cortical regions

  15. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

    DEFF Research Database (Denmark)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

    2014-01-01

    PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant...

  16. Impairment of Fos protein formation in the rat infarct borderzone by MK-801, but not by NBQX

    DEFF Research Database (Denmark)

    Christensen, Thomas; Jørgensen, M B; Diemer, Nils Henrik

    1993-01-01

    or a glutamate receptor antagonist; the non-competitive NMDA receptor antagonist MK-801 or the AMPA receptor antagonist NBQX which are known to be able to reduce infarct size in MCA occluded rats. The saline treated rats showed presence of Fos protein in nerve cell nuclei throughout the cortical and striatal...... infarct borderzone, but no staining in the infarct core or contralateral hemisphere. MK-801 almost totally abolished this expression of Fos protein whereas NBQX had no significant effect on Fos protein expression. It is suggested that the Fos protein induction is due to repeated spreading depressions...

  17. The impact of BWR MK I primary containment failure dynamics on secondary containment integrity

    International Nuclear Information System (INIS)

    Greene, S.R.

    1987-01-01

    During the past four years, the ORNL BWRSAT Program has developed a series of increasingly sophisticated BWR secondary containment models. These models have been applied in a variety of studies to evaluate the severe accident mitigation capability of BWR secondary containments. This paper describes the results of a recent ORNL study of the impact of BWR MK I primary containment failure dynamics on secondary containment integrity. A 26-cell MELCOR Browns Ferry secondary containment model is described and the predicted thermodynamic response of the secondary containment to a variety of postulated primary containment failure modes is presented. The effects of primary containment failure location, timing, and ultimate hole size on secondary containment response is investigated, and the potential impact of hydrogen deflagrations on secondary containment integrity is explored

  18. Influence of the metakaolin on porous structure of matrixes based in mk/cement

    Directory of Open Access Journals (Sweden)

    Frías, M.

    2000-09-01

    Full Text Available The incorporation of pozzolanic materials in the manufacturing of blended cement has a positive effect on the improvement of blended mortar and concretes performances. These active additions modify porous structure, impeding or delaying the access of aggressive solutions and, therefore materials more durable are possible of obtaining. An increase or decrease on the durability of blended pastes, mortars and concretes will depend on chemical and mineralogical compositions, fineness and reaction kinetics of these pozzolans. The current work shows the results of a research carried out in blended pastes to know the effect of activated material (metakaolin on the microporosity of pastes elaborated with different amounts of mk (0-25%. A water/ binder ratio of 0,55 was used. Samples were cured at 20ºC for 360 days. The evolution of total, capilary and gel porosity as well as average pore size were carried out through mercury intrusion porosimeter (MIP. Also, the helium pycnometer as alternative method to obtain additional information about porosity above 1,4 Å was used. A good correlation between both methods has been obtained. In addition, it is proposed the best mk content for the elaboration of mk-blended pastes.

    La incorporación de materiales puzolánicos presenta un efecto positivo en la mejora de las prestaciones de los morteros y hormigones mixtos. Estos modifican la estructura porosa, impidiendo o retrasando el acceso de los medios agresivos y, por lo tanto, contribución a la obtención de materiales mixtos más durables. La mayor o menor durabilidad de las pastas, morteros y hormigones mixtos dependerá de la composición química, mineralógica, finura y de la cinética de reacción de estas adiciones activas. En el presente trabajo se recogen los resultados de una investigación llevada a cabo para conocer el efecto de un material activado (metacaolin en la microporosidad de pastas, elaboradas con diferentes contenidos de

  19. Burnable poison calculations for Mk.III gas-cooled reactor systems

    Energy Technology Data Exchange (ETDEWEB)

    Gubbins, M E

    1971-02-15

    A method of calculating the reactivity and burn-up hisotry of a Mk.III GCR system containing burnable poisons has been described. The method allows for poison-fuel interaction. Using the method it has been shown that burn-up of the poison under a constant incident flux can give errors of the order of 1-2 niles. A calculation using the method described will take about 50% longer than a straightforward fuel burn-up calculation in the same number of groups. The multi-cell approach has a potential for handling greater geometrical complexity. It is intended to compare the method against experiment as soon as suitable experimental results become available.

  20. A Study on L-Asparaginase of Nocardia levis MK-VL_113

    Directory of Open Access Journals (Sweden)

    Alapati Kavitha

    2012-01-01

    Full Text Available An enzyme-based drug, L-asparaginase, was produced by Nocardia levis MK-VL_113 isolated from laterite soils of Guntur region. Cultural parameters affecting the production of L-asparaginase by the strain were optimized. Maximal yields of L-asparaginase were recorded from 3-day-old culture grown in modified asparagine-glycerol salts broth with initial pH 7.0 at temperature 30∘C. Glycerol (2% and yeast extract (1.5% served as good carbon and nitrogen sources for L-asparaginase production, respectively. Cell-disrupting agents like EDTA slightly enhanced the productivity of L-asparaginase. Ours is the first paper on the production of L-asparaginase by N. levis.

  1. Application of bone scintigrams in total knee replacement (Okayama MK-II type)

    Energy Technology Data Exchange (ETDEWEB)

    Umeda, T.; Inoue, S.; Matsui, N.; Moriya, H. (Chiba Univ. (Japan). School of Medicine)

    1982-02-01

    Eighteen patients with 21 total knee replacements (OKAYAMA MK-II type) were examined by radionuclide imaging in order to assess the prosthetic complaints such as loosening, infection, fracture and lasting pain. The following results and conclusions were obtained. 1) Bone imaging can reveal the condition of the attachment of bone and prosthesis. 2) Diffuse uptake gradually diminished until 18 months after surgery. 3) In front view on bone imaging, tibial uptake corresponded highly with the part of the weight area. 4) In cases of high uptake of posterior femoral component in lateral view, the range of knee flexion was mostly restricted. 5) Long-period persistent local uptake suggested loosening of the prosthesis or fracture of the tibial plateau. 6) Patello-femoral uptake showed no relation to the patellofemoral complaints. Radionuclide bone imaging is considered to represent one of the most valuable diagnostic procedures for assessing the clinical results after total knee replacement.

  2. Application of bone scintigrams in total knee replacement (Okayama MK-II type)

    International Nuclear Information System (INIS)

    Umeda, Tohru; Inoue, Shunichi; Matsui, Nobuo; Moriya, Hideshige

    1982-01-01

    Eighteen patients with 21 total knee replacements (OKAYAMA MK-II type) were examined by radionuclide imaging in order to assess the prosthetic complaints such as loosening, infection, fracture and lasting pain. The following results and conclusions were obtained. 1) Bone imaging can reveal the condition of the attachment of bone and prosthesis. 2) Diffuse uptake gradually diminished until 18 months after surgery. 3) In front view on bone imaging, tibial uptake corresponded highly with the part of the weight area. 4) In cases of high uptake of posterior femoral component in lateral view, the range of knee flexion was mostly restricted. 5) Long-period persistent local uptake suggested loosening of the prosthesis or fracture of the tibial plateau. 6) Patello-femoral uptake showed no relation to the patellofemoral complaints. Radionuclide bone imaging is considered to represent one of the most valuable diagnostic procedures for assessing the clinical results after total knee replacement. (author)

  3. Tvorba 3D modelu objektu ze snímků více kamer

    OpenAIRE

    Zemčík, Tomáš

    2016-01-01

    Tvorba 3D modelu objektu ze snímků několika kamer umožňuje bezkontaktní měření reálných objektů. Tato práce popisuje nutné teoretické a matematické zázemí pro pochopení problematiky a navrhuje možné hardwarové a softwarové řešení problému 3D rekonstrukce kukly se senzory EEG přímo na hlavě pacienta. Reconstruction of 3D model from multiple view images allows us to perform a contactless measurement of real world objects. This work contains theoretical and mathematical background necessary f...

  4. Developments in the design of the PS Frog Mk 5 wave energy converter

    Energy Technology Data Exchange (ETDEWEB)

    McCabe, A.P.; Bradshaw, A.; Meadowcroft, J.A.C.; Aggidis, G. [Department of Engineering, Lancaster University Renewable Energy Group, Lancaster LA1 4YR (United Kingdom)

    2006-02-01

    This paper describes one of the innovative wave energy converters under development by the Lancaster University Renewable Energy Group. An offshore point-absorber wave energy converter, PS Frog Mk 5 consists of a large buoyant paddle with an integral ballasted 'handle' hanging below it. The waves act on the blade of the paddle and the ballast beneath provides the necessary reaction. When the WEC is pitching, power is extracted by partially resisting the sliding of a power-take-off mass, which moves in guides above sea level. Totally enclosed in a steel hull, with no external moving parts, PS Frog Mk. 5 is at least as robust as a ship and the survivability of the device is currently under investigation, though such work is beyond the scope of this paper. Such a device could be very economic in terms of power output per unit of capital cost. New inventive steps with experimental results and computer studies have led to promising improvements to the hull shape. The WEC is maintained in a resonant state by the use of special means to maintain a high dynamic magnifier in irregular seas. A robust feedback control system has been developed to ensure stability and maintain efficient power take-off. Some of these developments are described and illustrated with the results of computer simulations that show power outputs and device motion over a range of conditions. It is shown that useful advances have been made, with the power capture bordering on 2MW in an increasing proportion of sea states. (author)

  5. JOYO MK-II core characteristics database. Update to JFS-3-J3.2R

    International Nuclear Information System (INIS)

    Ohkawachi, Yasushi; Maeda, Shigetaka; Sekine, Takashi

    2003-04-01

    The 'JOYO' MK-II core characteristics database was compiled and published in 1998. Comments and requests from many users led to the creation of a revised edition in 2001. The revisions include changes to the MAGI calculation code system to use the 70 group JFS-3-J3.2 constant set processed from the JENDL-3.2 library. However, after the database was published, it was recently found that there were errors in the process of making the group constant set JFS-3-J3.2, and it was revised at JFS-3-J3.2R. Then, the group constant set was updated at JFS-3-J3.2R in this database. The MK-II core management data nad core characteristics data were recorded on CD-ROM for user convenience. The structure of the database is the same as in the first edition. The 'Configuration Data' include the core arrangement and refueling record for each operational cycle. The 'Subassembly Library Data' include the atomic number density, neutron fluence, burn-up, integral power of 362 driver fuel subassemblies and 69 irradiation test subassemblies. The 'Output Data' contain the calculated neutron flux, gamma flux, power density, linear heat rate, coolant and fuel temperature distribution of all the fuel subassemblies at the beginning and end of each operational cycle. The 'Core Characteristics Data' include the measured excess reactivity, control rod worth calibration curve, and reactivity coefficients of temperature, power and burn-up. The effect of updating the group constant set, the calculation results of excess reactivity decreased by about 0.15Δk/kk', and the effects to other core characteristics were negligible. (author)

  6. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia.

    Science.gov (United States)

    Kesby, James P; Burne, Thomas H J; McGrath, John J; Eyles, Darryl W

    2006-09-15

    Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats. Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801. DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response. These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.

  7. Effects of MK-801 on vicarious trial-and-error and reversal of olfactory discrimination learning in weanling rats.

    Science.gov (United States)

    Griesbach, G S; Hu, D; Amsel, A

    1998-12-01

    The effects of dizocilpine maleate (MK-801) on vicarious trial-and-error (VTE), and on simultaneous olfactory discrimination learning and its reversal, were observed in weanling rats. The term VTE was used by Tolman (The determiners of behavior at a choice point. Psychol. Rev. 1938;46:318-336), who described it as conflict-like behavior at a choice-point in simultaneous discrimination learning. It takes the form of head movements from one stimulus to the other, and has recently been proposed by Amsel (Hippocampal function in the rat: cognitive mapping or vicarious trial-and-error? Hippocampus, 1993;3:251-256) as related to hippocampal, nonspatial function during this learning. Weanling male rats received systemic MK-801 either 30 min before the onset of olfactory discrimination training and its reversal, or only before its reversal. The MK-801-treated animals needed significantly more sessions to acquire the discrimination and showed significantly fewer VTEs in the acquisition phase of learning. Impaired reversal learning was shown only when MK-801 was administered during the reversal-learning phase, itself, and not when it was administered throughout both phases.

  8. A Randomized, Double-Blind, Crossover Comparison of MK-0929 and Placebo in the Treatment of Adults with ADHD

    Science.gov (United States)

    Rivkin, Anna; Alexander, Robert C.; Knighton, Jennifer; Hutson, Pete H.; Wang, Xiaojing J.; Snavely, Duane B.; Rosah, Thomas; Watt, Alan P.; Reimherr, Fred W.; Adler, Lenard A.

    2012-01-01

    Objective: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. Method: A randomized, double-blind, placebo-controlled, crossover study was conducted…

  9. N-methyl-D-aspartate receptor antagonist MK-801 impairs learning but not memory fixation or expression of classical fear conditioning in goldfish (Carassius auratus).

    Science.gov (United States)

    Xu, X; Davis, R E

    1992-04-01

    The amnestic effects of the noncompetitive antagonist MK-801 on visually mediated, classic fear conditioning in goldfish (Carassius auratus) was examined in 5 experiments. MK-801 was administered 30 min before the training session on Day 1 to look for anterograde amnestic effects, immediately after training to look for retrograde amnestic effects, and before the training or test session, or both, to look for state-dependence effects. The results showed that MK-801 produced anterograde amnesia at doses that did not produce retrograde amnesia or state dependency and did not impair the expression of conditioned or unconditioned branchial suppression responses (BSRs) to the conditioned stimulus. The results indicate that MK-801 disrupts the mechanism of learning of the conditioned stimulus-unconditioned stimulus relation. Evidence is also presented that the learning processes that are disrupted by MK-801 occur during the initial stage of BSR conditioning.

  10. Design and synthesis of enantiomerically enriched, radiolabeled MK-801 analogs as potential radiotracers for imaging and autoradiographic studies of the NMDA receptor-ion channel complex

    International Nuclear Information System (INIS)

    Eng, W.S.; Burns, H.D.; Gibson, R.E.; Ransom, R.W.; Thorpe, H.; Fioravanit, C.; Britcher, S.F.; Magill, C.A.; Solomon, H.F.; Dannals, R.F.; Wilson, A.A.; Ravert, H.T.; Wagner, H.N.

    1989-01-01

    MK-801 is a potent, non-competitive antagonist for the N-methyl-D-asspartate (NMDA) receptor-ion channel complex. This complex is though to be involved in nerve cell damage in stroke patients when excess calcium is released through the activated channel. A thorough understanding of drug interactions with the NMDA receptor complex could lead to improved therapy for reducing hypoxic-ischemic neuronal injuries in stroke patients. Based on the results of extensive structure-activity studies, the authors have developed several enantiomerically enriched, radiolabeled analogs of MK-801, including: 3-1231-MK-801 for Single Photon Emission Computed tomography (SPECT); 3-1251-MK-801 for in-vivo and in-vitro autoradiography; 8-11C-MeO-MK-801 for Positron Emission Tomography (PET). Details of the synthesis of these radiotracers and their application to both in-vitro and in-vivo studies are described

  11. Synthesis and characterization of a radiolabeled derivative of the phencyclidine/N-methyl-D-aspartate receptor ligand (+)MK-801 with high specific radioactivity

    International Nuclear Information System (INIS)

    Keana, J.F.W.; Scherz, M.W.; Quarum, M.; Sonders, M.S.; Weber, E.

    1988-01-01

    A [ 3 H]-labelled derivative of the drug (+)MK-801 with a high specific radioactivity was synthesized by first preparing a tribromo derivative of (+)MK-801 followed by catalytic reduction in the presence of [ 3 H]-gas and subsequent purification of the radioactive product by reversed-phase high performance liquid chromatography (RP-HPLC). This resulted in pure (+) [ 3 H]MK-801 with a specific radioactivity of 97 Ci/mmol. The (+) [ 3 H]MK-801 was shown to interact with high affinity and selectivity with the phencyclidine (PCP) receptor in guinea pig brain membrane suspensions. The PCP receptor is associated with a cation channel that is chemically gated by glutamate and N-methyl-D-aspartate (NMDA). Drugs that interact with the PCP receptor block this channel. The (+) [ 3 H]MK-801 described here will be useful to investigate the biochemistry of PCP/NMDA receptors in experiments where a high specific radioactivity is essential

  12. Synthesis and biological evaluation of [11C]MK-912 as an α2-adrenergic receptor radioligand for PET studies

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Pleus, Richard C.; Shiue, Grace G.; Rysavy, Joseph A.; Sunderland, John J.; Cornish, Kurtis G.; Young, Steven D.; Bylund, David B.

    1998-01-01

    ABSTRACT. In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo [2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent α 2 -adrenergic receptor antagonist with high affinity (K i = 0.42, 0.26 and 0.03 nM to α 2A , α 2B and α 2C , respectively) and high selectivity (α 2A /α 1A = 240; α 2A /D-1 = 3600; α 2A /D-2 3500; α 2A /5-HT 1 = 700; α 2A /5-HT 2 = 4100). The compound was labeled with 11 C and evaluated in rodents and monkey as a specific radioligand for studying α 2 -adrenergic receptors using PET. [ 11 C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [ 11 C]CH 3 I in (Bu 3 O)P=O at 85 deg. C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/μmol and the radiochemical purity was 97%. The initial uptake of [ 11 C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [ 11 C]MK-912 in rat olfactory tubercle, a brain region with high density of α 2 -adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [ 11 C]MK-912 with a potent α 2 -adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to α 2 -adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [ 11 C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density α 2 -adrenergic receptor brain regions exceeds a few millimeters in diameter

  13. MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia

    Science.gov (United States)

    Guest, Paul C.; Iwata, Keiko; Kato, Takahiro A.; Steiner, Johann; Schmitt, Andrea; Turck, Christoph W.; Martins-de-Souza, Daniel

    2015-01-01

    Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PGK), and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that

  14. FOXO/TXNIP pathway is involved in the suppression of hepatocellular carcinoma growth by glutamate antagonist MK-801

    International Nuclear Information System (INIS)

    Yamaguchi, Fuminori; Hirata, Yuko; Akram, Hossain; Kamitori, Kazuyo; Dong, Youyi; Sui, Li; Tokuda, Masaaki

    2013-01-01

    Accumulating evidence has suggested the importance of glutamate signaling in cancer growth, yet the signaling pathway has not been fully elucidated. N-methyl-D-aspartic acid (NMDA) receptor activates intracellular signaling pathways such as the extracellular-signal-regulated kinase (ERK) and forkhead box, class O (FOXO). Suppression of lung carcinoma growth by NMDA receptor antagonists via the ERK pathway has been reported. However, series of evidences suggested the importance of FOXO pathways for the regulation of normal and cancer cell growth. In the liver, FOXO1 play important roles for the cell proliferation such as hepatic stellate cells as well as liver metabolism. Our aim was to investigate the involvement of the FOXO pathway and the target genes in the growth inhibitory effects of NMDA receptor antagonist MK-801 in human hepatocellular carcinoma. Expression of NMDAR1 in cancer cell lines from different tissues was examined by Western blot. NMDA receptor subunits in HepG2, HuH-7, and HLF were examined by reverse transcriptase polymerase chain reaction (RT-PCR), and growth inhibition by MK-801 and NBQX was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of MK-801 on the cell cycle were examined by flow cytometry and Western blot analysis. Expression of thioredoxin-interacting protein (TXNIP) and p27 was determined by real-time PCR and Western blotting. Activation of the FOXO pathway and TXNIP induction were examined by Western blotting, fluorescence microscopy, Chromatin immunoprecipitation (ChIP) assay, and reporter gene assay. The effects of TXNIP on growth inhibition were examined using the gene silencing technique. NMDA receptor subunits were expressed in all cell lines examined, and MK-801, but not NBQX, inhibited cell growth of hepatocellular carcinomas. Cell cycle analysis showed that MK-801 induced G1 cell cycle arrest by down-regulating cyclin D1 and up-regulating p27. MK-801 dephosphorylated

  15. FOXO/TXNIP pathway is involved in the suppression of hepatocellular carcinoma growth by glutamate antagonist MK-801

    Science.gov (United States)

    2013-01-01

    Background Accumulating evidence has suggested the importance of glutamate signaling in cancer growth, yet the signaling pathway has not been fully elucidated. N-methyl-D-aspartic acid (NMDA) receptor activates intracellular signaling pathways such as the extracellular-signal-regulated kinase (ERK) and forkhead box, class O (FOXO). Suppression of lung carcinoma growth by NMDA receptor antagonists via the ERK pathway has been reported. However, series of evidences suggested the importance of FOXO pathways for the regulation of normal and cancer cell growth. In the liver, FOXO1 play important roles for the cell proliferation such as hepatic stellate cells as well as liver metabolism. Our aim was to investigate the involvement of the FOXO pathway and the target genes in the growth inhibitory effects of NMDA receptor antagonist MK-801 in human hepatocellular carcinoma. Methods Expression of NMDAR1 in cancer cell lines from different tissues was examined by Western blot. NMDA receptor subunits in HepG2, HuH-7, and HLF were examined by reverse transcriptase polymerase chain reaction (RT-PCR), and growth inhibition by MK-801 and NBQX was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of MK-801 on the cell cycle were examined by flow cytometry and Western blot analysis. Expression of thioredoxin-interacting protein (TXNIP) and p27 was determined by real-time PCR and Western blotting. Activation of the FOXO pathway and TXNIP induction were examined by Western blotting, fluorescence microscopy, Chromatin immunoprecipitation (ChIP) assay, and reporter gene assay. The effects of TXNIP on growth inhibition were examined using the gene silencing technique. Results NMDA receptor subunits were expressed in all cell lines examined, and MK-801, but not NBQX, inhibited cell growth of hepatocellular carcinomas. Cell cycle analysis showed that MK-801 induced G1 cell cycle arrest by down-regulating cyclin D1 and up-regulating p

  16. The CSIRO Mk3L climate system model version 1.0 – Part 1: Description and evaluation

    Directory of Open Access Journals (Sweden)

    S. J. Phipps

    2011-06-01

    Full Text Available The CSIRO Mk3L climate system model is a coupled general circulation model, designed primarily for millennial-scale climate simulations and palaeoclimate research. Mk3L includes components which describe the atmosphere, ocean, sea ice and land surface, and combines computational efficiency with a stable and realistic control climatology. This paper describes the model physics and software, analyses the control climatology, and evaluates the ability of the model to simulate the modern climate.

    Mk3L incorporates a spectral atmospheric general circulation model, a z-coordinate ocean general circulation model, a dynamic-thermodynamic sea ice model and a land surface scheme with static vegetation. The source code is highly portable, and has no dependence upon proprietary software. The model distribution is freely available to the research community. A 1000-yr climate simulation can be completed in around one-and-a-half months on a typical desktop computer, with greater throughput being possible on high-performance computing facilities.

    Mk3L produces realistic simulations of the larger-scale features of the modern climate, although with some biases on the regional scale. The model also produces reasonable representations of the leading modes of internal climate variability in both the tropics and extratropics. The control state of the model exhibits a high degree of stability, with only a weak cooling trend on millennial timescales. Ongoing development work aims to improve the model climatology and transform Mk3L into a comprehensive earth system model.

  17. Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood.

    Science.gov (United States)

    Liu, Weiqing; Wang, Xiuyan; Hong, Wenjuan; Wang, Dong; Chen, Xiaogang

    2017-02-01

    Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis. An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test. We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (Psocial isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats. MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. (11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

    Science.gov (United States)

    Van Laere, Koenraad J; Sanabria-Bohórquez, Sandra M; Mozley, David P; Burns, Donald H; Hamill, Terence G; Van Hecken, Anne; De Lepeleire, Inge; Koole, Michel; Bormans, Guy; de Hoon, Jan; Depré, Marleen; Cerchio, Kristine; Plalcza, John; Han, Lingling; Renger, John; Hargreaves, Richard J; Iannone, Robert

    2014-01-01

    The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity. Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level. The mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses. (11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

  19. Knockout of NMDA-receptors from parvalbumin interneurons sensitizes to schizophrenia-related deficits induced by MK-801

    Science.gov (United States)

    Bygrave, A M; Masiulis, S; Nicholson, E; Berkemann, M; Barkus, C; Sprengel, R; Harrison, P J; Kullmann, D M; Bannerman, D M; Kätzel, D

    2016-01-01

    It has been suggested that a functional deficit in NMDA-receptors (NMDARs) on parvalbumin (PV)-positive interneurons (PV-NMDARs) is central to the pathophysiology of schizophrenia. Supportive evidence come from examination of genetically modified mice where the obligatory NMDAR-subunit GluN1 (also known as NR1) has been deleted from PV interneurons by Cre-mediated knockout of the corresponding gene Grin1 (Grin1ΔPV mice). Notably, such PV-specific GluN1 ablation has been reported to blunt the induction of hyperlocomotion (a surrogate for psychosis) by pharmacological NMDAR blockade with the non-competitive antagonist MK-801. This suggests PV-NMDARs as the site of the psychosis-inducing action of MK-801. In contrast to this hypothesis, we show here that Grin1ΔPV mice are not protected against the effects of MK-801, but are in fact sensitized to many of them. Compared with control animals, Grin1ΔPVmice injected with MK-801 show increased stereotypy and pronounced catalepsy, which confound the locomotor readout. Furthermore, in Grin1ΔPVmice, MK-801 induced medial-prefrontal delta (4 Hz) oscillations, and impaired performance on tests of motor coordination, working memory and sucrose preference, even at lower doses than in wild-type controls. We also found that untreated Grin1ΔPVmice are largely normal across a wide range of cognitive functions, including attention, cognitive flexibility and various forms of short-term memory. Taken together these results argue against PV-specific NMDAR hypofunction as a key starting point of schizophrenia pathophysiology, but support a model where NMDAR hypofunction in multiple cell types contribute to the disease. PMID:27070406

  20. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    International Nuclear Information System (INIS)

    Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

    2014-01-01

    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma

  1. ATHENA X-IFU 300 K-50 mK cryochain demonstrator cryostat

    Science.gov (United States)

    Prouvé, T.; Duval, J. M.; Charles, I.; Yamasaki, N. Y.; Mitsuda, K.; Nakagawa, T.; Shinozaki, K.; Tokoku, C.; Yamamoto, R.; Minami, Y.; Le Du, M.; Andre, J.; Daniel, C.; Linder, M.

    2018-01-01

    In the framework of the ESA X-ray mission ATHENA, scheduled for launch in 2028, an ESA Core Technology Program (CTP) was started in 2016 to build a flight like cryostat demonstrator in parallel with the phase A studies of the ATHENA/X-IFU instrument [1,2]. As part of this CTP, called the Detector Cooling System (DCS), design, manufacturing and test of a cryostat including existing space coolers will be done. In addition to the validation of thermal performance, a Focal Plan Assembly (FPA) demonstrator using Transition Edge Sensors (TES) detector technology will be also integrated and its performance characterized versus the environment provided by the cryostat. This is a unique opportunity to validate many crucial issues of the cryogenic part of such a sensitive instrument. A dedicated activity within this CTP-DCS is the demonstration of the 300 K-50 mK cooling chain in a Ground System Equipment (GSE) cryostat. The studies are focused on the operation of the space coolers, which is made possible by the use of a ground cooler for cooling cryogenic shields and mechanical supports. Thanks to the modularity of the cryostat, several cooling chains could be tested. In the base line configuration described here, the low temperature stage is the CEA hybrid sorption/ADR 50 mK cooler with thermal interfaces at 4 K and 2 K. 4 K cooling is accomplished by a 4 K Joule-Thomson (JT) cryocooler and its Stirling precooler provided by JAXA. Regarding the 2 K stage, at first a 2 K JT from JAXA will be used. Alternatively, a 2 K JT cooler from RAL could replace the JAXA 2 K JT. In both cases new prototype(s) of a 2 K JT will be implemented, precooled by the EM 15 K pule tube cooler from Air Liquide. This test program is also the opportunity to validate the operation of the cryochain with respect to various requirements, such as time constant and temperature stabilities. This would bring us valuable inputs to integrate the cryochain in DCS cryostat or for the X-IFU phase A studies

  2. TREAT MK III Loop Thermoelastoplastic Stress Analysis for the L03 Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, James M.

    1981-03-01

    The STRAW code was used to analyze the static response of a TREAT MK III loop subjected to thermal and mechanical loadings arising from an accident situation for the purpose of determining the defiections and stresses. This analysis provides safety support for the L03 reactivity accident study. The analysis was subdivided into two tasks: (1) an analysis of a flow blockage accident (Cases A and B), where all the energy is assumed deposited in the test leg, resulting in a temperature increase from 530°F to 1720°F, with a small internal pressure throughout the loop and (2) an analysis of a second flow blockage accident (Cases C and D), where again, all the energy is assumed to he deposited in the test leg, resulting in a temperature rise from 530°F to 1845°F, with a small internal pressure throughout the loop. The purpose of these two tasks was to determine if loop failure can occur with the thermal differential across the pump and test legs. Also of interest is whether an undesirable amount of loop lateral deflection will be caused by the thermal differential. A two dimensional analysis of the TREAT MK III loop was performed. The analysis accounted for material nonlinearities, both as a function of temperature and stress, and geometric nonlinearities arising from large deflections. Straight beam elements with annular cross sections were used to model the loop. The analyses show that the maximum strains are less than 21% of their failure strains for all subcases of Cases A and B. For all subcases of cases C and D, the maximum strains are less than 53% of their failure strains. The failure strain is 27.9% for the material at 530°F, 38.1% at 1720°F and 17.8% at 1845°F. Large lateral deflections are observed when the loop is not constrained except at its clamped support--as much as 8.6 inches. However, by accounting for the constraint of the concrete biological shield, the maximum lateral deflection was reduced to less than 0.05 inches at the points of concern.

  3. Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

    Science.gov (United States)

    Brosnan-Watters, G; Ogimi, T; Ford, D; Tatekawa, L; Gilliam, D; Bilsky, E J; Nash, D

    2000-08-01

    1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA

  4. Preclinical evaluation and quantification of [18F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    International Nuclear Information System (INIS)

    Casteels, Cindy; Koole, Michel; Laere, Koen van; Celen, Sofie; Bormans, Guy

    2012-01-01

    [ 18 F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [ 18 F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [ 18 F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V T ) of [ 18 F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [ 18 F]MK-9470 in arterial plasma samples was 80 ± 23 % at 10 min, 38 ± 30 % at 40 min and 13 ± 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V T values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [ 18 F]MK-9470 V T , but was correlated. A correlation between [ 18 F]MK-9470 V T and SUV in the brain was also found (R 2 = 0.26-0.33; p ≤ 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [ 18 F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  5. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

    Science.gov (United States)

    Yap, Timothy A; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P; Swales, Karen; deSouza, Nandita M; Leach, Martin O; Garrett, Michelle D; Sullivan, Daniel M; de Bono, Johann S; Tolcher, Anthony W

    2014-11-15

    Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Patients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI. A total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Treatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488). ©2014 American Association for Cancer Research.

  6. Recovery of NMDA receptor currents from MK-801 blockade is accelerated by Mg2+ and memantine under conditions of agonist exposure

    Science.gov (United States)

    McKay, Sean; Bengtson, C. Peter; Bading, Hilmar; Wyllie, David J.A.; Hardingham, Giles E.

    2013-01-01

    MK-801 is a use-dependent NMDA receptor open channel blocker with a very slow off-rate. These properties can be exploited to ‘pre-block’ a population of NMDARs, such as synaptic ones, enabling the selective activation of a different population, such as extrasynaptic NMDARs. However, the usefulness of this approach is dependent on the stability of MK-801 blockade after washout. We have revisited this issue, and confirm that recovery of NMDAR currents from MK-801 blockade is enhanced by channel opening by NMDA, and find that it is further increased when Mg2+ is also present. In the presence of Mg2+, 50% recovery from MK-801 blockade is achieved after 10′ of 100 μM NMDA, or 30′ of 15 μM NMDA exposure. In Mg2+-free medium, NMDA-induced MK-801 dissociation was found to be much slower. Memantine, another PCP-site antagonist, could substitute for Mg2+ in accelerating the unblock of MK-801 in the presence of NMDA. This suggests a model whereby, upon dissociation from its binding site in the pore, MK-801 is able to re-bind in a process antagonized by Mg2+ or another PCP-site antagonist. Finally we show that even when all NMDARs are pre-blocked by MK-801, incubation of neurons with 100 μM NMDA in the presence of Mg2+ for 2.5 h triggers sufficient unblocking to kill >80% of neurons. We conclude that while synaptic MK-801 ‘pre-block’ protocols are useful for pharmacologically assessing synaptic vs. extrasynaptic contributions to NMDAR currents, or studying short-term effects, it is problematic to use this technique to attempt to study the effects of long-term selective extrasynaptic NMDAR activation. This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’. PMID:23402996

  7. Uji Performansi Getaran Mekanis dan Kebisingan Mist Blower Yanmar MK 150-B

    Directory of Open Access Journals (Sweden)

    Ahmad Noval Irvani

    2012-10-01

    Full Text Available Mist blower is one of the mechanization tool of agriculture considered as a tool that can assist humans in fertilizer and pesticides spreading activities. Levels of motor speed in the used mist blower were 1915, 4009, and 7227 rpm. Vibration measurements were conducted on the engine and handlebar control mist blower with the three-dimensional axes namely X, Y, and Z. Mist blower noise measurements were performed on the engine, operator's right ear and left ear. Based on the analysis of vibration and noise from the mist blower of type MK 150-B was obtained the safe limit values from the use of these tools. The safe limit of the use of mist blower in motor rotation speed of 1915, 4009, and 7227 rpm after being compared with the vibration and noise were 1 hour, 1 hour and 24 minutes respectively. The farther the distance from noise source, the lower the noise level too. Moreover objectivity study of operator was conducted. The first farmer was tired faster than the second farmer. In terms of age of farmer, the second farmer (60 years older than the first farmers (40 years, but this should not affect significantly. Activity on the previous day greatly affects the level of fatigue when operating the mist blower. This was because the first farmers did more activities and had rest periods that less than second farmer.

  8. Development of Cryogenic Engine for GSLV MkIII: Technological Challenges

    Science.gov (United States)

    Praveen, RS; Jayan, N.; Bijukumar, KS; Jayaprakash, J.; Narayanan, V.; Ayyappan, G.

    2017-02-01

    Cryogenic engine capable of delivering 200 kN thrust is being developed for the first time in the country by ISRO for powering the upper stage of GSLV Mk-III, the next generation launch vehicle of ISRO capable of launching four tonne class satellites to Geo-synchronous Transfer Orbit(GTO). Development of this engine started a decade ago when various sub-systems development and testing were taken up. Starting with injector element development, the design, realization and testing of the major sub-systems viz the gas generator, turbopumps, start-up system and thrust chamber have been successfully done in a phased manner before conducting a series of developmental tests in the integrated engine mode. Apart from the major sub-systems, many critical components like the igniter, control components etc were independently developed and qualified. During the development program many challenges were faced in almost all areas of propulsion engineering. Systems engineering of the engine was another key challenge in the realization. This paper gives an outlook on various technological challenges faced in the key areas related to the engine development, insight to the solutions and measures taken to overcome the challenges.

  9. MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity.

    Science.gov (United States)

    Layer, R T; Bland, L R; Skolnick, P

    1993-10-15

    Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists.

  10. Equilibrium shape of (4)He crystal under zero gravity below 200 mK.

    Science.gov (United States)

    Takahashi, Takuya; Ohuchi, Haruka; Nomura, Ryuji; Okuda, Yuichi

    2015-10-01

    Equilibrium crystal shape is the lowest energy crystal shape that is hardly realized in ordinary crystals because of their slow relaxation. (4)He quantum crystals in a superfluid have been expected as unique exceptions that grow extremely fast at very low temperatures. However, on the ground, gravity considerably deforms the crystals and conceals the equilibrium crystal shape, and thus, gravity-free environment is needed to observe the equilibrium shape of (4)He. We report the relaxation processes of macroscopic (4)He crystals in a superfluid below 200 mK under zero gravity using a parabolic flight of a jet plane. When gravity was removed from a gravity-flattened (4)He crystal, the crystal rapidly transformed into a shape with flat surfaces. Although the relaxation processes were highly dependent on the initial condition, the crystals relaxed to a nearly homothetic shape in the end, indicating that they were truly in an equilibrium shape minimizing the interfacial free energy. Thanks to the equilibrium shape, we were able to determine the Wulff's origin and the size of the c-facet together with the vicinal surface profile next to the c-facet. The c-facet size was extremely small in the quantum crystals, and the facet-like flat surfaces were found to be the vicinal surfaces. At the same time, the interfacial free energy of the a-facet and s-facet was also obtained.

  11. Assessment of gold flux monitor at irradiation facilities of MINT TRIGA MK II reactor

    International Nuclear Information System (INIS)

    Wee Boon Siong; Abdul Khalik Wood; Mohd Suhaimi Hamzah; Shamsiah Abdul Rahman; Md Suhaimi Elias; Nazaratul Ashifa Abd Salim

    2005-01-01

    Neutron source of MINTs TRIGA MK II reactor has been used for activation analysis for many years and neutron flux plays important role in activation of samples at various positions. Currently, two irradiation facilities namely the pneumatic transfer system and rotary rack are available to cater for short and long lived irradiation. Neutron flux variation for both irradiation facilities have been determined using gold wire and gold solution as flux monitor. However, the use of gold wire as flux monitor is costlier if compared to gold solution. The results from analysis of certified reference materials showed that gold solution as flux monitors yield satisfactory results and proved to safe cost on the purchasing of gold wire. Further experiment on self-shielding effects of gold solution at various concentrations has been carried out. This study is crucial in providing vital information on the suitable concentration for gold solution as flux monitor. In the near future, gold solution flux monitor will be applied for routine analysis and hence to improve the capability of the laboratory on neutron activation analysis. (Author)

  12. A mid- to far-infrared variability study of the intermediate Seyfert galaxy, Mk 6

    International Nuclear Information System (INIS)

    Clement, R.; Sembay, S.; Coe, M.J.; Hanson, C.G.

    1988-01-01

    A mid- to far-infrared (MFIR) variability study of the intermediate Seyfert galaxy, Mk 6, is presented using data from the Infrared Astronomical Satellite (IRAS). We have analysed 25 observations of this source covering a period of about 1 month. Within the expected errors, the source shows no evidence for variability and this may be an indication that there is a strong contribution to the MFIR emission from thermal re-radiation by dust. This interpretation is consistent with previous studies which suggest that the bulk of the far-infrared (30 -100 μm) emission in Seyfert galaxies originates from cool (35 - 75 K) dust associated with star formation regions in the surrounding envelope of the active nucleus. The lack of variability at 12 and 25 μm can also be readily explained by dust emission. However, in this case, the dust temperatures required to produce emission at these wavelengths makes the narrow-line region a more feasible location for the dust grains. (author)

  13. Preclinical evaluation and quantification of [(18)F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    OpenAIRE

    Casteels, Cindy; Koole, Michel; Celen, Sofie; Bormans, Guy; Van Laere, Koen

    2012-01-01

    PURPOSE: [(18)F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [(18)F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. METHODS: Dynamic small-animal PET scans with [(18)F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blo...

  14. In vivo binding and autoradiographic imaging of (+)-3-[125I]Iodo-MK-801 to the NMDA receptor-channel complex in rat brain

    International Nuclear Information System (INIS)

    Gibson, R.E.; Burns, H.D.; Thorpe, H.H.; Waisi Eng; Ransom, R.; Solomon, H.

    1992-01-01

    Radioiodinated (+)-3-Iodo-MK-801 is a high affinity radioligand for the N-methyl-D-aspartate (NMDA) receptor-channel complex. We have demonstrated in vivo localization in the CNS of rat which is stereoselective and blocked by coinjection of unlabeled MK-801. Autoradiography indicates localization in vivo which is in concordance with in vitro autoradiographic studies. These results indicate that radioiodinated (+)-3-Iodo-MK-801 is a useful probe for in vitro and in vivo autoradiographic studies and suggest that radioligands for the NMDA receptor may be developed which will provide in vivo images of receptor distribution in man. (author)

  15. Structural and physicochemical studies of two key intermediates and the impurity in the new synthesis route of vitamin MK-7

    Science.gov (United States)

    Łaszcz, Marta; Trzcińska, Kinga; Kubiszewski, Marek; Krajewski, Krzysztof

    2018-05-01

    The MK-7 homologues of vitamin K2 are characterized by the best bioavailability among other K vitamins and act effectively in the treatment of osteoporosis and cardiovascular diseases. In this article comprehensive structural studies of two intermediates 1,4-diethoxy-2-methylnaphtalene (M2) and 1,4-diethoxy-2-methyl-3-[(2E)-3-methyl-4-(phenylsulfonyl)-2-buten-1-yl]naphtalene (M3) from the multi-step synthesis of MK-7 vitamin were described. The compounds crystallize in a monoclinic system in P21/n and P21/c for M2 and M3, respectively. Also, the isomer (2E)-4-chloro-3-methyl-1-(phenylsulfonyl)but-2-ene (M1-E verso) was isolated and the single crystal studies were performed. These three compounds were fully characterized by the 1D and 2D NMR technique as well as by Fourier-transformed infrared and Raman spectroscopies.

  16. Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells

    Directory of Open Access Journals (Sweden)

    Mark C. Bagley

    2015-06-01

    Full Text Available Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2 inhibitors to study accelerated aging in Werner syndrome (WS cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS, and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.

  17. Neutron inelastic sattering from liquid 3He at 40 mK and at 1.2 K

    International Nuclear Information System (INIS)

    Skoeld, K.; Pelizzari, C.A.

