Conceptual Design of a Clinical BNCT Beam in an Adjacent Dry Cell of the Jozef Stefan Institute TRIGA Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maucec, Marko

2000-11-15

The MCNP4B Monte Carlo transport code is used in a feasibility study of the epithermal neutron boron neutron capture therapy facility in the thermalizing column of the 250-kW TRIGA Mark II reactor at the Jozef Stefan Institute (JSI). To boost the epithermal neutron flux at the reference irradiation point, the efficiency of a fission plate with almost 1.5 kg of 20% enriched uranium and 2.3 kW of thermal power is investigated. With the same purpose in mind, the TRIGA reactor core setup is optimized, and standard fresh fuel elements are concentrated partly in the outermost ring of the core. Further,more » a detailed parametric study of the materials and dimensions for all the relevant parts of the irradiation facility is carried out. Some of the standard epithermal neutron filter/moderator materials, as well as 'pressed-only' low-density Al{sub 2}O{sub 3} and AlF{sub 3}, are considered. The proposed version of the BNCT facility, with PbF{sub 2} as the epithermal neutron filter/moderator, provides an epithermal neutron flux of {approx}1.1 x 10{sup 9} n/cm{sup 2}.s, thus enabling patient irradiation times of <60 min. With reasonably low fast neutron and photon contamination ([overdot]D{sub nfast}/{phi}{sub epi} < 5 x 10{sup -13} Gy.cm{sup 2}/n and [overdot]D{sub {gamma}} /{phi}{sub epi} < 3 x 10{sup -13} Gy.cm{sup 2}/n), the in-air performances of the proposed beam are comparable to all existing epithermal BNCT facilities. The design presents an equally efficient alternative to the BNCT beams in TRIGA reactor thermal columns that are more commonly applied. The cavity of the dry cell, a former JSI TRIGA reactor spent-fuel storage facility, adjacent to the thermalizing column, could rather easily be rearranged into a suitable patient treatment room, which would substantially decrease the overall developmental costs.« less

SFC/MS in drug discovery at Pfizer, La Jolla

NASA Astrophysics Data System (ADS)

Bolaños, Ben; Greig, Michael; Ventura, Manuel; Farrell, William; Aurigemma, Christine M.; Li, Haitao; Quenzer, Terri L.; Tivel, Kathleen; Bylund, Jessica M. R.; Tran, Phuong; Pham, Catherine; Phillipson, Doug

2004-11-01

We report the use of supercritical fluid chromatography/mass spectrometry (SFC/MS) for numerous applications in drug discovery at Pfizer, La Jolla. Namely, SFC/MS has been heavily relied upon for analysis and purification of a diverse set of compounds from the in-house chemical library. Supporting high-speed SFC/MS quality control of the purified compounds is made possible at high flow rate SFC along with time-of-flight mass detection. The flexibility of SFC/MS systems has been extended with the integration of an atmospheric pressure photoionization source (APPI) for use with more non-polar compounds and enhancements in signal to noise. Further SFC/MS applications of note include chiral analysis for purification and assessment of enantiomers and SFC/MS analysis of difficult to separate hydrophobic peptides.

Anatomy of La Jolla submarine canyon system; offshore southern California

USGS Publications Warehouse

Paull, C.K.; Caress, D.W.; Lundsten, E.; Gwiazda, R.; Anderson, K.; McGann, M.; Conrad, J.; Edwards, B.; Sumner, E.J.

2013-01-01

An autonomous underwater vehicle (AUV) carrying a multibeam sonar and a chirp profiler was used to map sections of the seafloor within the La Jolla Canyon, offshore southern California, at sub-meter scales. Close-up observations and sampling were conducted during remotely operated vehicle (ROV) dives. Minisparker seismic-reflection profiles from a surface ship help to define the overall geometry of the La Jolla Canyon especially with respect to the pre-canyon host sediments. The floor of the axial channel is covered with unconsolidated sand similar to the sand on the shelf near the canyon head, lacks outcrops of the pre-canyon host strata, has an almost constant slope of 1.0° and is covered with trains of crescent shaped bedforms. The presence of modern plant material entombed within these sands confirms that the axial channel is presently active. The sand on the canyon floor liquefied during vibracore collection and flowed downslope, illustrating that the sediment filling the channel can easily fail even on this gentle slope. Data from the canyon walls help constrain the age of the canyon and extent of incision. Horizontal beds of moderately cohesive fine-grained sediments exposed on the steep canyon walls are consistently less than 1.232 million years old. The lateral continuity of seismic reflectors in minisparker profiles indicate that pre-canyon host strata extend uninterrupted from outside the canyon underneath some terraces within the canyon. Evidence of abandoned channels and point bar-like deposits are noticeably absent on the inside bend of channel meanders and in the subsurface of the terraces. While vibracores from the surface of terraces contain thin (< 10 cm) turbidites, they are inferred to be part of a veneer of recent sediment covering pre-canyon host sediments that underpin the terraces. The combined use of state of the art seafloor mapping and exploration tools provides a uniquely detailed view of the morphology within an active submarine canyon.

Benchmarking criticality analysis of TRIGA fuel storage racks.

PubMed

Robinson, Matthew Loren; DeBey, Timothy M; Higginbotham, Jack F

2017-01-01

A criticality analysis was benchmarked to sub-criticality measurements of the hexagonal fuel storage racks at the United States Geological Survey TRIGA MARK I reactor in Denver. These racks, which hold up to 19 fuel elements each, are arranged at 0.61m (2 feet) spacings around the outer edge of the reactor. A 3-dimensional model was created of the racks using MCNP5, and the model was verified experimentally by comparison to measured subcritical multiplication data collected in an approach to critical loading of two of the racks. The validated model was then used to show that in the extreme condition where the entire circumference of the pool was lined with racks loaded with used fuel the storage array is subcritical with a k value of about 0.71; well below the regulatory limit of 0.8. A model was also constructed of the rectangular 2×10 fuel storage array used in many other TRIGA reactors to validate the technique against the original TRIGA licensing sub-critical analysis performed in 1966. The fuel used in this study was standard 20% enriched (LEU) aluminum or stainless steel clad TRIGA fuel. Copyright © 2016. Published by Elsevier Ltd.

Operations of a TRIGA reactor at a small private liberal arts college

DOE Office of Scientific and Technical Information (OSTI.GOV)

Church, L.B.

A small private liberal arts college is not a very representative place to have a TRIGA reactor. Reed is a wholly undergraduate institution with a strong emphasis in the traditional liberal arts and fundamental sciences. Many of the larger state universities provide an excellence in nuclear science which is often presented to students in a somewhat distant manner. By providing a reactor that was immediately accessible to undergraduate students it has been realized that the excitement attendant with nuclear science would be available to them in an immediate hands-on manner.

Development of the ageing management database of PUSPATI TRIGA reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramli, Nurhayati, E-mail: nurhayati@nm.gov.my; Tom, Phongsakorn Prak; Husain, Nurfazila

Since its first criticality in 1982, PUSPATI TRIGA Reactor (RTP) has been operated for more than 30 years. As RTP become older, ageing problems have been seen to be the prominent issues. In addressing the ageing issues, an Ageing Management (AgeM) database for managing related ageing matters was systematically developed. This paper presents the development of AgeM database taking into account all RTP major Systems, Structures and Components (SSCs) and ageing mechanism of these SSCs through the system surveillance program.

Transition from HEU to LEU fuel in Romania`s 14-MW TRIGA reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bretscher, M.M.; Snelgrove, J.L.

1991-12-31

The 14-MW TRIGA steady state reactor (SSR) located in Pitesti, Romania, first went critical in the fall of 1979. Initially, the core configuration for full power operation used 29 fuel clusters each containing a 5 {times} 5 square array of HEU (10 wt%) -- ZrH -- Er (2.8 wt%) fuel-moderator rods (1.295 cm o.d.) clad in Incology. With a total inventory of 35 HEU fuel clusters, burnup considerations required a gradual expansion of the core from 29 to 32 and finally to 35 clusters before the reactor was shut down because of insufficient excess reactivity. At this time each ofmore » the original 29 fuel clusters had an overage {sup 235}U burnup in the range from 50 to 62%. Because of the US policy regarding the export of highly enriched uranium, fresh HEU TRIGA replacement fuel is not available. After a number of safety-related measurements, the SSR is expected to resume full power operation in the near future using a mixed core containing five LEU TRIGA clusters of the same geometry as the original fuel but with fuel-moderator rods containing 45 wt% U (19.7% {sup 235}U enrichment) and 1.1 wt% Er. Rods for 14 additional LEU fuel clusters will be fabricated by General Atomics. In support of the SSR mixed core operation numerous neutronic calculations have been performed. This paper presents some of the results of those calculations.« less

The SANS facility at the Pitesti 14MW TRIGA reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ionita, I.; Grabcev, B.; Todireanu, S.

2006-12-15

The SANS facility existing at the Pitesti 14MW TRIGA reactor is presented. The main characteristics and the preliminary evaluation of the installation performances are given. A monochromatic neutron beam with 1.5 A {<=} {lambda} {<=} 5 A is produced by a mechanical velocity selector with helical slots. A fruitful partnership was established between INR Pitesti (Romania) and JINR Dubna (Russia). The first step in this cooperation consists in the manufacturing in Dubna of a battery of gas-filled positional detectors devoted to the SANS instrument.

Computational analysis of the dose rates at JSI TRIGA reactor irradiation facilities.

PubMed

Ambrožič, K; Žerovnik, G; Snoj, L

2017-12-01

The JSI TRIGA Mark II, IJS research reactor is equipped with numerous irradiation positions, where samples can be irradiated by neutrons and γ-rays. Irradiation position selection is based on its properties, such as physical size and accessibility, as well as neutron and γ-ray spectra, flux and dose intensities. This paper presents an overview on the neutron and γ-ray fluxes, spectra and dose intensities calculations using Monte Carlo MCNP software and ENDF/B-VII.0 nuclear data libraries. The dose-rates are presented in terms of ambient dose equivalents, air kerma, and silicon dose equivalent. At full reactor power the neutron ambient dose equivalent ranges from 5.5×10 3 Svh -1 to 6×10 6 Svh -1 , silicon dose equivalent from 6×10 2 Gy/h si to 3×10 5 Gy/h si , and neutron air kerma from 4.3×10 3 Gyh -1 to 2×10 5 Gyh -1 . Ratio of fast (1MeVreactor power from 3.4×10 3 Svh -1 to 3.6×10 5 Svh -1 and γ air kerma range 3.1×10 3 Gyh -1 to 2.9×10 5 Gyh -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Supplemental Reactor Physics Calculations and Analysis of ELF Mk 1A Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pope, Michael A.

2014-10-01

These calculations supplement previous the reactor physics work evaluating the Enhanced Low Enriched Uranium (LEU) Fuel (ELF) Mk 1A element. This includes various additional comparisons between the current Highly Enriched Uranium (HEU) and LEU along with further characterization of the performance of the ELF fuel. The excess reactivity to be held down at BOC for ELF Mk 1A fuel is estimated to be approximately $2.75 greater than with HEU for a typical cycle. This is a combined effect of the absence of burnable poison in the ELF fuel and the reduced neck shim worth in LEU fuel compared to HEU.more » Burnable poison rods were conceptualized for use in the small B positions containing Gd2O3 absorber. These were shown to provide $2.37 of negative reactivity at BOC and to burn out in less than half of a cycle. The worth of OSCCs is approximately the same between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. This was evaluated by rotating all banks simultaneously. The safety rod worth is relatively unchanged between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. However, this should be reevaluated with different loadings. Neutron flux, both total and fast (>1 MeV), is either the same or reduced upon changing from HEU to ELF Mk 1A (LEU) fuels in the representative loading evaluated. This is consistent with the well-established trend of lower neutron fluxes for a given power in LEU than HEU.The IPT loop void reactivity is approximately the same or less positive with ELF Mk 1A (LEU) fuel than HEU in the representative loading evaluated.« less

Neutron detection of the Triga Mark III reactor, using nuclear track methodology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Espinosa, G., E-mail: espinosa@fisica.unam.mx; Golzarri, J. I.; Raya-Arredondo, R.

Nuclear Track Methodology (NTM), based on the neutron-proton interaction is one often employed alternative for neutron detection. In this paper we apply NTM to determine the Triga Mark III reactor operating power and neutron flux. The facility nuclear core, loaded with 85 Highly Enriched Uranium as fuel with control rods in a demineralized water pool, provide a neutron flux around 2 × 10{sup 12} n cm{sup −2} s{sup −1}, at the irradiation channel TO-2. The neutron field is measured at this channel, using Landauer{sup ®} PADC as neutron detection material, covered by 3 mm Plexiglas{sup ®} as converter. After exposure, plasticmore » detectors were chemically etched to make observable the formed latent tracks induced by proton recoils. The track density was determined by a custom made Digital Image Analysis System. The resulting average nuclear track density shows a direct proportionality response for reactor power in the range 0.1-7 kW. We indicate several advantages of the technique including the possibility to calibrate the neutron flux density measured at low reactor power.« less

77 FR 7613 - Dow Chemical Company; Dow Chemical TRIGA Research Reactor; Facility Operating License No. R-108

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-264; NRC-2012-0026] Dow Chemical Company; Dow Chemical TRIGA Research Reactor; Facility Operating License No. R-108 AGENCY: Nuclear Regulatory Commission... Facility Operating License No. R-108 (``Application''), which currently authorizes the Dow Chemical Company...

Relative fission product yield determination in the USGS TRIGA Mark I reactor

NASA Astrophysics Data System (ADS)

Koehl, Michael A.

Fission product yield data sets are one of the most important and fundamental compilations of basic information in the nuclear industry. This data has a wide range of applications which include nuclear fuel burnup and nonproliferation safeguards. Relative fission yields constitute a major fraction of the reported yield data and reduce the number of required absolute measurements. Radiochemical separations of fission products reduce interferences, facilitate the measurement of low level radionuclides, and are instrumental in the analysis of low-yielding symmetrical fission products. It is especially useful in the measurement of the valley nuclides and those on the extreme wings of the mass yield curve, including lanthanides, where absolute yields have high errors. This overall project was conducted in three stages: characterization of the neutron flux in irradiation positions within the U.S. Geological Survey TRIGA Mark I Reactor (GSTR), determining the mass attenuation coefficients of precipitates used in radiochemical separations, and measuring the relative fission products in the GSTR. Using the Westcott convention, the Westcott flux, modified spectral index, neutron temperature, and gold-based cadmium ratios were determined for various sampling positions in the USGS TRIGA Mark I reactor. The differential neutron energy spectrum measurement was obtained using the computer iterative code SAND-II-SNL. The mass attenuation coefficients for molecular precipitates were determined through experiment and compared to results using the EGS5 Monte Carlo computer code. Difficulties associated with sufficient production of fission product isotopes in research reactors limits the ability to complete a direct, experimental assessment of mass attenuation coefficients for these isotopes. Experimental attenuation coefficients of radioisotopes produced through neutron activation agree well with the EGS5 calculated results. This suggests mass attenuation coefficients of molecular

Automated power control system for reactor TRIGA PUSPATI

NASA Astrophysics Data System (ADS)

Ghazali, Anith Khairunnisa; Minhat, Mohd Sabri; Hassan, Mohd Khair

2017-01-01

Reactor TRIGA PUSPATI (RTP) Mark II type undergoes safe operation for more than 30 years and the only research reactor exists in Malaysia. The main safety feature of Instrumentation and Control (I&C) system design is such that any failure in the electronic, or its associated components, does not lead to an uncontrolled rate of reactivity. The existed controller using feedback approach to control the reactor power. This paper introduces proposed controllers such as Model Reference Adaptive Control (MRAC) and Proportional Integral Derivatives (PID) controller for the RTP simulation. In RTP, the most important considered parameter is the reactor power and act as nervous system. To design a controller for complex plant like RTP is quite difficult due to high cost and safety factors cause by the failure of the controller. Furthermore, to overcome these problems, a simulator can be used to replace functions the hardware and test could then be simulated using this simulator. In order to find the best controller, several controllers were proposed and the result will be analysed for study the performances of the controller. The output result will be used to find out the best RTP power controller using MATLAB/Simulink and gives result as close as the real RTP performances. Currently, the structures of RTP was design using MATLAB/Simulink tool that consist of fission chamber, controller, control rod position, height-to-worth of control rods and a RTP model. The controller will control the control rod position to make sure that the reactivity still under the limitation parameter. The results given from each controller will be analysed and validated through experiment data collected from RTP.

78 FR 5840 - Notice of License Termination for University of Illinois Advanced TRIGA Reactor, License No. R-115

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... University of Illinois Advanced TRIGA Reactor, License No. R-115 The U.S. Nuclear Regulatory Commission (NRC) is noticing the termination of Facility Operating License No. R-115, for the University of Illinois... Operating License No. R-115 is terminated. The above referenced documents may be examined, and/or copied for...

Northrop Triga facility decommissioning plan versus actual results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, F.W.

1986-01-01

This paper compares the Triga facility decontamination and decommissioning plan to the actual results and discusses key areas where operational activities were impacted upon by the final US Nuclear Regulatory Commission (NRC)-approved decontamination and decommissioning plan. Total exposures for fuel transfer were a factor of 4 less than planned. The design of the Triga reactor components allowed the majority of the components to be unconditionally released.

Analysis of JSI TRIGA MARK II reactor physical parameters calculated with TRIPOLI and MCNP.

PubMed

Henry, R; Tiselj, I; Snoj, L

2015-03-01

New computational model of the JSI TRIGA Mark II research reactor was built for TRIPOLI computer code and compared with existing MCNP code model. The same modelling assumptions were used in order to check the differences of the mathematical models of both Monte Carlo codes. Differences between the TRIPOLI and MCNP predictions of keff were up to 100pcm. Further validation was performed with analyses of the normalized reaction rates and computations of kinetic parameters for various core configurations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation of k0-INAA standardisation at ITU TRIGA Mark II research reactor, Turkey based on k0-IAEA software

NASA Astrophysics Data System (ADS)

Esen, Ayse Nur; Haciyakupoglu, Sevilay

2016-02-01

The purpose of this study is to test the applicability of k0-INAA method at the Istanbul Technical University TRIGA Mark II research reactor. The neutron spectrum parameters such as epithermal neutron flux distribution parameter (α), thermal to epithermal neutron flux ratio (f) and thermal neutron flux (φth) were determined at the central irradiation channel of the ITU TRIGA Mark II research reactor using bare triple-monitor method. HPGe detector calibrations and calculations were carried out by k0-IAEA software. The α, f and φth values were calculated to be -0.009, 15.4 and 7.92·1012 cm-2 s-1, respectively. NIST SRM 1633b coal fly ash and intercomparison samples consisting of clay and sandy soil samples were used to evaluate the validity of the method. For selected elements, the statistical evaluation of the analysis results was carried out by z-score test. A good agreement between certified/reported and experimental values was obtained.