    1978-01-01

    In a previous neutron scattering experiment on 3 He at T = 15 mK the present authors observed two peaks in the scattering function which were identified as the zero sound mode and the spin-fluctuation peak respectively. These results are different from those obtained by others at T = 0.63 K in which case no such structure was observed. In order to determine whether this discrepancy is due to the difference in the temperature of the two experiments, measurements have now been made at T = 40 mK and at T = 1.2 K. These results show that the two-peak structure persists at the higher temperature although measurable broadening is observed in the spin-fluctuation part of the spectrum. (author)

  18. MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

    Science.gov (United States)

    Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Kikuchi, Tetsuro; Stott, Colin; Riedel, Gernot

    2015-12-01

    Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.

  19. Identification of electrode respiring, hydrocarbonoclastic bacterial strain Stenotrophomonas maltophilia MK2 highlights the untapped potential for environmental bioremediation

    Directory of Open Access Journals (Sweden)

    Krishnaveni Venkidusamy

    2016-12-01

    Full Text Available Electrode respiring bacteria (ERB possess a great potential for many biotechnological applications such as microbial electrochemical remediation systems (MERS because of their exoelectrogenic capabilities to degrade xenobiotic pollutants. Very few ERB have been isolated from MERS, those exhibited a bioremediation potential towards organic contaminants. Here we report once such bacterial strain, Stenotrophomonas maltophilia MK2, a facultative anaerobic bacterium isolated from a hydrocarbon fed MERS, showed a potent hydrocarbonoclastic behavior under aerobic and anaerobic environments. Distinct properties of the strain MK2 were anaerobic fermentation of the amino acids, electrode respiration, anaerobic nitrate reduction and the ability to metabolize n-alkane components (C8-C36 of petroleum hydrocarbons including the biomarkers, pristine and phytane. The characteristic of diazoic dye decolorization was used as a criterion for pre-screening the possible electrochemically active microbial candidates. Bioelectricity generation with concomitant dye decolorization in MERS showed that the strain is electrochemically active. In acetate fed microbial fuel cells, maximum current density of 273±8 mA/m2 (1000Ω was produced (power density 113±7 mW/m2 by strain MK2 with a coulombic efficiency of 34.8 %. Further, the presence of possible alkane hydroxylase genes (alkB and rubA in the strain MK2 indicated that the genes involved in hydrocarbon degradation are of diverse origin. Such observations demonstrated the potential of facultative hydrocarbon degradation in contaminated environments. Identification of such a novel petrochemical hydrocarbon degrading ERB is likely to offer a new route to the sustainable bioremedial process of source zone contamination with simultaneous energy generation through MERS.

  20. "Interaction of different doses of Aspartame with Morphine-induced antinociception in the presence of MK-801, a NMDA antagonist "

    Directory of Open Access Journals (Sweden)

    Abdollahi M

    2002-07-01

    Full Text Available This study was designed to investigate the relative role of sweetness and comparative effects of different taste sensation of the non - caloric sweetener , aspartame on pain and its interaction with MK - 80] as a non - selective MMDA antagonist by formalin - test in mice. The formalin - test was chosen because it measures the response to a long - lasting nociceptive stimulus and closely resembles to the clinical pain. Morphine induced a dose dependent antinociception in the early and late phases of formalin test. Twelve days pretreatment of animals by aspartame ( 0.08% , 0.16% , 0.32% significantly potentiated morphine - induced (1.5-9 mg/kg analgesia in the early phase but significantly antagonized its analgesic effect in the late phase, dose dependently. Aspartame (0.16% alone showed a reduction in pain response . Naloxone (0.4 mg/kg significantly antagonized the antinociceptive effect of morphine in the presence of aspartame (0-0.32% in the early phase. Increasing the dose of aspartame decreased effects of naloxone. MK-801 (0.1 mg/kg as an N- Methyl - D - Aspartate (NMDA antagonist significantly potentiated the effect of aspartame on morphine - induced antinociception in the early phase. In the late phase, naloxone (0.4 mg/kg increased pain response but MK- 801 (0.1 mg/kg induced anti-inflammatory effect significantly. Treatment of animals with MK- 801 alone, significantly induced analgesia in both phases of formalin - test. This effect was potentiated with aspartame dose - dependently. Possible interaction of aspartame with NMDA receptors and its role to facilitate endogenous opioid system are proposed mechanisms of aspartame in modulating morphine - induced antinociception. Furthermore, the resulting association between morphine and aspartame chronic consumption may be explained as an interactive action rather than simple dose combination of both drugs.

  1. Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Scallet, A.C.; Holson, R.R.; Lipe, G.W.; Slikker, W. Jr.; Ali, S.F.

    1991-01-01

    The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [ 3 H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg 2+ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [ 3 H]dopamine and [ 3 H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg 2+ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg 2+ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg 2+ present, 1 mM glutamine increased glutamate release and induced the release of [ 3 H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%

  2. MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

    Science.gov (United States)

    Weihmuller, F B; O'Dell, S J; Marshall, J F

    1992-06-01

    Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. [123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801-induced rat schizophrenia model

    International Nuclear Information System (INIS)

    Huang, Yuan-Ruei; Shih, Jun-Ming; Chang, Kang-Wei; Huang, Chieh; Wu, Yu-Lung; Chen, Chia-Chieh

    2012-01-01

    Purpose: [ 123 I]Epidepride is a radio-tracer with very high affinity for dopamine D 2 /D 3 receptors in brain. The importance of alteration in dopamine D 2 /D 3 receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [ 123 I]epidepride could be used to evaluate the alterations of dopamine D 2 /D 3 receptor binding condition in specific brain regions. Method: Rats were given repeated injection of MK-801 (dissolved in saline, 0.3 mg/kg) or saline for 1 month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [ 123 I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [ 123 I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio. Result: Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [ 123 I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%), midbrain (41.73%) and substantia nigra (37.93%). In addition, [ 123 I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P 123 I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D 2 /D 3 receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.

  4. Synthesis of an 125I analog of MK-0591 and characterization of a 5-lipoxygenase activating protein binding assay

    International Nuclear Information System (INIS)

    Eggler, J.F.; Cheng, J.B.; Cooper, K.; Hanak, L.M.; Pillar, J.S.

    1994-01-01

    The 125 I analog of MK-0591,1, has been prepared for use as a radioligand for developing a 5-lipoxygenase activating protein (FLAP) binding assay. The radiosynthesis involves a two step oxidative iododestannylation-saponification procedure. A FLAP binding assay has been developed in human neutrophil membranes. The binding of 1 to human neutrophil FLAP is rapid, reversible, of high affinity, saturable and selective for FLAP inhibitors. (author)

  5. Kinetic analysis of the cannabinoid-1 receptor PET tracer [18F]MK-9470 in human brain

    International Nuclear Information System (INIS)

    Sanabria-Bohorquez, Sandra Marina; Hamill, Terence G.; Burns, H.D.; Goffin, Karolien; Laere, Koen van; Lepeleire, Inge de; Bormans, Guy

    2010-01-01

    Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [ 18 F]MK-9470 in human brain. [ 18 F]MK-9470 data were analysed using reversible models and the distribution volume V T and V ND k 3 (V ND k 3 = K 1 k 2 ) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K i and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. A reversible two-tissue compartment model using a global k 4 value was necessary to describe brain kinetics. Both V T and V ND k 3 were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K i . The linear relationship between K i and V ND k 3 demonstrated that K i or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K i and FUR was 18 F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [ 18 F]MK-9470 plasma kinetics can be assessed using a few venous samples. (orig.)

  6. Aerodynamic Loads and Separation Characteristics of the BLU-27B/B, MK- 82SE, and GBU-8 Weapons in the F-16 Aircraft Flow Field at Mach Numbers from 0.4 to 1.2

    Science.gov (United States)

    1976-10-01

    76-147 Cm 1.2 0.8 o.q 0 SIMBOL CONFIG = ~ STORE ® IS E 0.60 MK-SESE m 15 E 0.80 MK-SESE IS E 0.90 MK-82SE IS E 0.95 MK-B2SE PYLON RRCK 6 M...0 10 .0 1 2 6 A E D C - T R - 7 6 - 1 4 7 SIMBOL CONFIG = H. STORE PILON RICK ~tt 0 11 I0 0.80 MK-82SE 7 I - 3 0 B II 10 0.60 HR-B2SE 7 T

  7. Behavior of EBR-II Mk-V-type fuel elements in simulated loss-of-flow tests

    International Nuclear Information System (INIS)

    Liu, Y.Y.; Tsai, H.; Billone, M.C.; Kramer, J.M.

    1992-01-01

    The next step in the development of metal fuels for the integral fast reactor (IFR) is the conversion of the Experimental Breeder Reactor II (EBR-II) core to one containing the ternary U-20 Pu-10 Zr alloy clad with HT-9 cladding, i.e., the Mk-V core. This paper presents results of three hot-cell furnace simulation tests on irradiated Mk-V-type fuel elements (U-19 Pu-10 Zr/HT-9), which were performed to support the safety case for the Mk-V core. These tests were designed to envelop an umbrella (bounding) unlikely loss-of-flow (LOF) event in EBR-II during which the calculated peak cladding temperature would reach 776 degree C for < 2 min. The principal objectives of these tests were (a) demonstration of the safety margin of the fuel element, (b) investigation of cladding breaching behavior, and (c) provision of data for validation of the FPIN2 and LIFE-METAL codes

  8. A 10 mK scanning tunneling microscope operating in ultra high vacuum and high magnetic fields.

    Science.gov (United States)

    Assig, Maximilian; Etzkorn, Markus; Enders, Axel; Stiepany, Wolfgang; Ast, Christian R; Kern, Klaus

    2013-03-01

    We present design and performance of a scanning tunneling microscope (STM) that operates at temperatures down to 10 mK providing ultimate energy resolution on the atomic scale. The STM is attached to a dilution refrigerator with direct access to an ultra high vacuum chamber allowing in situ sample preparation. High magnetic fields of up to 14 T perpendicular and up to 0.5 T parallel to the sample surface can be applied. Temperature sensors mounted directly at the tip and sample position verified the base temperature within a small error margin. Using a superconducting Al tip and a metallic Cu(111) sample, we determined an effective temperature of 38 ± 1 mK from the thermal broadening observed in the tunneling spectra. This results in an upper limit for the energy resolution of ΔE = 3.5 kBT = 11.4 ± 0.3 μeV. The stability between tip and sample is 4 pm at a temperature of 15 mK as demonstrated by topography measurements on a Cu(111) surface.

  9. Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

    Science.gov (United States)

    Pınar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

    2015-08-11

    Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (ptest indicated a decrease in locomotor activity (plocomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

  10. Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity.

    Science.gov (United States)

    Hasegawa, Yasushi; Inoue, Tatsuro; Kawaminami, Satoshi; Fujita, Miho

    2016-07-01

    To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801. Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  11. Vitamin A depletion alters sensitivity of motor behavior to MK-801 in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Zhu Hui

    2010-01-01

    Full Text Available Abstract Background Vitamin A and its derivatives (retinoids are crucial for the development, maintenance and morphogenesis of the central nervous system (CNS. Although motor impairment has been reported in postnatal vitamin A depletion rodents, the effect of vitamin A depletion on homeostasis maintaining capability in response to external interference is not clear. Methods In the current study, we measured the effect of vitamin A depletion on motor ability and pain sensitivity under two different conditions: 1. prior to any injection and 2. after the injection of an N-methyl-D-aspartate (NMDA receptor antagonist (MK-801. Results Vitamin A depletion mice showed decreased body weight, enhanced locomotor activity, increased rearing and less tail flick latency. Vitamin A depletion also induced hypersensitivity of stereotypy, ataxia, rearing, and tail flick latency to MK-801, but hyposensitivity of locomotion to MK-801. Conclusions These findings suggest that vitamin A depletion affect broad basal behavior and disrupt homeostasis maintaining capability in response to glutamate perturbation. We provide a useful animal model for assessing the role of vitamin A depletion in regulating animal behavior, and for detecting how neurotransmitter pathways might be involved in vitamin A depletion related behavioral abnormalities.

  12. Rare variant testing across methods and thresholds using the multi-kernel sequence kernel association test (MK-SKAT).

    Science.gov (United States)

    Urrutia, Eugene; Lee, Seunggeun; Maity, Arnab; Zhao, Ni; Shen, Judong; Li, Yun; Wu, Michael C

    Analysis of rare genetic variants has focused on region-based analysis wherein a subset of the variants within a genomic region is tested for association with a complex trait. Two important practical challenges have emerged. First, it is difficult to choose which test to use. Second, it is unclear which group of variants within a region should be tested. Both depend on the unknown true state of nature. Therefore, we develop the Multi-Kernel SKAT (MK-SKAT) which tests across a range of rare variant tests and groupings. Specifically, we demonstrate that several popular rare variant tests are special cases of the sequence kernel association test which compares pair-wise similarity in trait value to similarity in the rare variant genotypes between subjects as measured through a kernel function. Choosing a particular test is equivalent to choosing a kernel. Similarly, choosing which group of variants to test also reduces to choosing a kernel. Thus, MK-SKAT uses perturbation to test across a range of kernels. Simulations and real data analyses show that our framework controls type I error while maintaining high power across settings: MK-SKAT loses power when compared to the kernel for a particular scenario but has much greater power than poor choices.

  13. JOYO MK-III modification work on heat transport system. Working plan and plant control

    International Nuclear Information System (INIS)

    Isozaki, K.; Ichige, S.; Ohshima, J.

    2002-07-01

    The MK-III project to improve the irradiation capability of the experimental fast reactor JOYO have been in underway since 1987. The increase of fast neutron flux and the enlargement of that field increase the reactor thermal rate from 100 MWt to 140 MWt. To increase cooling capacity of heat transport system, intermediate heat exchangers (IHXs), dump heat exchangers (DHXs), piping connecting to IHXs and DHXs, main motors on primary and secondary main circulation pumps were replaced. The replacement of these large components was carried out under following hard conditions. 1) Limitation of work space, 2) Fuel subassembly and molten sodium in the reactor vessel, 3) high radiation circumstances for primary cooling system, 4) treatment of radioactive sodium (radioactive sodium and corrosion product such as 60 Co, 54 Mn). There are little experiences of this kind of work in the world. Therefore the organization, working plan and safety management points were carefully examined and established, based on the previous experience of JOYO operation and maintenance, research and development results of safety treatment of sodium, experience of previous work on sodium facilities. Followings results were obtained and effectiveness was confirmed in the work. (1) Development of most suitable working plan derived from elements and full size mock up experiments, reduction of exposure time by workers training, reduction of radiation dose by installation of temporal radiation shielding were useful to reduce radiation dose. The usage of seal bag was useful to prevent the contamination spreading over. (2) The usage of seal bag, oxygen concentration monitoring in the seal bag, nitrogen concentration monitoring in the cooling system cover gas, low pressure control of cover gas were useful to reduce the inflow of oxygen to cooling system. (3) The bite cutting method for piping in air and press down cutting by roller cutter in the seal bag to prevent inflow of cutting piece, stopper

  14. OGLE-2013-BLG-1761Lb: A Massive Planet around an MK Dwarf

    Science.gov (United States)

    Hirao, Y.; Udalski, A.; Sumi, T.; Bennett, D. P.; Koshimoto, N.; Bond, I. A.; Rattenbury, N. J.; Suzuki, D.; Abe, F.; Asakura, Y.; hide

    2017-01-01

    We report the discovery and the analysis of the planetary microlensing event, OGLE-2013-BLG-1761. There are some degenerate solutions in this event because the planetary anomaly is only sparsely sampled. However, the detailed light curve analysis ruled out all stellar binary models and shows the lens to be a planetary system. There is the so-called close wide degeneracy in the solutions with the planet host mass ratio of q approx.(7.0+/-2.0) x 10(exp -3) and q approx.(8.1+/-2.6) x 10(exp -3) with the projected separation in Einstein radius units of s = 0.95 (close) and s = 1.18(wide), respectively. The microlens parallax effect is not detected, but the finite source effect is detected. Our Bayesian analysis indicates that the lens system is located -D(sub L) = 6.9(+ 1.0 -1.2)kpc away from us and the host star is an M/K dwarf with amass of M(sub L) = 0.33(+ 0.32- 1.9)Stellar Mass orbited by a super-Jupiter mass planet with a mass of m(sub p) = 2.7(+ 2.5 - 1.5) M(sub Jup) at the projected separation of a(sub l) = 1.8(+ 0.5 -0.5)au. The preference of the large lens distance in the Bayesian analysis is due to the relatively large observed source star radius. The distance and other physical parameters may be constrained by the future high-resolution imaging by large ground telescopes or HST. If the estimated lens distance is correct, then this planet provides another sample for testing the claimed deficit of planets in the Galactic bulge.

  15. A NMDA receptor antagonist, MK-801 impairs consolidating extinction of auditory conditioned fear responses in a Pavlovian model.

    Directory of Open Access Journals (Sweden)

    Jun-Li Liu

    Full Text Available BACKGROUND: In auditory fear conditioning, repeated presentation of the tone in the absence of shock leads to extinction of the acquired fear responses. The glutamate N-methyl-D-aspartate receptor (NMDAR is thought to be involved in the extinction of the conditioned fear responses, but its detailed role in initiating and consolidating or maintaining the fear extinction memory is unclear. Here we investigated this issue by using a NMDAR antagonist, MK-801. METHODS/MAIN FINDINGS: The effects of immediate (beginning at 10 min after the conditioning and delayed (beginning at 24 h after conditioning extinctions were first compared with the finding that delayed extinction caused a better and long-lasting (still significant on the 20(th day after extinction depression on the conditioned fear responses. In a second experiment, MK-801 was intraperitoneally (i.p. injected at 40 min before, 4 h or 12 h after the delayed extinction, corresponding to critical time points for initiating, consolidating or maintaining the fear extinction memory. i.p. injection of MK-801 at either 40 min before or 4 h after delayed extinction resulted in an impairment of initiating and consolidating fear extinction memory, which caused a long lasting increased freezing score that was still significant on the 7th day after extinction, compared with extinction group. However, MK-801 administered at 12 h after the delayed extinction, when robust consolidation has been occurred and stabilized, did not affect the established extinction memory. Furthermore, the changed freezing behaviors was not due to an alteration in general anxiety levels, since MK-801 treatment had no effect on the percentage of open-arm time or open-arm entries in an Elevated Plus Maze (EPM task. CONCLUSIONS/SIGNIFICANCE: Our data suggested that the activation of NMDARs plays important role in initiation and consolidation but not maintenance of fear extinction memory. Together with the fact that NMDA receptor is

  16. Detomidine and the combination of detomidine and MK-467, a peripheral alpha-2 adrenoceptor antagonist, as premedication in horses anaesthetized with isoflurane.

    Science.gov (United States)

    Pakkanen, Soile Ae; Raekallio, Marja R; Mykkänen, Anna K; Salla, Kati M; de Vries, Annemarie; Vuorilehto, Lauri; Scheinin, Mika; Vainio, Outi M

    2015-09-01

    To investigate MK-467 as part of premedication in horses anaesthetized with isoflurane. Experimental, crossover study with a 14 day wash-out period. Seven healthy horses. The horses received either detomidine (20 μg kg(-1) IV) and butorphanol (20 μg kg(-1) IV) alone (DET) or with MK-467 (200 μg kg(-1) IV; DET + MK) as premedication. Anaesthesia was induced with ketamine (2.2 mg kg(-1) ) and midazolam (0.06 mg kg(-1) ) IV and maintained with isoflurane. Heart rate (HR), mean arterial pressure (MAP), end-tidal isoflurane concentration, end-tidal carbon dioxide tension, central venous pressure, fraction of inspired oxygen (FiO2 ) and cardiac output were recorded. Blood samples were taken for blood gas analysis and to determine plasma drug concentrations. The cardiac index (CI), systemic vascular resistance (SVR), ratio of arterial oxygen tension to inspired oxygen (Pa O2 /FiO2 ) and tissue oxygen delivery (DO2 ) were calculated. Repeated measures anova was applied for HR, CI, MAP, SVR, lactate and blood gas variables. The Student's t-test was used for pairwise comparisons of drug concentrations, induction times and the amount of dobutamine administered. Significance was set at p detomidine concentrations were reduced in the group receiving MK-467. After DET+MK, the area under the plasma concentration time curve of butorphanol was smaller. MK-467 enhances cardiac function and tissue oxygen delivery in horses sedated with detomidine before isoflurane anaesthesia. This finding could improve patient safety in the perioperative period. The dosage of MK-467 needs to be investigated to minimise the effect of MK-467 on MAP. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  17. Different MK-801 administration schedules induce mild to severe learning impairments in an operant conditioning task: role of buspirone and risperidone in ameliorating these cognitive deficits.

    Science.gov (United States)

    Rapanelli, Maximiliano; Frick, Luciana Romina; Bernardez-Vidal, Micaela; Zanutto, Bonifacio Silvano

    2013-11-15

    Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and alterations in prefrontal cortex (PFC) functioning. Due to the critical role of the PFC in operant conditioning task learning, we evaluated the effects of acute, repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different administration schedules: injection 40 min before beginning the task (during) (n=12); injection twice daily for six consecutive days prior to beginning the experimental procedures (prior) (n=12); or twice daily subcutaneous injections from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated with the MK-801 schedule described above. The postnatal and prior administration schedules produced severe learning deficits, whereas injection of MK-801 just before training sessions had only mild effects on acquisition of an operant conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in the animals that were treated with MK-801 during and prior training sessions. In contrast, buspirone was only effective at mitigating the cognitive deficits induced by MK-801 when administered during the training procedures. The data demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a simple PFC-mediated operant conditioning task, and that buspirone and risperidone failed to attenuate the learning deficits when NMDA neurotransmission was blocked in the early stages of the postnatal period. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs.

    Science.gov (United States)

    Honkavaara, J M; Restitutti, F; Raekallio, M R; Kuusela, E K; Vainio, O M

    2011-08-01

    Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function. © 2010 Blackwell Publishing Ltd.

  19. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

    Science.gov (United States)

    Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

    2014-01-03

    Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

  20. W342F Mutation in CCaMK Enhances Its Affinity to Calmodulin But Compromises Its Role in Supporting Root Nodule Symbiosis in Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Edgard Jauregui

    2017-11-01

    Full Text Available The calcium/calmodulin-dependent protein kinase (CCaMK is regulated by free Ca2+ and Ca2+-loaded calmodulin. This dual binding is believed to be involved in its regulation and associated physiological functions, although direct experimental evidence for this is lacking. Here we document that site-directed mutations in the calmodulin-binding domain of CCaMK alters its binding capacity to calmodulin, providing an effective approach to study how calmodulin regulates CCaMK in terms of kinase activity and regulation of rhizobial symbiosis in Medicago truncatula. We observed that mutating the tryptophan at position 342 to phenylalanine (W342F markedly increased the calmodulin-binding capability of the mutant. The mutant CCaMK underwent autophosphorylation and catalyzed substrate phosphorylation in the absence of calcium and calmodulin. When the mutant W342F was expressed in ccamk-1 roots, the transgenic roots exhibited an altered nodulation phenotype. These results indicate that altering the calmodulin-binding domain of CCaMK could generate a constitutively activated kinase with a negative role in the physiological function of CCaMK.

  1. Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

    LENUS (Irish Health Repository)

    Robinson, G B

    1991-10-18

    The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

  2. Summary report of the experimental fast reactor JOYO MK-III performance test

    International Nuclear Information System (INIS)

    Maeda, Yukimoto; Aoyama, Takafumi; Yoshida, Akihiro

    2004-03-01

    An upgrading project (MK-III project) was started to improve the irradiation capability of the experimental fast reactor JOYO. In this project, core replacement and increase of the reactor thermal power by the factor 1.4 were necessary for increasing the maximum fast neutron flux by the factor 1.3 and doubling the capacity for irradiation rigs. The modification of the cooling system that included the replacement of the main intermediate heat exchangers and the dump heat exchangers was completed in September 2000. After a series of system function tests, the performance test, of which objective is to fully characterize the upgraded core and heat transfer system, was started in June 2003. Twenty eight tests were selected and carried out as performance test, in order to confirm that the whole plant satisfy the design criteria and have sufficient characteristics (data necessary for safe and steady operation, core management, reactor control and monitoring) as an irradiation bed. After attaining the initial criticality of the core on 2nd July 2003, core characteristics (the excess reactivity, the isotherm temperature reactivity coefficient, the power reactivity coefficient and so on), plant characteristics (the plant heat balance, the adjustment of the temperature control system, the plant behavior at transient), shielding characteristics (dose rate distribution). As the result, it was confirmed that all the criteria regulated was satisfied and the core and plant have sufficient margins for full power operation, which was increased by the factor 1.4. Especially, nuclear analysis accuracy was verified by comparing the calculation with measured core characteristics of the initial core which consists of fifty five fresh fuel subassemblies. The operational data which is supposed to be useful for developing in-core anomaly detection system were also obtained. The operation manual and training simulator and design of next reactor development were revised based on the results

  3. PEPSI deep spectra. II. Gaia benchmark stars and other M-K standards

    Science.gov (United States)

    Strassmeier, K. G.; Ilyin, I.; Weber, M.

    2018-04-01

    Context. High-resolution échelle spectra confine many essential stellar parameters once the data reach a quality appropriate to constrain the various physical processes that form these spectra. Aim. We provide a homogeneous library of high-resolution, high-S/N spectra for 48 bright AFGKM stars, some of them approaching the quality of solar-flux spectra. Our sample includes the northern Gaia benchmark stars, some solar analogs, and some other bright Morgan-Keenan (M-K) spectral standards. Methods: Well-exposed deep spectra were created by average-combining individual exposures. The data-reduction process relies on adaptive selection of parameters by using statistical inference and robust estimators. We employed spectrum synthesis techniques and statistics tools in order to characterize the spectra and give a first quick look at some of the science cases possible. Results: With an average spectral resolution of R ≈ 220 000 (1.36 km s-1), a continuous wavelength coverage from 383 nm to 912 nm, and S/N of between 70:1 for the faintest star in the extreme blue and 6000:1 for the brightest star in the red, these spectra are now made public for further data mining and analysis. Preliminary results include new stellar parameters for 70 Vir and α Tau, the detection of the rare-earth element dysprosium and the heavy elements uranium, thorium and neodymium in several RGB stars, and the use of the 12C to 13C isotope ratio for age-related determinations. We also found Arcturus to exhibit few-percent Ca II H&K and Hα residual profile changes with respect to the KPNO atlas taken in 1999. Based on data acquired with PEPSI using the Large Binocular Telescope (LBT) and the Vatican Advanced Technology Telescope (VATT). The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are the University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT

  4. [MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

    Science.gov (United States)

    Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

    2012-08-25

    This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

  5. Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

    Science.gov (United States)

    Gallant, S; Welch, L; Martone, P; Shalev, U

    2017-06-15

    Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Colletotrichum higginsianum Mitogen-Activated Protein Kinase ChMK1: Role in Growth, Cell Wall Integrity, Colony Melanization and Pathogenicity

    Directory of Open Access Journals (Sweden)

    Wei Wei

    2016-08-01

    Full Text Available Colletotrichum higginsianum is an economically important pathogen that causes anthracnose disease in a wide range of cruciferous crops. To facilitate the efficient control of anthracnose disease, it will be important to understand the mechanism by which the cruciferous crops and C. higginsianum interact. A key step in understanding this interaction is characterizing the mitogen-activated protein kinases (MAPK signaling pathway of C. higginsianum. MAPK plays important roles in diverse physiological processes of multiple pathogens. In this study, a Fus3/Kss1-related MAPK gene, ChMK1, from C. higginsianum was analyzed. The results showed that the Fus3/Kss1-related MAPK ChMK1 plays a significant role in cell wall integrity. Targeted deletion of ChMK1 resulted in a hypersensitivity to cell wall inhibitors, reduced conidiation and albinistic colonies. Further, the deletion mutant was also unable to form melanized appressorium, a specialized infection structure that is necessary for successful infection. Therefore, the deletion mutant loses pathogenicity on A. thaliana leaves, demonstrating that ChMK1 plays an essential role in the early infection step. In addition, the ChMK1 deletion mutant showed an attenuated growth rate that is different from that of its homologue in C. lagenarium, indicating the diverse roles that Fus3/Kss1-related MAPKs plays in phytopathogenic fungi. Furthermore, the expression level of three melanin synthesis associated genes were clearly decreased in the albinistic ChMK1 mutant compared to that of the wild type strain, suggesting that ChMK1 is also required for colony melanization in C. higginsianum.

  7. Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice

    Science.gov (United States)

    Uz, Tolga; Dimitrijevic, Nikola; Imbesi, Marta; Manev, Hari; Manev, Radmila

    2008-01-01

    A common biological pathway may contribute to the comorbidity of atherosclerosis and depression. Increased activity of the enzymatic 5-lipoxygenase (5-LOX; 5LO) pathway is a contributing factor in atherosclerosis and a 5-LOX inhibitor, MK-886, is beneficial in animal models of atherosclerosis. In the brain, MK-886 increases phosphorylation of the glutamate receptor subunit GluR1, and the increased phosphorylation of this receptor has been associated with antidepressant treatment. In this work, we evaluated the behavioral effects of MK-886 in an automated assay of mouse forced swimming, which identifies antidepressant activity as increased climbing behavior and/or decreased rest time. Whereas a single injection of MK-886 (3 and 10 mg/kg) did not affect forced swimming behaviors assayed 30 min later, 6 daily injections of 3 mg/kg MK-886 slightly increased climbing and significantly reduced rest time in wild-type mice but not in 5-LOX-deficient mice. A diet delivery of MK-886, 4 μg per 100 mg body-weight per day, required three weeks to affect forced swimming; it increased climbing behavior. Climbing behavior was also increased in naive 5-LOX-deficient mice compared to naive wild-type controls. These results suggest that 5-LOX inhibition and deficiency may be associated with antidepressant activity. Increased climbing in a forced swimming assay is a typical outcome of antidepressants that increase noradrenergic and dopaminergic activity. Interestingly, 5-LOX deficiency and MK-886 treatment have been shown to be capable of increasing the behavioral effects of a noradrenaline/dopamine-potentiating drug, cocaine. Future research is needed to evaluate the clinical relevance of our findings. PMID:18403121

  8. (/sup 3/H)MK-801 labels a site on the N-methyl-D-aspartate receptor channel complex in rat brain membranes

    Energy Technology Data Exchange (ETDEWEB)

    Wong, E H; Knight, A R; Woodruff, G N

    1988-01-01

    The potent noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist (/sup 3/H)MK-801 bound with nanomolar affinity to rat brain membranes in a reversible, saturable, and stereospecific manner. The affinity of (/sup 3/H)MK-801 was considerably higher in 5 mM Tris-HCl (pH 7.4) than in previous studies using Krebs-Henseleit buffer. (/sup 3/H)MK-801 labels a homogeneous population of sites in rat cerebral cortical membranes with KD of 6.3 nM and Bmax of 2.37 pmol/mg of protein. This binding was unevenly distributed among brain regions, with hippocampus greater than cortex greater than olfactory bulb = striatum greater than medulla-pons, and the cerebellum failing to show significant binding. Detailed pharmacological characterization indicated (/sup 3/H)MK-801 binding to a site which was competitively and potently inhibited by known noncompetitive NMDA receptor antagonists, such as phencyclidine, thienylcyclohexylpiperidine (TCP), ketamine, N-allylnormetazocine (SKF 10,047), cyclazocine, and etoxadrol, a specificity similar to sites labelled by (/sup 3/H)TCP. These sites were distinct from the high-affinity sites labelled by the sigma receptor ligand (+)-(/sup 3/H)SKF 10,047. (/sup 3/H)MK-801 binding was allosterically modulated by the endogenous NMDA receptor antagonist Mg2+ and by other active divalent cations. These data suggest that (/sup 3/H)MK-801 labels a high-affinity site on the NMDA receptor channel complex, distinct from the NMDA recognition site, which is responsible for the blocking action of MK-801 and other noncompetitive NMDA receptor antagonists.

  9. JOYO MK-III performance test. Criticality test, excess reactivity measurement and burn-up coefficient measurement

    International Nuclear Information System (INIS)

    Maeda, Shigetaka; Sekine, Takashi; Kitano, Akihiro; Nagasaki, Hideaki

    2005-03-01

    The MK-III performance test began in June 2003 to fully characterize the upgraded core and heat transfer system of the experimental fast reactor JOYO. This paper describes the results of the approach to criticality, the excess reactivity evaluation and the burn-up coefficient measurement. In the approach to criticality test, the MK-III core achieved initial criticality at the control rod bank position of 412.8 mm on 14:03 July 2nd, 2003. Because the replacement of the outer two rows of reflector subassemblies with shielding subassemblies reduced the source range monitor signals by a factor of 3 at the same reactor power compared with those in the MK-II core, we measured the change of the monitor's response and determined the count rate 2x10 4 cps.' as an appropriate value judging the zero power criticality. In the excess reactivity evaluation, the zero power excess reactivity at 250degC was 2.99±0.10%Δk/kk' based on the measured critical rod bank position and the measured control rod worths. The predicted value by the JOYO core management code system HESTIA was 3.13±0.16%Δk/kk', showing good agreement with the measured value. The measured excess reactivity was within the safety requirement limit. In the burn-up coefficient measurement, the excess reactivity change versus the reactor burn-up was evaluated. The measurement method adopted was to measure the control rod positions during the rated power operation. A value of -2.12x10 -4 Δk/kk'/MWd was obtained as a measured burn-up coefficient. The value calculated by HESTIA was -2.12x10 -4 Δk/kk'/MWd, and it agreed well with the measured value. All technical safety requirements for MK-III core were satisfied and the calculation accuracy of the core management code system HESTIA was confirmed. (author)

  10. Behavior of EBR-II Mk-V-type fuel elements in simulated loss-of-flow tests

    International Nuclear Information System (INIS)

    Liu, Y.Y.; Tsai, H.; Billone, M.C.; Holland, J.W.; Kramer, J.M.

    1993-01-01

    Three furnace heating tests were conducted with irradiated, HT9-clad and U-19wt%Pu-10wt%Zr-alloy, EBR-II Mk-V-type fuel elements to evaluate the behavior that could be expected during a loss-of-flow event in the reactor. In general, very significant safety margins for cladding breaching have been demonstrated in these tests, under conditions that would envelop a bounding unlikely loss-of-flow event in EBR-II. Highlights of the test results are presented, as are discussions of the cladding breaching mechanisms, axial fuel motion, and fuel surface liquefaction that were found in these tests. (orig.)

  11. Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity

    OpenAIRE

    HASEGAWA, Yasushi; INOUE, Tatsuro; KAWAMINAMI, Satoshi; FUJITA, Miho

    2016-01-01

    ObjectiveTo evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801).MethodsEffect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test.ResultsScallop shell extract significantly reduced scopolami...

  12. Electron Spin Resonance in CuSO45H2O down to 100 mK

    Science.gov (United States)

    Kadowaki, Kazuo; Chiba, Yoshiaki; Kindo, Koichi; Date, Muneyuki

    1988-12-01

    Copper sulfate pentahydrate CuSO45H2O is investigated by ESR at 9, 17, 24, 35 and 50 GHz regions down to about 100 mK using a combined cryostat of 3He and adiabatic demagnetization. The temperature dependent exchange interaction JAB between inequivalent site spins A and B is found. It is about 0.11 K at room temperature and increases with decreasing temperature up to 0.24 K. Temperature dependent resonance shifts are attributed to the exchange shift coming from non-resonant dissimilar spins. Partial order effect below 1 K is discussed.

  13. Study of compoisiton of saturated vapor of MF-CuF2 systems, where M=K, Rb, Cs

    International Nuclear Information System (INIS)

    Morozov, I.V.; Korenev, Yu.M.

    1993-01-01

    Investigation into composition of saturated vapor of MF-CuF 2 systems where M=K, Rb, Cs is conducted using high-temperature mass-spectrometry. Existence of MCuF 3 molecules in gas phase is determined. MCuF 3(r) dissociation enthalpies are calculated using the first law-of thermodynamics and are compared with theoretically determined values. Value Δ D G 0 944 (CsCuF 3(r) =105.6±6.3 kj/mol is determined

  14. KEBIJAKAN PENCIPTAAN LAPANGAN KERJA PEDESAAN ( Kajian Pembangunan Pasar Desa Proyek PDK-MK di Desa Nglundo, Sukomoro, Nganjuk

    Directory of Open Access Journals (Sweden)

    AGUS SOEHARTO

    2012-05-01

    Full Text Available ABSTRAK Kebijakan penciptaan lapangan kerja pedesaan melalui proyek PDK-MK ( Penanggulangan Dampak Kekeringan dan Masalah Ketenagakerjaan tahap II Tahun 1998/1999 merupakan salah satu kebijakan Nasional guna mengatasi dampak krisis ekonomi di sektor ketenagakerjaan. Penelitian yang dilaksanakan merupakan penelitian kebijakan sektor ketenagakerjaan dengan pokok masalah : diskripsi implementasi kebijakan desentralisasi suatu proyek penciptaan lapangan kerja di Desa Nglundo Kecamatan Sukomoro, Kabupaten Nganjuk. Tujuan penelitian ini adalah (1 mengkaji implementasi kebijakan penciptaan lapangan kerja di desa melalui proyek PDK-MK; (2 menganalisa dampak implementasi kebijakan desentralisasi penciptaan lapangan kerja melalui mekanisme usulan dari bawah terhadap kebutuhan akan lapangan kerja pedesaan. Methode penelitian yang dipergunakan adalah kualitatif, sedang pengumpulan data melalui observasi, wawancara, dokumentasi, dengan analisa data, secara kualitatif dan induktif. Hasil penelitian menunjukkan bahwa implementasi kebijakan desentralisasi penciptaan lapangan dengan melibatkan masyarakat melalui usulan dari bawah mendapat respon positif, meskipun terdapat kendala kesinambungan proyek namun telah dapat menciptakan lapangan kerja baru dan menyerap tenaga kerja di desa. Kata kunci: Lapangan kerja, pedesaan ABSTRACT Policy of creating Job Opportunity in villages by second period of the PDK – MK Project (Penanggulangan Dampak Kekeringan dan Masalah Ketenagakerjaan was one of National Policies in overcoming impact of economical crisis in any labor sectors. The main theme of the reaseach to the policy of the labor sector was the description of the decentralized policy implementation to the project of creating job opportunity in Nglundo village, Sukomoro subdistrict, Nganjuk Regency. Goals of this research are (1 to study the implementation of the policy in creating labor market in the village by the PDK – MK project, (2 to analyse the effect of

  15. Kinetic analysis of the cannabinoid-1 receptor PET tracer [{sup 18}F]MK-9470 in human brain

    Energy Technology Data Exchange (ETDEWEB)

    Sanabria-Bohorquez, Sandra Marina; Hamill, Terence G.; Burns, H.D. [Merck Research Laboratories, Imaging, West Point, PA (United States); Goffin, Karolien; Laere, Koen van [University Hospital and K.U. Leuven, Division of Nuclear Medicine, Leuven (Belgium); Lepeleire, Inge de [Merck Research Laboratories, Brussels (Belgium); Bormans, Guy [K.U. Leuven, Laboratory of Radiopharmacy, Leuven (Belgium)

    2010-05-15

    Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [{sup 18}F]MK-9470 in human brain. [{sup 18}F]MK-9470 data were analysed using reversible models and the distribution volume V{sub T} and V{sub ND} k{sub 3} (V{sub ND} k{sub 3} = K{sub 1} k{sub 2}) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K{sub i} and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. A reversible two-tissue compartment model using a global k{sub 4} value was necessary to describe brain kinetics. Both V{sub T} and V{sub ND} k{sub 3} were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K{sub i}. The linear relationship between K{sub i} and V{sub ND} k{sub 3} demonstrated that K{sub i} or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K{sub i} and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics. [{sup 18}F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [{sup 18}F]MK-9470 plasma kinetics can be assessed using a few venous samples. (orig.)

  16. Sensitization of human cancer cells to gemcitabine by the Chk1 inhibitor MK-8776: cell cycle perturbation and impact of administration schedule in vitro and in vivo

    International Nuclear Information System (INIS)

    Montano, Ryan; Thompson, Ruth; Chung, Injae; Hou, Huagang; Khan, Nadeem; Eastman, Alan

    2013-01-01

    Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence. Growth inhibition induced by gemcitabine plus MK-8776 was assessed across multiple cancer cell lines. Experiments used clinically relevant “bolus” administration of both drugs rather than continuous drug exposures. We assessed the effect of different treatment schedules on cell cycle perturbation and tumor cell growth in vitro and in xenograft tumor models. MK-8776 induced an average 7-fold sensitization to gemcitabine in 16 cancer cell lines. The time of MK-8776 administration significantly affected the response of tumor cells to gemcitabine. Although gemcitabine induced rapid cell cycle arrest, the stalled replication forks were not initially dependent on Chk1 for stability. By 18 h, RAD51 was loaded onto DNA indicative of homologous recombination. Inhibition of Chk1 at 18 h rapidly dissociated RAD51 leading to the collapse of replication forks and cell death. Addition of MK-8776 from 18–24 h after a 6-h incubation with gemcitabine induced much greater sensitization than if the two drugs were incubated concurrently for 6 h. The ability of this short incubation with MK-8776 to sensitize cells is critical because of the short half-life of MK-8776 in patients’ plasma. Cell cycle perturbation was also assessed in human pancreas tumor xenografts in mice. There was a dramatic accumulation of cells in S/G 2 phase 18 h after gemcitabine administration, but cells had started to recover by 42 h. Administration of MK-8776 18 h after gemcitabine caused significantly delayed tumor growth compared to either drug alone, or when the two drugs were administered with only a 30 min interval. There are two reasons why delayed

  17. Preclinical evaluation and quantification of [{sup 18}F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Koole, Michel; Laere, Koen van [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); Celen, Sofie; Bormans, Guy [K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); K.U. Leuven, Laboratory for Radiopharmacy, Leuven (Belgium)

    2012-09-15

    [{sup 18}F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [{sup 18}F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [{sup 18}F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V{sub T}) of [{sup 18}F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [{sup 18}F]MK-9470 in arterial plasma samples was 80 {+-} 23 % at 10 min, 38 {+-} 30 % at 40 min and 13 {+-} 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V{sub T} values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability ({<=}10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [{sup 18}F]MK-9470 V{sub T}, but was correlated. A correlation between [{sup 18}F]MK-9470 V{sub T} and SUV in the brain was also found (R {sup 2} = 0.26-0.33; p {<=} 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [{sup 18}F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  18. Kasutamata potensiaal saatkondade arhitektuuris / Andro Mänd

    Index Scriptorium Estoniae

    Mänd, Andro

    2008-01-01

    USA ja Põhjamaade suunast saatkonnahoonete arhitektuuris. Soome saatkonnahoonest (Mikko Heikkinen, Markku Komonen, 1994) Washingtonis, Põhjamaade (Taani, Islandi, Norra, Rootsi, Soome) saatkonnakompleksist (Alfred Berger, Tiina Parkkinen, 1999) Berliinis, Rootsi saatkonnahoonest (Gert Wingardh, Tomas Hansen, 2006) Washingtonis. Eesti uutest Riia ja Pekingi saatkonnahoonetest, ruumiprogrammist, konkursi tingimustest

  19. Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats

    Institute of Scientific and Technical Information of China (English)

    Li-sha XU; Li-xia YANG; Wei-wei HU; Xiao YU; Li MA; Lu-ying LIU; Er-qing WEI; Zhong CHEN

    2005-01-01

    Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 μg/site, ih) and the H2 antagonist cimetidine (2.5 μg/site,ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion:The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

  20. ZIP MK 2 : A Fortran code for calculating the eigenvalues (poles and zeros and frequency responses of large sets of linear equations representing complex dynamic systems)

    International Nuclear Information System (INIS)

    Sumner, H.M.

    1969-03-01

    The KDF9/EGDON program ZIP MK 2 is the third of a series of programs for off-line digital computer analysis of dynamic systems: it has been designed specifically to cater for the needs of the design or control engineer in having an input scheme which is minimally computer-oriented. It uses numerical algorithms which are as near fool-proof as the author could discover or devise, and has comprehensive diagnostic sections to help the user in the event of faulty data or machine execution. ZIP MK 2 accepts mathematical models comprising first order linear differential and linear algebraic equations, and from these computes and factorises the transfer functions between specified pairs of output and input variables; if desired, the frequency response may be computed from the computed transfer function. The model input scheme is fully compatible with the frequency response programs FRP MK 1 and MK 2, except that, for ZIP MK 2, transport, or time-delays must be converted by the user to Pade or Bode approximations prior to input. ZIP provides the pole-zero plot, (or complex plane analysis), while FRP provides the frequency response and FIFI the time domain analyses. The pole-zero method of analysis has been little used in the past for complex models, especially where transport delays occur, and one of its primary purposes is as a research tool to investigate the usefulness of this method, for process plant, whether nuclear, chemical or other continuous processes. (author)

  1. Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

    Science.gov (United States)

    Chen, Guangdong; Lin, Xiaodong; Li, Gongying; Jiang, Diego; Lib, Zhiruo; Jiang, Ronghuan; Zhuo, Chuanjun

    2017-01-01

    The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute N-methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations. PMID:28451387

  2. Analysis of the fast-neutron spectrum inside the experimental cavity of the NRU Mk4 FN rod

    International Nuclear Information System (INIS)

    Leung, T.C.

    1995-01-01

    The fast-neutron (FN) rods in the NRU reactor provide a facility to study the effects of irradiation on CANDU reactor materials. The Mark 4 (Mk4) FN rods use natural uranium and supply fast-neutrons for experiments on irradiation creep and growth, and corrosion, for pressure- and calandria-tube materials. The neutron fluxes above 1 MeV are up to 2.7x10 17 n.m -2 .s -1 . This paper describes a calculation of the fast-neutron spectrum inside the NRU Mk4 FN rod cavity. The calculation was performed using the WIMS-AECL code, which is a multi-group transport code with two dimensional capabilities using the collision-probability method. Results for the fast-neutron spectrum above 1 MeV are presented in nine groups. The analysis confirms that the spectrum in the fast-neutron irradiation facility in NRU is representative of the actual irradiation spectrum for fast-neutron damage in a CANDU reactor. The effects of changes in specimen holder size, temperature, coolant density and fuel burnup on the fast neutron spectrum are also presented. (author). 9 refs., 3 tabs., 4 figs

  3. Intercomparison of the LASCO-C2, SECCHI-COR1, SECCHI-COR2, and Mk4 Coronagraphs

    Science.gov (United States)

    Frazin, Richard A.; Vasquez, Alberto M.; Thompson, William T.; Hewett, Russell J.; Lamy, Philippe; Llebaria, Antoine; Vourlidas, Angelos; Burkepile, Joan

    2012-01-01

    In order to assess the reliability and consistency of white-light coronagraph measurements, we report on quantitative comparisons between polarized brightness [pB] and total brightness [B] images taken by the following white-light coronagraphs: LASCO-C2 on SOHO, SECCHI-COR1 and -COR2 on STEREO, and the ground-based MLSO-Mk4. The data for this comparison were taken on 16 April 2007, when both STEREO spacecraft were within 3.1 deg. of Earth’s heliographic longitude, affording essentially the same view of the Sun for all of the instruments. Due to the difficulties of estimating stray-light backgrounds in COR1 and COR2, only Mk4 and C2 produce reliable coronal-hole values (but not at overlapping heights), and these cannot be validated without rocket flights or ground-based eclipse measurements. Generally, the agreement between all of the instruments’ pB values is within the uncertainties in bright streamer structures, implying that measurements of bright CMEs also should be trustworthy. Dominant sources of uncertainty and stray light are discussed, as is the design of future coronagraphs from the perspective of the experiences with these instruments.

  4. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    Directory of Open Access Journals (Sweden)

    Chunmei Guo

    2010-01-01

    Full Text Available Neonatal blockade of N-methyl-D-aspartic acid (NMDA receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

  5. Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging

    International Nuclear Information System (INIS)

    Huang, Y.R.; Pai, C.W.; Cheng, K.H.; Kuo, W.I.; Chen, M.W.; Chang, K.W.

    2014-01-01

    Introduction: Epidepride is a compound with an affinity in picomolar range for D 2 /D 3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [ 123 I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3 mg/kg/day) or saline for 4 weeks. After 1-week administration of MK-801, rats in MK-801 + risperidone group received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [ 123 I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D 2 R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [ 123 I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [ 123 I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4 weeks. [ 123 I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D 2 R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [ 123 I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model

  6. Sensitization of Cancer Cells through Reduction of Total Akt and Downregulation of Salinomycin-Induced pAkt, pGSk3β, pTSC2, and p4EBP1 by Cotreatment with MK-2206

    Directory of Open Access Journals (Sweden)

    Ae-Ran Choi

    2014-01-01

    Full Text Available MK-2206 is an inhibitor of Akt activation. It has been investigated as an anticancer drug in clinical trials assessing the potential of pAkt targeting therapy. The purpose of this study was to identify conditions that increase the sensitivity of cancer cells to MK-2206. We found that the treatment of cancer cells with a high concentration of salinomycin (Sal reduced total Akt protein levels but increased activated Akt levels. When cancer cells were cotreated with MK-2206 and Sal, both pAkt and total Akt levels were reduced. Using microscopic observation, an assessment of cleaved PARP, FACS analysis of pre-G1 region, and Hoechst staining, we found that Sal increased apoptosis of MK-2206-treated cancer cells. These results suggest that cotreatment with MK-2206 and Sal sensitizes cancer cells via reduction of both pAkt and total Akt. Furthermore, cotreatment of cancer cells with Sal and MK-2206 reduced pp70S6K, pmTOR, and pPDK1 levels. In addition, Sal-induced activation of GSK3β, TSC2, and 4EBP1 was abolished by MK-2206 cotreatment. These results suggest that cotreatment using MK-2206 and Sal could be used as a therapeutic method to sensitize cancer cells through targeting of the PI3K/Akt/mTOR pathway. Our findings may contribute to the development of MK-2206-based sensitization therapies for cancer patients.

  7. A neuroligin-1-derived peptide stimulates phosphorylation of the NMDA receptor NR1 subunit and rescues MK-801-induced decrease in long-term potentiation and memory impairment

    DEFF Research Database (Denmark)

    Korshunova, Irina; Gjørlund, Michelle D; Jacobsen, Sylwia Owczarek

    2015-01-01

    neurolide-1 effects on short- and long-term social and spatial memory in social recognition, Morris water-maze, and Y-maze tests. We found that subcutaneous neurolide-1 administration, restored hippocampal LTP compromised by NMDA receptor inhibitor MK-801. It counteracted MK-801-induced memory deficit...... in the water-maze and Y-maze tests after long-term treatment (24 h and 1-2 h before the test), but not after short-term exposure (1-2 h). Long-term exposure to neurolide-1 also facilitated social recognition memory. In addition, neurolide-1-induced phosphorylation of the NMDA receptor NR1 subunit on a site...... receptor phosphorylation after treatment with NL1 or a mimetic peptide, neurolide-1, was quantified by immunoblotting. Subsequently, we investigated effects of neurolide-1 on long-term potentiation (LTP) induction in hippocampal slices compromised by NMDA receptor inhibitor MK-801. Finally, we investigated...

  8. Detection of the scintillation light emitted from direct-bandgap compound semiconductors by a Si avalanche photodiode at 150 mK

    International Nuclear Information System (INIS)

    Yasumune, Takashi; Takayama, Nobuyasu; Maehata, Keisuke; Ishibashi, Kenji; Umeno, Takahiro

    2008-01-01

    In this work, the direct-bandgap compound semiconductor materials are irradiated by α particles emitted from 241 Am for the detection of scintillation light at the temperature of 150 mK. For the irradiation experiment, two disk shaped samples were fabricated from an epoxy resin mixed with the powder of PbI 2 and CuI, respectively. Each disk-samples was cooled down to 150 mK by a compact liquid helium-free dilution refrigerator. A Si avalanche photodiode (APD) was employed for detecting the scintillation light emitted from the disk-sample inside the refrigerator. The detection signal current of Si APD was converted into the voltage pulses by a charge sensitive preamplifier. The voltage pulses of the scintillation light emitted from the direct-bandgap semiconductors were observed at the temperature of 150 mK. (author)

  9. Stimulation of the metabotropic glutamate (mGlu) 2 receptor attenuates the MK-801-induced increase in the immobility time in the forced swimming test in rats.

    Science.gov (United States)

    Kawaura, Kazuaki; Karasawa, Jun-Ichi; Hikichi, Hirohiko

    2016-02-01

    Negative symptoms of schizophrenia are poorly managed using the currently available antipsychotics. Previous studies indicate that agonists of the metabotropic glutamate (mGlu) 2/3 receptors may provide a novel approach for the treatment of schizophrenia. However, the effects of mGlu2/3 receptor agonists or mGlu2 receptor positive allosteric modulators have not yet been clearly elucidated in animal models of the negative symptoms of schizophrenia. Recently, we reported that the forced swimming test in rats treated with subchronic MK-801, an NMDA receptor antagonist, may be regarded as a useful test to evaluate the activities of drugs against the negative symptoms of schizophrenia. We evaluated the effects of LY379268, an mGlu2/3 receptor agonist, and BINA, an mGlu2 receptor positive allosteric modulator, on the hyperlocomotion induced by acute administration of MK-801 (0.15mg/kg, sc) and on the increase in the immobility time in the forced swimming test induced by subchronic treatment with MK-801 (0.5mg/kg, sc, twice a day for 7 days) in rats. Both LY379268 (3mg/kg, sc) and BINA (100mg/kg, ip) attenuated the increase in the immobility time induced by subchronic treatment with MK-801 at the same doses at which they attenuated the MK-801-induced increase in locomotor activity, but had no effect on the immobility time in saline-treated rats. The present results suggest that stimulation of the mGlu2 receptor attenuates the increase in the immobility time in the forced swimming test elicited by subchronic administration of MK-801, and may be potentially useful for treatment of the negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model

    Directory of Open Access Journals (Sweden)

    Yisong Qian

    2016-08-01

    Full Text Available Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC staining, neuronal damage was assessed by Haematoxylin Eosin (H&E staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  11. Neuroprotection by Combined Administration with Maslinic Acid, a Natural Product from Olea europaea, and MK-801 in the Cerebral Ischemia Model.

    Science.gov (United States)

    Qian, Yisong; Tang, Xuzhen; Guan, Teng; Li, Yunman; Sun, Hongbin

    2016-08-19

    Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of maslinic acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with maslinic acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of maslinic acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of maslinic acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, maslinic acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of maslinic acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of maslinic acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  12. Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Fujino, Aiko; Fukushima, Kei; Kubota, Takaharu; Kosugi, Tomomi; Takimoto-Kamimura, Midori, E-mail: m.kamimura@teijin.co.jp [Teijin Pharma Limited, 4-3-2 Asahigaoka, Hino-shi, Tokyo 191-8512 (Japan)

    2013-11-01

    The Gly-rich loop of cyclin-dependent kinase 2 (CDK2) bound to TEI-I01800 as an MK2 specific inhibitor forms a β-sheet which is a common structure in CDK2–ligand complexes. Here, the reason why TEI-I01800 does not become a strong inhibitor against CDK2 based on the conformation of TEI-I01800 is presented. Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2–TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2.

  13. Effect of antemortem and postmortem factors on [3H]MK-801 binding in the human brain: Transient elevation during early childhood

    International Nuclear Information System (INIS)

    Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.; Fritze, J.; Riederer, P.

    1989-01-01

    The effect of a number of antemortem and postmortem factors on [ 3 H]MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years [ 3 H]MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex

  14. mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task

    Science.gov (United States)

    LaCrosse, Amber L.; Burrows, Brian T.; Angulo, Rachel M.; Conrad, Phoebe R.; Himes, Sarah M.; Mathews, Nordia; Wegner, Scott A.; Taylor, Sara B.; Olive, M. Foster

    2014-01-01

    Rationale Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert pro-cognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives To determine the ability of the mGluR5 PAM 3-cyano-N-1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the NMDA receptor antagonist MK-801. Methods Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS→DMS or DMS→DNMS). In Experiment 1, rats were treated daily prior to each session with either vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle+MK−801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801, and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning and no other group differences were observed. Conclusions MK-801 induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in initial task learning or when treatment was initiated following task reversal. PMID:24973895

  15. The CSIRO Mk3L climate system model version 1.0 – Part 2: Response to external forcings

    Directory of Open Access Journals (Sweden)

    S. J. Phipps

    2012-05-01

    Full Text Available The CSIRO Mk3L climate system model is a coupled general circulation model, designed primarily for millennial-scale climate simulation and palaeoclimate research. Mk3L includes components which describe the atmosphere, ocean, sea ice and land surface, and combines computational efficiency with a stable and realistic control climatology. It is freely available to the research community. This paper evaluates the response of the model to external forcings which correspond to past and future changes in the climate system.

    A simulation of the mid-Holocene climate is performed, in which changes in the seasonal and meridional distribution of incoming solar radiation are imposed. Mk3L correctly simulates increased summer temperatures at northern mid-latitudes and cooling in the tropics. However, it is unable to capture some of the regional-scale features of the mid-Holocene climate, with the precipitation over Northern Africa being deficient. The model simulates a reduction of between 7 and 15% in the amplitude of El Niño-Southern Oscillation, a smaller decrease than that implied by the palaeoclimate record. However, the realism of the simulated ENSO is limited by the model's relatively coarse spatial resolution.

    Transient simulations of the late Holocene climate are then performed. The evolving distribution of insolation is imposed, and an acceleration technique is applied and assessed. The model successfully captures the temperature changes in each hemisphere and the upward trend in ENSO variability. However, the lack of a dynamic vegetation scheme does not allow it to simulate an abrupt desertification of the Sahara.

    To assess the response of Mk3L to other forcings, transient simulations of the last millennium are performed. Changes in solar irradiance, atmospheric greenhouse gas concentrations and volcanic emissions are applied to the model. The model is again broadly successful at simulating larger-scale changes in the

  16. The Search for a Non-Superallowed Branch in the β decay of ^38mK

    Science.gov (United States)

    Leach, Kyle; Bandyopadhyay, D.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Wong, J.; Ball, G. C.; Bassiachvilli, E.; Ettenauer, S.; Hackman, G.; Morton, A. C.; Mythili, S.; Newman, O.; Pearson, C. J.; Pearson, M. R.; Savajols, H.; Leslie, J. R.; Melconian, D.; Austin, R. A. E.; Barton, C.

    2007-10-01

    The study presented is part of an experimental program exploring the properties of superallowed Fermi β decays conducted at the Isotope Separator and Accelerator (ISAC) facility at TRIUMF in Vancouver, B.C. Canada. Using the 8π γ-ray spectrometer and the Scintillating Electron Positron Tagging Array (SCEPTAR), it was possible to set a new upper limit on an unobserved non-analogue branch in the decay of ^38mK. This branch is expected to be extremely weak, and the removal of contaminant isobaric decays and background radiation in the spectra was thus exceedingly important during the analysis. Our work has reduced the previous upper limit by approximately a factor of two and is approaching the theoretically predicted branching ratio.

  17. Experimental gonococcal infection in male volunteers: Cumulative experience with Neisseria gonorrhoeae strains FA1090 and MS11mkC

    Directory of Open Access Journals (Sweden)

    Marcia Metzgar Hobbs

    2011-05-01

    Full Text Available Experimental infection of male volunteers with Neisseria gonorrhoeae is safe and reproduces the clinical features of naturally acquired gonococcal urethritis. Human inoculation studies have helped define the natural history of experimental infection with two well-characterized strains of N. gonorrhoeae, FA1090 and MS11mkC. The human model has proved useful for testing the importance of putative gonococcal virulence factors for urethral infection in men. Studies with isogenic mutants have improved our understanding of the requirements for gonococcal LOS structures, pili, opacity proteins, IgA1 protease and the ability of infecting organisms to obtain iron from human transferrin and lactoferrin during uncomplicated urethritis. The model also presents opportunities to examine innate host immune responses that may be exploited or improved in development and testing of gonococcal vaccines. Here we review results to date with human experimental gonorrhea.

  18. A superconducting tunneling junction (STJ) detector for soft X-ray absorption spectroscopy at 50 mK

    International Nuclear Information System (INIS)

    Baev, Ivan; Ruescher, Jan-Hendrik; Martins, Michael; Viefhaus, Jens; Wurth, Wilfried

    2016-01-01

    Soft X-ray absorption spectroscopy (XAS) is an important technique at synchrotrons nowadays that allows to investigate electronic and magnetic properties in an element specific way. The investigation of non-conductive, soft organic or buried materials can't be carried out in total electron yield. In these cases an efficient fluorescence detector is needed to perform XAS measurements in partial fluorescence yield (PFY). The STJ detector is capable of count rates as high as 10 kcps per 100 μm"2 pixel size with an energy resolution of approximately 50 eV for 1.5 keV photons. The STJ is furthermore integrated into a 50 mK cryostat for XAS measurements at the P04 beamline at Petra III, DESY. We will present first measurements on a model system.

  19. Behavior of EBR-II Mk-V-type fuel elements in simulated loss-of-flow tests

    International Nuclear Information System (INIS)

    Liu, Y.Y.; Tsai, H.; Billone, M.C.; Holland, J.W.; Kramer, J.M.

    1992-11-01

    This report discusses three furnace heating tests which were conducted with irradiated, HT9-clad and U-19wt.%Pu-l0wt.%Zr-alloy fuel, Mk-V-type fuel elements in the Alpha-Gamma Hot Cell Facility at Argonne National Laboratory, Illinois. In general, very significant safety margins for fuel-element cladding breaching have been demonstrated in these tests, under conditions that would envelop a bounding unlikely loss-of-flow event in EBR-II. Highlights of the test results will be given, as well as discussions of the cladding breaching mechanisms, axial fuel motion, and fuel surface liquefaction found in high-temperature testing of irradiated metallic fuel elements

  20. Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs.

    Science.gov (United States)

    Hector, Rachel C; Rezende, Marlis L; Mama, Khursheed R; Steffey, Eugene P; Knych, Heather K; Hess, Ann M; Honkavaara, Juhana M; Raekallio, Marja R; Vainio, Outi M

    2017-07-01

    To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α 2 -adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs. Crossover experimental study. Six healthy, adult Beagle dogs weighing 12.6±0.9 kg (mean±standard deviation). Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO 2 and temperature were maintained at 40±5 mmHg (5.3±0.7 kPa) and 38±0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 μg kg -1 then 1.5 μg kg -1  hour -1 and 4.5 μg kg -1 then 4.5 μg kg -1  hour -1 ) or MK-467 (90 μg kg -1 then 90 μg kg -1  hour -1 and 180 μg kg -1 then 180 μg kg -1  hour -1 ); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at pbenefits of the addition of a peripheral α 2 -adrenergic antagonist to inhalation anesthesia in dogs. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  1. ESTUDIO COMPARATIVO DE PASTAS DE CEMENTO ADICIONADAS CON CATALIZADOR DE CRAQUEO CATALÍTICO USADO (FCC, Y METACAOLIN (MK

    Directory of Open Access Journals (Sweden)

    Janneth Torres Agredo

    2012-01-01

    Full Text Available Este artículo es parte de un proyecto de investigación cuyo objetivo principal es evaluar el desempeño de un residuo de una refinería de petróleo, como adición al cemento Portland con el fin de establecer la viabilidad de su aplicación en materiales de construcción. Este residuo denominado catalizador usado a partir del proceso de craqueo catalítico (fcc procede de las unidades de ruptura catalítica en lecho fluido y está compuesto principalmente por sílice y alúmina. Se analizó la hidratación en pastas de cemento adicionadas con el fcc, y se hizo una comparación con la adición de metacaolín (mk. Para realizar el estudio, se prepararon pastas de cemento Portland Ordinario (opc, adicionadas en porcentajes del 10 y 20% de fcc y mk como reemplazo de cemento. La actividad puzolánica de las adiciones y el tipo de productos de hidratación se determinaron mediante las técnicas de difracción de rayos X (drx y del análisis termogravimétrico (tg/dtg. Como fases principales del proceso de hidratación en las pastas adicionadas con fcc se encontraron silicatos cálcicos hidratados (csh, aluminatos cálcicos hidratados (cah, y silico aluminatos cálcicos (cash, productos similares a los obtenidos en pastas adicionadas con metacaolín.

  2. Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

    Science.gov (United States)

    2015-01-01

    Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

  3. DEVELOPMENTAL LEAD (PB) EXPOSURE REDUCES THE ABILITY OF THE NNDA ANTAGONIST MK801 TO SUPPRESS LONG-TERM POTENTIATION (LTP) IN THE RAT DENTATE GYRUS, IN VIVO

    Science.gov (United States)

    Chronic developmental lead (Pb) exposure increases the threshold and enhances decay of long-term potentiation (LTP) in the dentate gyrus of the hippocampal formation. MK-801 and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype impair induction of LT...

  4. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E

    2014-01-01

    achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK-0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected...

  5. p38- and MK2-dependent signalling promotes stress-induced centriolar satellite remodelling via 14-3-3-dependent sequestration of CEP131/AZI1

    DEFF Research Database (Denmark)

    Tollenaere, Maxim A X; Villumsen, Bine H; Blasius, Melanie

    2015-01-01

    Centriolar satellites (CS) are small granular structures that cluster in the vicinity of centrosomes. CS are highly susceptible to stress stimuli, triggering abrupt displacement of key CS factors. Here we discover a linear p38-MK2-14-3-3 signalling pathway that specifically targets CEP131 to trig...

  6. Higher Doses of (+)MK-801 (Dizocilpine) Induced Mortality and Procedural but Not Cognitive Deficits in Delayed Testing in the Active Place Avoidance With Reversal on the Carousel

    Czech Academy of Sciences Publication Activity Database

    Lobellová, Veronika; Brichtová, Eva; Petrásek, Tomáš; Valeš, Karel; Stuchlík, Aleš

    2015-01-01

    Roč. 64, č. 2 (2015), s. 269-275 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : Dizocilpine * (+)MK-801 * active place avoidance * Carousel * Long-Evans rats Subject RIV: FH - Neurology Impact factor: 1.643, year: 2015

  7. The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

    Science.gov (United States)

    Kamińska, Katarzyna; Rogóż, Zofia

    2015-12-01

    Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  8. Statistical optimization of culture conditions for the production of enniatins H, I, and MK1688 by Fusarium oxysporum KFCC 11363P.

    Science.gov (United States)

    Lee, Hee-Seok; Kang, Jea-Wook; Kim, Byung Hee; Park, Sang-Gyu; Lee, Chan

    2011-03-01

    The aim of this study was to optimize the culture conditions for the production of biological cyclic hexadepsipeptides (enniatins H, I and MK1688) from Fusarium oxysporum KFCC 11363P. Tests of 10 complete or chemically defined liquid culture media revealed that Fusarium defined medium was the best for the production of enniatins (produced amounts: enniatin H, 185.4 mg/L; enniatin I, 349.1mg/L; enniatin MK1688, 541.1mg/L; and total enniatins, 1075.6 mg/L). On the eighth day after inoculation, the maximal production of enniatins was observed at 25°C in Fusarium defined medium. The optimal carbon and nitrogen sources for producing biological cyclic hexadepsipeptides (enniatins H, I, and MK1688) were sucrose and NaNO(3), respectively, and their optimal concentrations were determined by the principle of response surface methodology. It was confirmed that using the optimized growth medium compositions increased the amounts of enniatins H, I, and MK1688, and total enniatins produced to 695.2, 882.4, 824.8, and 2398.5mg/L, respectively. These findings will assist in formulating microbiological media useful for enniatin research. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. Evaluation of a PCR and comparison with RLB for detection and differentiation of Theileria sp. MK and other Theileria and Babesia species of small ruminants.

    Science.gov (United States)

    Altay, Kursat; Aktas, Munir; Dumanli, Nazir; Aydin, Mehmet Fatih

    2008-07-01

    Theileria sp. MK in sheep and goats were detected first time by polymerase chain reaction (PCR) and detection limit of PCR and reverse line blotting (RLB) were compared. A part of 18S ssu rRNA gene was amplified from blood samples that were taken from sheep and goats naturally infected with Theileria sp. MK by PCR. Detection limit of both PCR and RLB methods was one infected cell in 10(7) sheep erythrocytes. Nine hundred twenty field samples that had been tested previously by RLB were evaluated by the PCR assay. As found by RLB previously, 12 of 920 (1.30%) samples were detected as positive by PCR. Two positive PCR products, one of which was from sheep and the other from goat, were sequenced. These sequences were identical to the reported nucleotide sequence of Theileria sp. MK. It is concluded that the PCR described in this study will be useful for epidemiological studies and for discrimination between Theileria sp. MK and other Theileria species. In addition, PCR has superiority over RLB because of its ease of use and time period required.

  10. In Vitro Activity of MK-7655, a Novel β-Lactamase Inhibitor, in Combination with Imipenem against Carbapenem-Resistant Gram-Negative Bacteria

    Science.gov (United States)

    Hirsch, Elizabeth B.; Ledesma, Kimberly R.; Chang, Kai-Tai; Schwartz, Michael S.; Motyl, Mary R.

    2012-01-01

    Carbapenem-resistant bacteria represent a significant treatment challenge due to the lack of active antimicrobials available. MK-7655 is a novel β-lactamase inhibitor under clinical development. We investigated the combined killing activity of imipenem and MK-7655 against four imipenem-resistant bacterial strains, using a mathematical model previously evaluated in our laboratory. Time-kill studies (TKS) were conducted with imipenem and MK-7655 against a KPC-2-producing Klebsiella pneumoniae isolate (KP6339) as well as 3 Pseudomonas aeruginosa isolates (PA24226, PA24227, and PA24228) with OprD porin deletions and overexpression of AmpC. TKS were performed using 25 clinically achievable concentration combinations in a 5-by-5 array. Bacterial burden at 24 h was determined in triplicate by quantitative culture and mathematically modeled using a three-dimensional response surface. Mathematical model assessments were evaluated experimentally using clinically relevant dosing regimens of imipenem, with or without MK-7655, in a hollow-fiber infection model (HFIM). The combination of imipenem and MK-7655 was synergistic for all strains. Interaction indices were as follows: for KP6339, 0.50 (95% confidence interval [CI], 0.42 to 0.58); for PA24226, 0.60 (95% CI, 0.58 to 0.62); for PA24227, 0.70 (95% CI, 0.66 to 0.74); and for PA24228, 0.55 (95% CI, 0.49 to 0.61). In the HFIM, imipenem plus MK-7655 considerably reduced the bacterial burden at 24 h, while failure with imipenem alone was seen against all isolates. Sustained suppression of bacterial growth at 72 h was achieved with simulated doses of 500 mg imipenem plus 500 mg MK-7655 in 2 (KP6339 and PA24227) strains, and it was achieved in an additional strain (PA24228) when the imipenem dose was increased to 1,000 mg. Additional studies are being conducted to determine the optimal dose and combinations to be used in clinical investigations. PMID:22526311

  11. A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle.

    Science.gov (United States)

    Lai, Yu-Chiang; Liu, Yang; Jacobs, Roxane; Rider, Mark H

    2012-10-01

    PKB (protein kinase B), also known as Akt, is a key component of insulin signalling. Defects in PKB activation lead to insulin resistance and metabolic disorders, whereas PKB overactivation has been linked to tumour growth. Small-molecule PKB inhibitors have thus been developed for cancer treatment, but also represent useful tools to probe the roles of PKB in insulin action. In the present study, we examined the acute effects of two allosteric PKB inhibitors, MK-2206 and Akti 1/2 (Akti) on PKB signalling in incubated rat soleus muscles. We also assessed the effects of the compounds on insulin-stimulated glucose uptake, glycogen and protein synthesis. MK-2206 dose-dependently inhibited insulin-stimulated PKB phosphorylation, PKBβ activity and phosphorylation of PKB downstream targets (including glycogen synthase kinase-3α/β, proline-rich Akt substrate of 40 kDa and Akt substrate of 160 kDa). Insulin-stimulated glucose uptake, glycogen synthesis and glycogen synthase activity were also decreased by MK-2206 in a dose-dependent manner. Incubation with high doses of MK-2206 (10 μM) inhibited insulin-induced p70 ribosomal protein S6 kinase and 4E-BP1 (eukaryotic initiation factor 4E-binding protein-1) phosphorylation associated with increased eEF2 (eukaryotic elongation factor 2) phosphorylation. In contrast, Akti only modestly inhibited insulin-induced PKB and mTOR (mammalian target of rapamycin) signalling, with little or no effect on glucose uptake and protein synthesis. MK-2206, rather than Akti, would thus be the tool of choice for studying the role of PKB in insulin action in skeletal muscle. The results point to a key role for PKB in mediating insulin-stimulated glucose uptake, glycogen synthesis and protein synthesis in skeletal muscle.

  12. Effects of a glycine transporter-1 inhibitor and D-serine on MK-801-induced immobility in the forced swimming test in rats.

    Science.gov (United States)

    Kawaura, Kazuaki; Koike, Hiroyuki; Kinoshita, Kohnosuke; Kambe, Daiji; Kaku, Ayaka; Karasawa, Jun-ichi; Chaki, Shigeyuki; Hikichi, Hirohiko

    2015-02-01

    Glutamatergic dysfunction, particularly the hypofunction of N-methyl-D-aspartate (NMDA) receptors, is involved in the pathophysiology of schizophrenia. The positive modulation of the glycine site on the NMDA receptor has been proposed as a novel therapeutic approach for schizophrenia. However, its efficacy against negative symptoms, which are poorly managed by current medications, has not been fully addressed. In the present study, the effects of the positive modulation of the glycine site on the NMDA receptor were investigated in an animal model of negative symptoms of schizophrenia. The subchronic administration of MK-801 increased immobility in the forced swimming test in rats without affecting spontaneous locomotor activity. The increased immobility induced by MK-801 was attenuated by the atypical antipsychotic clozapine but not by either the typical antipsychotic haloperidol or the antidepressant imipramine, indicating that the increased immobility induced by subchronic treatment with MK-801 in the forced swimming test may represent a negative symptom of schizophrenia. Likewise, positive modulation of the glycine sites on the NMDA receptor using an agonist for the glycine site, D-serine, and a glycine transporter-1 inhibitor, N-[(3R)-3-([1,1'-biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine hydrochloride (NFPS), significantly reversed the increase in immobility in MK-801-treated rats without reducing the immobility time in vehicle-treated rats. The present results show that the stimulation of the NMDA receptor through the glycine site on the receptor either directly with D-serine or by blocking glycine transporter-1 attenuates the immobility elicited by the subchronic administration of MK-801 and may be potentially useful for the treatment of negative symptoms of schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors.

    Science.gov (United States)

    Hudis, Clifford; Swanton, Charles; Janjigian, Yelena Y; Lee, Ray; Sutherland, Stephanie; Lehman, Robert; Chandarlapaty, Sarat; Hamilton, Nicola; Gajria, Devika; Knowles, James; Shah, Jigna; Shannon, Keith; Tetteh, Ernestina; Sullivan, Daniel M; Moreno, Carolina; Yan, Li; Han, Hyo Sook

    2013-11-19

    Trastuzumab is effective in human epidermal growth factor receptor 2 (HER2)-over-expressing breast and gastric cancers. However, patients may develop resistance through downstream signaling via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. This phase 1 trial was conducted to determine the safety and tolerability of the investigational AKT inhibitor MK-2206, to prepare for future studies to determine whether the combination with trastuzumab could inhibit compensatory signaling. Patients with HER2+ treatment-refractory breast and gastroesophageal cancer were enrolled. Treatment consisted of standard doses of intravenous trastuzumab and escalating dose levels of oral MK-2206 using either an every-other-day (45 mg and 60 mg QOD) or once-weekly (135 mg and 200 mg QW) schedule. A total of 34 patients with HER2+ disease were enrolled; 31 received study-drug. The maximum tolerated dose (MTD) for MK-2206 in combination with trastuzumab was 60 mg for the QOD schedule and 135 mg for the QW schedule, although a true MTD was not established due to early termination of the trial. The most common treatment-emergent toxicities included fatigue, hyperglycemia, and dermatologic rash, consistent with prior experience; one death unrelated to treatment was reported. There was one complete response in a patient with metastatic breast cancer, one patient achieved a partial response, and 5 patients had stable disease for at least 4 months, despite progression on multiple prior trastuzumab- and lapatinib-based therapies. Results also indicate that trastuzumab does not affect the pharmacokinetics of MK-2206. Results suggest the AKT inhibitor MK-2206 can be safely combined with trastuzumab, and is associated with clinical activity, supporting further investigation. ClinicalTrials.gov; identifier: NCT00963547.

  14. Combined Diazepam and MK-801 Therapy Provides Synergistic Protection from Tetramethylenedisulfotetramine-induced Tonic-Clonic Seizures and Lethality in Mice

    Science.gov (United States)

    Shakarjian, Michael P.; Ali, Mahil S.; Velíšková, Jana; Stanton, Patric K.; Heck, Diane E.; Velíšek, Libor

    2015-01-01

    The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl− channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 hour lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or

  15. Clozapine blockade of MK-801-induced learning/memory impairment in the mEPM: Role of 5-HT1A receptors and hippocampal BDNF levels.

    Science.gov (United States)

    López Hill, Ximena; Richeri, Analía; Scorza, María Cecilia

    2017-10-01

    Cognitive impairment associated with schizophrenia (CIAS) is highly prevalent and affects the overall functioning of patients. Clozapine (Clz), an atypical antipsychotic drug, significantly improves CIAS although the underlying mechanisms remain under study. The role of the 5-HT 1A receptor (5-HT 1A -R) in the ability of Clz to prevent the learning/memory impairment induced by MK-801 was investigated using the modified elevated plus-maze (mEPM) considering the Transfer latency (TL) as an index of spatial memory. We also investigated if changes in hippocampal brain-derived neurotrophic factor (BDNF) levels underlie the behavioral prevention induced by Clz. Clz (0.5 and 1mg/kg)- or vehicle-pretreated Wistar rats were injected with MK-801 (0.05mg/kg) or saline. TL was evaluated 35min later (TL1, acquisition session) while learning/memory performance was measured 24h (TL2, retention session) and 48h later (TL3, long-lasting effect). WAY-100635, a 5-HT 1A -R antagonist, was pre-injected (0.3mg/kg) to examine the presumed 5-HT 1A -R involvement in Clz action. At TL2, another experimental group treated with Clz and MK-801 and its respective control groups were added to measure BDNF protein levels by ELISA. TL1 and TL3 were not significantly modified by the different treatments. MK-801 increased TL2 compared to control group leading a disruption of spatial memory processing which was markedly attenuated by Clz. WAY-100635 suppressed this action supporting a relevant role of 5-HT 1A -R in the Clz mechanism of action to improve spatial memory dysfunction. Although a significant decrease of hippocampal BDNF levels underlies the learning/memory impairment induced by MK-801, this effect was not significantly prevented by Clz. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Effect of liquid epoxidized natural rubber (LENR) on mechanical properties and morphology of natural rubber/high density polyethylene/mengkuang fiber (NR/HDPE/MK) bio-composite

    Science.gov (United States)

    Piah, Mohd Razi Mat; Baharum, Azizah

    2016-11-01

    The use of mengkuang fiber (MK) fibers in NR/HDPE (40/60) blend was studied via surface modification of fiber. The MK fiber was pre-washed with 5%wt/v sodium hydroxide solution prior to treatment with liquid epoxidized natural rubber (LENR). The concentration of LENR were varied from 5%-20%wt in toluene. The effects of LENR concentrations were studied in terms of mechanical properties and morphology formed. Melt-blending was performed using an internal mixer (Haake Rheomix 600). The processing parameters identified were 135°C temperature, 45 rpm rotor speed, 12 minutes processing time and at 20%wt MK fiber loading. The optimum LENR treatment concentration was obtained at 5%wt with tensile strength, tensile modulus, and impact strength of 10.3 MPa, 414.2 MPa and 14.4 kJ/m2 respectively. The tensile modulus of LENR-treated MK fiber filled NR/HDPE bio-composite has shown enhancement up to 16.7% higher than untreated MK fiber. The tensile and impact strength were decreased with increasing LENR concentration due to the broken of MK fibers to smaller particles and adhered to each other. FESEM micrographs confirmed the formation of fiber-fiber agglomeration in NR/HDPE blends. The optical microscope analysis shows MK fibers is shorter than original fiber lengths after NaOH-LENR surface modification. The internal bonding forces of MK fiber seems to be weaker than external force exerted on it, therefore, the MK fiber has broken to smaller particles and reduced the mechanical properties of NR/HDPE/MK(20%) bio-composite.

  17. A dark matter detector based on the simultaneous measurement of phonons and ionization at 20 mK

    Energy Technology Data Exchange (ETDEWEB)

    Shutt, Thomas Alan [UC, Berkeley

    1993-01-01

    One of the most important issues in astrophysics and cosmology is understanding the nature of dark matter. One possibility is that it is made of weakly interacting subatomic particles created in the big bang, such as the lightest particle in supersymmetry models. These particles should scatter elastically of nuclei in a detector on earth at a rate of ~events/kg/week, and will deposit energies of a few keV. Current attempts to detect these interactions are limited by a radioactive background of photons and beta particles which scatter on electrons. We have developed a novel particle detector to look for dark matter based on the simultaneous measurement of ionization and phonons in a 60 g crystal of high purity germanium at a temperature of 20 mK. Background events can be distinguished by our detector because they produce more ionization per unit phonon energy than dark matter interactions. The phonon energy is measured as a temperature change in the detector by means of neutron transmutation doped germanium thermistors attached to the crystal. The ionization measurement is accomplished by applying a bias to implanted contacts on the faces of the disk. Charge collection differs from the normal situation at 77 K in that no thermally generated free charge exists in the crystal at 20 mK. The collection efficiency is good with an electric field of only ~0.2 V/cm after the charged impurities in the crystal have been neutralized by free charge created by particle interactions from a radioactive source. For fields below this charge collection is poor, and affects the amount of phonon energy measured. We have modeled this in terms of charge trapping. The r.m.s resolution of the detector is 800 eV in phonons and 600 eV in ionization. We have tested the background rejection capability of the detector by exposing it to neutrons from a 251Cf source which scatter elastically on nuclei. The neutrons are distinguished at energies of a few keV, and the current background rejection

  18. Effect of acute and chronic MK-801 administration on extracellular glutamate and ascorbic acid release in the prefrontal cortex of freely moving mice on line with open-field behavior.

    Science.gov (United States)

    Zuo, Dai-Ying; Zhang, Ya-Hong; Cao, Yue; Wu, Chun-Fu; Tanaka, Masatoshi; Wu, Ying-Liang

    2006-04-04

    The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

  19. Aspartic protease from Aspergillus (Eurotium) repens strain MK82 is involved in the hydrolysis and decolourisation of dried bonito (Katsuobushi).