Cooling Performance Analysis of ThePrimary Cooling System ReactorTRIGA-2000Bandung

NASA Astrophysics Data System (ADS)

Irianto, I. D.; Dibyo, S.; Bakhri, S.; Sunaryo, G. R.

2018-02-01

The conversion of reactor fuel type will affect the heat transfer process resulting from the reactor core to the cooling system. This conversion resulted in changes to the cooling system performance and parameters of operation and design of key components of the reactor coolant system, especially the primary cooling system. The calculation of the operating parameters of the primary cooling system of the reactor TRIGA 2000 Bandung is done using ChemCad Package 6.1.4. The calculation of the operating parameters of the cooling system is based on mass and energy balance in each coolant flow path and unit components. Output calculation is the temperature, pressure and flow rate of the coolant used in the cooling process. The results of a simulation of the performance of the primary cooling system indicate that if the primary cooling system operates with a single pump or coolant mass flow rate of 60 kg/s, it will obtain the reactor inlet and outlet temperature respectively 32.2 °C and 40.2 °C. But if it operates with two pumps with a capacity of 75% or coolant mass flow rate of 90 kg/s, the obtained reactor inlet, and outlet temperature respectively 32.9 °C and 38.2 °C. Both models are qualified as a primary coolant for the primary coolant temperature is still below the permitted limit is 49.0 °C.

Qualification of heavy water based irradiation device in the JSI TRIGA reactor for irradiations of FT-TIMS samples for nuclear safeguards

NASA Astrophysics Data System (ADS)

Radulović, Vladimir; Kolšek, Aljaž; Fauré, Anne-Laure; Pottin, Anne-Claire; Pointurier, Fabien; Snoj, Luka

2018-03-01

The Fission Track Thermal Ionization Mass Spectrometry (FT-TIMS) method is considered as the reference method for particle analysis in the field of nuclear Safeguards for measurements of isotopic compositions (fissile material enrichment levels) in micrometer-sized uranium particles collected in nuclear facilities. An integral phase in the method is the irradiation of samples in a very well thermalized neutron spectrum. A bilateral collaboration project was carried out between the Jožef Stefan Institute (JSI, Slovenia) and the Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA, France) to determine whether the JSI TRIGA reactor could be used for irradiations of samples for the FT-TIMS method. This paper describes Monte Carlo simulations, experimental activation measurements and test irradiations performed in the JSI TRIGA reactor, firstly to determine the feasibility, and secondly to design and qualify a purpose-built heavy water based irradiation device for FT-TIMS samples. The final device design has been shown experimentally to meet all the required performance specifications.

Adaptive control method for core power control in TRIGA Mark II reactor

NASA Astrophysics Data System (ADS)

Sabri Minhat, Mohd; Selamat, Hazlina; Subha, Nurul Adilla Mohd

2018-01-01

The 1MWth Reactor TRIGA PUSPATI (RTP) Mark II type has undergone more than 35 years of operation. The existing core power control uses feedback control algorithm (FCA). It is challenging to keep the core power stable at the desired value within acceptable error bands to meet the safety demand of RTP due to the sensitivity of nuclear research reactor operation. Currently, the system is not satisfied with power tracking performance and can be improved. Therefore, a new design core power control is very important to improve the current performance in tracking and regulate reactor power by control the movement of control rods. In this paper, the adaptive controller and focus on Model Reference Adaptive Control (MRAC) and Self-Tuning Control (STC) were applied to the control of the core power. The model for core power control was based on mathematical models of the reactor core, adaptive controller model, and control rods selection programming. The mathematical models of the reactor core were based on point kinetics model, thermal hydraulic models, and reactivity models. The adaptive control model was presented using Lyapunov method to ensure stable close loop system and STC Generalised Minimum Variance (GMV) Controller was not necessary to know the exact plant transfer function in designing the core power control. The performance between proposed adaptive control and FCA will be compared via computer simulation and analysed the simulation results manifest the effectiveness and the good performance of the proposed control method for core power control.

Simulation on reactor TRIGA Puspati core kinetics fueled with thorium (Th) based fuel element

NASA Astrophysics Data System (ADS)

Mohammed, Abdul Aziz; Pauzi, Anas Muhamad; Rahman, Shaik Mohmmed Haikhal Abdul; Zin, Muhamad Rawi Muhammad; Jamro, Rafhayudi; Idris, Faridah Mohamad

2016-01-01

In confronting global energy requirement and the search for better technologies, there is a real case for widening the range of potential variations in the design of nuclear power plants. Smaller and simpler reactors are attractive, provided they can meet safety and security standards and non-proliferation issues. On fuel cycle aspect, thorium fuel cycles produce much less plutonium and other radioactive transuranic elements than uranium fuel cycles. Although not fissile itself, Th-232 will absorb slow neutrons to produce uranium-233 (233U), which is fissile. By introducing Thorium, the numbers of highly enriched uranium fuel element can be reduced while maintaining the core neutronic performance. This paper describes the core kinetic of a small research reactor core like TRIGA fueled with a Th filled fuel element matrix using a general purpose Monte Carlo N-Particle (MCNP) code.

Operation and reactivity measurements of an accelerator driven subcritical TRIGA reactor

NASA Astrophysics Data System (ADS)

O'Kelly, David Sean

Experiments were performed at the Nuclear Engineering Teaching Laboratory (NETL) in 2005 and 2006 in which a 20 MeV linear electron accelerator operating as a photoneutron source was coupled to the TRIGA (Training, Research, Isotope production, General Atomics) Mark II research reactor at the University of Texas at Austin (UT) to simulate the operation and characteristics of a full-scale accelerator driven subcritical system (ADSS). The experimental program provided a relatively low-cost substitute for the higher power and complexity of internationally proposed systems utilizing proton accelerators and spallation neutron sources for an advanced ADSS that may be used for the burning of high-level radioactive waste. Various instrumentation methods that permitted ADSS neutron flux monitoring in high gamma radiation fields were successfully explored and the data was used to evaluate the Stochastic Pulsed Feynman method for reactivity monitoring.

Experimental study of radiation dose rate at different strategic points of the BAEC TRIGA Research Reactor.

PubMed

Ajijul Hoq, M; Malek Soner, M A; Salam, M A; Haque, M M; Khanom, Salma; Fahad, S M

2017-12-01

The 3MW TRIGA Mark-II Research Reactor of Bangladesh Atomic Energy Commission (BAEC) has been under operation for about thirty years since its commissioning at 1986. In accordance with the demand of fundamental nuclear research works, the reactor has to operate at different power levels by utilizing a number of experimental facilities. Regarding the enquiry for safety of reactor operating personnel and radiation workers, it is necessary to know the radiation level at different strategic points of the reactor where they are often worked. In the present study, neutron, beta and gamma radiation dose rate at different strategic points of the reactor facility with reactor power level of 2.4MW was measured to estimate the rising level of radiation due to its operational activities. From the obtained results high radiation dose is observed at the measurement position of the piercing beam port which is caused by neutron leakage and accordingly, dose rate at the stated position with different reactor power levels was measured. This study also deals with the gamma dose rate measurements at a fixed position of the reactor pool top surface for different reactor power levels under both Natural Convection Cooling Mode (NCCM) and Forced Convection Cooling Mode (FCCM). Results show that, radiation dose rate is higher for NCCM in compared with FCCM and increasing with the increase of reactor power. Thus, concerning the radiological safety issues for working personnel and the general public, the radiation dose level monitoring and the experimental analysis performed within this paper is so much effective and the result of this work can be utilized for base line data and code verification of the nuclear reactor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulation on reactor TRIGA Puspati core kinetics fueled with thorium (Th) based fuel element

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohammed, Abdul Aziz, E-mail: azizM@uniten.edu.my; Rahman, Shaik Mohmmed Haikhal Abdul; Pauzi, Anas Muhamad, E-mail: anas@uniten.edu.my

2016-01-22

In confronting global energy requirement and the search for better technologies, there is a real case for widening the range of potential variations in the design of nuclear power plants. Smaller and simpler reactors are attractive, provided they can meet safety and security standards and non-proliferation issues. On fuel cycle aspect, thorium fuel cycles produce much less plutonium and other radioactive transuranic elements than uranium fuel cycles. Although not fissile itself, Th-232 will absorb slow neutrons to produce uranium-233 ({sup 233}U), which is fissile. By introducing Thorium, the numbers of highly enriched uranium fuel element can be reduced while maintainingmore » the core neutronic performance. This paper describes the core kinetic of a small research reactor core like TRIGA fueled with a Th filled fuel element matrix using a general purpose Monte Carlo N-Particle (MCNP) code.« less

Radioactivity of spent TRIGA fuel

NASA Astrophysics Data System (ADS)

Usang, M. D.; Nabil, A. R. A.; Alfred, S. L.; Hamzah, N. S.; Abi, M. J. B.; Rawi, M. Z. M.; Abu, M. P.