    Science.gov (United States)

    Aoki, Kenji; Matsubara, Sayaka; Umeda, Mayo; Tachibanac, Shusaku; Doi, Mikiharu; Takenaka, Shinji

    2013-04-01

    Katsuobushi is a dried, smoked and fermented bonito used in Japanese cuisine. During the fermentation process with several Aspergillus species, the colour of Katsuobushi gradually changes from a dark reddish-brown derived from haem proteins to pale pink. The change in colour gives Katsuobushi a higher ranking and price. This study aimed to elucidate the mechanism of decolourisation of Katsuobushi. A decolourising factor from the culture supernatant of Aspergillus (Eurotium) repens strain MK82 was purified to homogeneity. The purification was monitored by measuring the decolourising activity using equine myoglobin and bovine haemoglobin as substrates. It was found that the decolourising factor had protease activity towards myoglobin and haemoglobin. Complete inhibition of the enzyme by the inhibitor pepstatin A and the internal amino acid sequence classified the protein as an aspartic protease. The enzyme limitedly hydrolysed myoglobin between 1-Met and 2-Gly, 43-Lys and 44-Phe, and 70-Leu and 71-Thr. The purified enzyme decolourised blood of Katsuwonus pelamis (bonito) and a slice of dried bonito. It is proposed that aspartic protease plays a role in the decolourisation of Katsuobushi by the hydrolysis of haem proteins that allows the released haem to aggregate in the dried bonito. © 2012 Society of Chemical Industry.

  20. Penerapan Fitur Warna Untuk Identifikasi Plasmodium Falciparum pada Sediaan Apus Darah Menggunakan MK-Means dan Jaringan Backpropagation

    Directory of Open Access Journals (Sweden)

    mustamin hamid

    2016-09-01

    Full Text Available Abstract - This research proposed a system to identify Plasmodium falciparum on blood smear  using the neural network  backpropagation. Modified K-Means (MK-Means is used to separate between the object with the background image because that method was able to equalize the value of fitness at all Center cluster so there is no dead center and can also cope with the local minimum value. The extraction of the features used in this study consists of color features i.e. calculation of the mean, standard deviation, skewness, curtosis and entropy of co-occurent matrix with the purpose to get the values of all the trait value image, obtained are then used to train a neural network with the backpropagation training algorithm. Method of backpropagation networks capable of acquiring knowledge even though there is no certainty, able to perform a generalization and extraction of a specific data pattern.                         The image of  the preparations  blood smear  are classified using the method of  neural network Backpropagation. The test results obtained from Tropozoit with the accuracy 100%, scizon 80% and gametocytes 80%. Identification is then obtained outcomes the introduction with an average accuracy of 86,66%.

  1. Postirradiation examination of JOYO MK-II control rod (CRM601). Irradiation performance of shroud type absorber pin

    International Nuclear Information System (INIS)

    Tanaka, Kosuke; Kikuchi, Shin; Katsuyama, Kozo; Nagamine, Tsuyoshi; Mitsugi, Takeshi; Uto, Manabu; Tatebe, Kazuaki; Onose, Shoji; Maruyama, Tadashi

    1998-10-01

    This paper describes the results of postirradiation examination and analysis by CORAL code for irradiation performance of CRM601 control rod, which was the 6th reloaded control rod with shroud type absorber pins for use in JOYO MK-II core. The detailed visual examination indicated that there was no cladding breach in absorber pins. However, sodium ingress from the vent tube was observed in four absorber pins among seven pins. While a remarkable oval deformation occurred in cladding tube of helium bonded absorber pins, a little or no diametral change was observed in the absorber pins in which sodium ingress took place. From metallurgical observations and the analysis by CORAL code, it was estimated that the shroud tube installed in helium bonded absorber pins were irradiated at 720degC, and those in sodium bonded absorber pins were irradiated at 420degC. It was confirmed that diametral change of cladding depended on the initial gap between shroud and cladding tube. The results of present investigation indicate that it is desirable to use the materials with low thermal expansion coefficient for shroud tubes, and that sodium bonded absorber pins were advantageous for obtaining long life control rods. (author)

  2. 3He flow in dilute 3He-4He mixtures at temperatures between 10 and 150 mK

    International Nuclear Information System (INIS)

    Castelijns, C.A.M.; Kuerten, J.G.M.; de Waele, A.T.A.M.; Gijsman, H.M.

    1985-01-01

    The mutual friction between 3 He and 4 He II below 150 mK has been studied. Empirical relations for the adiabatic and the nonadiabatic flow properties of 3 He moving through 4 He have been determined using a dilution refrigerator with a single mixing chamber. The validity of the relations is verified by osmotic-pressure measurements and by measuring the properties of a double-mixing-chamber system. It is shown that superleak shunts have a strong effect on the flow characteristics. From the nonadiabatic flow properties an expression is derived for the mutual-friction-force density between 3 He and 4 He II. This has a strong resemblance to the Gorter-Mellink mutual-friction-force density between the normal and the superfluid components in pure 4 He II. It is speculated that the 3 He flow in our systems generates a 4 He vortex tangle, which leads to the observed mutual friction between 3 He and 4 He and also to a strong clamping of the 4 He to the walls

  3. Boiling burnout in the inner annulus of the MK-IV fuel configuration containing ''W'' spring supports

    International Nuclear Information System (INIS)

    McSweeney, T.I.; Thorne, W.L.; Fitzsimmons, D.E.; Anderson, J.K.

    1978-09-01

    The establishment of reactor power limits for the NPR is based, to some extent, on the burnout heat transfer results obtained from electrically heated hydraulic models of the reactor coolant passages. Past tests have shown that the outer surface of the middle annulus of the MK-IV fuel configuration goes into burnout before any other surface. Past models have contained no supports in the region where burnout has occurred, yet the reactor configuration must contain supports. The primary purpose of this study is to determine the support influence on the location and magnitude of the burnout heat flux. A second purpose is to establish burnout limits at higher coolant enthalpies. A 2-foot long electrically heated model of the coolant passage, containing supports, has been tested in the high pressure loop of the Thermal Hydraulics Laboratory. Although several supports were located in the active region, a ''W'' spring support was placed in at the channel location where burnout occurred in previous test sections. Thus, the influence of this support has been determined experimentally. Analytically, it has been possible to extend this information to other possible configurations at low quality. A suggested method for using these initial high quality data in the setting of the reactor operating limits is presented

  4. Characterization of the Rhodococcus sp. MK1 strain and its pilot application for bioremediation of diesel oil-contaminated soil.

    Science.gov (United States)

    Kis, Ágnes Erdeiné; Laczi, Krisztián; Zsíros, Szilvia; Kós, Péter; Tengölics, Roland; Bounedjoum, Naila; Kovács, Tamás; Rákhely, Gábor; Perei, Katalin

    2017-12-01

    Petroleum hydrocarbons and derivatives are widespread contaminants in both aquifers and soil, their elimination is in the primary focus of environmental studies. Microorganisms are key components in biological removal of pollutants. Strains capable to utilize hydrocarbons usually appear at the contaminated sites, but their metabolic activities are often restricted by the lack of nutrients and/or they can only utilize one or two components of a mixture. We isolated a novel Rhodococcus sp. MK1 strain capable to degrade the components of diesel oil simultaneously. The draft genome of the strain was determined and besides the chromosome, the presence of one plasmid could be revealed. Numerous routes for oxidation of aliphatic and aromatic compounds were identified. The strain was tested in ex situ applications aiming to compare alternative solutions for microbial degradation of hydrocarbons. The results of bioaugmentation and biostimulation experiments clearly demonstrated that - in certain cases - the indigenous microbial community could be exploited for bioremediation of oil-contaminated soils. Biostimulation seems to be efficient for removal of aged contaminations at lower concentration range, whereas bioaugmentation is necessary for the treatment of freshly and highly polluted sites.

  5. Customer Relationship Management (CRM linking with Marketing Knowledge (mk in the electronic sector in Guadalajara, Jalisco, Mexico

    Directory of Open Access Journals (Sweden)

    José Sánchez Gutiérrez

    2016-02-01

    Full Text Available El propósito de este artículo es analizar cómo se relacionan las variables de la administración de la relación con los clientes, el desarrollo de nuevos productos y el conocimiento de mercadotecnia, en la industria electrónica en la ciudad de Guadalajara, Jalisco, México. También descubrir el impacto que estos factores tienen en la creación de nuevos productos, así como la implementación de información externa e interna en creaciones futuras. El análisis se llevó a cabo por medio de una investigación hecha a 25 empresas de la industria; la encuesta se realizó entre sus directivos. Además, las repercusiones de este estudio son los conocimientos en la práctica sobre la estructura de mk, las decisiones de desarrollo de productos con un enfoque de crm, así como las condiciones organizacionales que participan en el proceso.

  6. Measuring the microwave response of superconducting Nb:STO and Ti at mK temperatures using superconducting resonators

    Energy Technology Data Exchange (ETDEWEB)

    Thiemann, Markus; Beutel, Manfred; Dressel, Martin; Scheffler, Marc [1. Physikalisches Institut, Universitaet Stuttgart (Germany); Fillis-Tsirakis, Evangelos; Boschker, Hans; Mannhart, Jochen [Max Planck Institute for Solid State Research, Stuttgart (Germany)

    2016-07-01

    Niobium doped SrTiO{sub 3} is a superconductor, with the lowest charge carrier density among all superconductors. It shows a dome in the transition temperature as a function of doping concentration with a maximum T{sub c} ∼ 0.3 K. The superconducting dome may originate from the different bands being occupied depending on the doping level. The low energy scales of the system, as indicated by the low T{sub c} are within the GHz-regime. Therefore microwave measurements are a powerful technique to reveal the electronic properties of these superconductors. We preformed microwave measurements on Nb:STO of different doping levels in a dilution refrigerator, using superconducting stripline resonators. Measurements were done in a temperature and frequency range from 40-400 mK and 1-20 GHz, covering the normal and superconducting states. For comparison we also measured the temperature dependence of the surface impedance of superconducting titanium (T{sub c} ∼ 0.5 K), which can be well described by the Mattis-Bardeen equations with a ratio (2Δ)/(k{sub B}T{sub c}) = 3.56. Therefore titanium is an ideal reference sample representing a conventional BCS-superconductor.

  7. Concentration change of DA, DOPAC, Glu and GABA in brain tissues in schizophrenia developmental model rats induced by MK-801.

    Science.gov (United States)

    Liu, Yong; Tang, Yamei; Pu, Weidan; Zhang, Xianghui; Zhao, Jingping

    2011-08-01

    To explore the related neurobiochemical mechanism by comparing the concentration change of dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC), glutamate (Glu), and γ-aminobutyric acid (GABA) in the brain tissues in schizophrenia (SZ) developmental model rats and chronic medication model rats. A total of 60 neonatal male Spragur-Dawley (SD) rats were randomly assigned to 3 groups at the postnatal day 6: an SZ developmental rat model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg, Bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,Qd), and a normal control group (injection with 0.9% normal saline during the corresponding periods). DA, DOPAC, Glu, and GABA of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray electrochemic detection by high performance liquid chromatogram technique. The utilization rate of DA and Glu was calculated. Compared with the normal control group, the concentration of DA and DOPAC in the mPFC and the hippocampus in the SZ developmental model group significantly decreased (PGABA concentration and Glu utilization rate in the mPFC also decreased (PGABA system decrease in the mPFC and the DA system function reduces in the hippocampus of SZ developmental rats.

  8. UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: Comparison with the NMDA receptor antagonist MK-801

    DEFF Research Database (Denmark)

    Andreasen, Jesper T.; Bach, Anders; Gynther, Mikko

    2013-01-01

    Excessive N-Methyl-d-aspartate receptor (NMDAR)-dependent production of nitric oxide (NO) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein-95 (PSD-95). By binding to both the NMDAR and neuronal NO synthase (nNOS), PSD-95 mediates...... a specific coupling between NMDAR activation and NO production. NMDAR antagonism shows anti-nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions. An alternative approach to modulate the NMDAR-related activity is to perturb......'s adjuvant (CFA) model of inflammatory pain. To examine side-effect profiles we also compared the effects of UCCB01-125 and MK-801 in tests of attention, long-term memory, and motor performance. When administered concurrently with CFA, both MK-801 and UCCB01-125 prevented the development of CFA...

  9. Set-up of a high-resolution 300 mK atomic force microscope in an ultra-high vacuum compatible "3He/10 T cryostat

    International Nuclear Information System (INIS)

    Allwörden, H. von; Ruschmeier, K.; Köhler, A.; Eelbo, T.; Schwarz, A.; Wiesendanger, R.

    2016-01-01

    The design of an atomic force microscope with an all-fiber interferometric detection scheme capable of atomic resolution at about 500 mK is presented. The microscope body is connected to a small pumped "3He reservoir with a base temperature of about 300 mK. The bakeable insert with the cooling stage can be moved from its measurement position inside the bore of a superconducting 10 T magnet into an ultra-high vacuum chamber, where the tip and sample can be exchanged in situ. Moreover, single atoms or molecules can be evaporated onto a cold substrate located inside the microscope. Two side chambers are equipped with standard surface preparation and surface analysis tools. The performance of the microscope at low temperatures is demonstrated by resolving single Co atoms on Mn/W(110) and by showing atomic resolution on NaCl(001).

  10. Set-up of a high-resolution 300 mK atomic force microscope in an ultra-high vacuum compatible {sup 3}He/10 T cryostat

    Energy Technology Data Exchange (ETDEWEB)

    Allwörden, H. von; Ruschmeier, K.; Köhler, A.; Eelbo, T.; Schwarz, A., E-mail: aschwarz@physnet.uni-hamburg.de; Wiesendanger, R. [Department of Physics, University of Hamburg, Jungiusstrasse 11, 20355 Hamburg (Germany)

    2016-07-15

    The design of an atomic force microscope with an all-fiber interferometric detection scheme capable of atomic resolution at about 500 mK is presented. The microscope body is connected to a small pumped {sup 3}He reservoir with a base temperature of about 300 mK. The bakeable insert with the cooling stage can be moved from its measurement position inside the bore of a superconducting 10 T magnet into an ultra-high vacuum chamber, where the tip and sample can be exchanged in situ. Moreover, single atoms or molecules can be evaporated onto a cold substrate located inside the microscope. Two side chambers are equipped with standard surface preparation and surface analysis tools. The performance of the microscope at low temperatures is demonstrated by resolving single Co atoms on Mn/W(110) and by showing atomic resolution on NaCl(001).

  11. Development of a space-flight ADR providing continuous cooling at 50 mK with heat rejection at 10 K

    Science.gov (United States)

    Tuttle, James; Canavan, Edgar; DeLee, Hudson; DiPirro, Michael; Jahromi, Amir; James, Bryan; Kimball, Mark; Shirron, Peter; Sullivan, Dan; Switzer, Eric

    2017-12-01

    Future astronomical instruments will require sub-Kelvin detector temperatures to obtain high sensitivity. In many cases large arrays of detectors will be used, and the associated cooling systems will need performance surpassing the limits of present technologies. NASA is developing a compact cooling system that will lift heat continuously at temperatures below 50 mK and reject it at over 10 K. Based on adiabatic demagnetization refrigerators (ADRs), it will have high thermodynamic efficiency and vibration-free operation with no moving parts. It will provide more than 10 times the current flight ADR cooling power at 50 mK and will also continuously cool a 4 K stage for instruments and optics. In addition, it will include an advanced magnetic shield resulting in external field variations below 5 μT. We describe the cooling system here and report on the progress in its development.

  12. Effects of the noncompetitive N-methyl-d-aspartate receptor antagonists ketamine and MK-801 on pain-stimulated and pain-depressed behaviour in rats.

    Science.gov (United States)

    Hillhouse, T M; Negus, S S

    2016-09-01

    Pain is a significant public health concern, and current pharmacological treatments have problematic side effects and limited effectiveness. N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have emerged as one class of candidate treatments for pain because of the significant contribution of glutamate signalling in nociceptive processing. This study compared effects of the NMDA receptor antagonists ketamine and MK-801 in assays of pain-stimulated and pain-depressed behaviour in rats. The nonsteroidal anti-inflammatory drug ketoprofen was examined for comparison as a positive control. Intraperitoneal injection of dilute acid served as an acute visceral noxious stimulus to stimulate a stretching response or depress intracranial self-stimulation (ICSS) in male Sprague-Dawley rats. Ketamine (1.0-10.0 mg/kg) blocked acid-stimulated stretching but failed to block acid-induced depression of ICSS, whereas MK-801 (0.01-0.1 mg/kg) blocked both acid-stimulated stretching and acid-induced depression of ICSS. These doses of ketamine and MK-801 did not alter control ICSS in the absence of the noxious stimulus; however, higher doses of ketamine (10 mg/kg) and MK-801 (0.32 mg/kg) depressed all behaviour. Ketoprofen (1.0 mg/kg) blocked both acid-induced stimulation of stretching and depression of ICSS without altering control ICSS. These results support further consideration of NMDA receptor antagonists as analgesics; however, some NMDA receptor antagonists are more efficacious at attenuating pain-depressed behaviours. NMDA receptor antagonists produce dissociable effects on pain-depressed behaviour. Provides evidence that pain-depressed behaviours should be considered and evaluated when determining the antinociceptive effects of NMDA receptor antagonists. © 2016 European Pain Federation - EFIC®

  13. MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test.

    Science.gov (United States)

    Duda, Weronika; Wesierska, Malgorzata; Ostaszewski, Pawel; Vales, Karel; Nekovarova, Tereza; Stuchlik, Ales

    2016-09-15

    N-methyl-d-aspartate receptors (NMDARs) play a crucial role in spatial memory formation. In neuropharmacological studies their functioning strongly depends on testing conditions and the dosage of NMDAR antagonists. The aim of this study was to assess the immediate effects of NMDAR block by (+)MK-801 or memantine on short-term allothetic memory. Memory was tested in a working memory version of the Morris water maze test. In our version of the test, rats underwent one day of training with 8 trials, and then three experimental days when rats were injected intraperitoneally with low- 5 (MeL), high - 20 (MeH) mg/kg memantine, 0.1mg/kg MK-801 or 1ml/kg saline (SAL) 30min before testing, for three consecutive days. On each experimental day there was just one acquisition and one test trial, with an inter-trial interval of 5 or 15min. During training the hidden platform was relocated after each trial and during the experiment after each day. The follow-up effect was assessed on day 9. Intact rats improved their spatial memory across the one training day. With a 5min interval MeH rats had longer latency then all rats during retrieval. With a 15min interval the MeH rats presented worse working memory measured as retrieval minus acquisition trial for path than SAL and MeL and for latency than MeL rats. MK-801 rats had longer latency than SAL during retrieval. Thus, the high dose of memantine, contrary to low dose of MK-801 disrupts short-term memory independent on the time interval between acquisition and retrieval. This shows that short-term memory tested in a working memory version of water maze is sensitive to several parameters: i.e., NMDA receptor antagonist type, dosage and the time interval between learning and testing. Copyright © 2016. Published by Elsevier B.V.

  14. Validation and pharmacological characterisation of MK-801-induced locomotor hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics.

    Science.gov (United States)

    Bradford, Andrea M; Savage, Kevin M; Jones, Declan N C; Kalinichev, Mikhail

    2010-10-01

    We evaluated locomotor hyperactivity induced in BALB/C mice by an N-methyl-D-aspartate receptor antagonist MK-801 as an assay for the detection of antipsychotic drugs. We assessed the effects of antipsychotic drugs to validate the assay (study 1), selective dopamine and serotonin ligands for pharmacological characterisation of the model (study 2) and a number of compounds with efficacy in models of schizophrenia to understand the predictive validity of the model (study 3). Adult males (n  = 9/group) were pretreated with a test compound, habituated to locomotor activity cages before receiving MK-801 (0.32 mg/kg) and activity recorded for a further 75 or 120 min. In study 1, we tested haloperidol, clozapine, olanzapine, risperidone, ziprasidone, aripiprazole, sertindole and quetiapine. In study 2, we tested SCH23390 (D(1) antagonist), sulpiride (D(2)/D(3) antagonist), raclopride (D(2)/D(3) antagonist), SB-277011 (D(3) antagonist), L-745,870 (D(4) antagonist), WAY100635 (5-HT(1A) antagonist), 8-OH-DPAT (5-HT(1A) agonist), ketanserin (5-HT(2A)/5-HT(2C) antagonist) and SB-242084 (5-HT(2C) antagonist). In study 3, we tested xanomeline (M(1)/M(4) receptor agonist), LY379268 (mGluR2/3 receptor agonist), diazepam (GABA(A) modulator) and thioperamide (H(3) receptor antagonist). All antipsychotics suppressed MK-801-induced hyperactivity in a dose-dependent and specific manner. The effects of antipsychotics appear to be mediated via dopamine D(1), D(2) and 5-HT(2) receptors. Xanomeline, LY379268 and diazepam were active in this assay while thioperamide was not. MK-801-induced hyperactivity in BALB/C mice model of positive symptoms has shown predictive validity with novel compounds acing at M(1)/M(4), mGluR2/3 and GABA(A) receptors and can be used as a screening assay for detection of novel pharmacotherapies targeting those receptors.

  15. Antagonista NMDA-receptorů MK-801 narušuje rozeznávání pozice vzdáleného objektu

    Czech Academy of Sciences Publication Activity Database

    Levčík, David; Klement, Daniel; Nekovářová, Tereza; Valeš, Karel; Stuchlík, Aleš

    2010-01-01

    Roč. 14, Suppl.2 (2010), s. 15-18 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517; GA ČR(CZ) GA309/09/0286; GA MZd(CZ) NR9178; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : recognition of position * MK-801 * CHPG * mGluR Subject RIV: FH - Neurology

  16. Effect of alpha1-adrenergic antagonist prazosin on behavioral alterations induced by MK-801 in a spatial memory task in Long-Evans rats

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Petrásek, Tomáš; Valeš, Karel

    2009-01-01

    Roč. 58, č. 5 (2009), s. 733-740 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA309/09/0286; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : prazosin * MK-801 * learning Subject RIV: FH - Neuro logy Impact factor: 1.430, year: 2009

  17. Autoradiographical detection of cholecystokinin-A receptors in primate brain using 125I-Bolton Hunter CCK-8 and 3H-MK-329

    International Nuclear Information System (INIS)

    Hill, D.R.; Shaw, T.M.; Graham, W.; Woodruff, G.N.

    1990-01-01

    In vitro autoradiography was performed in order to visualize cholecystokinin-A (CCK-A) receptors in sections of Cynomolgus monkey brain. CCK-A receptors were defined as those which displayed high affinity for the selective non-peptide antagonist MK-329 (L-364,718) and were detected in several regions by selective inhibition of 125I-Bolton Hunter CCK using MK-329 or direct labeling with 3H-MK-329. In the caudal medulla, high densities of CCK-A sites were present in the nucleus tractus solitarius, especially the caudal and medial aspects, and also the dorsal motor nucleus of the vagus. CCK-A sites were localized to a number of hypothalamic nuclei such as the supraoptic and paraventricular nuclei, the dorsomedial and infundibular nuclei as well as the neurohypophysis. The mammillary bodies and supramammillary nuclei also contained CCK-A receptor sites. High concentrations of CCK-A receptors were present in the substantia nigra zona compacta and also the ventral tegmental area and may be associated with dopamine cell bodies. Binding of 3H-MK-329 was also detected in parts of the caudate nucleus and ventral putamen. The detection, by autoradiographical means, of CCK-A receptors throughout the Cynomolgus monkey brain contrasts with similar studies performed using rodents and suggests differences in the density and, perhaps, the importance of CCK-A receptors in the primate as opposed to the rodent. The data suggest the possibility that CCK-A receptors may be involved in a number of important brain functions as diverse as the processing of sensory information from the gut, the regulation of hormone secretion, and the activity of dopamine cell activity

  18. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

    Science.gov (United States)

    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  19. Assessing the Frequency and Material Consequences of Collisions with Vessels Lying at an Anchorage in Line with IALA iWrap MkII

    Directory of Open Access Journals (Sweden)

    Hans-Christoph Burmeister

    2014-03-01

    Full Text Available This paper proposes a collision model for ships underway and temporary objects as an extension to state-of-the-art maritime risk assessment like IALA iWrap MkII. It gives a brief review of frequency modeling's and consequence calculation theory as well as its applications, before it analogously derives a model to assess the risk of anchorage areas. Subsequently, its benefit is demonstrated by an example scenario.

  20. Early Adolescent MK-801 Exposure Impairs the Maturation of Ventral Hippocampal Control of Basolateral Amygdala Drive in the Adult Prefrontal Cortex

    Science.gov (United States)

    Thomases, Daniel R.; Cass, Daryn K.; Meyer, Jacqueline D.; Caballero, Adriana

    2014-01-01

    The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp–BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp–PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA. PMID:24990926

  1. Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

    International Nuclear Information System (INIS)

    Casteels, Cindy; Martinez, Emili; Camon, Lluisa; Vera, Nuria de; Planas, Anna M.; Bormans, Guy; Baekelandt, Veerle; Laere, Koen van

    2010-01-01

    Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD). Using [ 18 F]MK-9470 and small animal PET, we investigated cerebral changes in type 1 cannabinoid (CB 1 ) receptor binding in the quinolinic acid (QA) rat model of HD in relation to glucose metabolism, dopamine D 2 receptor availability and amphetamine-induced turning behaviour. Twenty-one Wistar rats (11 QA and 10 shams) were investigated. Small animal PET acquisitions were conducted on a Focus 220 with approximately 18 MBq of [ 18 F]MK-9470, [ 18 F]FDG and [ 11 C]raclopride. Relative glucose metabolism and parametric CB 1 receptor and D 2 binding images were anatomically standardized to Paxinos space and analysed voxel-wise using Statistical Parametric Mapping (SPM2). In the QA model, [ 18 F]MK-9470 uptake, glucose metabolism and D 2 receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p -5 ), while an increase for these markers was observed on the contralateral side (>5%, all p -4 ). [ 18 F]MK-9470 binding was also increased in the cerebellum (p = 2.10 -5 ), where it was inversely correlated to the number of ipsiversive turnings (p = 7.10 -6 ), suggesting that CB 1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p = 1.10 -6 ). These data point to in vivo changes in endocannabinoid transmission, specifically for CB 1 receptors in the QA model, with involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D 2 and CB 1 neurotransmission in the contralateral hemisphere. (orig.)

  2. The N-Methyl-d-Aspartate Receptor Antagonist MK-801 Prevents Thallium-Induced Behavioral and Biochemical Alterations in the Rat Brain.

    Science.gov (United States)

    Osorio-Rico, Laura; Villeda-Hernández, Juana; Santamaría, Abel; Königsberg, Mina; Galván-Arzate, Sonia

    2015-01-01

    Thallium (Tl(+)) is a toxic heavy metal capable of increasing oxidative damage and disrupting antioxidant defense systems. Thallium invades the brain cells through potassium channels, increasing neuronal excitability, although until now the possible role of glutamatergic transmission in this event has not been investigated. Here, we explored the possible involvement of a glutamatergic component in the Tl(+)-induced toxicity through the N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) in rats. The effects of MK-801 (1 mg/kg, intraperitoneally [ip]) on early (24 hours) motor alterations, lipid peroxidation, reduced glutathione (GSH) levels, and GSH peroxidase activity induced by Tl(+) acetate (32 mg/kg, ip) were evaluated in adult rats. MK-801 attenuated the Tl(+)-induced hyperactivity and lipid peroxidation in the rat striatum, hippocampus and midbrain, and produced mild effects on other end points. Our findings suggest that glutamatergic transmission via NMDA receptors might be involved in the Tl(+)-induced altered regional brain redox activity and motor performance in rats. © The Author(s) 2015.

  3. Development of a New Structural Class of Broadly Acting HCV Non-Nucleoside Inhibitors Leading to the Discovery of MK-8876

    Energy Technology Data Exchange (ETDEWEB)

    McComas, Casey C.; Palani, Anandan; Chang, Wei; Holloway, M. Katharine; Lesburg, Charles A.; Li, Peng; Liverton, Nigel; Meinke, Peter T.; Olsen, David B.; Peng, Xuanjia; Soll, Richard M.; Ummat, Ajay; Wu, Jie; Wu, Jin; Zorn, Nicolas; Ludmerer, Steven W. (Merck); (WuXi App Tec)

    2017-07-25

    Studies directed at developing a broadly acting non-nucleoside inhibitor of HCV NS5B led to the discovery of a novel structural class of 5-aryl benzofurans that simultaneously interact with both the palm I and palm II binding regions. An initial candidate was potent in vitro against HCV GT1a and GT1b replicons, and induced multi-log reductions in HCV viral load when orally dosed to chronic GT1 infected chimpanzees. However, in vitro potency losses against clinically relevant GT1a variants prompted a further effort to develop compounds with sustained potency across a broader array of HCV genotypes and mutants. Ultimately, a biology and medicinal chemistry collaboration led to the discovery of the development candidate MK-8876. MK-8876 demonstrated a pan-genotypic potency profile and maintained potency against clinically relevant mutants. It demonstrated moderate bioavailability in rats and dogs, but showed low plasma clearance characteristics consistent with once-daily dosing. Herein we describe the efforts which led to the discovery of MK-8876, which advanced into Phase 1 monotherapy studies for evaluation and characterization as a component of an all-oral direct-acting drug regimen for the treatment of chronic HCV infection.

  4. Thermographic imaging of superficial temperature in dogs sedated with medetomidine and butorphanol with and without MK-467 (L-659'066).

    Science.gov (United States)

    Vainionpää, Mari; Salla, Kati; Restitutti, Flávia; Raekallio, Marja; Junnila, Jouni; Snellman, Marjatta; Vainio, Outi

    2013-03-01

    To record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature. Randomized crossover part-blinded experimental study. Eight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3-4 years. Each dog was sedated four times. Treatments were medetomidine 20 μg kg(-1) and butorphanol 0.1 mg kg(-1) (MB) with or without MK-467 500 μg kg(-1) (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging. The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment. At 60 minutes after drug administration, MFT was higher (p temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone. The sedation protocol may influence core temperature loss, and may also have an effect on thermographic images. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  5. Effect of the MK 801 and (-) nicotine intracerebral administration on Glu and Gaba extracellular concentration in the pedunculopontine nucleus from rats

    International Nuclear Information System (INIS)

    Blanco Lezcano, Lisette; Lorigados Pedre, Lourdes del Carmen; Gonzalez Fraguela, Maria Elena and others

    2011-01-01

    Although the pharmacological manipulation of the glutamatergic and cholinergic systems have been studied in animal models of Parkinson's Disease (PD), only some authors have done work on this topic at the pedunculopontine nucleus (PPN). The present work studied the changes in glutamate (Glu) and δ-aminobutyric acid (GABA) extracellular concentrations (EC) in the PPN from hemiparkinsonian rats by 6hydroxydopamine injection. The rats were locally perfused by MK-801 (10 μ mol/l) or (-) nicotine (10 mm) solutions by cerebral microdialysis. The biochemical studies were carried out through high performance liquid chromatography coupled to fluorescence detection. Mk-801 infusion induced a significant decrease of Glu (p< 0.01) and GABA (p< 0.01) EC in PPN. On the other hand (-) nicotine infusion induced a significant increase of Glu (p< 0.001) and GABA (p< 0.001) EC in PPN from hemiparkinsonian rats. The local blockade of NMDA receptors by MK-801 infusion facilitates the interaction between Glu and their metabotropic receptors that take part in presynaptic inhibition mechanisms and interfere with neurotransmitters release. Meanwhile, the nicotine infusion sums the effects of nicotinic receptor activation with the glutamatergic and gabaergic neurotransmission changes produced in the PPN in the parkinsonian condition. The cholinergic and glutamergic drug infusion in PPN impose a new adjustment to the neurotransmission at this level that is added to the neurochemical changes associated to dopaminergic denervation.

  6. Heterometallic clusters arising from cubic Ni3M'O4 (M'=K and Na) entity: Solvothermal synthesis with/without the assistance of microwave

    International Nuclear Information System (INIS)

    Zhang Shuhua; Zhou Yanling; Sun Xiaojun; Wei, Lian-Qiang; Zeng Minghua; Liang Hong

    2009-01-01

    Solvothermal reaction assisted with microwave leads to the formation of two unique heterometallic cubic clusters [Ni 3 M'(L) 3 (OH)(CH 3 CN) 3 ] 2 .CH 3 CN (M'=K for 1 and M'=Na for 2, where L is an anion of 2-[(2-hydroxy-3-methoxy-benzylidene)-amino]-ethanesulfonate) with higher efficiency, yields and purity than those without it. The 6-metallacrown-3 [Ni 3 (OH)(L) 3 ] - groups exhibit interesting ion trapping and self-assembly of size-different Na + and K + through form recognition and coordination activity in 1 and 2. The magnetic studies for 1 and 2 suggest that the {Ni 3 M'O 4 } (M'=K and Na) cores both display dominant ferromagnetic interactions from the nature of the binding modes of μ 3 -O (oxidophenyl) and μ 3 -OH. - Graphical abstract: Solvothermal reaction assisted with microwave leads to two heterometallic cubic clusters with 6-metallacrown-3 structure [Ni 3 O 3 (OH)] - acting as a host for a K + or Na + ion. The {Ni 3 M'O 4 } (M'=K, Na) cores display dominant ferromagnetic interactions.

  7. Effects of hypoxia-ischemia and MK-801 treatment on the binding of a phencyclidine analogue in the developing rat brain

    International Nuclear Information System (INIS)

    Silverstein, F.S.; McDonald, J.W. III; Bommarito, M.; Johnston, M.V.

    1990-01-01

    The phencyclidine analogue [ 3 H](1-[2-thienyl]cyclohexyl)piperidine ( 3 H-TCP) binds to the ion channel associated with the N-methyl-D-aspartate receptor channel complex. In vitro autoradiography indicates that the distribution of 3 H-TCP binding in brain closely parallels that of [ 3 H]glutamate binding to the N-methyl-D-aspartate receptor. In nine 7-day-old rats, an acute focal hypoxic-ischemic insult produced by unilateral carotid artery ligation and subsequent exposure to 8% oxygen acutely reduced 3 H-TCP binding ipsilateral to the ligation by 30% in the CA1, by 27% in the CA3, by 26% in the dentate gyrus, and by 17% in the striatum compared with values from the contralateral hemisphere. In 10 littermates that received 1 mg/kg of the neuroprotective noncompetitive N-methyl-D-aspartate antagonist MK-801 immediately before hypoxic exposure, the regional distribution of 3 H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in 3 H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, 3 H-TCP binding was reduced by 15-35%; similar bilateral suppression of 3 H-TCP binding was detected in MK-801-treated ligates. Our data indicate that 3 H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke

  8. The prognostic value of monosomal karyotype (MK) in higher-risk patients with myelodysplastic syndromes treated with 5-Azacitidine. A retrospective analysis of the Hellenic (Greek) MDS Study Group.

    Science.gov (United States)

    Papageorgiou, Sotirios G; Vasilatou, Diamantina; Kontos, Christos K; Kotsianidis, Ioannis; Symeonidis, Argiris; Galanopoulos, Athanasios G; Hatzimichael, Eleftheria; Megalakaki, Aekaterini; Poulakidas, Elias; Diamantopoulos, Panagiotis; Vassilakopoulos, Theodoros; Zikos, Panagiotis; Papadaki, Helen; Mparmparousi, Despoina; Bouronikou, Eleni; Panayiotidis, Panayiotis; Viniou, Nora-Athina; Pappa, Vassiliki

    2018-04-16

    In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk MDS patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P=0.029), IPSS-R (PMDS treated with 5-AZA. Furthermore, we showed that in MDS with high or very-high IPSS-R risk score, MK can further distinguish patients with worse outcome. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  9. A novel selective androgen receptor modulator (SARM) MK-4541 exerts anti-androgenic activity in the prostate cancer xenograft R-3327G and anabolic activity on skeletal muscle mass & function in castrated mice.

    Science.gov (United States)

    Chisamore, Michael J; Gentile, Michael A; Dillon, Gregory Michael; Baran, Matthew; Gambone, Carlo; Riley, Sean; Schmidt, Azriel; Flores, Osvaldo; Wilkinson, Hilary; Alves, Stephen E

    2016-10-01

    The androgen receptor (AR) is a member of the nuclear hormone receptor super family of transcription factors. Androgens play an essential role in the development, growth, and maintenance of male sex organs, as well as the musculoskeletal and central nervous systems. Yet with advancing age, androgens can drive the onset of prostate cancer, the second leading cause of cancer death in males within the United States. Androgen deprivation therapy (ADT) by pharmacologic and/or surgical castration induces apoptosis of prostate cells and subsequent shrinkage of the prostate and prostate tumors. However, ADT is associated with significant musculoskeletal and behavioral adverse effects. The unique pharmacological activity of selective androgen receptor modulator (SARM) MK-4541 recently has been reported as an AR antagonist with 5α-reductase inhibitor function. The molecule inhibits proliferation and induces apoptosis in AR positive, androgen dependent prostate cancer cells. Importantly, MK-4541 inhibited androgen-dependent prostate growth in male rats yet maintained lean body mass and bone formation following ovariectomy in female rats. In the present study, we evaluated the effects of SARM MK-4541 in the androgen-dependent Dunning R3327-G prostate carcinoma xenograft mouse model as well as on skeletal muscle mass and function, and AR-regulated behavior in mice. MK-4541 significantly inhibited the growth of R3327-G prostate tumors, exhibited anti-androgen effects on the seminal vesicles, reduced plasma testosterone concentrations in intact males, and inhibited Ki67 expression. MK-4541 treated xenografts appeared similar to xenografts in castrated mice. Importantly, we demonstrate that MK-4541 exhibited anabolic activity in androgen deficient conditions, increasing lean body mass and muscle function in adult castrated mice. Moreover, MK-4541 treatment restored general activity levels in castrated mice. Thus, MK-4541 exhibits an optimum profile as an adjuvant therapy to ADT

  10. Neuropeptide S ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 through activation of cognate receptor-expressing neurons in the subiculum complex.

    Science.gov (United States)

    Shao, Yu-Feng; Wang, Can; Xie, Jun-Fan; Kong, Xiang-Pan; Xin, Le; Dong, Chao-Yu; Li, Jing; Ren, Wen-Ting; Hou, Yi-Ping

    2016-07-01

    Our previous studies have demonstrated that neuropeptide S (NPS), via selective activation of the neurons bearing NPS receptor (NPSR) in the olfactory cortex, facilitates olfactory function. High level expression of NPSR mRNA in the subiculum complex of hippocampal formation suggests that NPS-NPSR system might be involved in the regulation of olfactory spatial memory. The present study was undertaken to investigate effects of NPS on the scopolamine- or MK801-induced impairment of olfactory spatial memory using computer-assisted 4-hole-board spatial memory test, and by monitoring Fos expression in the subiculum complex in mice. In addition, dual-immunofluorescence microscopy was employed to identify NPS-induced Fos-immunereactive (-ir) neurons that also bear NPSR. Intracerebroventricular administration of NPS (0.5 nmol) significantly increased the number of visits to switched odorants in recall trial in mice suffering from odor-discriminating inability induced by scopolamine, a selective muscarinic cholinergic receptor antagonist, or MK801, a N-methyl-D-aspartate receptor antagonist, after training trials. The improvement of olfactory spatial memory by NPS was abolished by the NPSR antagonist [D-Val(5)]NPS (40 nmol). Ex vivo c-Fos and NPSR immunohistochemistry revealed that, as compared with vehicle-treated mice, NPS markedly enhanced Fos expression in the subiculum complex encompassing the subiculum (S), presubiculum (PrS) and parasubiculum (PaS). The percentages of Fos-ir neurons that also express NPSR were 91.3, 86.5 and 90.0 % in the S, PrS and PaS, respectively. The present findings demonstrate that NPS, via selective activation of the neurons bearing NPSR in the subiculum complex, ameliorates olfactory spatial memory impairment induced by scopolamine and MK801 in mice.

  11. MK-801 impairs cognitive coordination on a rotating arena (Carousel and contextual specificity of hippocampal immediate-early gene expression in a rat model of psychosis

    Directory of Open Access Journals (Sweden)

    Štěpán eKubík

    2014-03-01

    Full Text Available Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena - Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801 used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not fire together before. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between

  12. MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis.

    Science.gov (United States)

    Kubík, Stěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena - Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated

  13. Identification of selected in vitro generated phase-I metabolites of the steroidal selective androgen receptor modulator MK-0773 for doping control purposes.