2015-04-01

Some of the oldest TRIGA fuel in the Malaysian Reaktor TRIGA PUSPATI (RTP) is approaching the limit of its end of life with burn-up of around 20%. Hence it is prudent for us to start planning on the replacement of the fuel in the reactor and other derivative activities associated with it. In this regard, we need to understand all of the risk associated with such operation and one of them is to predict the radioactivity of the fuel, so as to estimate the safety of our working conditions. The radioactivity of several fuels are measured and compared with simulation results to confirm the burnup levels of the selected fuels. The radioactivity measurement are conducted inside the water tank to reduce the risk of exposure and in this case the detector wrapped in plastics are lowered under water. In nuclear power plant, the general practice was to continuously burn the fuel. In research reactor, most operations are based on the immediate needs of the reactor and our RTP for example operate periodically. By integrating the burnup contribution for each core configuration, we simplify the simulation of burn up for each core configuration. Our results for two (2) fuel however indicates that the dose from simulation underestimate the actual dose from our measurements. Several postulates are investigated but the underlying reason remain inconclusive.

Temperature feedback of TRIGA MARK-II fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Usang, M. D., E-mail: mark-dennis@nuclearmalaysia.gov.my; Minhat, M. S.; Rabir, M. H.

2016-01-22

We study the amount of temperature feedback on reactivity for the three types of TRIGA fuel i.. ST8, ST12 and LEU fuel, are used in the TRIGA MARK II reactor in Malaysia Nuclear Agency. We employ WIMSD-5B for the calculation of kin f for a single TRIGA fuel surrounded by water. Typical calculations of TRIGA fuel reactivity are usually limited to ST8 fuel, but in this paper our investigation extends to ST12 and LEU fuel. We look at the kin f of our model at various fuel temperatures and calculate the amount reactivity removed. In one instance, the water temperaturemore » is kept at room temperature of 300K to simulate sudden reactivity increase from startup. In another instance, we simulate the sudden temperature increase during normal operation where the water temperature is approximately 320K while observing the kin f at various fuel temperatures. For accidents, two cases are simulated. The first case is for water temperature at 370K and the other is without any water. We observe that the higher Uranium content fuel such as the ST12 and LEU have much smaller contribution to the reactivity in comparison to the often studied ST8 fuel. In fact the negative reactivity coefficient for LEU fuel at high temperature in water is only slightly larger to the negative reactivity coefficient for ST8 fuel in void. The performance of ST8 fuel in terms of negative reactivity coefficient is cut almost by half when it is in void. These results are essential in the safety evaluation of the reactor and should be carefully considered when choices of fuel for core reconfiguration are made.« less

Temperature feedback of TRIGA MARK-II fuel

NASA Astrophysics Data System (ADS)

Usang, M. D.; Minhat, M. S.; Rabir, M. H.; M. Rawi M., Z.

2016-01-01

We study the amount of temperature feedback on reactivity for the three types of TRIGA fuel i.. ST8, ST12 and LEU fuel, are used in the TRIGA MARK II reactor in Malaysia Nuclear Agency. We employ WIMSD-5B for the calculation of kin f for a single TRIGA fuel surrounded by water. Typical calculations of TRIGA fuel reactivity are usually limited to ST8 fuel, but in this paper our investigation extends to ST12 and LEU fuel. We look at the kin f of our model at various fuel temperatures and calculate the amount reactivity removed. In one instance, the water temperature is kept at room temperature of 300K to simulate sudden reactivity increase from startup. In another instance, we simulate the sudden temperature increase during normal operation where the water temperature is approximately 320K while observing the kin f at various fuel temperatures. For accidents, two cases are simulated. The first case is for water temperature at 370K and the other is without any water. We observe that the higher Uranium content fuel such as the ST12 and LEU have much smaller contribution to the reactivity in comparison to the often studied ST8 fuel. In fact the negative reactivity coefficient for LEU fuel at high temperature in water is only slightly larger to the negative reactivity coefficient for ST8 fuel in void. The performance of ST8 fuel in terms of negative reactivity coefficient is cut almost by half when it is in void. These results are essential in the safety evaluation of the reactor and should be carefully considered when choices of fuel for core reconfiguration are made.

Assessment and mitigation of power quality problems for PUSPATI TRIGA Reactor (RTP)

NASA Astrophysics Data System (ADS)

Zakaria, Mohd Fazli; Ramachandaramurthy, Vigna K.

2017-01-01

An electrical power systems are exposed to different types of power quality disturbances. Investigation and monitoring of power quality are necessary to maintain accurate operation of sensitive equipment especially for nuclear installations. This paper will discuss the power quality problems observed at the electrical sources of PUSPATI TRIGA Reactor (RTP). Assessment of power quality requires the identification of any anomalous behavior on a power system, which adversely affects the normal operation of electrical or electronic equipment. A power quality assessment involves gathering data resources; analyzing the data (with reference to power quality standards) then, if problems exist, recommendation of mitigation techniques must be considered. Field power quality data is collected by power quality recorder and analyzed with reference to power quality standards. Normally the electrical power is supplied to the RTP via two sources in order to keep a good reliability where each of them is designed to carry the full load. The assessment of power quality during reactor operation was performed for both electrical sources. There were several disturbances such as voltage harmonics and flicker that exceeded the thresholds. To reduce these disturbances, mitigation techniques have been proposed, such as to install passive harmonic filters to reduce harmonic distortion, dynamic voltage restorer (DVR) to reduce voltage disturbances and isolate all sensitive and critical loads.

Bacterial Diversity Across a Turbidite-Stranded Sediment-Water Interface, La Jolla Canyon, CA

NASA Astrophysics Data System (ADS)

Harrison, B. K.; Flood, B.; Myrbo, A.; Bailey, J.

2016-12-01

The emplacement of gravity-driven sediment flows imposes a significant physical and geochemical impact on underlying sediment and microbial communities. Although previous studies have established lasting mineralogical (e.g., McKay and Pederson, 2014) and biological signatures (e.g., Anschutz et al., 2002) of turbidite deposition, the response of prokaryotes within and beneath debris flows remains poorly constrained. Both bacterial cells associated with the underlying sediment and allocthonous material must respond to substantially altered selective pressures. As a consequence, turbidites and underlying sediments provide an exceptional opportunity to examine 1) microbial community response to sedimentation 2) preservation and identification of microbial dispersal mechanisms. We collected Illumina MiSeq sequence libraries across an intact marine turbidite boundary at 25cm sediment depth in La Jolla canyon off the coast of California. 16S rRNA gene signatures of relict and active bacterial populations exhibit persistent differences attributable to turbidite deposition. In particular, the sedimentary boundary is sharply demarcated at the cm scale by the diversity and abundance of Chloroflexi, Planctomycetes, and Actinobacteria. Variations in the abundance of putative dissimilatory sulfate-reducing Deltaproteobacteria across the stranded sediment-water interface reflect persistent turbidite-induced changes to the geochemical environment. This work raises the possibility that abrupt sedimentological events may alter the microbial community in a manner that persists with burial.

[3H]MK-801 binding sites in post-mortem human frontal cortex.

PubMed

Kornhuber, J; Mack-Burkhardt, F; Kornhuber, M E; Riederer, P

1989-03-29

The binding of [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) was investigated in extensively washed homogenates of post-mortem human frontal cortex. The association of [3H]MK-801 proceeded slowly (t1/2 = 553 min) and reached equilibrium only after a prolonged incubation (greater than 24 h). The dissociation of [3H]MK-801 from the binding site was also slow (t1/2 = 244 min). Glutamate, glycine and magnesium markedly increased the rate of association (t1/2 = 14.8 min) and dissociation (t1/2 = 36.5 min). At equilibrium, the binding was not altered by these substances. Specific binding was linear with protein concentration, was saturable, reversible, stereoselective, heat-labile and was nearly absent in the white matter. Scatchard analysis of the saturation curves obtained at equilibrium indicated that there was a high-affinity (Kd1 1.39 +/- 0.21 nM, Bmax1 0.483 +/- 0.084 pmol/mg protein) and a low-affinity (Kd2 116.25 +/- 50.79 nM, Bmax2 3.251 +/- 0.991 pmol/mg protein) binding site. All competition curves obtained with (+)-MK-801, (-)-MK-801, phencyclidine and ketamine had Hill coefficients of less than unity and were best explained by a two-site model. Thus, our results demonstrate the presence of binding sites for MK-801 in post-mortem human brains and provide evidence for binding site heterogeneity. Furthermore, glutamate, glycine and magnesium accelerate the association and dissociation of [3H]MK-801 to and from its binding sites. The results add support to the hypothesis that MK-801, glutamate, glycine and magnesium all bind to different sites on the NMDA receptor-ion channel complex.

Vibro-acoustic Imaging at the Breazeale Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, James Arthur; Jewell, James Keith; Lee, James Edwin

2016-09-01

The INL is developing Vibro-acoustic imaging technology to characterize microstructure in fuels and materials in spent fuel pools and within reactor vessels. A vibro-acoustic development laboratory has been established at the INL. The progress in developing the vibro-acoustic technology at the INL is the focus of this report. A successful technology demonstration was performed in a working TRIGA research reactor. Vibro-acoustic imaging was performed in the reactor pool of the Breazeale reactor in late September of 2015. A confocal transducer driven at a nominal 3 MHz was used to collect the 60 kHz differential beat frequency induced in a spentmore » TRIGA fuel rod and empty gamma tube located in the main reactor water pool. Data was collected and analyzed with the INLDAS data acquisition software using a short time Fourier transform.« less

Early Days of Superfluid ^3He: An Experimenter's View

NASA Astrophysics Data System (ADS)

Lee, David

2010-03-01

The formulation of the BCS theory led theorists to investigate possible non-S-wave pairing in liquid ^3He. Unfortunately as time went on, estimates for the pairing temperature became unattainably low. Nevertheless, the push to lower temperatures by experimentalists continued and was facilitated by the invention of the dilution refrigerator. Nuclear adiabatic demagnetization could then be used to cool liquid ^3He to ˜1 mK as demonstrated by Goodkind. An alternate approach, suggested by Pomeranchuk, involved adiabatic compression of liquid ^3He into the solid phase. Efforts to develop this technique at the Kapitza Institute, La Jolla and Cornell achieved success in demonstrating cooling of mixtures of liquid and solid ^3He to ˜ 1 mK following dilution refrigerator pre-cooling. Although there was great pessimism regarding the possible observation of pairing in liquid ^3He, the unsettled problem of magnetic ordering in solid ^3He beckoned. Ultimately two phase transition along the melting curve were observed by Osheroff et al at Cornell. Although first associated with solid ^3He, extensive NMR studies showed them to be two new phases of liquid ^3He. A brief history of experiments at various laboratories following the discovery is given, along with early interpretations given by Anderson and Morel and Balian and Werthamer. The key role of Leggett's spin dynamics is also discussed.