    Science.gov (United States)

    Lagojda, Andreas; Kuehne, Dirk; Krug, Oliver; Thomas, Andreas; Wigger, Tina; Karst, Uwe; Schänzer, Wilhelm; Thevis, Mario

    2016-01-01

    Research into developing anabolic agents for various therapeutic purposes has been pursued for decades. As the clinical utility of anabolic-androgenic steroids has been found to be limited because of their lack of tissue selectivity and associated off-target effects, alternative drug entities have been designed and are commonly referred to as selective androgen receptor modulators (SARMs). While most of these SARMs are of nonsteroidal structure, the drug candidate MK-0773 comprises a 4-aza-steroidal nucleus. Besides the intended therapeutic use, SARMs have been found to be illicitly distributed and misused as doping agents in sport, necessitating frequently updated doping control analytical assays. As steroidal compounds reportedly undergo considerable metabolic transformations, the phase-I metabolism of MK-0773 was simulated using human liver microsomal (HLM) preparations and electrochemical conversion. Subsequently, major metabolic products were identified and characterized employing liquid chromatography-high-resolution/high- accuracy tandem mass spectrometry with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) as well as nuclear magnetic resonance (NMR) spectroscopy. MK-0773 produced numerous phase-I metabolites under the chosen in vitro incubation reactions, mostly resulting from mono- and bisoxygenation of the steroid. HLM yielded at least 10 monooxygenated species, while electrochemistry-based experiments resulted predominantly in three monohydroxylated metabolites. Elemental composition data and product ion mass spectra were generated for these analytes, ESI/APCI measurements corroborated the formation of at least two N-oxygenated metabolites, and NMR data obtained from electrochemistry-derived products supported structures suggested for three monohydroxylated compounds. Hereby, the hydroxylation of the A-ring located N- bound methyl group was found to be of particular intensity. In the absence of controlled elimination studies, the

  14. Framing Analysis In Media Television News MetroTVOne Related Arrest by the Chairman MK Akil Mocktar Commission Case of Corruption

    Directory of Open Access Journals (Sweden)

    Aryadi Aryadi

    2014-07-01

    Full Text Available Aryadi, G331.10.0018.Framing  Analysis In Media Television News Metro TVOne Related Arrest by   the   Chairman   MK  Akil   Mocktar   Commission   Case   of  Corruption   Skripsi   :  Program   S1   of Communication University of Semarang. This research aims to understand how the framing of television-related  news in the arrest of the chairman of the Constitutional Court AkilMocktar by the Commission on cases of corruption. Impressions is catching  news MK chairman  AkilMocktar  on Metro TV and TVOne. Theoretical  foundation,  framing analysis model of Murray Edelman, the theory is used to understand the reality of diverse and irregular into a reality that has meaning, using the categorization, the use of a particular perspective with certain words is also a word that signifies how the facts or reality understood. Qualitative research methods and strategies for framing the analysis, the study was conducted by observing the video sempel news on Metro TV and TVOne selected. Based on the research results, the general conclusion of each media that Metro TV and TVOne has a different way of constructing a bribery case Mocktar chairman MK Akil is in its message. Metro TV tend to highlight cases of bribery Court of facts, Metro TV does not describe the alleged emerging society. While TVOne looks construct audiences with growing allegations in the news

  15. GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

    Science.gov (United States)

    Zhou, Dongsheng; Lv, Dan; Wang, Zhen; Zhang, Yanhua; Chen, Zhongming; Wang, Chuang

    2018-01-01

    Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. PMID:29695955

  16. MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

    Science.gov (United States)

    Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated

  17. Surface modification with MK-2 organic dye in a ZnO/P3HT hybrid solar cell: Impact on device performance

    Directory of Open Access Journals (Sweden)

    Yu Jin Kim

    2014-07-01

    Full Text Available The photovoltaic performance of a hybrid ZnO/P3HT heterojunction was improved by modifying the device surface with the MK-2 dye. This organic dye enhanced the compatibility between the polymer and the metal oxide, increased the exciton separation efficiency, and improved the molecular ordering in the charge transport network. The resulting device displayed a substantial enhancement in the photocurrent, open circuit voltage, and fill factor, leading to a 12-fold increase in the power conversion efficiency relative to the unmodified device, from 0.13% to 1.53%.

  18. Adiabatic Demagnetization Refrigerator Field Mapping and Shielding Models for a 70 mK Superconducting Transition Edge Sensor Array and Associated Electronics

    Science.gov (United States)

    Ladner, D. R.; Martinez-Galarce, D. S.; McCammon, D.

    2006-04-01

    An X-ray detection instrument to be flown on a sounding rocket experiment (the Advanced Technology Solar Spectroscopic Imager - ATSSI) for solar physics observations is being developed by the Lockheed Martin Solar and Astrophysics Laboratory (LMSAL). The detector is a novel class of microcalorimeter, a superconducting Transition-Edge Sensor (TES), that coupled with associated SQUID and feedback electronics requires high temperature stability at ~70 mK to resolve the energy of absorbed X-ray photons emitted from the solar corona. The cooling system incorporates an existing Adiabatic Demagnetization Refrigerator (ADR) developed at the University of Wisconsin (UW), which was previously flown to study the diffuse cosmic X-ray background. The Si thermistor detectors for that project required 130 K shielded JFET electronic components that are much less sensitive to the external field of the ADR solenoid than are the 1st (~70 mK) and 2nd (~2 K) SQUID stages used with TESs for solar observations. Modification of the Wisconsin ADR design, including TES focal plane and electronics re-positioning, therefore requires a tradeoff between the existing ADR solenoid nulling coil geometry and a low mass passive solenoid shield, while preserving the vibration isolation features of the existing design. We have developed models to accurately compute the magnetic field with and without shielding or nulling coils at critical locations to guide the re-design of the detector subsystem. The models and their application are described.

  19. EFECTO DE LA ADMINISTRACIÓN INTRACEREBRAL DE MK-801 Y (- NICOTINA EN LAS CONCENTRACIONES EXTRACELULARES DE GLU Y GABA EN EL NÚCLEO PEDUNCULOPONTINO DE RATAS.

    Directory of Open Access Journals (Sweden)

    Lisette Blanco

    2011-01-01

    Full Text Available Aunque la manipulación farmacológica de los sistemas glutamatérgico y colinérgico se ha tratado en modelos experimentales de enfermedad de Parkinson (EP, pocos autores han realizado estudios de esta temática a nivel del núcleo pedunculopontino (NPP. El presente trabajo aborda los cambios en las concentraciones extracelulares (CE de glutamato (Glu y ácido δ-amino butírico (GABA en el NPP de ratas hemiparkinsonizadas por inyección de 6-hidroxidopamina (6-OHDA y sometidas a la infusión local de MK-801 (10 mol/L o (- nicotina (10mM. La infusión se realizó mediante microdiálisis cerebral y la determinación de las CE de los neurotransmisores se realizó a través de cromatografía líquida de alta resolución acoplada a detección de fluorescencia. La infusión de MK-801 en el NPP produjo una disminución significativa de las CE de Glu (p

  20. Development of a standard database for FBR core nuclear design (XI). Analysis of the Experimental Fast Reactor 'JOYO' MK-I start-up test and operation data

    International Nuclear Information System (INIS)

    Yokoyama, Kenji; Numata, Kazuyuki

    2000-03-01

    As a recent research, Japan Nuclear Cycle Development Institute (JNC) develops a database of integral data in addition to the JUPITER experiments, aiming at further improvement for accuracy and reliability. In this report, the authors describe the evaluation of the C/E values and the sensitivity analysis for the Experimental Fast Reactor 'JOYO' MK-I core. The minimal criticality, sodium void reactivity worth, fuel assembly worth and burn-up coefficient were analyzed. The results of both the minimal criticality and the fuel assembly worth, which were calculated by the standard analytical method for JUPITER experiments, agreed well with the measured values. On the other hand, the results of the sodium void reactivity worth have a tendency to overestimate. As for the burn-up coefficient, it was seen that the C/E values had a dispersion among the operation cycles. The authors judged that further investigation for the estimation of the experimental error will increase the applicability of the integral data to the adjusted library. Furthermore, sensitivity analyses for the minimal criticality, sodium void reactivity worth and fuel assembly worth showed the characteristics of 'JOYO' MK-I core in comparison with ZPPR-9 core of JUPITER experiments. (J.P.N.)

  1. Expression of Each Cistron in the gal Operon Can Be Regulated by Transcription Termination and Generation of a galK-Specific mRNA, mK2

    Science.gov (United States)

    Wang, Xun; Ji, Sang Chun; Yun, Sang Hoon; Jeon, Heung Jin; Kim, Si Wouk

    2014-01-01

    The gal operon of Escherichia coli has 4 cistrons, galE, galT, galK, and galM. In our previous report (H. J. Lee, H. J. Jeon, S. C. Ji, S. H. Yun, H. M. Lim, J. Mol. Biol. 378:318–327, 2008), we identified 6 different mRNA species, mE1, mE2, mT1, mK1, mK2, and mM1, in the gal operon and mapped these mRNAs. The mRNA map suggests a gradient of gene expression known as natural polarity. In this study, we investigated how the mRNAs are generated to understand the cause of natural polarity. Results indicated that mE1, mT1, mK1, and mM1, whose 3′ ends are located at the end of each cistron, are generated by transcription termination. Since each transcription termination is operating with a certain frequency and those 4 mRNAs have 5′ ends at the transcription initiation site(s), these transcription terminations are the basic cause of natural polarity. Transcription terminations at galE-galT and galT-galK junctions, making mE1 and mT1, are Rho dependent. However, the terminations to make mK1 and mM1 are partially Rho dependent. The 5′ ends of mK2 are generated by an endonucleolytic cleavage of a pre-mK2 by RNase P, and the 3′ ends are generated by Rho termination 260 nucleotides before the end of the operon. The 5′ portion of pre-mK2 is likely to become mE2. These results also suggested that galK expression could be regulated through mK2 production independent from natural polarity. PMID:24794565

  2. GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses MK-801-induced impairment in prepulse inhibition and working memory in Y-maze test in mice

    Science.gov (United States)

    Suryavanshi, P S; Ugale, R R; Yilmazer-Hanke, D; Stairs, D J; Dravid, S M

    2014-01-01

    Background and Purpose Despite ample evidence supporting the N-methyl-d-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, progress in the development of effective therapeutics based on this hypothesis has been limited. Facilitation of NMDA receptor function by co-agonists (d-serine or glycine) only partially alleviates the symptoms in schizophrenia; other means to facilitate NMDA receptors are required. NMDA receptor sub-types differ in their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting different physiological, biochemical and pharmacological properties. CIQ is a positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA receptors (Mullasseril et al.). Experimental Approach The effect of systemic administration of CIQ was tested on impairment in prepulse inhibition (PPI), hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment in working memory in Y-maze spontaneous alternation test. Key Results We found that systemic administration of CIQ (20 mg·kg−1, i.p.) in mice reversed MK-801 (0.15 mg·kg−1, i.p.)-induced, but not methamphetamine (3 mg·kg−1, i.p.)-induced, deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- and methamphetamine-induced hyperlocomotion and stereotyped behaviours. Additionally, CIQ reversed the MK-801-induced working memory deficit in spontaneous alternation in a Y-maze. Conclusion and Implications Together, these results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve as an important therapeutic strategy for treating positive and cognitive symptoms in schizophrenia. PMID:24236947

  3. A 350 mK, 9 T scanning tunneling microscope for the study of superconducting thin films on insulating substrates and single crystals.

    Science.gov (United States)

    Kamlapure, Anand; Saraswat, Garima; Ganguli, Somesh Chandra; Bagwe, Vivas; Raychaudhuri, Pratap; Pai, Subash P

    2013-12-01

    We report the construction and performance of a low temperature, high field scanning tunneling microscope (STM) operating down to 350 mK and in magnetic fields up to 9 T, with thin film deposition and in situ single crystal cleaving capabilities. The main focus lies on the simple design of STM head and a sample holder design that allows us to get spectroscopic data on superconducting thin films grown in situ on insulating substrates. Other design details on sample transport, sample preparation chamber, and vibration isolation schemes are also described. We demonstrate the capability of our instrument through the atomic resolution imaging and spectroscopy on NbSe2 single crystal and spectroscopic maps obtained on homogeneously disordered NbN thin film.

  4. Observing electron spin resonance between 0.1 and 67 GHz at temperatures between 50 mK and 300 K using broadband metallic coplanar waveguides

    Science.gov (United States)

    Wiemann, Yvonne; Simmendinger, Julian; Clauss, Conrad; Bogani, Lapo; Bothner, Daniel; Koelle, Dieter; Kleiner, Reinhold; Dressel, Martin; Scheffler, Marc

    2015-05-01

    We describe a fully broadband approach for electron spin resonance (ESR) experiments, where it is possible to tune not only the magnetic field but also the frequency continuously over wide ranges. Here, a metallic coplanar transmission line acts as compact and versatile microwave probe that can easily be implemented in different cryogenic setups. We perform ESR measurements at frequencies between 0.1 and 67 GHz and at temperatures between 50 mK and room temperature. Three different types of samples (Cr3+ ions in ruby, organic radicals of the nitronyl-nitroxide family, and the doped semiconductor Si:P) represent different possible fields of application for the technique. We demonstrate that an extremely large phase space in temperature, magnetic field, and frequency for ESR measurements, substantially exceeding the range of conventional ESR setups, is accessible with metallic coplanar lines.

  5. Economic, energy and GHG emissions performance evaluation of a WhisperGen Mk IV Stirling engine μ-CHP unit in a domestic dwelling

    International Nuclear Information System (INIS)

    Conroy, G.; Duffy, A.; Ayompe, L.M.

    2014-01-01

    Highlights: • The performance of a Stirling engine MK IV micro-CHP unit was evaluated in a domestic dwelling in Ireland. • The performance of the micro-CHP was compare to that of a condensing gas boiler. • The micro-CHP unit resulted in an annual cost saving of €180 compared to the condensing gas boiler. • Electricity imported from the grid decreased by 20.8% while CO 2 emissions decreased by 16.1%. • The micro-CHP unit used 2889 kW h of gas more than the condensing gas boiler during one year of operation. - Abstract: This paper presents an assessment of the energy, economic and greenhouse gas emissions performances of a WhisperGen Mk IV Stirling engine μ-CHP unit for use in a conventional house in the Republic of Ireland. The energy performance data used in this study was obtained from a field trial carried out in Belfast, Northern Ireland during the period June 2004–July 2005 by Northern Ireland Electricity and Phoenix Gas working in collaboration with Whispertech UK. A comparative performance analysis between the μ-CHP unit and a condensing gas boiler revealed that the μ-CHP unit resulted in an annual cost saving of €180 with an incremental simple payback period of 13.8 years when compared to a condensing gas boiler. Electricity imported from the grid decreased by 20.8% while CO 2 emissions decreased by 16.1%. The μ-CHP unit used 2889 kW h of gas more than the condensing gas boiler

  6. Fabrication and testing of a 4-node micro-pocket fission detector array for the Kansas State University TRIGA Mk. II research nuclear reactor

    Science.gov (United States)

    Reichenberger, Michael A.; Nichols, Daniel M.; Stevenson, Sarah R.; Swope, Tanner M.; Hilger, Caden W.; Unruh, Troy C.; McGregor, Douglas S.; Roberts, Jeremy A.

    2017-08-01

    Advancements in nuclear reactor core modeling and computational capability have encouraged further development of in-core neutron sensors. Micro-Pocket Fission Detectors (MPFDs) have been fabricated and tested previously, but successful testing of these prior detectors was limited to single-node operation with specialized designs. Described in this work is a modular, four-node MPFD array fabricated and tested at Kansas State University (KSU). The four sensor nodes were equally spaced to span the length of the fuel-region of the KSU TRIGA Mk. II research nuclear reactor core. The encapsulated array was filled with argon gas, serving as an ionization medium in the small cavities of the MPFDs. The unified design improved device ruggedness and simplified construction over previous designs. A 0.315-in. (8-mm) penetration in the upper grid plate of the KSU TRIGA Mk. II research nuclear reactor was used to deploy the array between fuel elements in the core. The MPFD array was coupled to an electronic support system which has been developed to support pulse-mode operation. Neutron-induced pulses were observed on all four sensor channels. Stable device operation was confirmed by testing under steady-state reactor conditions. Each of the four sensors in the array responded to changes in reactor power between 10 kWth and full power (750 kWth). Reactor power transients were observed in real-time including positive transients with periods of 5, 15, and 30 s. Finally, manual reactor power oscillations were observed in real-time.

  7. 3D-QSAR and molecular docking studies on derivatives of MK-0457, GSK1070916 and SNS-314 as inhibitors against Aurora B kinase.

    Science.gov (United States)

    Zhang, Baidong; Li, Yan; Zhang, Huixiao; Ai, Chunzhi

    2010-11-02

    Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q(2) = 0.605, r(2) (pred) = 0.826), (q(2) = 0.52, r(2) (pred) = 0.798) and (q(2) = 0.582, r(2) (pred) = 0.971) for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond donating capacity showed a great impact on the inhibitory activity for the derivatives of GSK1070916. Additionally, the predictive model of the SNS-314 class revealed the great importance of hydrophobic favorable contour, since hydrophobic favorable substituents added to this region bind to a deep and narrow hydrophobic pocket composed of residues that are hydrophobic in nature and thus enhanced the inhibitory activity. Moreover, based on the docking study, a further comparison of the binding modes was accomplished to identify a set of critical residues that play a key role in stabilizing the drug-target interactions. Overall, the high level of consistency between the 3D contour maps and the topographical features of binding sites led to our identification of several key structural requirements for more potency inhibitors. Taken together, the results will serve as a basis for future drug development of inhibitors against Aurora B kinase for various tumors.

  8. 3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors against Aurora B Kinase

    Directory of Open Access Journals (Sweden)

    Chunzhi Ai

    2010-11-01

    Full Text Available Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA, comparative molecular similarity indices analysis (CoMSIA, homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q2 = 0.605, r2pred = 0.826, (q2 = 0.52, r2pred = 0.798 and (q2 = 0.582, r2pred = 0.971 for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond donating capacity showed a great impact on the inhibitory activity for the derivatives of GSK1070916. Additionally, the predictive model of the SNS-314 class revealed the great importance of hydrophobic favorable contour, since hydrophobic favorable substituents added to this region bind to a deep and narrow hydrophobic pocket composed of residues that are hydrophobic in nature and thus enhanced the inhibitory activity. Moreover, based on the docking study, a further comparison of the binding modes was accomplished to identify a set of critical residues that play a key role in stabilizing the drug-target interactions. Overall, the high level of consistency between the 3D contour maps and the topographical features of binding sites led to our identification of several key structural requirements for more potency inhibitors. Taken together, the results will serve as a basis for future drug development of inhibitors against Aurora B kinase for various tumors.

  9. "Jairus, His Daughter, and the Haemorrhaging Woman (Mk. 5:21-43; Mt. 9:18-26; Lk. 8:40-56): Research Survey of a Gospel Story about People in Distress."

    NARCIS (Netherlands)

    Zwiep, A.W.

    2015-01-01

    This article examines the history of interpretation of the pericope of the healing of the haemorrhaging woman and the raising of Jairus’ daughter (Mk 5.21-43; Mt. 9.18-26; Lk. 8.40-56). It starts with the earliest attempts to harmonize the synoptic accounts, and reviews medieval allegorical

  10. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY)

    DEFF Research Database (Denmark)

    Sulkowski, Mark; Hezode, Christophe; Gerstoft, Jan

    2015-01-01

    BACKGROUND: Both hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected patients are in need of safe, effective, all-oral HCV regimens. In a phase 2 study we aimed to assess the efficacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK-8742......; HCV NS5A inhibitor) in patients with HCV mono-infection and HIV/HCV co-infection. METHODS: The C-WORTHY study is a phase 2, multicentre, randomised controlled trial of grazoprevir plus elbasvir with or without ribavirin in patients with HCV; here, we report findings for previously untreated (genotype......%) and was associated with emergence of resistance-associated variants to one or both drugs. The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients. No patient discontinued due to an adverse event or laboratory abnormality. The most common adverse...

  11. Design and performance of an ultra-high vacuum spin-polarized scanning tunneling microscope operating at 30 mK and in a vector magnetic field.

    Science.gov (United States)

    von Allwörden, Henning; Eich, Andreas; Knol, Elze J; Hermenau, Jan; Sonntag, Andreas; Gerritsen, Jan W; Wegner, Daniel; Khajetoorians, Alexander A

    2018-03-01

    We describe the design and performance of a scanning tunneling microscope (STM) that operates at a base temperature of 30 mK in a vector magnetic field. The cryogenics is based on an ultra-high vacuum (UHV) top-loading wet dilution refrigerator that contains a vector magnet allowing for fields up to 9 T perpendicular and 4 T parallel to the sample. The STM is placed in a multi-chamber UHV system, which allows in situ preparation and exchange of samples and tips. The entire system rests on a 150-ton concrete block suspended by pneumatic isolators, which is housed in an acoustically isolated and electromagnetically shielded laboratory optimized for extremely low noise scanning probe measurements. We demonstrate the overall performance by illustrating atomic resolution and quasiparticle interference imaging and detail the vibrational noise of both the laboratory and microscope. We also determine the electron temperature via measurement of the superconducting gap of Re(0001) and illustrate magnetic field-dependent measurements of the spin excitations of individual Fe atoms on Pt(111). Finally, we demonstrate spin resolution by imaging the magnetic structure of the Fe double layer on W(110).

  12. An ultrahigh-vacuum cryostat for simultaneous scanning tunneling microscopy and magneto-transport measurements down to 400 mK.

    Science.gov (United States)

    Liebmann, Marcus; Bindel, Jan Raphael; Pezzotta, Mike; Becker, Stefan; Muckel, Florian; Johnsen, Tjorven; Saunus, Christian; Ast, Christian R; Morgenstern, Markus

    2017-12-01

    We present the design and calibration measurements of a scanning tunneling microscope setup in a 3 He ultrahigh-vacuum cryostat operating at 400 mK with a hold time of 10 days. With 2.70 m in height and 4.70 m free space needed for assembly, the cryostat fits in a one-story lab building. The microscope features optical access, an xy table, in situ tip and sample exchange, and enough contacts to facilitate atomic force microscopy in tuning fork operation and simultaneous magneto-transport measurements on the sample. Hence, it enables scanning tunneling spectroscopy on microstructured samples which are tuned into preselected transport regimes. A superconducting magnet provides a perpendicular field of up to 14 T. The vertical noise of the scanning tunneling microscope amounts to 1 pm rms within a 700 Hz bandwidth. Tunneling spectroscopy using one superconducting electrode revealed an energy resolution of 120 μeV. Data on tip-sample Josephson contacts yield an even smaller feature size of 60 μeV, implying that the system operates close to the physical noise limit.

  13. Design and performance of an ultra-high vacuum spin-polarized scanning tunneling microscope operating at 30 mK and in a vector magnetic field

    Science.gov (United States)

    von Allwörden, Henning; Eich, Andreas; Knol, Elze J.; Hermenau, Jan; Sonntag, Andreas; Gerritsen, Jan W.; Wegner, Daniel; Khajetoorians, Alexander A.

    2018-03-01

    We describe the design and performance of a scanning tunneling microscope (STM) that operates at a base temperature of 30 mK in a vector magnetic field. The cryogenics is based on an ultra-high vacuum (UHV) top-loading wet dilution refrigerator that contains a vector magnet allowing for fields up to 9 T perpendicular and 4 T parallel to the sample. The STM is placed in a multi-chamber UHV system, which allows in situ preparation and exchange of samples and tips. The entire system rests on a 150-ton concrete block suspended by pneumatic isolators, which is housed in an acoustically isolated and electromagnetically shielded laboratory optimized for extremely low noise scanning probe measurements. We demonstrate the overall performance by illustrating atomic resolution and quasiparticle interference imaging and detail the vibrational noise of both the laboratory and microscope. We also determine the electron temperature via measurement of the superconducting gap of Re(0001) and illustrate magnetic field-dependent measurements of the spin excitations of individual Fe atoms on Pt(111). Finally, we demonstrate spin resolution by imaging the magnetic structure of the Fe double layer on W(110).

  14. Quasi-simultaneous observations of the BL Lac object MK 501 in X-ray, UV, visible, IR and radio frequencies

    Science.gov (United States)

    Kondo, D. M.; Worrall, D. M.; Mushotzky, R. F.; Hackney, R. L.; Hackney, K. H.; Oke, J. B.; Yee, H.; Neugebauer, G.; Matthews, K.; Feldman, P. A.

    1980-01-01

    Quasi-simultaneous observations of the BL Lacertae (Lac) objects MK 501 were performed for the first time at X-ray, ultraviolet, visible, infrared, and radio frequencies. The observed spectral slope from the X-ray to UV regions is positive and continuous, but that from the mid UV to visible light region becomes gradually flat and possibly turns down toward lower frequencies; the optical radio emission can not be accounted for by a single power law. Several theoretical models were considered for the emission mechanism. A quantitative comparison was performed with the synchrotron-self-Compton model; the total spectrum is found consistent with this model. The spectrum from visible light to X-ray is consistent with synchrotron radiation or with inverse-Compton scattering by a hot thermal cloud of electrons. The continuity of the spectral slope from X-ray to UV implied by the current data suggests that the previous estimates of the total luminosity of this BL Lac object is underestimated by a factor of about three or four.

  15. Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

    Science.gov (United States)

    Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

    2010-06-01

    Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

  16. Application of NEA/CSNI standard problem 3 (blowdown and flow reversal in the IETA-1 rig) to the validation of the RELAP-UK Mk IV code

    International Nuclear Information System (INIS)

    Bryce, W.M.

    1977-10-01

    NEA/CSNI Standard Problem 3 consists of the modelling of an experiment on the IETI-1 rig, in which there is initially flow upwards through a feeder, heated section and riser. The inlet and outlet are then closed and a breach opened at the bottom so that the flow reverses and the rig depressurises. Calculations of this problem by many countries using several computer codes have been reported and show a wide spread of results. The purpose of the study reported here was the following. First, to show the sensitivity of the calculation of Standard Problem 3. Second, to perform an ab initio best estimate calculation using the RELAP-UK Mark IV code with the standard recommended options, and third, to use the results of the sensitivity study to show where tuning of the RELAP-UK Mark IV recommended model options was required. This study has shown that the calculation of Standard Problem 3 is sensitive to model assumptions and that the use of the loss-of-coolant accident code RELAP-UK Mk IV with the standard recommended model options predicts the experimental results very well over most of the transient. (U.K.)

  17. MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

    Science.gov (United States)

    Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2017-11-01

    Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1MK-801, attenuated these effects of high-dose DM, whereas an opioid antagonist, naloxone, did not affect DM-induced neurotoxicity. Moreover, pretreatment with a highly specific GluN2B subunit inhibitor, traxoprodil, was selectively effective in preventing DM-induced c-Fos expression and apoptotic changes. These results suggest that high-dose DM produces convulsive behaviors by activating GluN2B/NMDA signaling that leads to pro-apoptotic changes. Copyright © 2017. Published by Elsevier Inc.

  18. Development of a standard data base for FBR core nuclear design. 10. Reevaluation of atomic number density of JOYO Mk-II core

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazuyuki; Sato, Wakaei [Japan Nuclear Cycle Development Inst., Oarai, Ibaraki (Japan). Oarai Engineering Center; Ishikawa, Makoto; Arii, Yoshio [Nuclear Energy System Incorporation, Tokyo (Japan)

    1999-07-01

    The material composition of JOYO Mk-II core components in its initial core was reevaluated as a part of the effort for developing a standard data base for FBR core nuclear design. The special feature of the reevaluation is to treat the decay of Pu-241 isotope, so that the atomic number densities of Pu-241 and Am-241 in fuel assemblies can be exactly evaluated on the initial critical date, Nov. 22nd, 1982. Further, the atomic number densities of other core components were also evaluated to improve the analytical accuracy. Those include the control rods which were not so strictly evaluated in the past, and the dummy fuels and the neutron sources which were not treated in the analytical model so far. The results of the present reevaluation were as follows: (1) The changes of atomic number densities of the major nuclides such as Pu-239, U-235 and U-238 were about {+-}0.2 to 0.3%. On the other hand, the number density of Pu-241, which was the motivation of the present work, was reduced by 12%. From the fact, the number densities in the past analysis might be based on the isotope measurement of the manufacturing point of time without considering the decay of Pu-241. (2) As the other core components, the number densities of control rods and outer reflector-type A were largely improved. (author)

  19. An ultrahigh-vacuum cryostat for simultaneous scanning tunneling microscopy and magneto-transport measurements down to 400 mK

    Science.gov (United States)

    Liebmann, Marcus; Bindel, Jan Raphael; Pezzotta, Mike; Becker, Stefan; Muckel, Florian; Johnsen, Tjorven; Saunus, Christian; Ast, Christian R.; Morgenstern, Markus

    2017-12-01

    We present the design and calibration measurements of a scanning tunneling microscope setup in a 3He ultrahigh-vacuum cryostat operating at 400 mK with a hold time of 10 days. With 2.70 m in height and 4.70 m free space needed for assembly, the cryostat fits in a one-story lab building. The microscope features optical access, an xy table, in situ tip and sample exchange, and enough contacts to facilitate atomic force microscopy in tuning fork operation and simultaneous magneto-transport measurements on the sample. Hence, it enables scanning tunneling spectroscopy on microstructured samples which are tuned into preselected transport regimes. A superconducting magnet provides a perpendicular field of up to 14 T. The vertical noise of the scanning tunneling microscope amounts to 1 pmrms within a 700 Hz bandwidth. Tunneling spectroscopy using one superconducting electrode revealed an energy resolution of 120 μeV. Data on tip-sample Josephson contacts yield an even smaller feature size of 60 μeV, implying that the system operates close to the physical noise limit.

  20. Environmental hardening of a mobile-manipulator system for nuclear environments

    International Nuclear Information System (INIS)

    Jones, S.L.; Cable, T.; Tulenko, J.S.; Toshkov, S.; Sias, F.R. Jr.

    1993-01-01

    This research report discusses the radiation hardening of a commercially available mobile robot, the REMOTEC ANDROS. This hardening effort is culminating in the availability of a megarad hardened mobile platform to access areas in nuclear facilities with extremely high levels of radiation (0.1 to 1 Mrad). These radiation levels may be encountered both during routine repair and monitoring activities and accident situations. The project has completed a phase-I U.S. Department of Energy Small Business Innovative Research contract and is now in a phase-II effort with completion scheduled in early 1995. The research involves the evaluation of the material and electrical components of an ANDROS robot to determine the anticipated radiation hardness of the current production version and evaluation of the components that must be replaced or modified to harden the system to higher radiation levels. The work being reported is based on an evaluation of the complete list of all electronic, electrical, and mechanical parts used in the robot and includes initial experimental radiation evaluations performed at the University of Florida

  1. Effect of 3-bromopyruvate and atovaquone on infection during in vitro interaction of Toxoplasma gondii and LLC-MK2 cells.

    Science.gov (United States)

    de Lima, Loyze Paola O; Seabra, Sergio H; Carneiro, Henrique; Barbosa, Helene S

    2015-09-01

    Toxoplasma gondii infection can be severe during pregnancy and in immunocompromised patients. Current therapies for toxoplasmosis are restricted to tachyzoites and have little or no effect on bradyzoites, which are maintained in tissue cysts. Consequently, new therapeutic alternatives have been proposed as the use of atovaquone has demonstrated partial efficacy against tachyzoites and bradyzoites. This work studies the effect of 3-bromopyruvate (3-BrPA), a compound that is being tested against cancer cells, on the infection of LLC-MK2 cells with T. gondii tachyzoites, RH strain. No effect of 3-BrPA on host cell proliferation or viability was observed, but it inhibited the proliferation of T. gondii. The incubation of cultures with lectin Dolichos biflorus agglutinin (DBA) showed the development of cystogenesis, and an ultrastructural analysis of parasite intracellular development confirmed morphological characteristics commonly found in tissue cysts. Moreover, the presence of degraded parasites and the influence of 3-BrPA on endodyogeny were observed. Infected cultures were alternatively treated with a combination of this compound plus atovaquone. This resulted in a 73% reduction in intracellular parasites after 24 h of treatment and a 71% reduction after 48 h; cyst wall formation did not occur in these cultures. Therefore, we conclude that the use of 3-BrPA may serve as an important tool for the study of (i) in vitro cystogenesis; (ii) parasite metabolism, requiring a deeper understanding of the target of action of this compound on T. gondii; (iii) the alternative parasite metabolic pathways; and (iv) the molecular/cellular mechanisms that trigger parasite death. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. ANALISIS MAQÂṢID ASY-SYARÎ’AH TERHADAP PUTUSAN MK NOMOR 46/PUU-VIII/2010 DAN IMPLIKASINYA TERHADAP HUKUM KELUARGA ISLAM DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Muhammad Ubayyu Rikza

    2017-12-01

    Full Text Available The Constitutional Court made a revolutionary decision through the decision of Constitutional Court Number 46/PUU-VIII/2010 about the status of children outside of marriage. The decision stated that childrens born outside of marriage not only had a civil relationship with their mother and mother's family but also had a civil relationship with their biological father. Its implicates that children outside of marriage have the same rights with legal children, such as  earning a living, inheritance and equality before the law. Seen from the concept of maqâṣid asy-syarî'ah, the decision does not violate the Islamic law, otherwhise it is in the line with the principles of maqâṣid asy-syarî'ah especially the principles of ḥifẓ an-nasl and ḥifẓ an-nafs.   [Mahkamah Konstitusi telah membuat putusan revolusioner dalam putusan MK Nomor 46/PUU-VIII/2010 tentang status anak di luar perkawinan. Putusan tersebut menyatakan bahwa anak yang dilahirkan di luar perkawinan mempunyai hubungan perdata dengan ibu dan keluarga ibunya dan mempunyai hubungan perdata dengan ayah biologisnya yang dibuktikan berdasarkan ilmu pengetahuan dan teknologi. Implikasinya adalah anak di luar perkawinan mendapat hak sama dengan anak sah, mendapatkan nafkah, waris dan persamaan di hadapan hukum. Dilihat dari konsep maqâṣid asy-syarî’ah, putusan tersebut tidak melanggar hukum Islam, sebaliknya, ia sejalan dengan prinsip-prinsip maqâṣid asy-syarî’ah terutama prinsip ḥifẓ an-nasl dan ḥifẓ an-nafs.

  3. Dizocilpine (MK-801) impairs learning in the active place avoidance task but has no effect on the performance during task/context alternation.

    Science.gov (United States)

    Vojtechova, Iveta; Petrasek, Tomas; Hatalova, Hana; Pistikova, Adela; Vales, Karel; Stuchlik, Ales

    2016-05-15

    The prevention of engram interference, pattern separation, flexibility, cognitive coordination and spatial navigation are usually studied separately at the behavioral level. Impairment in executive functions is often observed in patients suffering from schizophrenia. We have designed a protocol for assessing these functions all together as behavioral separation. This protocol is based on alternated or sequential training in two tasks testing different hippocampal functions (the Morris water maze and active place avoidance), and alternated or sequential training in two similar environments of the active place avoidance task. In Experiment 1, we tested, in adult rats, whether the performance in two different spatial tasks was affected by their order in sequential learning, or by their day-to-day alternation. In Experiment 2, rats learned to solve the active place avoidance task in two environments either alternately or sequentially. We found that rats are able to acquire both tasks and to discriminate both similar contexts without obvious problems regardless of the order or the alternation. We used two groups of rats, controls and a rat model of psychosis induced by a subchronic intraperitoneal application of 0.08mg/kg of dizocilpine (MK-801), a non-competitive antagonist of NMDA receptors. Dizocilpine had no selective effect on parallel/sequential learning of tasks/contexts. However, it caused hyperlocomotion and a significant deficit in learning in the active place avoidance task regardless of the task alternation. Cognitive coordination tested by this task is probably more sensitive to dizocilpine than spatial orientation because no hyperactivity or learning impairment was observed in the Morris water maze. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Kuulujuttude juhtimine firmas - kas nali või reaalsus? / Andro Kullerkupp

    Index Scriptorium Estoniae

    Kullerkupp, Andro

    2006-01-01

    Ülevaade uurimusest, mis käsitleb kuulujuttude tekkimist ja levikut ning nende positiivset mõju ja levitamist firma huvides. Diagramm: Kuulujuttude tekkepõhjused. Skeem: Kuulujutu teekond. Lisad: Katkine telefon; Mõned näited elust enesest

  5. IMPACT STUDY: MK-0646 (DALOTUZUMAB, INSULIN GROWTH FACTOR 1 RECEPTOR (IGF-1R ANTIBODY COMBINED WITH PEMETREXED AND CISPLATIN IN STAGE IV METASTATIC NON-SQUAMOUS LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Chao H Huang

    2016-01-01

    Full Text Available Background: Insulin-like growth factor 1 receptor (IGF-1R regulates cell growth, proliferation and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D is a humanized monoclonal antibody that targets IGF-1R. Pemetrexed (P has higher activity in non-squamous lung cancer (NSQL. We initiated a randomized phase II trial to test the combination of P and Cisplatin (C +/- D in NSQL.Methods: Eligibility criteria: untreated NSQL stage IIIB or IV, ECOG 0 or 1, measurable disease, adequate renal, hepatic and hematologic function, and no other intercurrent illness. P at 500mg/m2 and C at 75mg/m2 IV were given every 3 weeks. D was given at 10mg/kg IV weekly on days 1, 8 and 15 of every 3-week cycle in the experimental group. The patients had a radiographic assessment after every 2 cycles and were treated for a maximum of 6 cycles if there was a response or stable disease. The primary objective of the study was to compare the clinical response rates of PC vs PC+D. Results: From 1/2009 to 2/2011, the study accrued 26 subjects: 16 male and 10 female, with a median age of 59; 14 were treated with PC and 12 were treated with PC+D. We observed 2 partial responses (PR, 7 stable disease (SD, 3 progressive disease (PD, and 2 were not evaluable (NE in the PC arm. In comparison, for the PC+D arm there were: 3 PR, 4 SD, 4 PD and 1 NE. The hematologic toxicity was similar in both groups. There higher incidence of hyperglycemia the experimental group; 4 cases with grade 3 and 1 case with grade 4. Conclusion: PC+D had a similar response rate compared to PC, with a higher rate of hyperglycemia. Identification of responders using predictive markers would be key to continuing the study of D in NSQL.

  6. Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats.

    Science.gov (United States)

    Abekawa, Tomohiro; Ito, Koki; Nakagawa, Shin; Koyama, Tsukasa

    2007-06-01

    Neurodevelopmental deficits of parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)ergic interneurons in prefrontal cortex have been reported in schizophrenia. Glutamate influences the proliferation of this type of interneuron by an N-methyl-D-aspartate (NMDA)-receptor-mediated mechanism. The present study hypothesized that prenatal blockade of NMDA receptors would disrupt GABAergic neurodevelopment, resulting in differences in effects on behavioral responses to a noncompetitive NMDA antagonist, phencyclidine (PCP), and a dopamine releaser, methamphetamine (METH). GABAergic neurons were immunohistochemically stained with parvalbumin antibody. Psychostimulant-induced hyperlocomotion was measured using an infrared sensor. Prenatal exposure (E15-E18) to the NMDA receptor antagonist MK-801 reduced the density of parvalbumin-immunoreactive neurons in rat medial prefrontal cortex on postnatal day 63 (P63) and enhanced PCP-induced hyperlocomotion but not the acute effects of METH on P63 or the development of behavioral sensitization. Prenatal exposure to MK-801 reduced the number of parvalbumin-immunoreactive neurons even on postnatal day 35 (P35) and did not enhance PCP-induced hyperlocomotion, the acute effects of METH on P35, or the development of behavioral sensitization to METH. These findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring. GABAergic deficit is unrelated to the effects of METH. This GABAergic neurodevelopmental disruption and the enhanced PCP-induced hyperlocomotion in adult offspring prenatally exposed to MK-801 may prove useful as a new model of the neurodevelopmental process of pathogenesis of treatment-resistant schizophrenia via an NMDA-receptor-mediated hypoglutamatergic mechanism.

  7. Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74.

    Science.gov (United States)

    Miller, Philip S; Barwell, James; Poyner, David R; Wigglesworth, Mark J; Garland, Stephen L; Donnelly, Dan

    2010-01-01

    The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A and α1-adrenergic receptors.

    Science.gov (United States)

    Romón, Tamara; Planas, Anna M; Adell, Albert

    2014-02-01

    Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce positive and negative symptomatology as well as impairment of cognitive function that closely resemble those present in schizophrenia. In rats, these drugs induce a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an enhanced glutamatergic transmission in the medial prefrontal cortex, and damage to retrosplenial cortical neurons in adult rats, which was measured as the induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the present work, we have examined the existence of possible differences among different antipsychotic drugs in their capacity to block immunolabeling of Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA receptor antagonist, MK- 801. In addition, the effects of selective monoaminergic agents were also studied to delineate the particular receptors responsible for the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine, olanzapine, ziprasidone--and to a lesser extent haloperidol-reduced the formation of Hsp72/73 protein in the rat retrosplenial cortex after the administration of MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT2 (M100907) and α1- adrenoceptors (prazosin) as well as agonism at 5-HT1A receptors (BAY x 3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73. Each of these effects may contribute to antipsychotic action. The results suggest that the efficacy of atypical antipsychotic drugs in the clinic may result from a combined effect on 5-HT2, 5-HT1A and α1-adrenergic receptors added to the classical dopamine D2 receptor antagonism.

  9. Analysis of sensitivity to MK-801 treatment in a novel active allothetic place avoidance task and in the working memory version of the Morris water maze reveals differences between Long-Evans and Wistar rats

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Bubeníková-Valešová, V.; Klement, Daniel; Stuchlík, Aleš

    2006-01-01

    Roč. 55, č. 4 (2006), s. 383-388 ISSN 0168-0102 R&D Projects: GA MZd(CZ) NL7684; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GP309/03/P126; GA ČR(CZ) GA309/06/1231 Institutional research plan: CEZ:AV0Z50110509 Keywords : Wistar/Long-Evans rats * MK-801 * cognition Subject RIV: FH - Neurology Impact factor: 1.953, year: 2006

  10. Cloning of regions required for contact hemolysis and entry into LLC-MK2 cells from Shigella sonnei form I plasmid: virF is a positive regulator gene for these phenotypes.

    OpenAIRE

    Kato, J; Ito, K; Nakamura, A; Watanabe, H

    1989-01-01

    Two distinct regions required for both contact hemolysis and entry into LLC-MK2 cells were cloned into Escherichia coli from the Shigella sonnei form I plasmid, pSS120. The first region was cloned into an E. coli HB101 strain containing noninvasive Tn1 insertion mutants of the form I plasmid, and expression of ipa (invasion plasmid antigen) gene products was restored. The plasmid carrying the first region was then transformed into E. coli lacking the form I plasmid, and additional DNA fragmen...

  11. NMDA receptor antagonism by repetitive MK801 administration induces schizophrenia-like structural changes in the rat brain as revealed by voxel-based morphometry and diffusion tensor imaging.