Research reactor decommissioning experience - concrete removal and disposal -

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manning, Mark R.; Gardner, Frederick W.

1990-07-01

Removal and disposal of neutron activated concrete from biological shields is the most significant operational task associated with research reactor decommissioning. During the period of 1985 thru 1989 Chem-Nuclear Systems, Inc. was the prime contractor for complete dismantlement and decommissioning of the Northrop TRIGA Mark F, the Virginia Tech Argonaut, and the Michigan State University TRIGA Mark I Reactor Facilities. This paper discusses operational requirements, methods employed, and results of the concrete removal, packaging, transport and disposal operations for these (3) research reactor decommissioning projects. Methods employed for each are compared. Disposal of concrete above and below regulatory release limitsmore » for unrestricted use are discussed. This study concludes that activated reactor biological shield concrete can be safely removed and buried under current regulations.« less

Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801.

PubMed

Mahmood, Danish; Akhtar, Mohd; Jahan, Kausar; Goswami, Dipanjan

2016-09-01

Animal models based on N-methyl-d-aspartate receptor blockade have been extensively used for schizophrenia. Ketamine and MK-801 produce behaviors related to schizophrenia and exacerbated symptoms in patients with schizophrenia, which led to the use of PCP (phencyclidine)- and MK-801 (dizocilpine)-treated animals as models for schizophrenia. The study investigated the effect of subchronic dosing (once daily, 7 days) of histamine H3 receptor (H3R) antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p.) on MK-801 (0.2 mg/kg, i.p.)-induced locomotor activity and also measured dopamine and histamine levels in rat's brain homogenates. The study also included clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively. Atypical and typical antipsychotic was used to serve as clinically relevant reference agents to compare the effects of the H3R antagonists. MK-801 significantly increased horizontal locomotor activity, which was reduced with CPX and CBP. MK-801-induced locomotor hyperactivity attenuated by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised striatal dopamine level, which was reduced in rats pretreated with CPX and CBP. CPZ also significantly lowered striatal dopamine levels, although the decrease was less robust compared to CLZ, CPX, and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increased histamine levels in the hypothalamus compared to MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.), counteracted the effect of CPX and CBP. The present study shows the positive effects of CPX and CBP on MK-801-induced schizophrenia-like behaviors in rodents.

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

PubMed

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.

Tracking Transport and Transformation of Aerosols using C and O-triple Isotopic Composition of Carbonates: CSI La Jolla

NASA Astrophysics Data System (ADS)

Thiemens, M. H.; Shaheen, R.; Chong, K.; Hill, A.; Wong, J.; Zhang, Z.; Dominguez, G.

2012-12-01

Aerosols affect climate in numerous ways, including change in the earth's energy balance by absorbing and scattering solar radiations, alteration of the hydrological cycle by serving as cloud condensation nuclei, change in biogeochemical cycles by providing nutrients. Another significant process is the effect on the chemical composition of the atmosphere by providing surfaces for heterogeneous chemical reactions. Fine particles of aerodynamic diameter less than 2.5μm (PM2.5) also impinge upon human health by admission to the respiratory system causing a range of cardiopulmonary diseases. Both climate and public health aspects depend on their physical and chemical properties, therefore, understanding physico-chemical and photochemical transformations on aerosol surfaces is important for predicting their effects on climate change, atmospheric chemistry and human health. Here we present initial findings on the processes occurring on aerosol surfaces using isotopes to delineate day and night time chemistry, thus resolving photochemistry effects, and to identify their sources by way of the carbon isotopes. Aerosols were collected on filter papers for 12h during the day and at night time from June-Dec. 2011in La Jolla, CA., using high volume, multi stage cascade impactors. CO2 released after treating these filter papers with 100% phosphoric acid at 27oC was collected, purified chromatographically and analyzed for both C and O isotopes. Our data indicate that both C and O isotopes can be used to distinguish between heterogeneous and photochemical transformations. Aerosol carbonates collected during the day time were depleted in δ13Cday = -23 to -28‰ and δ18Oday = +3 to +10‰ and were isotopically distinct from the carbonates collected at night time δ13Cnight = 0 to -12‰, δ18Onightnight = +23 to +32‰. Higher chloride concentration in the samples collected at night time indicated the transport of marine air masses whereas higher nitrate and sulfate concentration

An investigation into the feasibility of thorium fuels utilization in seed-blanket configurations for TRIGA PUSPATI Reactor (RTP)

NASA Astrophysics Data System (ADS)

Damahuri, Abdul Hannan Bin; Mohamed, Hassan; Aziz Mohamed, Abdul; Idris, Faridah

2018-01-01

Thorium is one of the elements that needs to be explored for nuclear fuel research and development. One of the popular core configurations of thorium fuel is seed-blanket configuration or also known as Radkowsky Thorium Fuel concept. The seed will act as a supplier of neutrons, which will be placed inside of the core. The blanket, on the other hand, is the consumer of neutrons that is located at outermost of the core. In this work, a neutronic analysis of seed-blanket configuration for the TRIGA PUSPATI Reactor (RTP) is carried out using Monte Carlo method. The reactor, which has been operated since 1982 use uranium zirconium hydride (U-ZrH1.6) as the fuel and have multiple uranium weight which are 8.5, 12 and 20 wt.%. The pool type reactor is one and only research reactor that located in Malaysia. The design of core included the Uranium Zirconium Hydride located at the centre of the core that will act as the seed to supply neutron. The thorium oxide that will act as blanket situated outside of seed region will receive neutron to transmute 232Th to 233U. The neutron multiplication factor or criticality of each configuration is estimated. Results show that the highest initial criticality achieved is 1.30153.

A high performance neutron powder diffractometer at 3 MW Triga Mark-II research reactor in Bangladesh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamal, I., E-mail: imtiaz-kamal26@yahoo.com; Yunus, S. M., E-mail: yunussm11@yahoo.com; Datta, T. K., E-mail: tk-datta4@yahoo.com

2016-07-12

A high performance neutron diffractometer called Savar Neutron Diffractometer (SAND) was built and installed at radial beam port-2 of TRIGA Mark II research reactor at AERE, Savar, Dhaka, Bangladesh. Structural studies of materials are being done by this technique to characterize materials crystallograpohically and magnetically. The micro-structural information obtainable by neutron scattering method is very essential for determining its technological applications. This technique is unique for understanding the magnetic behavior in magnetic materials. Ceramic, steel, electronic and electric industries can be benefited from this facility for improving their products and fabrication process. This instrument consists of a Popovicimonochromator with amore » large linear position sensitive detector array. The monochromator consists of nine blades of perfect single crystal of silicon with 6 mm thickness each. The monochromator design was optimized to provide maximum flux on 3 mm diameter cylindrical sample with a relatively flat angular dependence of resolution. Five different wave lengths can be selected by orienting the crystal at various angles. A sapphire filter was used before the primary collimator to minimize the first neutron. The detector assembly is composed of 15 linear position sensitive proportional counters placed at either 1.1 m or 1.6 m from the sample position and enclosed in a air pad supported high density polythene shield. Position sensing is obtained by charge division using 1-wide NIM position encoding modules (PEM). The PEMs communicate with the host computer via USB. The detector when placed at 1.1 m, subtends 30° (2θ) at each step and covers 120° in 4 steps. When the detector is placed at 1.6 m it subtends 20° at each step and covers 120° in 6 steps. The instrument supports both low and high temperature sample environment. The instrument supports both low and high temperature sample environment. The diffractometer is a state-of-the art

A high performance neutron powder diffractometer at 3 MW Triga Mark-II research reactor in Bangladesh

NASA Astrophysics Data System (ADS)

Kamal, I.; Yunus, S. M.; Datta, T. K.; Zakaria, A. K. M.; Das, A. K.; Aktar, S.; Hossain, S.; Berliner, R.; Yelon, W. B.