    Science.gov (United States)

    Wu, H; Wang, X; Gao, Y; Lin, F; Song, T; Zou, Y; Xu, L; Lei, H

    2016-05-13

    Animal models of N-methyl-d-aspartate receptor (NMDAR) antagonism have been widely used for schizophrenia research. Less is known whether these models are associated with macroscopic brain structural changes that resemble those in clinical schizophrenia. Magnetic resonance imaging (MRI) was used to measure brain structural changes in rats subjected to repeated administration of MK801 in a regimen (daily dose of 0.2mg/kg for 14 consecutive days) known to be able to induce schizophrenia-like cognitive impairments. Voxel-based morphometry (VBM) revealed significant gray matter (GM) atrophy in the hippocampus, ventral striatum (vStr) and cortex. Diffusion tensor imaging (DTI) demonstrated microstructural impairments in the corpus callosum (cc). Histopathological results corroborated the MRI findings. Treatment-induced behavioral abnormalities were not measured such that correlation between the brain structural changes observed and schizophrenia-like behaviors could not be established. Chronic MK801 administration induces MRI-observable brain structural changes that are comparable to those observed in schizophrenia patients, supporting the notion that NMDAR hypofunction contributes to the pathology of schizophrenia. Imaging-derived brain structural changes in animal models of NMDAR antagonism may be useful measurements for studying the effects of treatments and interventions targeting schizophrenia. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Toxoplasma gondii: effects of 60 Co ionizing radiation in the viability and infectivity, detected in vitro in LLC-MK2 cells and in vivo in C57BL/6J mice

    International Nuclear Information System (INIS)

    Hiramoto, Roberto M.; Almeida, Beatriz S.V.; Cardoso, Roselaine P.A.; Andrade Junior, Heitor F.

    1997-01-01

    Toxoplasmosis, caused by Toxoplasma gondii, promotes devasting disease in fetus and AIDS patients. The longlife immunity of natural infection is inefficient in eliminate tissue infective cysts. Few immunization programs were tested, mostly with attenuated strains. Ionizing radiation were used with successful in vaccine production, without reproductive ability with a relatively normal physiology until reproduction. Here, we tested several schedules of 60 Co irradiation of tachzoites from RH strain of T. gondii, from peritoneal exudate or suspensions of LLC-MK2 infected cells, to optimize the viability and sterility of the irradiated agents. The tachzoites were exposed to 50, 100 and 200 Gy in a GammaCell 220 at 366 Gy/h. The viability was tested by motility, integrity and Trypan Blue dye exclusion. All irradiation schedules maintained a high (>90%) viability of the parasites. Dilutions were injected in C57Bl/6j mice with induction of specific antibodies, no clinical disease but uncertain sterility. Infection of LLC--MK2 cells showed that viable and reproductive parasites were often found in 50 Gy irradiated cells, rarely found in 100 Gy irradiated cells, rarely found in 100 Gy irradied cells, with no growth occuring with 200 Gy irradiated tachzoites. Our data show that 200 Gy 60 Co irradiation blocks the reproductive capacity without affecting the short term viability of tachzoites of T. gondii. (author). 11 refs., 1 fig

  13. Observing electron spin resonance between 0.1 and 67 GHz at temperatures between 50 mK and 300 K using broadband metallic coplanar waveguides

    International Nuclear Information System (INIS)

    Wiemann, Yvonne; Simmendinger, Julian; Clauss, Conrad; Bogani, Lapo; Dressel, Martin; Scheffler, Marc; Bothner, Daniel; Koelle, Dieter; Kleiner, Reinhold

    2015-01-01

    We describe a fully broadband approach for electron spin resonance (ESR) experiments, where it is possible to tune not only the magnetic field but also the frequency continuously over wide ranges. Here, a metallic coplanar transmission line acts as compact and versatile microwave probe that can easily be implemented in different cryogenic setups. We perform ESR measurements at frequencies between 0.1 and 67 GHz and at temperatures between 50 mK and room temperature. Three different types of samples (Cr 3+ ions in ruby, organic radicals of the nitronyl-nitroxide family, and the doped semiconductor Si:P) represent different possible fields of application for the technique. We demonstrate that an extremely large phase space in temperature, magnetic field, and frequency for ESR measurements, substantially exceeding the range of conventional ESR setups, is accessible with metallic coplanar lines

  14. Observing electron spin resonance between 0.1 and 67 GHz at temperatures between 50 mK and 300 K using broadband metallic coplanar waveguides

    Energy Technology Data Exchange (ETDEWEB)

    Wiemann, Yvonne; Simmendinger, Julian; Clauss, Conrad; Bogani, Lapo; Dressel, Martin; Scheffler, Marc [1. Physikalisches Institut, Universität Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart (Germany); Bothner, Daniel; Koelle, Dieter; Kleiner, Reinhold [Physikalisches Institut and Center for Collective Quantum Phenomena in LISA+, Universität Tübingen, Auf der Morgenstelle 14, 72076 Tübingen (Germany)

    2015-05-11

    We describe a fully broadband approach for electron spin resonance (ESR) experiments, where it is possible to tune not only the magnetic field but also the frequency continuously over wide ranges. Here, a metallic coplanar transmission line acts as compact and versatile microwave probe that can easily be implemented in different cryogenic setups. We perform ESR measurements at frequencies between 0.1 and 67 GHz and at temperatures between 50 mK and room temperature. Three different types of samples (Cr{sup 3+} ions in ruby, organic radicals of the nitronyl-nitroxide family, and the doped semiconductor Si:P) represent different possible fields of application for the technique. We demonstrate that an extremely large phase space in temperature, magnetic field, and frequency for ESR measurements, substantially exceeding the range of conventional ESR setups, is accessible with metallic coplanar lines.

  15. Guanidine-acylguanidine bioisosteric approach in the design of radioligands: synthesis of a tritium-labeled N(G)-propionylargininamide ([3H]-UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist.

    Science.gov (United States)

    Keller, Max; Pop, Nathalie; Hutzler, Christoph; Beck-Sickinger, Annette G; Bernhardt, Günther; Buschauer, Armin

    2008-12-25

    Synthesis and characterization of (R)-N(alpha)-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)-N(omega)-([2,3-(3)H]-propanoyl)argininamide ([(3)H]-UR-MK114), an easily accessible tritium-labeled NPY Y(1) receptor (Y(1)R) antagonist (K(B): 0.8 nM, calcium assay, HEL cells) derived from the (R)-argininamide BIBP 3226, is reported. The radioligand binds with high affinity (K(D), saturation: 1.2 nM, kinetic experiments: 1.1 nM, SK-N-MC cells) and selectivity for Y(1)R over Y(2), Y(4), and Y(5) receptors. The title compound is a useful pharmacological tool for the determination of Y(1)R ligand affinities, quantification of Y(1)R binding sites, and autoradiography.

  16. Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)–A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Jack D.; Li, Sarah W.; Brunskill, Andrew P.J.; Chen, Xia; Cox, Kathleen; Cumming, Jared N.; Forman, Mark; Gilbert, Eric J.; Hodgson, Robert A.; Hyde, Lynn A.; Jiang, Qin; Iserloh, Ulrich; Kazakevich, Irina; Kuvelkar, Reshma; Mei, Hong; Meredith, John; Misiaszek, Jeffrey; Orth, Peter; Rossiter, Lana M.; Slater, Meagan; Stone, Julie; Strickland, Corey O.; Voigt, Johannes H.; Wang, Ganfeng; Wang, Hongwu; Wu, Yusheng; Greenlee, William J.; Parker, Eric M.; Kennedy, Matthew E.; Stamford, Andrew W. (Merck)

    2016-12-08

    Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer’s disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans. In this annotation, we describe the discovery of 3, including design, validation, and selected SAR around the novel iminothiadiazinane dioxide core as well as aspects of its preclinical and Phase 1 clinical characterization.

  17. New experimental perspectives for soft x-ray absorption spectroscopies at ultra-low temperatures below 50 mK and in high magnetic fields up to 7 T

    International Nuclear Information System (INIS)

    Beeck, T.; Baev, I.; Gieschen, S.; Meyer, H.; Meyer, S.; Palutke, S.; Martins, M.; Feulner, P.; Uhlig, K.; Wurth, W.

    2016-01-01

    A new ultra-low temperature experiment including a superconducting vector magnet has been developed for soft x-ray absorption spectroscopy experiments at third generation synchrotron light sources. The sample is cooled below 50 mK by a cryogen free "3He-"4He dilution refrigerator. At the same time, magnetic fields of up to ±7 T in the horizontal direction and ±0.5 T in the vertical direction can be applied by a superconducting vector magnet. The setup allows to study ex situ and in situ prepared samples, offered by an attached UHV preparation chamber with load lock. The transfer of the prepared samples between the preparation section and the dilution refrigerator is carried out under cryogenic temperatures. First commissioning studies have been carried out at the Variable Polarization XUV Beamline P04 at PETRA III and the influence of the incident photon beam to the sample temperature has been studied.

  18. Design of a self-aligned, wide temperature range (300 mK-300 K) atomic force microscope/magnetic force microscope with 10 nm magnetic force microscope resolution

    Energy Technology Data Exchange (ETDEWEB)

    Karcı, Özgür [NanoMagnetics Instruments Ltd., Hacettepe - İvedik OSB Teknokent, 1368. Cad., No: 61/33, 06370, Yenimahalle, Ankara (Turkey); Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, 06800 Ankara (Turkey); Dede, Münir [NanoMagnetics Instruments Ltd., Hacettepe - İvedik OSB Teknokent, 1368. Cad., No: 61/33, 06370, Yenimahalle, Ankara (Turkey); Oral, Ahmet, E-mail: orahmet@metu.edu.tr [Department of Physics, Middle East Technical University, 06800 Ankara (Turkey)

    2014-10-01

    We describe the design of a wide temperature range (300 mK-300 K) atomic force microscope/magnetic force microscope with a self-aligned fibre-cantilever mechanism. An alignment chip with alignment groves and a special mechanical design are used to eliminate tedious and time consuming fibre-cantilever alignment procedure for the entire temperature range. A low noise, Michelson fibre interferometer was integrated into the system for measuring deflection of the cantilever. The spectral noise density of the system was measured to be ~12 fm/√Hz at 4.2 K at 3 mW incident optical power. Abrikosov vortices in BSCCO(2212) single crystal sample and a high density hard disk sample were imaged at 10 nm resolution to demonstrate the performance of the system.

  19. Design of a self-aligned, wide temperature range (300 mK-300 K) atomic force microscope/magnetic force microscope with 10 nm magnetic force microscope resolution

    International Nuclear Information System (INIS)

    Karcı, Özgür; Dede, Münir; Oral, Ahmet

    2014-01-01

    We describe the design of a wide temperature range (300 mK-300 K) atomic force microscope/magnetic force microscope with a self-aligned fibre-cantilever mechanism. An alignment chip with alignment groves and a special mechanical design are used to eliminate tedious and time consuming fibre-cantilever alignment procedure for the entire temperature range. A low noise, Michelson fibre interferometer was integrated into the system for measuring deflection of the cantilever. The spectral noise density of the system was measured to be ∼12 fm/√Hz at 4.2 K at 3 mW incident optical power. Abrikosov vortices in BSCCO(2212) single crystal sample and a high density hard disk sample were imaged at 10 nm resolution to demonstrate the performance of the system

  20. 「常陽」MK-IIB型特殊燃料集合体(PFB031)の照射後試験; 集合体及び燃料要素の非破壊試験

    OpenAIRE

    小泉 敦裕; 平澤 久夫

    1988-01-01

    「常陽」MK-2B型特殊燃料集合体(PFB031)の健全性の確認及び照射初期の挙動を把握することを目的に照射後試験を実施した。試験は、外観検査を始めとする集合体試験、コンパートメント試験、さらにX線ラジオグラフィー等のピン試験を行った。本集合体は、MK-2第12´(出力上昇時燃料組成変化測定試験)サイクルで照射されたものであり、その燃焼度はコンパートメント平均で約80MWd/tである。本試験の結果は以下のとおりである。(1)集合体試験、コンパートメント試験、ピン試験の結果から、本集合体の健全性を確認した。(2)X線ラジオグラフィーの結果から、「もんじゅ」仕様ピンに中心空孔が観察された。...

  1. Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

    Science.gov (United States)

    Yeh, D Y-W; Yang, Y-C; Wang, J-J

    2015-05-01

    Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization.

    Directory of Open Access Journals (Sweden)

    Jennifer A Corcoran

    2015-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC neoplasm Kaposi's sarcoma (KS. KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5' to 3' decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

  3. Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits

    Science.gov (United States)

    Uttl, Libor; Petrasek, Tomas; Sengul, Hilal; Svojanovska, Marketa; Lobellova, Veronika; Vales, Karel; Radostova, Dominika; Tsenov, Grygoriy; Kubova, Hana; Mikulecka, Anna; Svoboda, Jan; Stuchlik, Ales

    2018-01-01

    The role of NMDA receptors in learning, memory and hippocampal function has long been recognized. Post-mortem studies have indicated that the expression or subunit composition of the NMDA glutamate receptor subtype might be related to the impaired cognitive functions found in schizophrenia patients. NMDA receptor antagonists have been used to develop animal models of this disorder. There is accumulating evidence showing that not only the acute but also the chronic application of NMDA receptor antagonists may induce schizophrenia-like alterations in behavior and brain functions. However, limited evidence is available regarding the consequences of NMDA receptor blockage during periods of adolescence and early adulthood. This study tested the hypothesis that a 2-week treatment of male Long-Evans and Wistar rats with dizocilpine (MK-801; 0.5 mg/kg daily) starting at postnatal days (PD) 30 and 60 would cause a long-term cognitive deficit and changes in the levels of NMDA receptor subunits. The working memory version of the Morris water maze (MWM) and active place avoidance with reversal on a rotating arena (Carousel) requiring cognitive coordination and flexibility probed cognitive functions and an elevated-plus maze (EPM) was used to measure anxiety-like behavior. The western blot method was used to determine changes in NMDA receptor subunit levels in the hippocampus. Our results showed no significant changes in behaviors in Wistar rats. Slightly elevated anxiety-like behavior was observed in the EPM in Long-Evans rats with the onset of treatment on PD 30. Furthermore, Long-Evans rats treated from PD 60 displayed impaired working memory in the MWM. There were; however, no significant changes in the levels of NMDA receptor subunits because of MK-801 administration. These findings suggest that a 2-week treatment starting on PD 60 in Long-Evans rats leads to long-term changes in working memory, but this deficit is not paralleled by changes in NMDA receptor subunits. These

  4. Robotic cleaning of radwaste tank nozzles

    International Nuclear Information System (INIS)

    Boughman, G.; Jones, S.L.

    1992-01-01

    The Susquehanna radwaste processing system includes two reactor water cleanup phase separator tanks and one waste sludge phase separator tank. A system of educator nozzles and associated piping is used to provide mixing in the tanks. The mixture pumped through the nozzles is a dense resin-and-water slurry, and the nozzles tend to plug up during processing. The previous method for clearing the nozzles had been for a worker to enter the tanks and manually insert a hydrolaser into each nozzle, one at a time. The significant radiation exposure and concern for worker safety in the tank led the utility to investigate alternate means for completing this task. The typical tank configuration is shown in a figure. The initial approach investigated was to insert a manipulator arm in the tank. This arm would be installed by workers and then teleoperated from a remote control station. This approach was abandoned because of several considerations including educator location and orientation, excessive installation time, and cost. The next approach was to use a mobile platform that would operate on the tank floor. This approach was selected as being the most feasible solution. After a competitive selection process, REMOTEC was selected to provide the mobile platform. Their proposal was based on the commercial ANDROS Mark 5 platform

  5. Legaalne maailmarevolutsioon : poliitiline lisaväärtus eelisena legaalsuse ja superlegaalsuse korral / Carl Schmitt ; tõlkinud Andro Kitus

    Index Scriptorium Estoniae

    Schmitt, Carl

    2003-01-01

    Legaalsusest, legitiimsusest ja superlegaalsusest, eelfašistlikust Saksamaast ja Prantsusmaast, Hitleri legaalsest revolutsioonist ning inimkonnast konstitutsioonilise võimu kandjana. Lisatud tõlkija kommentaar

  6. Effective enhancement of polylactic acid-degrading enzyme production by Amycolatopsis sp. strain SCM_MK2-4 using statistical and one-factor-at-a-time approaches.

    Science.gov (United States)

    Penkhrue, Watsana; Kanpiengjai, Apinun; Khanongnuch, Chartchai; Masaki, Kazuo; Pathom-Aree, Wasu; Punyodom, Winita; Lumyong, Saisamorn

    2017-08-09

    This study aims to find the optimal medium and conditions for polylactic acid (PLA)-degrading enzyme production by Amycolatopsis sp. SCM_MK2-4. Screening of the most effective components in the enzyme production medium by Plackett-Burman design revealed that the silk cocoon and PLA film were the most significant variables enhancing the PLA-degrading enzyme production. After an response surface methodology, a maximum amount of PLA-degrading enzyme activity at 0.74 U mL -1 was predicted and successfully validated at 95% after 0.39% (w/v) silk cocoon and 1.62% (w/v) PLA film were applied to the basal medium. The optimal initial pH value, temperature, and inoculum size were evaluated by a method considering one-factor-at-a-time. The values were recorded at an initial pH in the range of 7.5-9.0, a temperature of 30-32°C, and an inoculum size of 4-10%. The highest activity of approximately 0.95 U mL -1 was achieved after 4 days of cultivation using the optimized medium and under optimized conditions in a shake flask. Upscaling to the use of a 3-L stirred tank fermenter was found to be successful with a PLA-degrading activity of 5.53 U mL -1 ; which represents a 51-fold increase in the activity compared with that obtained from the nonoptimized medium and conditions in the shake flask.

  7. Ion mobility and conductivity in the M{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} (M=K, Rb) solid solutions with fluorite structure

    Energy Technology Data Exchange (ETDEWEB)

    Kavun, V. Ya., E-mail: kavun@ich.dvo.ru [Institute of Chemistry FEBRAS, 159, Pr. 100-letya Vladivostoka, Vladivostok 690022 (Russian Federation); Uvarov, N.F. [Institute of Solid State Chemistry and Mechanochemistry, SB RAS, 18, Kutateladze Str., Novosibirsk 630128 (Russian Federation); Slobodyuk, A.B.; Polyantsev, M.M.; Merkulov, E.B. [Institute of Chemistry FEBRAS, 159, Pr. 100-letya Vladivostoka, Vladivostok 690022 (Russian Federation); Ulihin, A.S. [Institute of Solid State Chemistry and Mechanochemistry, SB RAS, 18, Kutateladze Str., Novosibirsk 630128 (Russian Federation); Goncharuk, V.K. [Institute of Chemistry FEBRAS, 159, Pr. 100-letya Vladivostoka, Vladivostok 690022 (Russian Federation)

    2017-05-15

    Ionic mobility and conductivity in the K{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} and Rb{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} (x=0.05, 0.09) solid solutions with the fluorite structure have been investigated using the methods of {sup 19}F NMR, X-ray diffraction and impedance spectroscopy. Types of ionic motions in the fluoride sublattice of solid solutions have been established and temperature ranges of their realization have been determined (150–450 K). Diffusion of fluoride ions is a dominating type of ionic motions in the fluoride sublattice of solid solutions under study above 350 K. Due to high ionic conductivity, above 10{sup –3} S/cm at 450 K, these solid solutions can be used as solid electrolytes in various electrochemical devices and systems. - Graphical abstract: Temperature dependence of the concentration of mobile (2, 4) and immobile (1, 3) F ions in the K{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} solid solutions. - Highlights: • Studied the ion mobility, conductivity in M{sub 0.5–x}Pb{sub x}Bi{sub 0.5}F{sub 2+x} solid solutions (M=K, Rb). • An analysis of {sup 19}F NMR spectra made it possible to identify types of ion mobility. • The main type of ion motion above 300 K in solid solutions is a diffusion of ions F{sup –}. • The ionic conductivity of the solid solutions studied more than 10{sup –3} S/cm at 450 K.

  8. Long-Term Retrospective Clinical and Radiographic Follow-up of 205 Brånemark System Mk III TiUnite Implants Submitted to Either Immediate or Delayed Loading.

    Science.gov (United States)

    Imburgia, Mario; Del Fabbro, Massimo

    2015-10-01

    Studies are needed to evaluate long-term performance of immediately loaded implants with moderately rough surface. This retrospective study evaluated long-term survival and periimplant soft and hard tissue conditions in patients treated with TiUnite implants. Forty-one consecutive patients (mean age, 52.6 years) received 205 Brånemark System Mk III TiUnite implants (145 maxillary, 60 mandibular). The indication was single tooth (n = 7 implants), partial (n = 94), or full arches (n = 104). One hundred thirteen implants were immediately loaded. Cumulative survival rate (CSR) of implants was assessed. Long-term marginal bone remodeling, probing pocket depth (PPD), and periimplant mucosa conditions were assessed. Follow-up averaged 8.8 years (range, 6.6-10.6 years). Eight implants in 5 patients failed. CSR was 96.1% (implant basis) and 87.8% (patient basis) up to 10 years. At the longest follow-up, bone loss averaged 0.43 ± 1.15 mm (n = 173), PPD averaged 3.64 ± 0.74 mm, and periimplant mucosa was healthy in 74.6% of cases. Furthermore, 50.3% and 35.5% of implants scored negative for plaque and bleeding, respectively. No significant difference in CSR and hard and soft tissue conditions was found in the long term between immediately and delayed loaded implants. Implants with TiUnite surface demonstrated excellent long-term survival, marginal bone response, and soft tissue conditions, despite a nonoptimal level of oral hygiene.

  9. PUNCH. GENIE MK.2.2 manual

    International Nuclear Information System (INIS)

    David, W.I.F.; Johnson, M.W.; Knowles, K.J.; Crosbie, G.D.; Graham, S.P.; Campbell, E.P.; Lyall, J.S.

    1986-01-01

    GENIE is a language for spectrum manipulation and display, that has been developed to satisfy the data-analysis requirements for all the neutron-scattering instruments at the spallation neutron source. The manual contains: the GENIE 'keyboard' commands, GENIE 'GCL' commands, command file examples, and the adding of non-standard facilities. (U.K.)

  10. Depot Acquisition Management and Engineering Support for Close-in Weapon System (CIWS) Phalanx Mk 15 and FCS Mk 92/Gun Mount Mk 75 Overhaul Programs.

    Science.gov (United States)

    1980-12-01

    thle reactions to the management itructurcs and orqoanizatiena1 assignments pre- sented in thu oririinal maiagement .dJan, we have reach-d the...be obtained. Any method of duplication which will provide the necessary quantity of black. legibl- copies will be acceptable. 9 3.6.1 Typography

  11. COMPLEXES MO Agwara*, PT Ndifon and MK Ndikontar Departme

    African Journals Online (AJOL)

    a

    synthesis of Zn(HMTA)X2, X = halide, which was used as a catalyst in the vulcanisation ... paper [9], we reported the synthesis and characterisation of some ... using the Gouy method, with mercury tetrathiocyanato-cobaltate(II) as calibrant [12].

  12. Developments at the EVN MkIV Correlator at JIVE

    Science.gov (United States)

    Campbell, Robert M.

    If you haven't had an EVN experiment recently, you might well be pleasantly surprised by what you now encounter. Many people at several institutions have worked actively to improve the reliability of all aspects of your experiments, while the capabilities of the correlator continue to advance. You would find that there is much more pro-active liaison prior to your observations, that station problems are often pre-empted before they affect your data thanks to ftp fringe-tests, and that pipelining and the EVN Archive make using your correlated data more straightforward. You would see that some correlator features that were fledgling at the time of the previous EVN symposium in 2004 (e.g., Gbps playback) have now largely matured and that some new features currently in development are nearing fruition (e.g., recirculation, incorporating more than 2 MERLIN stations into an EVN correlation). Here, we will review recent operational and technical developments that pertain directly to the kinds of experiments you can do. e-VLBI and real-time correlation are not explicitly addressed in this paper (see Szomoru, these proceedings). Operationally, the practical differences between e-VLBI and traditional EVN experiments lie in the pre-observation stages, since the time frame from proposal to observationis compressed significantly (currently only 2 weeks). Once projects are approved by the EVN PC, JIVE handles the scheduling. Thus, it is critical that proposals are thorough enough to allow this, and an extra premium is placed upon consulting with the Science Operations & Support group at the proposal-creation stage. There are also numerous initiatives being investigated under the aegis of the RadioNet ALBUS programme in the areas of user software development and the extension of the data product distributed following correlation (see van Langevelde, these proceedings).

  13. First level analysis report: comparative testing of HVS Mk IV+ and HVS Mk III on road D2388 near Cullinan

    CSIR Research Space (South Africa)

    Morton, B

    2003-03-01

    Full Text Available , result in variations in pavement response and test results. Based on this concern and in an effort to ensure uniformity throughout APT with the HVS, a comparative testing project was initiated to compare the effect of the two machines on pavement...

  14. Heat transfer at a sapphire - Indium interface in the 30 mK - 300 mK temperature range

    NARCIS (Netherlands)

    Liberadzka, J.; Koettig, T.; Bremer, J.; Van Der Post, C. C.W.; Ter Brake, H. J.M.

    2017-01-01

    Within the framework of the AEgIS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) project a direct measurement of the Earth's gravitational acceleration on antihydrogen will be carried out. In order to obtain satisfactory precision of the measurement, the thermal movement of the

  15. 「常陽」MK-2B型特殊燃料集合体(FAB.NO.PFB000)の照射後試験(1) : 集合体及び燃料要素の非破壊試験

    OpenAIRE

    浅賀 健男; 榎戸 裕二; 長谷川 間恭

    1985-01-01

    「常陽」MK-II特殊燃料集合体の最初の照射後試験供試体として,B型特殊燃料集合体((Fab.No.PFB000),平均燃焼度約5,100MWD/MTM)を受け入れ,集合体外観検査を初めとする集合体試験,コンパートメントの健全性を評価するコンパートメント試険,および燃料ピンに関する詳細試験を実施した。試験結果の概要は下記の通りである。1)集合体試験外観,ラッパー管対面間寸法,X線ラジオグラフィーによる内部観察等の試検では,製造時データに比し有意な変化は認められなく,構造体の健全性が確認された。2)コンパートメント試験コンパートメント内容物の装筒状態は全く正常でありリグの健全性が確認できた。また,外観寸法検査では,製造時データと比較して,有意な変化は生じてはいない。3)ピン試験X線ラジオグラフィで測定した燃料スタック長に製造時データからの変化が認められたが,その他の寸法,重量については全く変化はない。ピン内ガス圧はプレナム容積の大きいピンで最大897Torr,小さいピンで913Torr程度であった。4)集合体等の遠隔探作性と再装荷評価集合体の解体,コンパートメント解体等,遠隔操作性...

  16. Andrographolide Enhances Proliferation and Prevents Dedifferentiation of Rabbit Articular Chondrocytes: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    Li-ke Luo

    2015-01-01

    Full Text Available As the main active constituent of Andrographis paniculata that was applied in treatment of many diseases including inflammation in ancient China, andrographolide (ANDRO was found to facilitate reduction of edema and analgesia in arthritis. This suggested that ANDRO may be promising anti-inflammatory agent to relieve destruction and degeneration of cartilage after inflammation. In this study, the effect of ANDRO on rabbit articular chondrocytes in vitro was investigated. Results showed that not more than 8 μM ANDRO did no harm to chondrocytes (P0.05. The viability assay, hematoxylin-eosin, safranin O, and immunohistochemical staining also showed better performances in ANDRO groups. As to the doses, 3 μM ANDRO showed the best performance. The results indicate that ANDRO can accelerate proliferation of rabbit articular chondrocytes in vitro and meanwhile maintain the phenotype, which may provide valuable references for further exploration on arthritis.

  17. The Things of Caesar: Mark-ing the Plural (Mk 12:13–17

    Directory of Open Access Journals (Sweden)

    Warren Carter

    2014-09-01

    Full Text Available This article observes the rarely-discussed phenomenon that the Marcan paying-the-tax scene refers to tax in the singular, whilst the concluding saying uses the plural ‘the things of Caesar and of God’. The article accounts for this phenomenon by means of developing traditions. The section under the heading ‘Mark’s scene and saying about taxes (12:13–17’ counters the common claim that scene and saying originated as a unit from the historical Jesus. It proposes that whilst the saying may have originated with Jesus, the scene as we have it did not. The section under the heading ‘Social memory, orality, and a multi-referential saying?’ suggests some contexts that the saying about the things of Caesar addressed pre-Mark. And under the section ‘Trauma and Mark’s scene’ it is argued that Mark created a unit comprising scene and saying to negotiate the ‘ trauma’ of the 66–70 war. The unit evaluates freshly-asserted Roman power as idolatrous and blasphemous whilst simultaneously authorising the continued involvement of Jesus-believers in imperial society.

  18. CMS Tracker Readout Prototype Front-End Driver PCI Mezzanine Card (Mk1) (connector side)

    CERN Multimedia

    J.Coughlan

    1998-01-01

    The tracking system of the CMS detector at the LHC employs Front End Driver (FED) cards to digitise, buffer and sparsify analogue data arriving via optical links from on detector pipeline chips. This paper describes a prototype version of the FED based upon the popular commercial PCI bus Mezzanine Card (PMC) form factor. The FED-PMC consists of an 8 channel, 9 bit ADC, card, providing a 1 MByte data buffer and operating at the LHC design frequency of 40 MHz. The core of the card is a re-programmable FPGA which allows the functionality of the card to be conveniently modified. The card is supplied with a comprehensive library of C routines.The PMC form factor allows the card to be plugged onto a wide variety of processor carrier boards and even directly into PCI based PCs. The flexibility of the FPGA based design permits the card to be used in a variety of ADC based applications.

  19. Hardware for quasi-single-shot multifrequency magnetic induction tomography (MIT): the Graz Mk2 system

    International Nuclear Information System (INIS)

    Scharfetter, H; Köstinger, A; Issa, S

    2008-01-01

    Magnetic induction tomography (MIT) has been suggested by several groups for the contact-less mapping of the passive electrical properties of tissues via AC magnetic fields in the frequency range between several tens of kHz and several tens of MHz. Multifrequency MIT as an analog to multifrequency EIT has been tried and first image reconstructions have been demonstrated with phantoms. MIT appears to yield comparable images to EIT but offers the advantage of being non-contacting. In the beta-dispersion range of most tissues the method is challenging because the signals are very small and buried in noise. In order to minimize drifts and systematic errors fast data acquisition is therefore pivotal. This paper presents a method for single-shot MIT which allows us to acquire the data for a multifrequency image with an analog bandwidth of 50 kHz–1.5 MHz which covers a good part of the β-dispersion of many tissues. The transmit (TX) coils are simultaneously driven by individual power amplifiers with a multisinus pattern with up to 3 A pp . The amplifiers are configured as current sources so as not to perturb the excitation fields by inappropriately terminated coils. The separation of the different TX channels after reception is achieved by splitting up the carrier frequencies into individual subcarriers with a narrow spacing of at most 300 Hz. In this way every TX coil is identifiable by its own subcarrier but the whole excitation band is contained within a few kHz. The real and imaginary parts of the received signals are extracted efficiently with FFT. The system noise and the sources for low-frequency perturbations are analyzed and characterized

  20. Lessons Learned from Outsourcing the Pearl Harbor MK-48 Intermediate Maintenance Activity

    National Research Council Canada - National Science Library

    Gansler, Jacques S; Lucyshyn, William; Alarcon-Deza, Benigno

    2008-01-01

    During the 1990s, active duty sailor resources were in large demand. In an effort to return sailors to the fleet, the operation of the Navy's Heavyweight Torpedo Intermediate Maintenance Activities (IMA...

  1. Experimental results from MK. III GCR physics programme, October-December 1969. Addendum 1

    Energy Technology Data Exchange (ETDEWEB)

    Maddison, R. J.

    1970-06-15

    Measurements have been made in HECTOR of the effect of heating the central region of five cores, three of these being the loop cores and the later two having a larger heated central test region. These measurements have been calibrated by the use of BINAL (boron-aluminium), stainless steel and copper poison tubes. The results of these measurements of temperature coefficient and of poison tube worth are described in sections 2 and 3 respectively.

  2. p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage

    DEFF Research Database (Denmark)

    Borisova, Marina E; Voigt, Andrea; Tollenaere, Maxim A X

    2018-01-01

    quantitative phosphoproteomics and protein kinase inhibition to provide a systems view on protein phosphorylation patterns induced by UV light and uncover the dependencies of phosphorylation events on the canonical DNA damage signaling by ATM/ATR and the p38 MAP kinase pathway. We identify RNA-binding proteins......Ultraviolet (UV) light radiation induces the formation of bulky photoproducts in the DNA that globally affect transcription and splicing. However, the signaling pathways and mechanisms that link UV-light-induced DNA damage to changes in RNA metabolism remain poorly understood. Here we employ...

  3. Calculation of plate temperatures in a Mk 4 LEU fuel element

    International Nuclear Information System (INIS)

    Haack, K.

    1988-09-01

    A calculation method for estimating the axial temperature distributions of each tube in each of the 26 fuel elements of the DR 3 core is described and demonstrated. With input data for fuel element power, D2O outlet temperature and main D2O circulator combination, a computer code calculates all important temperatures in the fuel element. 11 tabs., 32 ills. 8 refs. (author)

  4. Role of BWR MK I secondary containments in severe accident mitigation

    International Nuclear Information System (INIS)

    Greene, S.R.

    1986-01-01

    The recent advent of detailed containment analysis codes such as CONTAIN and MELCOR has facilitated the development of the first large-scale, architectural-based BWR secondary containment models. During the past year ORNL has developed detailed, plant-specific models of the Browns Ferry and Peach Bottom secondary containments, and applied these models in a variety of studies designed to evaluate the role and effectiveness of BWR secondary containments in severe accident mitigation. The topology and basis for these models is discussed, together with some of the emerging insights from these studies

  5. 75 FR 19209 - Airworthiness Directives; British Aerospace Regional Aircraft Model HP.137 Jetstream Mk.1...

    Science.gov (United States)

    2010-04-14

    ... fatigue life needed further reduction and published inspection criteria and a revised formula for... release torque of the piston rod end fitting to determine a new safe life (remaining fatigue life) for individual units. The revised safe life was calculated in accordance with the formula provided in associated...

  6. 75 FR 3418 - Airworthiness Directives; British Aerospace Regional Aircraft Model HP.137 Jetstream Mk.1...

    Science.gov (United States)

    2010-01-21

    ... release torque of the piston rod end fitting to determine a new safe life (remaining fatigue life) for individual units. The revised safe life was calculated in accordance with the formula provided in associated... that the remaining fatigue life needed further reduction and published inspection criteria and a...

  7. Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475

    Science.gov (United States)

    2018-03-30

    ALK Gene Mutation; BRAF Gene Mutation; EGFR Gene Mutation; Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; ROS1 Gene Mutation; Stage III Non-Small Cell Lung Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  8. MK-2.0: Secretos a voces del social-media

    OpenAIRE

    María Aránzazu Sulé Alonso; Javier Prieto García

    2010-01-01

    Las redes sociales son un fenómeno emergente al que cada día se suman nuevos adeptos convirtiéndose en un sector exitoso que los expertos en marketing digital tienen que aprovechar. Esta investigación evidencia que la multidisciplinariedad entre ambas puede tener efectos muy beneficiosos y que su puesta en práctica es ya una realidad. Pepsi, Starbucks, Avon, Adidas, infinidad de marcas de reconocido prestigio internacional han apostado muy fuerte por estos nuevos canales de actuación obtenien...

  9. Vonis Mati Bandar Dan Pengedar Narkoba Antara Putusan Mk Dan Sema (Perspektif Hukum Pidana Islam)

    OpenAIRE

    Irfan, M Nurul

    2014-01-01

    : The Dead Penalty for the Drug Dealers in the Constitutional Court and the Sema (an Islamic Criminal Law Perspective). The death sentence set by the Supreme Court for the agents and drug dealers has attracted attention of criminal law experts. Constitutional Court Decision No. 34 / PUU-X /2013 which annuls Article 268 paragraph (3) Criminal Procedure Code-stating that the submission PK (judicial review) can only be done once- has open a chance that the PK can be submitted more than once. Thi...

  10. Total Quality Management Analysis of LAMPS MK 1 Aviation Maintenance Data

    Science.gov (United States)

    1992-06-05

    Qualit Control? The Japanese Way by Dr. Kaoru Ishikawa translated by David J. Lu offers the Japanese version of Total Quality Management. Dr...causes to an effect or problem. It is called the Ishikawa Diagram after its inventor Kaoru Ishikawa , a pioneer in quality control. The name fishbone...pathways involved. 2) Cause and Effect Diagram (also known as an Ishikawa Diagram or a Fishbone Diagram). This diagram used to identify the causes, and

  11. Instrumenting a pressure suppression experiment for a MK I boiling water reactor: another measurements engineering challenge

    International Nuclear Information System (INIS)

    Shay, W.M.; Brough, W.G.; Miller, T.B.

    1977-01-01

    A scale test facility of a pressure suppression system from a boiling water reactor was instrumented with seven types of transducers to obtain high-accuracy experimental data during a hypothetical loss-of-coolant accident. The instrumentation verified the analysis of the dynamic loading of the pressure suppression system

  12. Calculation of plate temperatures in a Mk 4 LEU fuel element

    International Nuclear Information System (INIS)

    Haack, K.

    1991-10-01

    A calculation method for estimating the axial temperature distributions of each tube in each of the 26 fuel elements of the DR 3 core is described and demonstrated. With input data for fuel element power, D 2 O outlet temperature and main D 2 O circulator combination, a computer code calculates all important temperatures in the fuel element. Preface to Second Edition Oct. 1991. The second edition is based on the more reliable thermophysical heavy water properties made available by the investigations of Professor J. Bukovsky. The values in the tables are replaced and a new set of fuel element temperature curves is enclosed as an example of the temperature distributions in a low enriched uranium (19,8% 235 U as U 3 Si 2 ). (author) 11 tabs., 32 ills., 9 refs

  13. Study of the Deposition of Ammonium Perchlorate Following the Static Firing of MK-58 Rocket Motors

    Science.gov (United States)

    2008-10-01

    hyperthyroidism , gas generators, electrolytes for lithium cells, and as chemical reagents. The occurrence of perchlorate in the environment is...and prevent their movement by the rocket motor plume (Fig. 5). The water in the traps was collected using 1-l amber glass containers and the exact...them. On day one, after the firing of the second motor, heavy rain and lightning prevented the collection of samples from the witness plates. Only

  14. Verification of MCNP simulation of neutron flux parameters at TRIGA MK II reactor of Malaysia.

    Science.gov (United States)

    Yavar, A R; Khalafi, H; Kasesaz, Y; Sarmani, S; Yahaya, R; Wood, A K; Khoo, K S

    2012-10-01

    A 3-D model for 1 MW TRIGA Mark II research reactor was simulated. Neutron flux parameters were calculated using MCNP-4C code and were compared with experimental results obtained by k(0)-INAA and absolute method. The average values of φ(th),φ(epi), and φ(fast) by MCNP code were (2.19±0.03)×10(12) cm(-2)s(-1), (1.26±0.02)×10(11) cm(-2)s(-1) and (3.33±0.02)×10(10) cm(-2)s(-1), respectively. These average values were consistent with the experimental results obtained by k(0)-INAA. The findings show a good agreement between MCNP code results and experimental results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Atomic resolution scanning tunneling microscopy in a cryogen free dilution refrigerator at 15 mK

    International Nuclear Information System (INIS)

    Haan, A. M. J. den; Wijts, G. H. C. J.; Galli, F.; Oosterkamp, T. H.; Usenko, O.; Baarle, G. J. C. van; Zalm, D. J. van der

    2014-01-01

    Pulse tube refrigerators are becoming more common, because they are cost efficient and demand less handling than conventional (wet) refrigerators. However, a downside of a pulse tube system is the vibration level at the cold-head, which is in most designs several micrometers. We implemented vibration isolation techniques which significantly reduced vibration levels at the experiment. These optimizations were necessary for the vibration sensitive magnetic resonance force microscopy experiments at milli-kelvin temperatures for which the cryostat is intended. With these modifications we show atomic resolution scanning tunneling microscopy on graphite. This is promising for scanning probe microscopy applications at very low temperatures

  16. In vitro antianaerobic activity of ertapenem (MK-0826) compared to seven other compounds.

    Science.gov (United States)

    Hoellman, Dianne B; Kelly, Linda M; Credito, Kim; Anthony, Lauren; Ednie, Lois M; Jacobs, Michael R; Appelbaum, Peter C

    2002-01-01

    Ertapenem, imipenem, meropenem, ceftriaxone, piperacillin, piperacillin-tazobactam, clindamycin, and metronidazole were agar dilution MIC tested against 431 anaerobes. Imipenem, meropenem, and ertapenem were the most active beta-lactams (MICs at which 50% of the strains are inhibited [MIC(50)s], 0.125 to 0.25 microg/ml; MIC(90)s, 1.0 to 2.0 microg/ml). Time-kill studies revealed that ertapenem at two times the MIC was bactericidal for 9 of 10 strains after 48 h. The kinetics for other beta-lactams were similar to those of ertapenem.

  17. Evaluating the release of a large store from the BAE Hawk Mk120

    CSIR Research Space (South Africa)

    Jamison, Kevin

    2010-11-01

    Full Text Available -Stokes Computational Fluid Dynamics (CFD) code where applicable to calculate the carriage loads; calculating the rigid and flexible structural dynamic responses from the ejection forces and using a three-component look-up table to model the loads on the store in free...