2016-07-01

A high performance neutron diffractometer called Savar Neutron Diffractometer (SAND) was built and installed at radial beam port-2 of TRIGA Mark II research reactor at AERE, Savar, Dhaka, Bangladesh. Structural studies of materials are being done by this technique to characterize materials crystallograpohically and magnetically. The micro-structural information obtainable by neutron scattering method is very essential for determining its technological applications. This technique is unique for understanding the magnetic behavior in magnetic materials. Ceramic, steel, electronic and electric industries can be benefited from this facility for improving their products and fabrication process. This instrument consists of a Popovicimonochromator with a large linear position sensitive detector array. The monochromator consists of nine blades of perfect single crystal of silicon with 6mm thickness each. The monochromator design was optimized to provide maximum flux on 3mm diameter cylindrical sample with a relatively flat angular dependence of resolution. Five different wave lengths can be selected by orienting the crystal at various angles. A sapphire filter was used before the primary collimator to minimize the first neutron. The detector assembly is composed of 15 linear position sensitive proportional counters placed at either 1.1 m or 1.6 m from the sample position and enclosed in a air pad supported high density polythene shield. Position sensing is obtained by charge division using 1-wide NIM position encoding modules (PEM). The PEMs communicate with the host computer via USB. The detector when placed at 1.1 m, subtends 30˚ (2θ) at each step and covers 120˚ in 4 steps. When the detector is placed at 1.6 m it subtends 20˚ at each step and covers 120˚ in 6 steps. The instrument supports both low and high temperature sample environment. The instrument supports both low and high temperature sample environment. The diffractometer is a state-of-the art technology

Validation of absolute axial neutron flux distribution calculations with MCNP with 197Au(n,γ)198Au reaction rate distribution measurements at the JSI TRIGA Mark II reactor.

PubMed

Radulović, Vladimir; Štancar, Žiga; Snoj, Luka; Trkov, Andrej

2014-02-01

The calculation of axial neutron flux distributions with the MCNP code at the JSI TRIGA Mark II reactor has been validated with experimental measurements of the (197)Au(n,γ)(198)Au reaction rate. The calculated absolute reaction rate values, scaled according to the reactor power and corrected for the flux redistribution effect, are in good agreement with the experimental results. The effect of different cross-section libraries on the calculations has been investigated and shown to be minor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neutron flux and gamma dose measurement in the BNCT irradiation facility at the TRIGA reactor of the University of Pavia

NASA Astrophysics Data System (ADS)

Bortolussi, S.; Protti, N.; Ferrari, M.; Postuma, I.; Fatemi, S.; Prata, M.; Ballarini, F.; Carante, M. P.; Farias, R.; González, S. J.; Marrale, M.; Gallo, S.; Bartolotta, A.; Iacoviello, G.; Nigg, D.; Altieri, S.

2018-01-01

University of Pavia is equipped with a TRIGA Mark II research nuclear reactor, operating at a maximum steady state power of 250 kW. It has been used for many years to support Boron Neutron Capture Therapy (BNCT) research. An irradiation facility was constructed inside the thermal column of the reactor to produce a sufficient thermal neutron flux with low epithermal and fast neutron components, and low gamma dose. In this irradiation position, the liver of two patients affected by hepatic metastases from colon carcinoma were irradiated after borated drug administration. The facility is currently used for cell cultures and small animal irradiation. Measurements campaigns have been carried out, aimed at characterizing the neutron spectrum and the gamma dose component. The neutron spectrum has been measured by means of multifoil neutron activation spectrometry and a least squares unfolding algorithm; gamma dose was measured using alanine dosimeters. Results show that in a reference position the thermal neutron flux is (1.20 ± 0.03) ×1010 cm-2 s-1 when the reactor is working at the maximum power of 250 kW, with the epithermal and fast components, respectively, 2 and 3 orders of magnitude lower than the thermal component. The ratio of the gamma dose with respect to the thermal neutron fluence is 1.2 ×10-13 Gy/(n/cm2).

Analytical analyses of startup measurements associated with the first use of LEU fuel in Romania`s 14-MW TRIGA reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bretscher, M.M.; Snelgrove, J.L.; Ciocanescu, M.

1992-12-01

The 14-MW TRIGA steady state reactor (SSR) is located in Pitesti, Romania. Beginning with an HEU core (10 wt% U), the reactor first went critical in November 1979 but was shut down ten years later because of insufficient excess reactivity. Last November the Institute for Nuclear Research (INR), which operates the SSR, received from the ANL RERTR program a shipment of 125 LEU pins fabricated by General Atomics and of the same geometry as the original fuel but with an enrichment of 19.7% 235U and a loading of 45 wt% U. Using 100 of these pins, four LEU clusters, eachmore » containing a 5 x 5 square array of fuel rods, were assembled. These four LEU clusters replaced the four most highly burned HEU elements in the SSR. The reactor resumed operations last February with a 35-element mixed HEU/LEU core configuration. In preparation for full power operation of the SSR with this mixed HEU/LEU core, a number of measurements were made. These included control rod calibrations, excess reactivity determinations, worths of experiment facilities, reaction rate distributions, and themocouple measurements of fuel temperatures as a function of reactor power. This paper deals with a comparison of some of these measured reactor parameters with corresponding analytical calculations.« less

Confirmation of a realistic reactor model for BNCT dosimetry at the TRIGA Mainz

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziegner, Markus, E-mail: Markus.Ziegner.fl@ait.ac.at; Schmitz, Tobias; Hampel, Gabriele

2014-11-01

Purpose: In order to build up a reliable dose monitoring system for boron neutron capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer model for the entire reactor was established, simulating the radiation field by means of the Monte Carlo method. The impact of different source definition techniques was compared and the model was validated by experimental fluence and dose determinations. Methods: The depletion calculation code ORIGEN2 was used to compute the burn-up and relevant material composition of each burned fuel element from the day of first reactor operation to its current core. The material composition ofmore » the current core was used in a MCNP5 model of the initial core developed earlier. To perform calculations for the region outside the reactor core, the model was expanded to include the thermal column and compared with the previously established ATTILA model. Subsequently, the computational model is simplified in order to reduce the calculation time. Both simulation models are validated by experiments with different setups using alanine dosimetry and gold activation measurements with two different types of phantoms. Results: The MCNP5 simulated neutron spectrum and source strength are found to be in good agreement with the previous ATTILA model whereas the photon production is much lower. Both MCNP5 simulation models predict all experimental dose values with an accuracy of about 5%. The simulations reveal that a Teflon environment favorably reduces the gamma dose component as compared to a polymethyl methacrylate phantom. Conclusions: A computer model for BNCT dosimetry was established, allowing the prediction of dosimetric quantities without further calibration and within a reasonable computation time for clinical applications. The good agreement between the MCNP5 simulations and experiments demonstrates that the ATTILA model overestimates the gamma dose contribution. The detailed model can be used for the planning of

Calculation and comparison of xenon and samarium reactivities of the HEU, LEU core in the low power research reactor.

PubMed

Dawahra, S; Khattab, K; Saba, G

2015-07-01

Comparative studies for the conversion of the fuel from HEU to LEU in the Miniature Neutron Source Reactor (MNSR) have been performed using the MCNP4C and GETERA codes. The precise calculations of (135)Xe and (149)Sm concentrations and reactivities were carried out and compared during the MNSR operation time and after shutdown for the existing HEU fuel (UAl4-Al, 90% enriched) and the potential LEU fuels (U3Si2-Al, U3Si-Al, U9Mo-Al, 19.75% enriched and UO2, 12.6% enriched) in this paper using the MCNP4C and GETERA codes. It was found that the (135)Xe and (149)Sm reactivities did not reach their equilibrium reactivities during the daily operating time of the reactor. The (149)Sm reactivities could be neglected compared to (135)Xe reactivities during the reactor operating time and after shutdown. The calculations for the UAl4-Al produced the highest (135)Xe reactivity in all the studied fuel group during the reactor operation (0.39 mk) and after the reactor shutdown (0.735 mk), It followed by U3Si-Al (0.34 mk, 0.653 mk), U3Si2-Al (0.33 mk, 0.634 mk), U9Mo-Al (0.3 mk, 0.568 mk) and UO2 (0.24 mk, 0.448 mk) fuels, respectively. Finally, the results showed that the UO2 was the best candidate for fuel conversion to LEU in the MNSR since it gave the lowest (135)Xe reactivity during the reactor operation and after shutdown. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decommissioning of the TRIGA mark II and III and radioactive waste management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doo Seong Hwang; Yoon Ji Lee; Gyeong Hwan Chung

2013-07-01

KAERI has carried out decommissioning projects for two research reactors (KRR-1 and 2). The decommissioning project of KRR-1 (TRIGA Mark II) and 2 (TRIGA Mark III) was launched in 1997 with a total budget of 23.25 million US dollars. KRR-2 and all auxiliary facilities were already decommissioned, and KRR-1 is being decommissioned now. Much more dismantled waste is generated than in any other operations of nuclear facilities. Thus, the waste needs to be reduced and stabilized through decontamination or treatment before disposal. This paper introduces the current status of the decommissioning projects and describes the volume reduction and conditioning ofmore » decommissioning waste for final disposal. (authors)« less

Testing the applicability of the k0-NAA method at the MINT's TRIGA MARK II reactor

NASA Astrophysics Data System (ADS)

Siong, Wee Boon; Dung, Ho Manh; Wood, Ab. Khalik; Salim, Nazaratul Ashifa Abd.; Elias, Md. Suhaimi

2006-08-01

The Analytical Chemistry Laboratory at MINT is using the NAA technique since 1980s and is the only laboratory in Malaysia equipped with a research reactor, namely the TRIGA MARK II. Throughout the years the development of NAA technique has been very encouraging and was made applicable to a wide range of samples. At present, the k0 method has become the preferred standardization method of NAA ( k0-NAA) due to its multi-elemental analysis capability without using standards. Additionally, the k0 method describes NAA in physically and mathematically understandable definitions and is very suitable for computer evaluation. Eventually, the k0-NAA method has been adopted by MINT in 2003, in collaboration with the Nuclear Research Institute (NRI), Vietnam. The reactor neutron parameters ( α and f) for the pneumatic transfer system and for the rotary rack at various locations, as well as the detector efficiencies were determined. After calibration of the reactor and the detectors, the implemented k0 method was validated by analyzing some certified reference materials (including IAEA Soil 7, NIST 1633a, NIST 1632c, NIST 1646a and IAEA 140/TM). The analysis results of the CRMs showed an average u score well below the threshold value of 2 with a precision of better than ±10% for most of the elemental concentrations obtained, validating herewith the introduction of the k0-NAA method at the MINT.

Benchmarking of Neutron Flux Parameters at the USGS TRIGA Reactor in Lakewood, Colorado

NASA Astrophysics Data System (ADS)

Alzaabi, Osama E.

The USGS TRIGA Reactor (GSTR) located at the Denver Federal Center in Lakewood Colorado provides opportunities to Colorado School of Mines students to do experimental research in the field of neutron activation analysis. The scope of this thesis is to obtain precise knowledge of neutron flux parameters at the GSTR. The Colorado School of Mines Nuclear Physics group intends to develop several research projects at the GSTR, which requires the precise knowledge of neutron fluxes and energy distributions in several irradiation locations. The fuel burn-up of the new GSTR fuel configuration and the thermal neutron flux of the core were recalculated since the GSTR core configuration had been changed with the addition of two new fuel elements. Therefore, a MCNP software package was used to incorporate the burn up of reactor fuel and to determine the neutron flux at different irradiation locations and at flux monitoring bores. These simulation results were compared with neutron activation analysis results using activated diluted gold wires. A well calibrated and stable germanium detector setup as well as fourteen samplers were designed and built to achieve accuracy in the measurement of the neutron flux. Furthermore, the flux monitoring bores of the GSTR core were used for the first time to measure neutron flux experimentally and to compare to MCNP simulation. In addition, International Atomic Energy Agency (IAEA) standard materials were used along with USGS national standard materials in a previously well calibrated irradiation location to benchmark simulation, germanium detector calibration and sample measurements to international standards.

Neutron measurement at the thermal column of the Malaysian Triga Mark II reactor using gold foil activation method and TLD

NASA Astrophysics Data System (ADS)

Shalbi, Safwan; Salleh, Wan Norhayati Wan; Mohamad Idris, Faridah; Aliff Ashraff Rosdi, Muhammad; Syahir Sarkawi, Muhammad; Liyana Jamsari, Nur; Nasir, Nur Aishah Mohd

2018-01-01

In order to design facilities for boron neutron capture therapy (BNCT), the neutron measurement must be considered to obtain the optimal design of BNCT facility such as collimator and shielding. The previous feasibility study showed that the thermal column could generate higher thermal neutrons yield for BNCT application at the TRIGA MARK II reactor. Currently, the facility for BNCT are planned to be developed at thermal column. Thus, the main objective was focused on the thermal neutron and epithermal neutron flux measurement at the thermal column. In this measurement, pure gold and cadmium were used as a filter to obtain the thermal and epithermal neutron fluxes from inside and outside of the thermal column door of the 200kW reactor power using a gold foil activation method. The results were compared with neutron fluxes using TLD 600 and TLD 700. The outcome of this work will become the benchmark for the design of BNCT collimator and the shielding

Fission products detection in irradiated TRIGA fuel by means of gamma spectroscopy and MCNP calculation.

PubMed

Cagnazzo, M; Borio di Tigliole, A; Böck, H; Villa, M

2018-05-01

Aim of this work was the detection of fission products activity distribution along the axial dimension of irradiated fuel elements (FEs) at the TRIGA Mark II research reactor of the Technische Universität (TU) Wien. The activity distribution was measured by means of a customized fuel gamma scanning device, which includes a vertical lifting system to move the fuel rod along its vertical axis. For each investigated FE, a gamma spectrum measurement was performed along the vertical axis, with steps of 1 cm, in order to determine the axial distribution of the fission products. After the fuel elements underwent a relatively short cooling down period, different fission products were detected. The activity concentration was determined by calibrating the gamma detector with a standard calibration source of known activity and by MCNP6 simulations for the evaluation of self-absorption and geometric effects. Given the specific TRIGA fuel composition, a correction procedure is developed and used in this work for the measurement of the fission product Zr 95 . This measurement campaign is part of a more extended project aiming at the modelling of the TU Wien TRIGA reactor by means of different calculation codes (MCNP6, Serpent): the experimental results presented in this paper will be subsequently used for the benchmark of the models developed with the calculation codes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of the H3 Antagonist, Thioperamide, on Behavioral Alterations Induced by Systemic MK-801 Administration in Rats

PubMed Central

Bardgett, Mark E.; Points, Megan; Roflow, John; Blankenship, Meredith; Griffith, Molly S.

2009-01-01

Rationale Recent studies have raised the possibility that antagonists of H3 histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia. Objectives The purpose of this study was to determine if a prototypical H3 antagonist, thioperamide, could alter behavioral deficits caused by the NMDA receptor antagonist, MK-801, in adult male rats. MK-801 was chosen for study since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia. Methods The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0 & 10 mg/kg) followed 20 minutes later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, & 0.30 mg/kg). Results Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity, however its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of two lower doses of MK801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment. Conclusions H3 receptors modulate responses to NMDA antagonists in behaviorally-specific ways and dependent upon the level of NMDA receptor blockade. PMID:19466392

High-temperature Chemical Compatibility of As-fabricated TRIGA Fuel and Type 304 Stainless Steel Cladding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dennis D. Keiser, Jr.; Jan-Fong Jue; Eric Woolstenhulme

2012-09-01

Chemical interaction between TRIGA fuel and Type-304 stainless steel cladding at relatively high temperatures is of interest from the point of view of understanding fuel behavior during different TRIGA reactor transient scenarios. Since TRIGA fuel comes into close contact with the cladding during irradiation, there is an opportunity for interdiffusion between the U in the fuel and the Fe in the cladding to form an interaction zone that contains U-Fe phases. Based on the equilibrium U-Fe phase diagram, a eutectic can develop at a composition between the U6Fe and UFe2 phases. This eutectic composition can become a liquid at aroundmore » 725°C. From the standpoint of safe operation of TRIGA fuel, it is of interest to develop better understanding of how a phase with this composition may develop in irradiated TRIGA fuel at relatively high temperatures. One technique for investigating the development of a eutectic phase at the fuel/cladding interface is to perform out-of-pile diffusion-couple experiments at relatively high temperatures. This information is most relevant for lightly irradiated fuel that just starts to touch the cladding due to fuel swelling. Similar testing using fuel irradiated to different fission densities should be tested in a similar fashion to generate data more relevant to more heavily irradiated fuel. This report describes the results for TRIGA fuel/Type-304 stainless steel diffusion couples that were annealed for one hour at 730 and 800°C. Scanning electron microscopy with energy- and wavelength-dispersive spectroscopy was employed to characterize the fuel/cladding interface for each diffusion couple to look for evidence of any chemical interaction. Overall, negligible fuel/cladding interaction was observed for each diffusion couple.« less

The H3 Antagonist, Ciproxifan, Alleviates the Memory Impairment but Enhances the Motor Effects of MK-801 (Dizocilpine) in Rats.

PubMed Central

Bardgett, Mark E.; Points, Megan; Kleier, Jennifer; Blankenship, Meredith; Griffith, Molly S.

2010-01-01

Summary Antagonists of H3-type histamine receptors exhibit cognitive-enhancing properties in various memory paradigms as well as evidence of antipsychotic activity in normal animals. The present study determined if a prototypical H3 antagonist, ciproxifan, could reverse the behavioral effects of MK-801, a drug used in animals to mimic the hypoglutamatergic state suspected to exist in schizophrenia. Four behaviors were chosen for study, locomotor activity, ataxia, prepulse inhibition (PPI), and delayed spatial alternation, since their modification by dizocilpine (MK-801) has been well characterized. Adult male Long-Evans rats were tested after receiving a subcutaneous injection of ciproxifan or vehicle followed twenty minutes later by a subcutaneous injection of MK-801 or vehicle. Three doses of MK-801 (0.05, 0.1, & 0.3 mg/kg) increased locomotor activity. Each dose of ciproxifan (1.0 & 3.0 mg/kg) enhanced the effect of the moderate dose of MK-801, but suppressed the effect of the high dose. Ciproxifan (3.0 mg/kg) enhanced the effects of MK-801 (0.1 & 0.3 mg/kg) on fine movements and ataxia. Deficits in PPI were observed after treatment with MK-801 (0.05 & 0.1 mg/kg), but ciproxifan did not alter these effects. Delayed spatial alternation was significantly impaired by MK-801 (0.1 mg/kg) at a longer delay, and ciproxifan (3.0 mg/kg) alleviated this impairment. These results indicate that some H3 antagonists can alleviate the impact of NMDA receptor hypofunction on some forms of memory, but may exacerbate its effect on other behaviors. PMID:20621107

The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats.