  18. Flow properties of MK-based geopolymer pastes. A comparative study with standard Portland cement pastes.

    Science.gov (United States)

    Favier, Aurélie; Hot, Julie; Habert, Guillaume; Roussel, Nicolas; d'Espinose de Lacaillerie, Jean-Baptiste

    2014-02-28

    Geopolymers are presented in many studies as alternatives to ordinary Portland cement. Previous studies have focused on their chemical and mechanical properties, their microstructures and their potential applications, but very few have focussed on their rheological behaviour. Our work highlights the fundamental differences in the flow properties, which exist between geopolymers made from metakaolin and Ordinary Portland Cement (OPC). We show that colloidal interactions between metakaolin particles are negligible and that hydrodynamic effects control the rheological behaviour. Metakaolin-based geopolymers can then be described as Newtonian fluids with the viscosity controlled mainly by the high viscosity of the suspending alkaline silicate solution and not by the contribution of direct contacts between metakaolin grains. This fundamental difference between geopolymers and OPC implies that developments made in cement technology to improve rheological behaviour such as plasticizers will not be efficient for geopolymers and that new research directions need to be explored.

  19. http://bulletin.mfd.org.mk/volumes/Volume%2051/51_005.pdf

    Directory of Open Access Journals (Sweden)

    Tatjana Kadifkova Panovska

    2005-09-01

    Full Text Available The present study describes the ability of different extracts of H. plicatum obtained from flowers, stems and leaves, to act as natural antioxidants in different in vitro experimental models in which free radical reactions are involved: inhibition of DPPH (1,1-diphenyl-2- picrylhydrazyl radical, inhibition of hydroxyl radicals and protection of β-carotene-linoleic acid model system. Investigate extracts showed radical scavenging activity with IC50 from 6 to 11 mg/ml. The extracts are capable to reacting with OH• radical with inhibition of its production ranged between 33-58%. The high preventive activity against the bleaching of beta-carotene (15-49% of initial value after 120 minutes was also observed. The antioxidative activity of the extracts in the experimental systems was compared with that of reference substances: luteolin, quercetin, BHA, BHT and sylimarin (the main agent of the well-known milk thistle – Silybum marianum L.. Results of this study suggest that Helichrysum plicatum represent a natural source with antioxidant potential.

  20. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591: a novel HIV-1 reverse transcriptase translocation inhibitor.

    Science.gov (United States)

    Markowitz, Martin; Sarafianos, Stefan G

    2018-07-01

    4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action, unique structure, and amongst NRTIs, unparalleled anti-HIV-1 activity. We will summarize its structure and function, antiviral activity, resistance profile, and potential as an antiretroviral for use in the treatment and preexposure prophylaxis of HIV-1 infection. EFdA is active against wild-type (EC50 as low as 50 pmol/l) and most highly NRTI-resistant viruses. The active metabolite, EFdA-triphosphate, has been shown to have a prolonged intracellular half-life in human and rhesus (Rh) blood cells. As a result, single drug doses tested in simian immunodeficiency virus mac251-infected Rh macaques and HIV-1-infected individuals exhibited robust antiviral activity of 7-10 days duration. Preclinical studies of EFdA as preexposure prophylaxis in the Rh macaque/simian/human immunodeficiency virus low-dose intrarectal challenge model have shown complete protection when given in clinically relevant doses. EFdA is a novel antiretroviral with activity against both wild-type and NRTI-resistant viruses. As a result of the prolonged intracellular half-life of its active moiety, it is amenable to flexibility in dosing of at least daily to weekly and perhaps longer.

  1. MK-2.0: Secretos a voces del social-media

    Directory of Open Access Journals (Sweden)

    María Aránzazu Sulé Alonso

    2010-12-01

    Full Text Available Las redes sociales son un fenómeno emergente al que cada día se suman nuevos adeptos convirtiéndose en un sector exitoso que los expertos en marketing digital tienen que aprovechar. Esta investigación evidencia que la multidisciplinariedad entre ambas puede tener efectos muy beneficiosos y que su puesta en práctica es ya una realidad. Pepsi, Starbucks, Avon, Adidas, infinidad de marcas de reconocido prestigio internacional han apostado muy fuerte por estos nuevos canales de actuación obteniendo resultados lo suficientemente reveladores como para hablar de nuevas modalidades de negocio, y aún más en este momento cuando parece que las formas de hacer marketing y publicidad convencionales están perdiendo protagonismo. Cada vez pasamos menos tiempo frente al televisor y más conectados a la red. Si una marca quiere encontrarnos, es probable que allí pueda hacerlo. Las redes sociales aportan grandes dosis de viralidad a los procesos de comunicación, las cuales son de gran calidad ya que, ¿hay mejores prescriptores que nuestros familiares y amigos?. Y todo esto para satisfacer a un agente que tiene mucho que decir: tu.Social media is an emerging phenomenon which wins new followers every day becoming a succesful sector that digital marketing experts have to make the most of. This research shows that multidisciplinarity between can have beneficial effects and its practice it's already a reality. Pepsi, Starbucks, Avon, Adidas, and most of the well-known international brands have bet strongly for these new marketing chanels getting such good results that we can talk about new business methods and more evennow this moment where traditional marketing and advertising are losing prominence. Every day we spend less time in front of TV but more time surfing the internet. If a brand wants to find us it will probably find us there. Social media contributes to get virality to the communication processes and of course quality because, are there better prescriptors than our relatives and friends? And everythig to satisfy an agent that has a lot of to say: you.

  2. Lessons Learned from Outsourcing the Pearl Harbor MK-48 Intermediate Maintenance Activity

    Science.gov (United States)

    2008-03-01

    transfer of ownership of assets. However, outsourcing is not simply a procurement decision. All organizations procure elements of their operations...systems, commercialization, and franchising (Office of Management and Budget, 2004). Strengths of Outsourcing Outsourcing is more efficient than...operating the IMA with organic resources vs . the cost of a comparable service provided by a contractor. Activity-based costing would also help managers

  3. A phase II study of vorinostat (MK-0683) in patients with polycythaemia vera and essential thrombocythaemia

    DEFF Research Database (Denmark)

    Andersen, Christen L; McMullin, Mary F; Ejerblad, Elisabeth

    2013-01-01

    objective was to evaluate if vorinostat was followed by a decline in clonal myeloproliferation as defined by European Leukaemia Net. Thirty patients (48%) completed the intervention period (24 weeks of therapy). An intention-to-treat response rate of 35% was identified. Pruritus was resolved [19% to 0% (P=0...... (5 patients). In conclusion, vorinostat showed effectiveness by normalizing elevated leucocyte and platelet counts, resolving pruritus and significantly reducing splenomegaly. However, vorinostat was associated with significant side effects resulting in a high discontinuation rate. A lower dose...... of vorinostat in combination with conventional and/or novel targeted therapies may be warranted in future studies....

  4. Pro-neurogenic effects of andrographolide on RSC96 Schwann cells in vitro

    Science.gov (United States)

    Xu, Fuben; Wu, Huayu; Zhang, Kun; Lv, Peizhen; Zheng, Li; Zhao, Jinmin

    2016-01-01

    Nerve regeneration remains a challenge to the treatment of peripheral nerve injury. Andrographolide (Andro) is the main active constituent of Andrographis paniculata, which has been applied in the treatment of several diseases, including inflammation, in ancient China. Andro has been reported to facilitate the reduction of edema and to exert analgesic effects in the treatment of various diseases. These findings suggest that Andro may be considered a promising anti-inflammatory agent that may suppress destruction and accelerate proliferation of Schwann cells following peripheral nerve injury. In the present study, the effects of Andro on RSC96 cells were investigated in vitro. The RSC96 cell line is a spontaneously immortalized rat Schwann cell line, which was originally derived from a long-term culture of rat primary Schwann cells. RSC96 cells were treated with a range of 0 to 50 µM Andro prior to the MTT assay. Cell proliferation, morphology, synthesis and nerve-specific gene expression were performed to detect the effect of Andro on RSC96 cells. The results of the present study demonstrated that the recommended doses of Andro ranged between 0.78 and 12.5 µM, among which the most obvious response was observed when used at 3.125 µM (P<0.05). DNA content was improved in Andro groups compared with the control group (P<0.05). In addition, Andro was able to promote the gene expression of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, ciliary neurotrophic factor, and the specific Schwann cell marker S100β (P<0.05). The results of a viability assay, hematoxylin-eosin staining, and immunohistochemistry were also improved in Andro groups. These results indicated that Andro may accelerate proliferation of RSC96 cells in vitro, whilst maintaining the Schwann cell phenotype; therefore, the present study may provide valuable evidence for the further exploration of the effects of Andro on peripheral nerves. PMID:27599453

  5. Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF-κB and TGF-β1/Smad2 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Liteng Lin

    2018-01-01

    Full Text Available Liver fibrosis is characterized by activated hepatic stellate cells (HSC and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4 and the mice were intraperitoneally injected with Andro for 6 weeks. HSC cell line (LX-2 and primary HSC were also treated with Andro in vitro. Treatment of CCl4-induced mice with Andro decreased the levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST, Sirius red staining as well as the expression of α smooth muscle actin (α-SMA and transforming growth factor- (TGF- β1. Furthermore, the expression of Toll-like receptor (TLR4 and NF-κB p50 was also inhibited by Andro. Additionally, in vitro data confirmed that Andro treatment not only attenuated the expression of profibrotic and proinflammatory factors but also blocked the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways. These results demonstrate that Andro prevents liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways, highlighting Andro as a potential therapeutic strategy for liver fibrosis.

  6. Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

    Directory of Open Access Journals (Sweden)

    Lorena Varela-Nallar

    2015-01-01

    Full Text Available Andrographolide (ANDRO is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β, a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

  7. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways

    Science.gov (United States)

    Yang, Tingfang; Yao, Shuluan; Zhang, Xianfeng; Guo, Yan

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro), the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 μg/mL Andro could significantly induce Jurkat cells’ apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro’s dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days. PMID:27114702

  8. Andrographolide inhibits growth of human T-cell acute lymphoblastic leukemia Jurkat cells by downregulation of PI3K/AKT and upregulation of p38 MAPK pathways

    Directory of Open Access Journals (Sweden)

    Yang T

    2016-04-01

    Full Text Available Tingfang Yang,1 Shuluan Yao,2 Xianfeng Zhang,3 Yan Guo2 1Department of Pediatrics, Jining No 1 People’s Hospital, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Jining Medical University Affiliated Hospital, Shandong Province, People’s Republic of China; 3Department of Psychiatry, Jining Psychiatric Hospital, Shandong Province, People’s Republic of China Abstract: T-cell acute lymphoblastic leukemia (T-ALL as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro, the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death. Cell apoptosis was assayed by flow cytometry, and the signaling transduction for Andro was analyzed by Western blotting. The results indicated 10 µg/mL Andro could significantly induce Jurkat cells’ apoptosis, depending on the inhibition of PI3K/AKT pathway. Moreover, Andro-induced apoptosis is enhanced by AKT-selective inhibitor LY294002. ERK- or JNK-selective inhibitors PD98059 and SP600125 had no effect on Andro-induced apoptosis. In addition, p38 inhibitor SB203580 could reverse Andro-induced apoptosis in Jurkat cells. We also found that the protein expression of p-p53 and p-p38 were increased after Andro treatments. The result of an in vivo study also demonstrated Andro’s dose-dependent inhibition in subcutaneous Jurkat xenografts. In conclusion, our findings explained a novel mechanism of drug action by Andro in Jurkat cells and suggested that Andro might be developed into a new candidate therapy for T-ALL patients in the coming days. Keywords: andrographolide, PI3K, AKT, Burkitt lymphoma, Jurkat cell

  9. Reaction Characteristics of Andrographolide and its Analogue AL-1 with GSH, as a Simple Chemical Simulation of NF-κB Inhibition

    Directory of Open Access Journals (Sweden)

    Yuqiang Wang

    2012-01-01

    Full Text Available 14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2 is an analogue of andrographolide (Andro, 1 coupled to α-lipoic acid (LA, 4. AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3 was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.

  10. Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

    NARCIS (Netherlands)

    Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco

    2017-01-01

    Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-kB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the

  11. 77 FR 23531 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-04-19

    ... apply to Streaming Quote Traders (``SQTs''), \\5\\ Remote Streaming Quote Traders (``RSQTs'') \\6\\ and... generate and submit option quotations electronically in options to which such SQT is assigned. \\6\\ A Remote....C. 552, will be available for Web site viewing and printing in the Commission's Public Reference...

  12. Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Tao Peng

    2015-01-01

    Full Text Available Andrographolide (Andro has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC. However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibited the proliferation and invasion of NPC cells (P<0.05, resp.. These anticancer activities were associated with cell apoptosis, cell death and induction of cell cycle arrest, and the downregulation of NF-κB target genes. This work provides evidence that NF-κB pathway is a potential therapeutic target and may also be indispensable in the Andro-mediated anticancer activities in nasopharyngeal carcinoma.

  13. Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Hui-Hsuan [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chou, Fen-Pi [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Wang, Chau-Jong [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Hsuan, Shu-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China); Wang, Cheng-Kun [E-Chyun Dermatology Clinic, No.70, Sec. 3, Jhonghua E. Rd., East District, Tainan, Taiwan (China); Chen, Jing-Hsien [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China)

    2011-02-01

    Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

  14. Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells

    International Nuclear Information System (INIS)

    Lin, Hui-Hsuan; Tsai, Chia-Wen; Chou, Fen-Pi; Wang, Chau-Jong; Hsuan, Shu-Wen; Wang, Cheng-Kun; Chen, Jing-Hsien

    2011-01-01

    Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) in A549 cells. HIF-1α plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1α was correlated with a rapid ubiquitin-dependent degradation of HIF-1α, and was accompanied by increased expressions of hydroxyl-HIF-1α and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1α inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGFβ1/PHD2/HIF-1α pathway, as demonstrated by the transfection of TGFβ1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1α transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

  15. Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Mazen Alzaharna

    Full Text Available Andrographolide (Andro has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death.

  16. Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells

    Science.gov (United States)

    Alzaharna, Mazen; Alqouqa, Iyad; Cheung, Hon-Yeung

    2017-01-01

    Andrographolide (Andro) has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi) has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS)-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α) decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP) plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death. PMID:28182713

  17. First report of a lipopeptide biosurfactant from thermophilic bacterium Aneurinibacillus thermoaerophilus MK01 newly isolated from municipal landfill site.

    Science.gov (United States)

    Sharafi, Hakimeh; Abdoli, Mahya; Hajfarajollah, Hamidreza; Samie, Nima; Alidoust, Leila; Abbasi, Habib; Fooladi, Jamshid; Zahiri, Hossein Shahbani; Noghabi, Kambiz Akbari

    2014-07-01

    A biosurfactant-producing thermophile was isolated from the Kahrizak landfill of Tehran and identified as a bacterium belonging to the genus Aneurinibacillus. A thermostable lipopeptide-type biosurfactant was purified from the culture medium of this bacterium and showed stability in the temperature range of 20-90 °C and pH range of 5-10. The produced biosurfactant could reduce the surface tension of water from 72 to 43 mN/m with a CMC of 1.21 mg/mL. The strain growing at a temperature of 45 °C produces a substantial amount of 5 g/L of biosurfactant in the medium supplemented with sunflower oil as the sole carbon source. Response surface methodology was employed to optimize the biosurfactant production using sunflower oil, sodium nitrate, and yeast extract as variables. The optimization resulted in 6.75 g/L biosurfactant production, i.e., 35% improved as compared to the unoptimized condition. Thin-layer chromatography, FTIR spectroscopy, 1H-NMR spectroscopy, and biochemical composition analysis confirmed the lipopeptide structure of the biosurfactant.

  18. Deuterium to helium plasma-wall change-over experiments in the JET MkII-gas box divertor

    International Nuclear Information System (INIS)

    Hillis, D.L.; Loarer, T.; Bucalossi, J.; Pospieszczyk, A.; Fundamenski, W.; Matthews, G.; Meigs, A.; Morgan, P.; Phillips, V.; Pitts, R.; Stamp, M.; Hellermann, M. von

    2003-01-01

    The deuterium and helium dynamics in the plasma and subdivertor regions of JET are compared during a sequence of similar ohmic and ICRH pulses where 100% He gas is injected into the JET vacuum vessel, whose graphite walls were previously saturated with deuterium. After the first six He fueled change-over discharges, only He plasma operation was performed. Following this investigation, the situation is reversed and the change-over from an initially saturated He wall is investigated when only D 2 plasma fuelling is used. The He concentration is measured in the subdivertor with a species selective Penning gauge. Comparison of the time dependence of the divertor concentrations with those at the edge and strike point shows significant differences during the first six discharges. This difference along with a global He particle balance is used to assess the status of the wall saturation over the initial 6-7 He change-over discharges

  19. GMS 3: A users manual for an improved generalised multigroup scheme using WDSN MK2 for the KDF9 computer

    International Nuclear Information System (INIS)

    Barnett, M.R.; Ward, J.A.

    1968-08-01

    GMS 3 is an extension of GMS1 written for the KDF9 computer. An improved DSN routine has been incorporated, with consequent reduction in running time in many instances. Three alternative nuclear data libraries are now available, the latest of these being entirely consistent with that of WIMS. A treatment of neutron streaming in simple voids is now incorporated in the routine which prepares few-group macroscopic parameters. This report is primarily a Users Manual, but in addition includes details of theory and programming. (author)

  20. Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria Gonorrhoeae Strains FA1090 and MS11mkC

    Science.gov (United States)

    2011-05-31

    variation and pathogenic- ity during 35 months in vitro. J. Bacteriol. 96, 596–605. Kellogg,D. S. Jr., Peacock ,W. L. Jr., Dea- con, W. E., Brown, L., and...and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and

  1. Tyre-pavement contact stress patterns from the test tyres of the Gautrans heavy vehicle simulator (HVS) MK IV+

    CSIR Research Space (South Africa)

    De Beer, Morris

    2005-07-01

    Full Text Available premises. A test matrix of five load levels and six inflation pressures was used on both HVS test tyres at creep speed conditions (<6km/hr). The results indicated that at constant inflation pressure the vertical tyre contactpattern (“fingerprint”) is highly...

  2. Remnant magnetization of Fe8 high-spin molecules: X-ray magnetic circular dichroism at 300 mK

    Science.gov (United States)

    Letard, Isabelle; Sainctavit, Philippe; dit Moulin, Christophe Cartier; Kappler, Jean-Paul; Ghigna, Paolo; Gatteschi, Dante; Doddi, Bruno

    2007-06-01

    Fe8 high-spin molecules exhibit quantum spin tunneling at very low temperatures. Eight Fe3+ ions are sixfold coordinated and magnetically coupled through oxygen bridges. The net magnetization (MS=20 μB per molecule) results from competing antiferromagnetic interactions between the various Fe3+ ions (S =5/2). Because of the structural anisotropy of these molecules, the magnetization curve presents a hysteresis loop with staircases below 2 K. The staircases of the hysteresis loop are due to the quantum spin tunneling, which is temperature dependent for 400 mKmolecule. It has been possible to register an XMCD remnant signal, without magnetic field applied, at the iron L2,3 edges. XMCD coupled with ligand field multiplet calculations has allowed to determine the spin and orbit contributions to the magnetization of the Fe3+ ions.

  3. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    Science.gov (United States)

    2018-05-15

    Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  4. Negotiating for Civilian Control: Strategy and Tactics of Umkhonto We Sizwe (MK) in the Democratic Transition of South Africa

    National Research Council Canada - National Science Library

    Mollo, Lekoa

    2000-01-01

    ... other nations. Nevertheless, the history of the establishment of democratic civilian control in South Africa offers potentially valuable lessons for other nations to adapt and apply to their own challenges...

  5. Crystal structures of the SAM-III/S[subscript MK] riboswitch reveal the SAM-dependent translation inhibition mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Lu, C.; Smith, A.M.; Fuchs, R.T.; Ding, F.; Rajashankar, K.; Henkin, T.M.; Ke, A. (Cornell); (OSU)

    2010-01-07

    Three distinct classes of S-adenosyl-L-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-{angstrom} crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti-Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions with the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions.

  6. A Novel MK-based Geopolymer Composite Activated with Rice Husk Ash and KOH: Performance at High Temperature

    International Nuclear Information System (INIS)

    Villaquirán-Caicedo, M.A.; Mejía de Gutiérrez, R.; Gallego, N.C.

    2017-01-01

    Geopolymers were produced using an environmentally friendly alkali activator (based on Rice Husk Ash and potassium hydroxide). Aluminosilicates particles, carbon and ceramic fibres were used as reinforcement materials. The effects of reinforcement materials on the flexural strength, linear-shrinkage, thermophysical properties and microstructure of the geopolymers at room and high temperature (1200 °C) were studied. The results indicated that the toughness of the composites is increased 110.4% for geopolymer reinforced by ceramic fibres (G-AF) at room temperature. The presence of particles improved the flexural behaviour 265% for geopolymer reinforced by carbon fibres and particles after exposure to 1200 .C. Linear-shrinkage for geopolymer reinforced by ceramic fibres and particles and the geopolymer G-AF compared with reference sample (without fibres and particles) is improved by 27.88% and 7.88% respectively at 900 °C. The geopolymer materials developed in this work are porous materials with low thermal conductivity and good mechanical properties with potential thermal insulation applications for building applications. [es

  7. Türkiye’de “Sosyal” Güvenceli Esneklik Mümkün mü?

    Directory of Open Access Journals (Sweden)

    Hicran ATATANIR

    2012-08-01

    Full Text Available Küreselleşme ve teknolojik ilerlemelerin etkisiyle yeniden yapılanan dünya ekonomisinde köklü değişikliler yaşanmakta ve bu değişim çalışma ilişkileri ile emek piyasalarını da derinden etkilemektedir. Küreselleşmenin temel aktörleri olan şirketlerin, serbest piyasa koşullarına uyum sağlamak ve rekabet güçlerini korumaya çalışmak adına uyguladıkları yöntemler, işgücü açısından daha esnek uygulamaları gündeme getirmektedir. Emek piyasalarının esnekleşmesiyle değişen iş güvencesi ve sosyal güvenlik anlayışının yeniden tanımlandığı bu dönüşümde güvenceli esneklik kavramı, tartışmaların anahtar kelimesini oluşturmaktadır. Güvenceli esneklik işverenlerin esneklik arayışlarını, buna karşılık çalışanların güvence gereksinimlerini karşılama hedefi ni sağlamaya yönelik sosyal taraflar arasında uzlaşıyı gerekli kılan bir süreçtir. Bu çalışmada Türkiye’de de sıkça tartışılan kavramın, sosyal güvenlik sistemimizin esnek çalışanlar için güvenceli esneklik alanı oluşturma düzeyi çerçevesinde açıklanması amaçlanmıştır.

  8. MK17, a specific marker closely linked to the gynoecium suppression region on the Y chromosome in Silene latifolia

    Czech Academy of Sciences Publication Activity Database

    Hobza, Roman; Hrušáková, P.; Šafář, Jan; Bartoš, Jan; Janoušek, Bohuslav; Žlůvová, Jitka; Michu, Elleni; Doležel, Jaroslav; Vyskot, Boris

    2006-01-01

    Roč. 113, č. 2 (2006), s. 280-287 ISSN 0040-5752 R&D Projects: GA ČR(CZ) GA521/06/0056; GA ČR(CZ) GD204/05/H505; GA ČR(CZ) GA521/05/2076; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50380511 Keywords : sex chromosomes * melandrium-album * evolution Subject RIV: BO - Biophysics Impact factor: 2.715, year: 2006

  9. Visuospatial working memory is impaired in an animal model of schizophrenia induced by acute MK-801: An effect of pretraining

    Czech Academy of Sciences Publication Activity Database

    Zemanová, Anna; Staňková, Anna; Lobellová, Veronika; Svoboda, Jan; Valeš, Karel; Vlček, Kamil; Kubík, Štěpán; Fajnerová, Iveta; Stuchlík, Aleš

    2013-01-01

    Roč. 106, May 2013 (2013), s. 117-123 ISSN 0091-3057 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : working memory * place avoidance * rats * behavior Subject RIV: FH - Neurology Impact factor: 2.820, year: 2013

  10. Discovery of MK-3697: a selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia.

    Science.gov (United States)

    Roecker, Anthony J; Reger, Thomas S; Mattern, M Christa; Mercer, Swati P; Bergman, Jeffrey M; Schreier, John D; Cube, Rowena V; Cox, Christopher D; Li, Dansu; Lemaire, Wei; Bruno, Joseph G; Harrell, C Meacham; Garson, Susan L; Gotter, Anthony L; Fox, Steven V; Stevens, Joanne; Tannenbaum, Pamela L; Prueksaritanont, Thomayant; Cabalu, Tamara D; Cui, Donghui; Stellabott, Joyce; Hartman, George D; Young, Steven D; Winrow, Christopher J; Renger, John J; Coleman, Paul J

    2014-10-15

    Orexin receptor antagonists have demonstrated clinical utility for the treatment of insomnia. The majority of clinical efforts to date have focused on the development of dual orexin receptor antagonists (DORAs), small molecules that antagonize both the orexin 1 and orexin 2 receptors. Our group has recently disclosed medicinal chemistry efforts to identify highly potent, orally bioavailable selective orexin 2 receptor antagonists (2-SORAs) that possess acceptable profiles for clinical development. Herein we report additional SAR studies within the 'triaryl' amide 2-SORA series focused on improvements in compound stability in acidic media and time-dependent inhibition of CYP3A4. These studies resulted in the discovery of 2,5-disubstituted isonicotinamide 2-SORAs such as compound 24 that demonstrated improved stability and TDI profiles as well as excellent sleep efficacy across species. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Culham conceptual Tokamak reactor MkII. Conceptual layout of buildings for a twin reactor power station

    International Nuclear Information System (INIS)

    Guthrie, J.A.S.; Harding, N.H.

    1981-01-01

    This paper discusses the conceptual design of the nuclear complex of a 2400 MWe twin fusion reactor power station utilising common services and a single containment building. The design is based upon environmental and maintenance logistical requirements, the provision of adequate storage, workshop and construction facilities and the constraints imposed by the geometry of the main and auxiliary reactor coolant systems. (author)

  12. Design and manufacture of mechanical forceps to pick up objects at the bottom of the pool reactor TRIGA MK II

    International Nuclear Information System (INIS)

    Kankunku, K.P.; Lukanda, M.V.

    2011-01-01

    This design helps us to pick up any objects felt in bottom of swimming pool, which is a radioactive area, due to the presence of spent nuclear fuel. Its great advantage is its sample designing and made with local material.

  13. A Novel MK-based Geopolymer Composite Activated with Rice Husk Ash and KOH: Performance at High Temperature

    Directory of Open Access Journals (Sweden)

    M. A. Villaquirán-Caicedo

    2017-02-01

    Full Text Available Geopolymers were produced using an environmentally friendly alkali activator (based on Rice Husk Ash and potassium hydroxide. Aluminosilicates particles, carbon and ceramic fibres were used as reinforcement materials. The effects of reinforcement materials on the flexural strength, linear-shrinkage, thermophysical properties and microstructure of the geopolymers at room and high temperature (1200 ÅãC were studied. The results indicated that the toughness of the composites is increased 110.4% for geopolymer reinforced by ceramic fibres (G-AF at room temperature. The presence of particles improved the flexural behaviour 265% for geopolymer reinforced by carbon fibres and particles after exposure to 1200 .C. Linear-shrinkage for geopolymer reinforced by ceramic fibres and particles and the geopolymer G-AF compared with reference sample (without fibres and particles is improved by 27.88% and 7.88% respectively at 900 ÅãC. The geopolymer materials developed in this work are porous materials with low thermal conductivity and good mechanical properties with potential thermal insulation applications for building applications.

  14. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.

    Directory of Open Access Journals (Sweden)

    Zhong Rong Zhang

    Full Text Available Andrographolide (Andro suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC, alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.

  15. Taxifolin Enhances Andrographolide-Induced Mitotic Arrest and Apoptosis in Human Prostate Cancer Cells via Spindle Assembly Checkpoint Activation

    Science.gov (United States)

    Wong, Matthew Man-Kin; Chiu, Sung-Kay; Cheung, Hon-Yeung

    2013-01-01

    Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC. PMID:23382917

  16. Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

    Directory of Open Access Journals (Sweden)

    Su M

    2017-11-01

    Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET

  17. Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

    Science.gov (United States)

    Hsu, Ya-Hsin; Hsu, Yu-Ling; Liu, Sheng-Hung; Liao, Hsin-Chia; Lee, Po-Xuan; Lin, Chao-Hsiung; Lo, Lee-Chiang; Fu, Shu-Ling

    2016-01-01

    Andrographolide (ANDRO) is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD). ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90) and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

  18. Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

    Directory of Open Access Journals (Sweden)

    Ya-Hsin Hsu

    Full Text Available Andrographolide (ANDRO is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD. ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90 and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

  19. Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

    Science.gov (United States)

    Zhang, Huan-Tian; Yang, Jie; Liang, Gui-Hong; Gao, Xue-Juan; Sang, Yuan; Gui, Tao; Liang, Zu-Jian; Tam, Man-Seng; Zha, Zhen-Gang

    2017-12-01

    Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Тартуский Колледж Здравоохранения = Tartu Healthcare College / Мария Фадеева

    Index Scriptorium Estoniae

    Фадеева, Мария

    2014-01-01

    Tartu Tervishoiu Kõrgkooli uus hoone. Arhitektid Siiri Vallner, Indrek Peil, Johannes Feld, Andro Mänd, Sten-Mark Mändmaa, Ragnar Põllukivi (Kavakava). Sisearhitekt Tarmo Piirmets (PINK). Valmimisaasta: 2011

  1. AcEST: DK945145 [AcEST

    Lifescience Database Archive (English)

    Full Text Available ephen F., Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lip...andro A. Schaffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), Gapped BLAST and PSI

  2. Новый корпус средней школы, Вильянди = Extension of Viljandi Secondary School / Михкель Кару

    Index Scriptorium Estoniae

    Кару, Михкель, 1983-

    2013-01-01

    Viljandi Riigigümnaasiumi uuest hoonest. Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Andro Mänd, Margus Tamm (Salto Arhitektid), sisekujunduse autor Pille Lausmäe. Vana maja fassaadi renoveerimisprojekti autor Eva Laarmann

  3. Tartu Tervishoiu Kõrgkool = Tartu Health Care College / Ingrid Ruudi

    Index Scriptorium Estoniae

    Ruudi, Ingrid, 1978-

    2012-01-01

    2012. aastal valminud Tartu Tervishoiu Kõrgkooli hoone arhitektuursest lahendusest. Arhitektid Indrek Peil ja Siiri Vallner, kaasautorid Johannes Feld, Sten-Mark Mändmaa, Andro Mänd ja Ragnar Põllukivi (Kavakava). Sisearhitekt Tarmo Piirmets (Pink). Projekt: 2006-2009

  4. Haruldused moekateedris / Kaidi Malk

    Index Scriptorium Estoniae

    Malk, Kaidi

    1997-01-01

    Eesti Kunstiakadeemia moeosakonnas 1967-1996 õppinud 10 meesüliõpilasest: Gennadi Skvartsov, mongol Tsendsuren Badamsureni, Len Girin, Kalju Kivi, Ivo Nikkolo, Andrei Jakovlev, Tarvo Jaansoo, Hannes Võrno, Andrus Paumeri, Andro Kööp

  5. Andrographolide Ameliorates Abdominal Aortic Aneurysm Progression by Inhibiting Inflammatory Cell Infiltration through Downregulation of Cytokine and Integrin Expression

    Science.gov (United States)

    Ren, Jun; Liu, Zhenjie; Wang, Qiwei; Giles, Jasmine; Greenberg, Jason; Sheibani, Nader; Kent, K. Craig

    2016-01-01

    Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P < 0.05). Immunohistochemistry analyses revealed that Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB–mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms. PMID:26483397

  6. Computational study on the molecular inclusion of andrographolide by cyclodextrin

    Science.gov (United States)

    Zhou, Hongwei; Lai, Wai-Ping; Zhang, Zhiqiang; Li, Wai-Kee; Cheung, Hon-Yeung

    2009-03-01

    Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin ( xCD, where x is α, β or γ). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and βCD with andro's decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes.

  7. Detecting and classifying method based on similarity matching of Android malware behavior with profile.

    Science.gov (United States)

    Jang, Jae-Wook; Yun, Jaesung; Mohaisen, Aziz; Woo, Jiyoung; Kim, Huy Kang

    2016-01-01

    Mass-market mobile security threats have increased recently due to the growth of mobile technologies and the popularity of mobile devices. Accordingly, techniques have been introduced for identifying, classifying, and defending against mobile threats utilizing static, dynamic, on-device, and off-device techniques. Static techniques are easy to evade, while dynamic techniques are expensive. On-device techniques are evasion, while off-device techniques need being always online. To address some of those shortcomings, we introduce Andro-profiler, a hybrid behavior based analysis and classification system for mobile malware. Andro-profiler main goals are efficiency, scalability, and accuracy. For that, Andro-profiler classifies malware by exploiting the behavior profiling extracted from the integrated system logs including system calls. Andro-profiler executes a malicious application on an emulator in order to generate the integrated system logs, and creates human-readable behavior profiles by analyzing the integrated system logs. By comparing the behavior profile of malicious application with representative behavior profile for each malware family using a weighted similarity matching technique, Andro-profiler detects and classifies it into malware families. The experiment results demonstrate that Andro-profiler is scalable, performs well in detecting and classifying malware with accuracy greater than 98 %, outperforms the existing state-of-the-art work, and is capable of identifying 0-day mobile malware samples.

  8. Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

    Science.gov (United States)

    2017-07-01

    Small Cell Lung Cancer and Brain Metastases PRINCIPAL INVESTIGATOR: Sarah B. Goldberg, MD CONTRACTING ORGANIZATION: Yale University New Haven, CT...benefit in patients with non- small cell lung cancer (NSCLC). However, the overall response rate is only 20-30% and there is no clearly-defined...9. Appendices……………………………………………………………14 4 1. INTRODUCTION: Lung cancer is the leading cause of cancer death in the United States, resulting in more

  9. Note on the power divergence in lattice calculations of ΔI=1/2 K→ππ amplitudes at MK=Mπ

    International Nuclear Information System (INIS)

    Golterman, Maarten; Lin, C.-J. David; Pallante, Elisabetta

    2004-01-01

    In this Brief Report, we clarify a point concerning the power divergence in lattice calculations of ΔI=1/2 K→ππ decay amplitudes. There have been worries that this divergence might show up in the Minkowski amplitudes at M K =M π with all the mesons at rest. Here we demonstrate, via an explicit calculation in leading-order chiral perturbation theory, that the power divergence is absent at the above kinematic point, as predicted by CPS symmetry

  10. A quartet of fermionic expressions for M(k,2k±1 Virasoro characters via half-lattice paths

    Directory of Open Access Journals (Sweden)

    Olivier Blondeau-Fournier

    2017-11-01

    We also derive a bosonic version of the generating functions of length L half-lattice paths, this expression being notable in that it involves q-trinomial coefficients. Taking the L→∞ limit shows that the generating functions for infinite length half-lattice paths are indeed the Virasoro characters χr,sk,2k±1.

  11. Acute systemic MK-801 induced functional uncoupling between hippocampal areas CA3 and CA1 with distant effect in the retrosplenial cortex

    Czech Academy of Sciences Publication Activity Database

    Buchtová, Helena; Fajnerová, Iveta; Stuchlík, Aleš; Kubík, Štěpán

    2017-01-01

    Roč. 27, č. 2 (2017), s. 134-144 ISSN 1050-9631 R&D Projects: GA ČR(CZ) GA14-03627S Institutional support: RVO:67985823 Keywords : Arc * Homer1a * ensemble coding * cognitive control * hypersynchrony * hyperassociation * psychosis * NMDA antagonist * schizophrenia * animal model Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.945, year: 2016

  12. MK-801 impairs cognitive coordination on a rotating arena (Carousel) and contextual specificity of hippocampal immediate-early gene expression in a rat model of psychosis

    Czech Academy of Sciences Publication Activity Database

    Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

    2014-01-01

    Roč. 8, Mar 12 (2014), s. 75 ISSN 1662-5153 R&D Projects: GA ČR(CZ) GPP303/10/P191 Grant - others:EC(XE) PIR06-GA/2009-256581 Institutional support: RVO:67985823 Keywords : cognitive coordination * learning * dizocilpine * animal model * psychosis Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  13. Dizocilpine (MK-801) impairs learning in the active place avoidance task but has no effect on the performance during task/context alternation

    Czech Academy of Sciences Publication Activity Database

    Vojtěchová, Iveta; Petrásek, Tomáš; Hatalová, Hana; Pištíková, Adéla; Valeš, Karel; Stuchlík, Aleš

    2016-01-01

    Roč. 305, May 15 (2016), s. 247-257 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GA14-03627S Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : task alternation * context alternation * active place avoidance * Morris water maze * Dizocilpine * schizophrenia Subject RIV: FH - Neurology Impact factor: 3.002, year: 2016

  14. Two learning tasks provide evidence for disrupted behavioural flexibility in an animal model of schizophrenia-like behaviour induced by acute MK-801: A dose–response study

    Czech Academy of Sciences Publication Activity Database

    Lobellová, Veronika; Entlerová, Marie; Svojanovská, Barbora; Hatalová, Hana; Prokopová, Iva; Petrásek, Tomáš; Valeš, Karel; Kubík, Štěpán; Fajnerová, Iveta; Stuchlík, Aleš

    2013-01-01

    Roč. 246, č. 1 (2013), s. 55-62 ISSN 0166-4328 R&D Projects: GA MZd(CZ) NT13386 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204 Institutional support: RVO:67985823 Keywords : flexibility * dizocilpine * learning Subject RIV: FH - Neurology Impact factor: 3.391, year: 2013

  15. Clinical applications of PD-1-based therapy: a focus on pembrolizumab (MK-3475 in the management of melanoma and other tumor types

    Directory of Open Access Journals (Sweden)

    Gangadhar TC

    2015-04-01

    Full Text Available Tara C Gangadhar,1 April KS Salama2 1Division of Hematology/Oncology, Department of Medicine, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Preclinical work has led to an increased understanding of the immunomodulatory mechanisms involved in the regulation of the antitumor response in a variety of tumor types. PD-1 (programmed death 1 appears to be a key checkpoint involved in immune suppression in the tumor microenvironment, even in diseases not previously thought to be sensitive to immune manipulation. More recently, the subsequent clinical development of PD-1-based therapy has resulted in a major breakthrough in the field of oncology. Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape. Future work will center on rationally designed combination strategies in order to potentiate the antitumor immune response and overcome mechanisms of resistance. Keywords: PD-1, cancer, pembrolizumab, nivolumab, immunotherapy, antitumor activity 

  16. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b.

    Science.gov (United States)

    Rajaram, Murugesan V S; Ni, Bin; Morris, Jessica D; Brooks, Michelle N; Carlson, Tracy K; Bakthavachalu, Baskar; Schoenberg, Daniel R; Torrelles, Jordi B; Schlesinger, Larry S

    2011-10-18

    Contact of Mycobacterium tuberculosis (M.tb) with the immune system requires interactions between microbial surface molecules and host pattern recognition receptors. Major M.tb-exposed cell envelope molecules, such as lipomannan (LM), contain subtle structural variations that affect the nature of the immune response. Here we show that LM from virulent M.tb (TB-LM), but not from avirulent Myocobacterium smegmatis (SmegLM), is a potent inhibitor of TNF biosynthesis in human macrophages. This difference in response is not because of variation in Toll-like receptor 2-dependent activation of the signaling kinase MAPK p38. Rather, TB-LM stimulation leads to destabilization of TNF mRNA transcripts and subsequent failure to produce TNF protein. In contrast, SmegLM enhances MAPK-activated protein kinase 2 phosphorylation, which is critical for maintaining TNF mRNA stability in part by contributing microRNAs (miRNAs). In this context, human miRNA miR-125b binds to the 3' UTR region of TNF mRNA and destabilizes the transcript, whereas miR-155 enhances TNF production by increasing TNF mRNA half-life and limiting expression of SHIP1, a negative regulator of the PI3K/Akt pathway. We show that macrophages incubated with TB-LM and live M.tb induce high miR-125b expression and low miR-155 expression with correspondingly low TNF production. In contrast, SmegLM and live M. smegmatis induce high miR-155 expression and low miR-125b expression with high TNF production. Thus, we identify a unique cellular mechanism underlying the ability of a major M.tb cell wall component, TB-LM, to block TNF biosynthesis in human macrophages, thereby allowing M.tb to subvert host immunity and potentially increase its virulence.

  17. D2 and 5-HT2 receptor blockade partially alleviates the behavioral deficit of rats induced by MK-801 administration in an active place avoidance task

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Valešová, V.; Rambousek, Lukáš; Valeš, Karel

    Vol. 18, Suppl. 1 (2007), S51-S52 ISSN 0955-8810. [Biennial Meeting of the European Behavioural Pharmacology Society /12./. 31.08.2007-03.09.2007, Tübingen] R&D Projects: GA ČR(CZ) GA309/07/0341; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554; GA ČR(CZ) GA309/06/1231; GA MZd(CZ) NR9178 Institutional research plan: CEZ:AV0Z50110509 Keywords : memory Subject RIV: FH - Neuro logy

  18. Luminescence – structure relationships in MYP{sub 2}O{sub 7}:Eu{sup 3+} (M=K, Rb, Cs)

    Energy Technology Data Exchange (ETDEWEB)

    Watras, A., E-mail: A.Watras@int.pan.wroc.pl [Institute of Low Temperature and Structure Research, PAS, Okolna 2, 50-422 Wroclaw (Poland); Boutinaud, P. [Université Clermont Auvergne, SIGMA Clermont, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand (France); Pązik, R.; Dereń, P.J. [Institute of Low Temperature and Structure Research, PAS, Okolna 2, 50-422 Wroclaw (Poland)

    2016-07-15

    In this work we present the series of MYP{sub 2}O{sub 7} phosphates doped with 3% of Eu{sup 3+} ions. All samples were prepared using wet-chemistry methods. The structural properties were characterized by XRD and Raman spectroscopy. The detailed spectroscopic properties like emission spectra at 10 and 300 K, VUV excitation spectra, luminescence kinetics and luminescence temperature quenching were performed to determine the influence of alkali metal ion. In MYP{sub 2}O{sub 7} compounds, the Eu{sup 3+} ions enter two different sites – one with C{sub 1} symmetry (Y{sup 3+} sites) and one with S{sub 4} site (M{sup +} site). All phosphors have a broad charge transfer (CT) absorption band located in the UV region (200–250 nm). The ratio between CT and 4f–4f bands is decreasing with increasing the alkali metal ion size. The mechanisms responsible of luminescence temperature quenching are thermalization of higher lying {sup 5}D{sub J} levels, energy transfer between two nearby Eu{sup 3+} sites and non-radiative losses on defects in the host lattices.

  19. The Effect of a Monocular Helmet-Mounted Display on Aircrew Health: A Longitudinal Cohort Study of Apache AH Mk 1 Pilots -(Vision and Handedness)

    Science.gov (United States)

    2015-05-19

    the day, night, and in adverse weather through the use of nose-mounted, forward-looking infrared (FLIR) pilotage and targeting sensors that provide a...sensor video and/or symbology to each crewmember via a helmet display unit (HDU). The HDU contains a 1-inch (in.) diameter cathode ray tube (CRT...American Association for Pediatric Ophthalmology and Strabismus, 12(4): 365–369. Sale, D. F., and Lund, G. J. 1993. AH-64 Apache program update

  20. MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test

    Czech Academy of Sciences Publication Activity Database

    Duda, W.; Wesierska, M.; Ostaszewski, P.; Valeš, Karel; Nekovářová, Tereza; Stuchlík, Aleš

    2016-01-01

    Roč. 311, Sep 15 (2016), s. 15-23 ISSN 0166-4328 R&D Projects: GA MŠk(CZ) LH14053; GA ČR(CZ) GA14-03627S Institutional support: RVO:67985823 Keywords : short-term memory * spatial working memory * memantine * dizocilpine * Morris water maze Subject RIV: FH - Neurology Impact factor: 3.002, year: 2016

  1. Využití vlnkové transformace pro zpracování snímků sítnice

    OpenAIRE

    Portyš, Jakub

    2010-01-01

    Práce je zaměřena na využití vlnkové transformace v diagnostice chorob očního pozadí resp. sítnice. Vlnková transformace umožňuje dekompozici obrazu očního pozadí. S následnou segmentací pomocí prahování to vede k lepší přehlednosti obrazu a jednodušší diagnostice morfologicko-anatomických změn na očním pozadí. Součástí práce je též seznámení s vlnkovou transformací a rodinou mateřských vlnek. Zběžně je v práci rozebrán rozklad obrazu dle RGB barevného modelu, filtrace obrazu a prahování. V ú...

  2. X-ray characteristics and thermal transformations of double diphosphates MLnP2O7 (M-K, Rb, Cs; Ln-REE of yttrium subgroup)

    International Nuclear Information System (INIS)

    Anisimova, N.Yu.; Chudinova, N.N.; Trunov, V.K.; AN SSSR, Moscow

    1993-01-01

    Results on studying double diphosphates of rare earth metals with K, Rb and Cs are studied by methods of X-ray analysis, high-temperature roentgenography and DTA. Double diphosphates of rare earth and alkali metals are crystallized in three structural types: monoclinic, rhombic and hexagonal, whereby rhombic form by heating inversely transforms into hexagonal one. MLnP 2 O 7 thermal transformations are studied

  3. Changes in Cell Adhesivity and Cytoskeleton-Related Proteins During Imatinib-Induced Apoptosis of Leukemic JURL-MK1 Cells

    Czech Academy of Sciences Publication Activity Database

    Kuželová, K.; Pluskalová, M.; Grebeňová, D.; Pavlásková, Kateřina; Halada, Petr; Hrkal, Z.

    2010-01-01

    Roč. 111, č. 6 (2010), s. 1413-1425 ISSN 0730-2312 R&D Projects: GA MŠk LC07017; GA MZd NR9243 Institutional research plan: CEZ:AV0Z50200510 Keywords : imatinib * adhesion * cytoskeleton Subject RIV: CE - Biochemistry Impact factor: 3.122, year: 2010

  4. The difference in effect of mGlu2/3 and mGlu5 receptor agonists on cognitive impairment induced by MK-801

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Svoboda, Jan; Benkovičová, Kristína; Bubeníková-Valešová, V.; Stuchlík, Aleš

    2010-01-01

    Roč. 639, 1-3 (2010), s. 91-98 ISSN 0014-2999 R&D Projects: GA MZd(CZ) NR9178 Institutional research plan: CEZ:AV0Z50110509 Keywords : animal model of schizophrenia * metabotropic glutamate receptor * cognition Subject RIV: FH - Neurology Impact factor: 2.737, year: 2010

  5. Acute administration of MK-801 in an animal model of psychosis in rats interferes with cognitively demanding forms of behavioral flexibility on a rotating arena

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Jan; Staňková, Anna; Entlerová, Marie; Stuchlík, Aleš

    2015-01-01

    Roč. 9, APR 1 (2015), s. 75 ISSN 1662-5153 R&D Projects: GA ČR(CZ) GA14-03627S Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204; GA MŠk(CZ) ED2.1.00/03.0078 Institutional support: RVO:67985823 Keywords : flexibility * memory * reversal learning Subject RIV: FH - Neurology Impact factor: 3.392, year: 2015

  6. Limits on heavy neutrino mixing from the beta decay of 38mK confined in a magneto-optical trap

    International Nuclear Information System (INIS)

    Trinczek, M.C.

    2001-01-01

    This thesis details the search for mixing between electron neutrinos and possible heavy neutrinos using the positron decay of 38m K produced at ISAC, TRIUMF's new radioactive beam facility. Using the novel technique of laser atom trapping to confine 38m K, direct limits on such mixing in β-decay are determined for the mass range of 0.7 MeV/c 2 to 3.8 MeV/c 2 . The results, for part of this mass range, provide the best direct limits for the mixing of heavy neutrinos with the electron neutrino in the literature to date. The Standard Model of electroweak physics has been able to describe a wide range of experimental results, but an unresolved question arises in accounting for lepton masses. The charged leptons (electrons, muons and taus) have masses which vary enormously from one to another (m e = 0.511 MeV/c 2 , m μ = 106 MeV/c 2 , m τ = 1777 MeV/c 2 ), while their accompanying neutrinos appear to have no (or very little) mass. If neutrinos have finite mass, then mixing could occur among the different neutrino species. Thus, evidence of mixing would indicate the existence of non-zero neutrino mass and of the need to modify or extend the Standard Model. Consequently, this is a highly active field of physics. Evidence of possible neutrino mass and oscillation has been recently observed by the detection of energetic neutrinos from the atmosphere. The TRINAT collaboration at TRIUMF has searched for evidence of physics beyond the Standard Model using a radioactive source of 38m K atoms held in a neutral atom trap. The trap provides a source of several thousand atoms confined to a volume of less than a cubic millimeter, suspended in a vacuum vessel, in which the 38m K undergoes radioactive decay with the emission of a positron and a neutrino. This results in the creation of a daughter nucleus, 38 Ar , with momentum equal to the vector sum of the momenta of the positron and the neutrino. The unperturbed nucleus then recoils from the trap and is detected in coincidence with the positron. Through the measurement of the positron's direction and energy along with the nucleus' direction and time of flight, the neutrino momentum is deduced. The emission of a heavy neutrino would change the momentum distribution of the system and thus alter the time of flight of the recoiling nucleus as a function of positron energy. The technique permits the reconstruction of the data event-by-event, which results in an increase in both the mass range and sensitivity of the search for the possible emission of heavy neutrinos. The data were reconstructed for the recoiling nucleus' time of flight and compared to detailed Monte Carlo simulations of the TRINAT detection system. A 2-dimensional maximum likelihood search in recoil time of flight and positron energy was used to place limits on the fraction of decays involving the emission of a heavy neutrino as a function of the mass of that neutrino. (author)

  7. Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-06-26

    Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  8. Progress report: qualitative differences between first and second order fit of pressure data - 1/5 scale Mk I BWR pressure suppression experiment and analysis program

    International Nuclear Information System (INIS)

    Carr, E.; Lai, W.; McCauley, E.

    1979-01-01

    Results are presented for the 1/5-scale Mark I boiling water reactor pressure suppression experiment. The objective of this study is to calculate the hydrodynamic vertical load function (HVLF) and the maximum download and maximum upload ratios for the 90 0 sector to 7.5 0 section (i.e., the 3D to 2D ratios) together with their associated error bounds. Special graphs are presented of the pressure data that are useful in diagnostic studies of the HVLF. These graphs are three dimensional plots which depict the spatially dependent pressure as a function of time. These plots are qualitative but present an overview, not available by other means, which permits grasp of the subtle complex pattern of transient spatial changes in pressure excited by the dynamics in the pool. Sufficient text is included to describe the general feature of each plot

  9. Welcoming outsiders: The nascent Jesus community as a locus of hospitality and equality (Mk 9:33–42; 10:2–16

    Directory of Open Access Journals (Sweden)

    Zorodzai Dube

    2014-05-01

    Full Text Available The recent global economic crisis left millions of people destitute without formal work and further alienated the poor from the rich. As a remedy, modern Neoliberalism proposes that the poor must hope and steadily work their way up the economic ladder. What is the solution to such unbridgeable social and economic chasm? This article used the contemporary situation of economic inequality to imagine events during the first century, during Jesus’ time, whereby the rich increasingly amassed wealth to the disadvantage of the poor majority. In this article, Mark 9:33–42 and 10:10–16 was used to explore how Jesus developed an alternative economic system − one that contrasted itself in every respect from that of the hierarchical and patriarchal Roman Empire. This article argued that Jesus formed communities that directly responded to the economic challenges faced by the landless and the homeless majority by creating an alternative economy based on love and hospitality. This was done by proposing that Mark 9:33–42 and 10:2–16 are amongst the passages where the two rival economies were contrasted by way of two different household economies. Firstly, the economic system outside the house that typified the hierarchical Roman economy, and secondly, the economic system inside the house that referred to Jesus’ alternative system whereby he taught his disciples to welcome the homeless, the landless and the poor. Before developing this further, the plausible social context of the stories was attended to.

  10. Welcoming outsiders: The nascent Jesus community as a locus of hospitality and equality (Mk 9:33–42; 10:2–16

    Directory of Open Access Journals (Sweden)

    Zorodzai Dube

    2014-05-01

    Full Text Available The recent global economic crisis left millions of people destitute without formal work and further alienated the poor from the rich. As a remedy, modern Neoliberalism proposes that the poor must hope and steadily work their way up the economic ladder. What is the solution to such unbridgeable social and economic chasm? This article used the contemporary situation of economic inequality to imagine events during the first century, during Jesus’ time, whereby the rich increasingly amassed wealth to the disadvantage of the poor majority. In this article, Mark 9:33–42 and 10:10–16 was used to explore how Jesus developed an alternative economic system − one that contrasted itself in every respect from that of the hierarchical and patriarchal Roman Empire. This article argued that Jesus formed communities that directly responded to the economic challenges faced by the landless and the homeless majority by creating an alternative economy based on love and hospitality. This was done by proposing that Mark 9:33–42 and 10:2–16 are amongst the passages where the two rival economies were contrasted by way of two different household economies. Firstly, the economic system outside the housethat typified the hierarchical Roman economy, and secondly, the economic system inside the housethat referred to Jesus’ alternative system whereby he taught his disciples to welcome the homeless, the landless and the poor. Before developing this further, the plausible social context of the stories was attended to.

  11. ASAS KEPASTIAN HUKUM DAN ASAS KEBEBASAN BERKONTRAK SEBAGAI PERTIMBANGAN UTAMA DALAM PENYELESAIAN SENGKETA PERBANKAN SYARIAH (Kajian Yuridis Putusan MK Nomor 93/PUU-X/2012

    Directory of Open Access Journals (Sweden)

    Edi Hudiata

    2014-03-01

    The  emergence  of  the  Constitutional  Court  verdict  No.  93/PUU-X/2012  which substantially states that the explanation of Article 55 paragraph (2 of Law No. 21 of 2008 does not have binding force, basically does not violate the principle of freedom of contract which is common in contract law. The  parties  are  allowed  to  make  a  dispute  resolution  agreement  out  of  religious  court  based  on provisions as Act No. 30 of 1999 on Arbitration and Alternative Dispute Resolution.

  12. VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.

    Science.gov (United States)

    Siegel, David S; Dimopoulos, Meletios; Jagannath, Sundar; Goldschmidt, Hartmut; Durrant, Simon; Kaufman, Jonathan L; Leleu, Xavier; Nagler, Arnon; Offner, Fritz; Graef, Thorsten; Eid, Joseph E; Houp, Jennifer; Gause, Christine; Vuocolo, Scott; Anderson, Kenneth C

    2016-06-01

    The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents. Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate. The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat. The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838). Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Design and Testing of 100 mK High-voltage Electrodes for AEgIS (Proc. 25th ICEC & ICMC2014 conference)

    NARCIS (Netherlands)

    Derking, J.H.; Liberadzka, Joanna; Koettig, T.; Bremer, J.

    2015-01-01

    The AEgIS (Antimatter Experiment: Gravity, Interferometry, Spectroscopy) experiment at CERN has as main goal to perform the first direct measurement of the Earth's gravitational acceleration on antihydrogen atoms within 1% precision. To reach this precision, the antihydrogen should be cooled down to

  14. Where Does the Teaching of Advertising Belong?: The Case for the Business School Environment. Faculty Working Paper No. MK 78-28.

    Science.gov (United States)

    Patti, Charles H.

    Compelling arguments have been offered supporting both the journalism/ communication school and the business school as the ideal setting for advertising education. While relatively few advertising programs now exist in business schools, a growing number of undergraduates are finding the study of advertising in a business school environment to be…

  15. Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88.

    Science.gov (United States)

    Shao, Fenli; Tan, Tao; Tan, Yang; Sun, Yang; Wu, Xingxin; Xu, Qiang

    2016-09-01

    Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1β in the skin. The improvement in imiquimod-induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1β but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1β, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

    Directory of Open Access Journals (Sweden)

    Juan Du

    2018-04-01

    Full Text Available Andrographolide (ANDRO has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains were subjected to 3 and 21% of O2 for various times (0–12 h to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

  17. Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yan Liang

    2017-01-01

    Full Text Available Adipose tissue-derived stromal cells (ADSCs are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9. Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.

  18. Andrographolide Suppress Tumor Growth by Inhibiting TLR4/NF-κB Signaling Activation in Insulinoma

    Science.gov (United States)

    Zhang, Qian-Qian; Ding, Yi; Lei, Yan; Qi, Cui-Ling; He, Xiao-Dong; Lan, Tian; Li, Jiang-Chao; Gong, Ping; Yang, Xuesong; Geng, Jian-Guo; Wang, Li-Jing

    2014-01-01

    Insulinomas are rare tumors, and approximately 10% of insulinomas are malignant. Accumulating evidence has implicated that we still lack effective therapy to treat the patients who are diagnosed with rare malignant insulinoma. Previous studies have reported that Andrographolide (Andro) could inhibit cell cycle progression, reduce cell invasion and induce cell apoptosis in many common cancer cells. However, the effects of andro are cell type-dependent. So we emplored the β-TC-6 cells and the RIP1-Tag2 transgenic mouse model of endogenously growing insulinoma model to elucidate the possible anti-cancer effect of Andro on insulinoma, an uncommon type of malignant cancers in this study. Our experiments revealed that Andro significantly inhibited tumor growth at both the early-stage and the advanced-stage of insulinoma through targeting the TLR4/NF-κB signaling pathway. This work initially provides the evidence that the TLR4/NF-κB signaling pathway might be vital as a potential therapeutic target, and also indispensable in Andro-mediated anti-cancer effect in insulinoma. PMID:24719558

  19. Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model

    Directory of Open Access Journals (Sweden)

    Li CX

    2016-02-01

    Full Text Available Chun-xiao Li,* Hua-guo Li,* Hui Zhang,* Ru-hong Cheng, Ming Li, Jian-ying Liang, Yan Gu, Bo Ling, Zhi-rong Yao, Hong Yu Department of Dermatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Atopic dermatitis (AD is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO, a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. Objective: To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. Methods: We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. Results: ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. Conclusion: Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP. Keywords: atopic dermatitis, thymic stromal lymphopoietin, andrographolide, human mast cell

  20. Andrographolide Inhibits Mechanical and Thermal Hyperalgesia in a Rat Model of HIV-Induced Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Zhihua Yi

    2018-06-01

    Full Text Available Aim: In this study, we investigated whether andrographolide (Andro can alleviate neuropathic pain induced by HIV gp120 plus ddC treatment and the mechanism of its action.Methods: The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in all groups of the rats, including control group, control combined with Andro treatment group, sham group, gp120 combined with ddC treatment group, gp120 plus ddC combined with A438079 treatment group, and gp120 plus ddC combined with Andro treatment by intrathecally injecting at a dose of 25 μg/20 μl group. The protein expression levels of the P2X7 receptor, tumor necrosis factor-α-receptor (TNFα-R, interleukin-1β (IL-1β, IL-10, phospho-extracellular regulated protein kinases (ERK (p-ERK in the L4–L6 dorsal root ganglia (DRG were measured by western blotting. Real-time quantitative polymerase chain reaction was used to test the mRNA expression level of the P2X7 receptor. Double-labeling immunofluorescence was used to identify the co-localization of the P2X7 receptor with glial fibrillary acidic protein (GFAP in DRG. Molecular docking was performed to identify whether the Andro interacted perfectly with the rat P2X7 (rP2X7 receptor.Results: Andro attenuated the mechanical and thermal hyperalgesia in gp120+ddC-treated rats and down-regulated the P2X7 receptor mRNA and protein expression in the L4–L6 DRGs of gp120+ddC-treated rats. Additionally, Andro simultaneously decreased the expression of TNFα-R and IL-1β protein, increased the expression of IL-10 protein in L4–L6 DRGs, and inhibited the activation of ERK signaling pathways. Moreover, Andro decreased the co-expression of GFAP and the P2X7 receptor in the SGCs of L4–L6 DRG on 14th day after surgery.Conclusion: Andro decreased the hyperalgesia induced by gp120 plus ddC.

  1. Mobile Phones Coupled with Remote Sensors for Surveillance

    Science.gov (United States)

    2012-03-01

    Buildroot, that supports C/C++ and Java programming languages. The use of the configuration GUI is supported by an internet browser. 7 For remote...C++, Flash 9, Flex, Java , LabVIEW, Python, Max/MSP, and Cocoa [4]. The following are the specifications of the 1072 PhidgetSBC2 from the product...Gyroscope can measure angular rotation up to ±400° per second.  Magnetometer, or compass, measures the magnetic field up to ±4 Gauss. It reports

  2. The UK Army officers’ Experience with the ROCC Model and its Implications for Captains Education in the US Army

    Science.gov (United States)

    2011-06-10

    analysis of how the demographics impact the research. Table 2. Responses to Survey Question 1 JOLP1 JOLP2 JOLP3 MK1 MK2 MK2a MA1 MA2 MA3 JOTAC...programmes of instruction you completed.158 Table 2. Responses to Survey Question 1 JOLP1 JOLP2 JOLP3 MK1 MK2 MK2a MA1 MA2 MA3 JOTAC JOTES ET

  3. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women

    Directory of Open Access Journals (Sweden)

    Sato Toshiro

    2012-11-01

    Full Text Available Abstract Background Vitamin K2 contributes to bone and cardiovascular health. Therefore, two vitamin K2 homologues, menaquinone-4 (MK-4 and menaquinone-7 (MK-7, have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women. Findings Single dose administration of MK-4 (420 μg; 945 nmol or MK-7 (420 μg; 647 nmol was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 μg; 135 nmol or MK-7 (60 μg; 92 nmol for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects. Conclusions We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.

  4. Andrographolide inhibits hypoxia-inducible factor-1 through phosphatidylinositol 3-kinase/AKT pathway and suppresses breast cancer growth

    Directory of Open Access Journals (Sweden)

    Li J

    2015-02-01

    Full Text Available Jie Li,1 Chao Zhang,1 Hongchuan Jiang,1 Jiao Cheng21Department of General Surgery, 2Department of Gynaecology and Obstetrics, Beijing Chao-Yang Hospital, Beijing, People’s Republic of ChinaAbstract: Hypoxia-inducible factor-1 (HIF-1 is a master regulator of the transcriptional response to hypoxia. HIF-1α is one of the most compelling anticancer targets. Andrographolide (Andro was newly identified to inhibit HIF-1 in T47D cells (a half maximal effective concentration [EC50] of 1.03×10-7 mol/L, by a dual-luciferase reporter assay. It suppressed HIF-1α protein and gene accumulation, which was dependent on the inhibition of upstream phosphatidylinositol 3-kinase (PI3K/AKT pathway. It also abrogated the expression of HIF-1 target vascular endothelial growth factor (VEGF gene and protein. Further, Andro inhibited T47D and MDA-MB-231 cell proliferation and colony formation. In addition, it exhibited significant in vivo efficacy and antitumor potential against the MDA-MB-231 xenograft in nude mice. In conclusion, these results highlighted the potential effects of Andro, which inhibits HIF-1, and hence may be developed as an antitumor agent for breast cancer therapy in future.Keywords: Andrographolide (Andro, HIF-1α, inhibit, breast cancer, hypoxia, PI3k/AKT/mTOR pathway

  5. Grunge kodukujunduses / Ene Vool

    Index Scriptorium Estoniae

    Vool, Ene, 1948-

    2004-01-01

    Low-tech, campi ja grunge ehitus- ja sisustusstiilidest meil ja mujal - kommenteerivad Andro Kööp ja Ain Nurmela. Tutvustatakse ka Mari-Mira projekti Pariisis, mis kujutab endast nn. mutant-küla, putka- ja onnikultuuri koketeriid. Artikli lõpus kommenteerib kunstiteadlane Karin Paulus grungestiili muusikas, riietuses ja sisekujunduses.

  6. AcEST: DK953429 [AcEST

    Lifescience Database Archive (English)

    Full Text Available andro A. Schaffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), Gapped BLAST and PSI...2.2.19 [Nov-02-2008] Reference: Altschul, Stephen F., Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Zheng Zhang, Web

  7. Tartu Tervishoiu Kõrgkool = Tartu Health Care College

    Index Scriptorium Estoniae

    2015-01-01

    Tartu Tervishoiu Kõrgkool Nooruse tänav 5, valminud 2011. Arhitektid Indrek Peil, Siiri Vallner (Kavakava), kaasautorid Johannes Feld, Sten-Mark Mändmaa, Andro Mänd, Ragnar Põllukivi. Sisearhitekt Tarmo Piirmets (Pink). Konstruktorid Ivar Muuk, Andres Hirve (Pike)

  8. Development of a 10 kGy(Si) rad hard controller for a mobile robot using COTS

    International Nuclear Information System (INIS)

    Alexandre, J.M.; Marceau, M.

    1999-01-01

    The CEA has developed a 10 kGy(Si) hardened controller using only COTS (Commercial-Off-The-Shelf devices), to equip the mobile robot Andros. An electronic architecture adapted to the constraint of hardening have been carried out, leading to the construction of a complete set of electronics modules (power electronic, control computer). (authors)

  9. Finding the Average Speed of a Light-Emitting Toy Car with a Smartphone Light Sensor

    Science.gov (United States)

    Kapucu, Serkan

    2017-01-01

    This study aims to demonstrate how the average speed of a light-emitting toy car may be determined using a smartphone's light sensor. The freely available Android smartphone application, "AndroSensor," was used for the experiment. The classroom experiment combines complementary physics knowledge of optics and kinematics to find the…

  10. Männiku sotsiaalelamu = Social housing in Männiku / Peeter Pere

    Index Scriptorium Estoniae

    Pere, Peeter, 1957-

    2012-01-01

    2012. a. Tallinnas Männiku tee 92 valminud inva- ja peremajutamiseks mõeldud sotsiaalelamu, vana ühiselamu ümberprojekteerimine. Arhitektid: Siiri Vallner, Indrek Peil, Kaire Nõmm, kaasautorid: Ragnar Põllukivi, Andro Mänd, Kadri Klementi (Kavakava). Sisearhitekt Tarmo Piirmets (Pink). Projekt: 2010-2011

  11. Performance-Enhancing Drugs: Know the Risks

    Science.gov (United States)

    ... edge by taking muscle-building supplements or other performance-enhancing drugs? Learn how these drugs work and how they can affect your health. By ... to testosterone and estradiol in both men and women. Andro is available legally ... use as a performance-enhancing drug is illegal in the United States. ...

  12. Riigi kultuuristipendiumid jagatud / Reet Weidebaum

    Index Scriptorium Estoniae

    Weidebaum, Reet

    2000-01-01

    Kultuuriminister Signe Kivi määras 2000. a. riigi kultuuristipendiumide II jaotuse kümme 24000 kroonist stipendiumi (kunstiinimestest Andro Kööp, Ave Räkk, Mariann Raisma, Epi Tohvri). III jaotuse avaldusi võetakse vastu 20. aug.-ni.

  13. I.L.U. kauplused = I.L.U. stores

    Index Scriptorium Estoniae

    2010-01-01

    Tallinnas Rocca al Mare kaubanduskeskuses, Tartus Lõunakeskuses ja Pärnus Pärnu Keskuses asuvate I.L.U. kosmeetikakaupkuste sisekujundusest. Sisekujunduse autorid: Triinu Kuub, Andro Kööp, Andri Valk (Torpedo OÜ), nende tähtsamate tööde loetelu. Graafiline disain: reklaamifirma Tank

  14. Kujundusideid / Ketlin Priilinn

    Index Scriptorium Estoniae

    Priilinn, Ketlin, 1982-

    2006-01-01

    Eesti sisearhitektide Annes Arro, Jorma Holmi, Kaire Kemp-Tishleri (kamina sepised Heigo Jelle), Andro Kööbi, Rein Lauri (seintel Anne Parmasto ja Rein Kelpmanni maalid), Taso Mähari (eramu arhitekt Emil Urbel, seinal Lemming Nageli maal "Punane joon all - Burn Out"), Eerik Olle, Meelis Pressi ja Anu Vainomäe kujundatud elutoad. 33 värv. ill

  15. Andrographolide induces degradation of mutant p53 via activation of Hsp70.

    Science.gov (United States)

    Sato, Hirofumi; Hiraki, Masatsugu; Namba, Takushi; Egawa, Noriyuki; Baba, Koichi; Tanaka, Tomokazu; Noshiro, Hirokazu

    2018-05-22

    The tumor suppressor gene p53 encodes a transcription factor that regulates various cellular functions, including DNA repair, apoptosis and cell cycle progression. Approximately half of all human cancers carry mutations in p53 that lead to loss of tumor suppressor function or gain of functions that promote the cancer phenotype. Thus, targeting mutant p53 as an anticancer therapy has attracted considerable attention. In the current study, a small-molecule screen identified andrographlide (ANDRO) as a mutant p53 suppressor. The effects of ANDRO, a small molecule isolated from the Chinese herb Andrographis paniculata, on tumor cells carrying wild-type or mutant p53 were examined. ANDRO suppressed expression of mutant p53, induced expression of the cyclin-dependent kinase inhibitor p21 and pro-apoptotic proteins genes, and inhibited the growth of cancer cells harboring mutant p53. ANDRO also induced expression of the heat-shock protein (Hsp70) and increased binding between Hsp70 and mutant p53 protein, thus promoting proteasomal degradation of p53. These results provide novel insights into the mechanisms regulating the function of mutant p53 and suggest that activation of Hsp70 may be a new strategy for the treatment of cancers harboring mutant p53.

  16. NCBI nr-aa BLAST: CBRC-TTRU-01-0857 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-0857 ref|YP_073322.1| NADH dehydrogenase subunit 2 [Neomaskellia andro...pogonis] gb|AAS75448.1| NADH dehydrogenase subunit 2 [Neomaskellia andropogonis] YP_073322.1 5e-04 23% ...

  17. NCBI nr-aa BLAST: CBRC-DNOV-01-2150 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-2150 ref|YP_073317.1| NADH dehydrogenase subunit 6 [Neomaskellia andro...pogonis] gb|AAS75443.1| NADH dehydrogenase subunit 6 [Neomaskellia andropogonis] YP_073317.1 0.86 27% ...

  18. NCBI nr-aa BLAST: CBRC-BTAU-01-1417 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-1417 ref|YP_073322.1| NADH dehydrogenase subunit 2 [Neomaskellia andro...pogonis] gb|AAS75448.1| NADH dehydrogenase subunit 2 [Neomaskellia andropogonis] YP_073322.1 0.025 25% ...

  19. Viljandi Riigigümnaasium = Viljandi Upper Secondary School

    Index Scriptorium Estoniae

    2015-01-01

    Viljandi Riigigümnaasiumi uus hoone Hariduse tänav 2, valminud 2013. Arhitektuuri sihtkapitali arhitektuuripreemia 2013 ja Arhitektuuri sihtkapitali renoveerimispreemia 2013. Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Andro Mänd, Margus Tamm (Salto Arhitektid), Eva Laarmann. Sisearhitektid Pille Lausmäe, Kristina Roots, Kerli Lepp. Muinsuskaitse eritingimused Mart Siilivask

  20. Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Richard J Servatius

    2016-08-01

    Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  1. Hrázděné stěny v podkrovích českých a moravských zámků

    Czech Academy of Sciences Publication Activity Database

    Bláha, Jiří

    2016-01-01

    Roč. 14, č. 1 (2016), s. 255-270 ISSN 1802-8128 R&D Projects: GA MŠk(CZ) LO1219 Keywords : built heritage * chateaux and castles * timber framed constructions * half–timbered walls * roof timber frames * attics Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: History (history of science and technology to be 6.3, history of specific sciences to be under the respective headings)

  2. Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment

    OpenAIRE

    Paulus, A; Akhtar, S; Yousaf, H; Manna, A; Paulus, S M; Bashir, Y; Caulfield, T R; Kuranz-Blake, M; Chitta, K; Wang, X; Asmann, Y; Hudec, R; Springer, W; Ailawadhi, S; Chanan-Khan, A

    2017-01-01

    Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9?3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed ...

  3. Sosyolojik Teoriler Bağlamında Yapısalcı Analizin İmkânı ve Sınırlılıkları

    OpenAIRE

    Keskin, İbrahim

    2014-01-01

    The Concept of subject representing the central position in the modern social sciences has been criticized seriously by the structuralism, putting the structure instead of the subject. In addition to this, the structuralism has criticized the understanding of evolutionist history which is from the basic features of the modern thought. The criticism of subject in the structuralism have been transformed to the post- structuralism, by making it more radical. The post-structuralism claims that t...

  4. Dlouhodobá dynamika šíření bolševníku velkolepého (Heracleum mantegazzianum) v krajině: využití leteckých snímků

    Czech Academy of Sciences Publication Activity Database

    Müllerová, Jana; Pyšek, Petr; Pergl, Jan; Jarošík, Vojtěch

    2008-01-01

    Roč. 43, Mater. 23 (2008), s. 91-102 ISSN 1212-3323. [Rostlinné invaze v ČR: situace, výzkum a management. Praha, 30.11.2007-01.12.2007] R&D Projects: GA AV ČR IAA600050811; GA MŠk LC06073 Grant - others:EK(XE) GIANT ALIEN (EVK2-CT-2001-00128) Institutional research plan: CEZ:AV0Z60050516 Keywords : history of invasion * giant hogweed * rate of invasion Subject RIV: EF - Botanics

  5. WATER DEPTH - AVERAGE and Reflectance- Intensity collected from LADS Mk II Airborne System in Caribbean Sea and Puerto Rico from 2006-04-07 to 2006-05-15 (NCEI Accession 0153360)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These images represent LiDAR (Light Detection & Ranging) data collected by NOAA from the shoreline of southwestern Puerto Rico to about 50 meters in depth....

  6. Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits

    Czech Academy of Sciences Publication Activity Database

    Uttl, Libor; Petrásek, Tomáš; Sengul, Hilal; Svojanovská, Markéta; Lobellová, Veronika; Valeš, Karel; Radostová, Dominika; Tsenov, Grygoriy; Kubová, Hana; Mikulecká, Anna; Svoboda, Jan; Stuchlík, Aleš

    2018-01-01

    Roč. 9, Feb 12 (2018), č. článku 42. ISSN 1663-9812 R&D Projects: GA MŠk(CZ) LM2015062; GA ČR NV17-30833A Grant - others:AV ČR(CZ) PAN-17-07 Program:Bilaterální spolupráce Institutional support: RVO:67985823 Keywords : schizophrenia * animal model * dizocilpine * rats * chronic treatment * western blot * behavior Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.400, year: 2016

  7. Památky starověké Núbie na známkách světa // Monuments of Ancient Nubia on postage stamps of the modern world

    Directory of Open Access Journals (Sweden)

    Břetislav Vachala

    2015-06-01

    Full Text Available The successful International UNESCO Campaign to Save the Monuments of (Egyptian and Sudanese Nubia became an important motif on the postage stamps of 47 countries of the world in the years 1960–1980. The stamps host famous rescued temples (listed here according to frequency of the used motifs, including general views, details of architecture and relief decoration of Abu Simbel, Philae, Wadi es-Sebua, and Dakka, the Kiosk of Qertassi and the South - ern temple of Buhen. Moreover, some of the unique painted murals found in the episcopal cathedral at Faras were reproduced on Polish stamps. The philatelic contribution to the campaign was far from symbolic. The total philatelic revenue (including income from the Philae Medals reached 112,665.64 US dollars. The philatelic activity of 47 countries substantially contributed to the publicity of the UNESCO Nubia Campaign around the world.

  8. Prediction of Propellant and Explosive Cook-Off for the 30-mm HEI-T and Raufoss MPLD-T Rounds Chambered in a Hot MK44 Barrel (Advanced Amphibious Assault Vehicle - AAAV

    National Research Council Canada - National Science Library

    Witherell, Mark

    2001-01-01

    ... interior ballistics program. Heat transfer between the barrel, projectile, and the environment during a simulated misfire event was modeled using the ABAQUS finite element program with the initial barrel temperature distribution...

  9. Právní ochrana loga z hlediska autorského zákona a zákona o ochranných známkách

    OpenAIRE

    Krbová, Lucie

    2012-01-01

    In this thesis I explain the problematic situation presented by the legal protection of logos in the Czech Republic. I chose this topic because logos are a daily part of everyones' lives helping us make important every day decisions. Yet logo is not a legal term and sometimes it can be difficult to define what logo actually is. This doesn't mean to say that logos do not have legal protection. It always depends on the definition of logo. Usually a logo enjoys the same rights as the brand it re...

  10. Systemic administration of MK-801, a non-competitive NMDA-receptor antagonist, elicits a behavioural deficit of rats in the Active Allothetic Place Avoidance (AAPA) task irrespectively of their intact spatial pretraining

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Valeš, Karel

    2005-01-01

    Roč. 159, č. 1 (2005), s. 163-171 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GP309/03/P126; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z5011922 Keywords : schizophrenia * animal model * rat Subject RIV: FH - Neurology Impact factor: 2.865, year: 2005

  11. Určování mikrostrukturních deskriptorů z digitálních snímků pórovitých látek

    Czech Academy of Sciences Publication Activity Database

    Hejtmánek, Vladimír; Čapek, P.; Brabec, Libor; Zikánová, Arlette; Kočiřík, Milan

    2009-01-01

    Roč. 103, č. 6 (2009), s. 496-502 ISSN 0009-2770 R&D Projects: GA ČR GA203/05/0347; GA AV ČR IAA400400501 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z40400503 Keywords : porosity * image processing * phase function Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.717, year: 2009

  12. K periferním lexikálním přejímkám středověkého slovníkáře

    Czech Academy of Sciences Publication Activity Database

    Nejedlý, Petr

    2015-01-01

    Roč. 98, č. 5 (2015), s. 238-242 ISSN 0027-8203 R&D Projects: GA ČR GAP406/10/1153 Institutional support: RVO:68378092 Keywords : lexical reconstruction * Master Klaret * Old Czech * lexicon * meaning * origin of the word * semantics Subject RIV: AI - Linguistics

  13. Comment on: Shukla, M.K. et al., 2006: Physical and chemical properties of soils under some pinon-juniper-oak canopies in a semi-arid ecosystem in New Mexico

    DEFF Research Database (Denmark)

    Mollerup, Mikkel; Jensen, Jens Raunsø

    2008-01-01

    The paper by Shukla et al. [2006. Physical and chemical properties of soils under some pinon-juniper-oak canopies in an semi-arid ecosystem in New Mexico. Journal of Arid Environment 66, 673-685] treats interesting topics of sustainability of different ecosystems and their water availability....... However, the physical-based infiltration theories by Green and Ampt [1911. Studies on soil physics, I, flow of air and water through soils. Journal of Agricultural Science 4, 1-24] and Philip [1957. The theory of infiltration: 1. The infiltration equation and its solution. Soil Science 83, 345-357] seems...... to be applied without necessary reflections. The actual analysis can have resulted in coefficients without their original physical significance...

  14. Scenario-Based Systems Engineering Application to Mine Warfare

    Science.gov (United States)

    2015-12-01

    hunter- killer capabilities to find, classify, and destroy moored and bottom mines with sonar and video systems, cable cutting devices, and mine...Method: Serial 3 LCS MH-60s LCS: RMS with AN/AQS-20, MH-60s: Archerfish Hunt Method: Serial 1M MK18 MH-60s LCS: MK18 Mod 2, MH-60s...Archerfish Hunt Method: Serial 2M MK18 MH-60s LCS: MK18 Mod 2, MH-60s: Archerfish Hunt Method: Serial 3M MK18 MH-60s LCS: MK18

  15. Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Ruo-Jing Wei

    2018-01-01

    Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer (PCa cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPr1, and LNCaP cells were treated with Andrographolide (Andro and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction (PCR and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species (ROS in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.

  16. Formal Methods for Biological Systems: Languages, Algorithms, and Applications

    Science.gov (United States)

    2016-09-01

    Statistical tests, Pancreatic cancer, Phage-based bacteria killing, Prostate cancer treatment, C. elegans For My Beloved Mom & Dad iv Abstract As...structured objects and to use pattern-based rules to encode their interactions. So that, a rich yet concise description of signaling proteins and their...effects of CAS and to delay the time to relapse, intermittent andro- gen suppression (IAS) was proposed aiming to limit the duration of androgen- poor

  17. Korporatiivspaa koolitab tallinlastest tallinklasi / Urmas Oja

    Index Scriptorium Estoniae

    Oja, Urmas, 1981-2012

    2007-01-01

    Tallink Spa & Conference Hotel Tallinnas Sadama 11a. Arhitektid: Indrek Tiigi, Ülar Mark, AB Urban Mark. Sisearhitektid: Andro Kööp, Tairo Pärnamets, SAB Torpedo Interior. Ehituse peatöövõtja: AS Merko Ehitus. Hotellitubade seintel on Heiki-Erich Merila fotod, spaa-alal Hannes Starkopfi kujud. Ehituse kestus: veebruar 2006-märts 2007. A. Kööbi ja I. Tiigi kommentaar. Välisvaade, 5 sisevaadet

  18. Pärnu Keskkonnahariduskeskus = Pärnu Environmental Education Centre

    Index Scriptorium Estoniae

    2015-01-01

    Pärnu Keskkonnahariduskeskus A.H. Tammsaare puiestee 57, valminud 2013. Arhitektuurivõistlus 2006, jagatud III koht. Võistlustöö autorid Maarja Kask, Karli Luik, Ralf Lõoke (Salto Arhitektuuribüroo). Arhitektid Maarja Kask, Karli Luik, Ralf Lõoke, Helin Kukk, Andro Mänd, Helen Rebane, Margus Tamm. Pärnumaa püsinäituse kujundus Malle Jürgenson, Krista Lepland (Laika, Belka & Strelka)

  19. Tartu Ülikooli Narva Kolledž = Narva College of the University of Tartu

    Index Scriptorium Estoniae

    2015-01-01

    Tartu Ülikooli Narva Kolledž Raekoja plats 2, valminud 2012. Eesti kultuurkapitali aastapreemia 2013. Arhitektid Siiri Vallner, Katrin Koov, Indrek Peil (Kavakava), kaasautorid Heidi Urb, Andro Mänd, Sten-Mark Mändmaa, Maarja Tüür, sisearhitekt Hannes Praks. Kaasa töötasid Kadri Tamme, Kristjan Holm, Liisi Murula, Toomas Pääsuke, Ahti Grünberg, Daniel Marius Reisser, Helen Sarapuu

  20. The 17th Annual Intelligent Ground Vehicle Competition: Intelligent Robots Built by Intelligent Students

    Science.gov (United States)

    2009-11-23

    intelligent mobile robots. The competition has been highly praised by faculty advisors as an excellent multidisciplinary design experience for...States Naval Academy Robo -Goat 60 0:54 21 Oakland University Moonwalker 54 0:22 22 Tennessee Technological University Andros 53 1:06 23 California...Naval Academy Robo -Goat 622.00 20 University of Michigan – Dearborn Rhino 568.50 21 Georgia Institute of Technology Candiii 533.00 22 Rose-Hulman