PubMed

Bardgett, Mark E; Points, Megan; Kleier, Jennifer; Blankenship, Meredith; Griffith, Molly S

2010-11-01

Antagonists of H(3)-type histamine receptors exhibit cognitive-enhancing properties in various memory paradigms as well as evidence of antipsychotic activity in normal animals. The present study determined if a prototypical H(3) antagonist, ciproxifan, could reverse the behavioral effects of MK-801, a drug used in animals to mimic the hypoglutamatergic state suspected to exist in schizophrenia. Four behaviors were chosen for study, locomotor activity, ataxia, prepulse inhibition (PPI), and delayed spatial alternation, since their modification by dizocilpine (MK-801) has been well characterized. Adult male Long-Evans rats were tested after receiving a subcutaneous injection of ciproxifan or vehicle followed 20 min later by a subcutaneous injection of MK-801 or vehicle. Three doses of MK-801 (0.05, 0.1, & 0.3 mg/kg) increased locomotor activity. Each dose of ciproxifan (1.0 & 3.0 mg/kg) enhanced the effect of the moderate dose of MK-801, but suppressed the effect of the high dose. Ciproxifan (3.0 mg/kg) enhanced the effects of MK-801 (0.1 & 0.3 mg/kg) on fine movements and ataxia. Deficits in PPI were observed after treatment with MK-801 (0.05 & 0.1 mg/kg), but ciproxifan did not alter these effects. Delayed spatial alternation was significantly impaired by MK-801 (0.1 mg/kg) at a longer delay, and ciproxifan (3.0 mg/kg) alleviated this impairment. These results indicate that some H(3) antagonists can alleviate the impact of NMDA receptor hypofunction on some forms of memory, but may exacerbate its effect on other behaviors. Copyright © 2010 Elsevier Ltd. All rights reserved.

The CME Rate over Four Solar Cycles: Filling the Final Gap with MLSO MK3 Observations [1989-1996

NASA Astrophysics Data System (ADS)

St Cyr, O. C.; Flint, Q.; Quirk, C. A.; Burkepile, J.; Webb, D. F.; Lecinski, A. R.

2013-12-01

Coronal mass ejections (CMEs) were discovered in the early 1970's by the OSO-7 coronagraph, and large numbers were characterized for the first time by the Skylab ATM coronagraph. Since 1973 there has been only a single major gap in CME coverage in white light. Instruments that have contributed to estimates of the rate and properties of CMEs have included: Skylab ATM (1973-1974); Helios photometers (1974-1981); Solwind (1979-1985); SMM C/P (1980; 1984-1989); SOHO LASCO (1996-present); the Solar Mass Ejection Imager (SMEI, 2003-2011); and STEREO SECCHI (2006-present). We report here the first attempt to fill the 1989-1996 gap in the CME rate using the Mauna Loa Solar Observatory's MK3 K-coronameter. The MK3 instrument observed routinely several hours most days beginning in 1980 until it was upgraded to MK4 in 1998. MK3 CMEs detected from 1980-1989 were compared with Solwind and SMM and reported by St. Cyr et al. (1999). Since spaceborne instruments have more complete duty cycles than a groundbased instrument at a single location, we have 'calibrated' the MK3-derived CME rate from 1989 with the SMM C/P coronagraph, and from 1996 with the SOHO LASCO coronagraphs. CME rate calculations have been documented in Webb & Howard (1994), St. Cyr et al. (2000) and Robbrecht et al. (2009). Here we provide the preliminary CME rate calculation for 1989-1996 using the MLSO MK3 coronameter.

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

PubMed

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

2016-12-01

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. The antidepressant effects of (+)-MK-801 (0.1mg/kg) and (-)-MK-801 (0.1mg/kg) in the social defeat stress model were examined. 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. Both stereoisomers of MK-801 induced rapid antidepressant effects in the social defeat stress model, although neither produced a long-lasting effect (7 days). © The Author 2016. Published by Oxford University Press on behalf of CINP.

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

PubMed Central

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, D.J.; Ciliax, B.J.; Van Dort, M.E.

1989-06-01

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-({sup 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 ({sup 3}H)N-(1-(2-thienyl)cyclohexyl)piperidine (({sup 3}H)TCP) binding with an IC50 of 1 microM, which is a 10-fold lower binding affinity than that of (+/-)MK-801.more » 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.« less

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

PubMed Central

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

(+)-3-( sup 123 I)Iodo-MK-801: Synthesis and characterization of binding to the N-methyl-D-aspartate receptor complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ransom, R.W.; Wai-si Eng; Burns, H.D.

1990-01-01

Synthetic methods have been established for preparing high specific activity (+)-3-({sup 123}I)Iodo-MK-801 in high radiochemical yield. The binding of the radiotracer to rat cortical membranes has been examine to assess its potential use as an in vivo imaging agent for the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. Under the conditions of the assay, specific (+)-3-({sup 123}I)Iodo-MK-801 binding to membrane homogenates represented greater than 95% of the total binding. Several structurally distinct, noncompetitive NMDA receptor antagonists inhibited binding with potencies in accordance with their reported inhibitory activity at the receptor complex. The concentration of ({plus minus})-3-Iodo-MK-801 required to inhibit 50% of (+)-3-({supmore » 123}I)Iodo-MK-801 binding (IC{sub 50}) was 3.4 nM when using a low ionic strength assay buffer and 5.5 nM in a physiological buffer. In a thoroughly washed membrane preparation, (+)-3-({sup 123}I)Iodo-MK-801 binding was enhanced by L-glutamate and glycine at concentrations known to activate the NMDA receptor. The results indicate that (+)-3-({sup 123}I)Iodo-MK-801 specifically labels the NMDA receptor complex in rat brain membranes and the retention of high affinity under near physiological assay conditions suggests that it may be useful as a SPECT imaging agent for the receptor in vivo.« less

Commercial valerian interactions with [3H]Flunitrazepam and [3H]MK-801 binding to rat synaptic membranes.

PubMed

Ortiz, José G; Rassi, Nicole; Maldonado, Patricia M; González-Cabrera, Silvia; Ramos, Igmeris

2006-09-01

Valeriana officinalis extracts are used in folkloric medicine for their sedative, hypnotic and tranquilizer effects. Using [3H]flunitrazepam binding as an indicator, the interactions of commercial Valerian extracts with GABA(A) receptors were examined. There was considerable fluctuation among the different extracts, some mildly enhanced [3H]flunitrazepam binding, others had no effect and others had inhibitory effects, independent of standardization by valerenic acid. Central depression can also be accomplished by a reduction of excitatory transmission. Valerian extracts had modest inhibitory effects on [3H]MK-801 binding, an indicator of NMDA-Valerian interactions. Spectral analyses (UV region) did not show marked differences among the different extracts. The inhibitory effects of one of the extracts on [3H]flunitrazepam binding was somewhat stable, while on [3H]MK-801 binding the inhibitory effects were lost within months. These results suggest that particular care should be taken in analysing and interpreting results from commercial Valerian preparations. Copyright (c) 2006 John Wiley & Sons, Ltd.

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

PubMed

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.

Characterization of fast neutron spectrum in the TRIGA for hardness testing of electronic components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, George W.

1986-07-01

Argonne National Laboratory-West, operated by the University of Chicago, is located near Idaho Falls, ID, on the Idaho National Engineering Laboratory Site. ANL-West performs work in support of the Liquid Metal Fast Breeder Reactor Program (LMFBR) sponsored by the United States Department of Energy. The NRAD reactor is located at the Argonne Site within the Hot Fuel Examination Facility/North, a large hot cell facility where both non-destructive and destructive examinations are performed on highly irradiated reactor fuels and materials in support of the LMFBR program. The NRAD facility utilizes a 250-kW TRIGA reactor and is completely dedicated to neutron radiographymore » and the development of radiography techniques. Criticality was first achieved at the NRAD reactor in October of 1977. Since that time, a number of modifications have been implemented to improve operational efficiency and radiography production. This paper describes the modifications and changes that significantly improved operational efficiency and reliability of the reactor and the essential auxiliary reactor systems. (author)« less

Calculations to Support On-line Neutron Spectrum Adjustment by Measurements with Miniature Fission Chambers in the JSI TRIGA Reactor

NASA Astrophysics Data System (ADS)

Kaiba, Tanja; Radulović, Vladimir; Žerovnik, Gašper; Snoj, Luka; Fourmentel, Damien; Barbot, LoÏc; Destouches, Christophe AE(; )

2018-01-01

Preliminary calculations were performed with the aim to establish optimal experimental conditions for the measurement campaign within the collaboration between the Jožef Stefan Institute (JSI) and Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA Cadarache). The goal of the project is to additionally characterize the neutron spectruminside the JSI TRIGA reactor core with focus on the measurement epi-thermal and fast part of the spectrum. Measurements will be performed with fission chambers containing different fissile materials (235U, 237Np and 242Pu) covered with thermal neutron filters (Cd and Gd). The changes in the detected signal and neutron flux spectrum with and without transmission filter were studied. Additional effort was put into evaluation of the effect of the filter geometry (e.g. opening on the top end of the filter) on the detector signal. After the analysis of the scoping calculations it was concluded to position the experiment in the outside core ring inside one of the empty fuel element positions.

AMS analyses of I-129 from the Fukushima Daiichi nuclear accident in the Pacific Ocean waters of the Coast La Jolla--San Diego, USA.

PubMed

Stan-Sion, C; Enachescu, M; Petre, A R

2015-05-01

This paper presents the results of an experimental study we performed by using the Accelerator Mass Spectrometry (AMS) method with iodine 129 (T1/2 = 15.7 My), to determine the increase of the radionuclide content in the USA West Pacific Coast waters, two years after the March 2011 Fukushima Daiichi nuclear power plant accident. The collection of the water samples took place between April and July 2013 at regular intervals of time, from the Pacific Ocean, at the cove of La Jolla, San Diego, USA. The results of the experiments showed a significant increase of the radionuclide concentration during the late spring of 2013. Compared to the isotopic ratio (129)I/(127)I, measured at a 40 km distance, offshore of Fukushima and immediately after the accident, our results show an increase on the USA West Coast that was more than a 2.5 factor higher. Also, compared with the pre-Fukushima background values, our results show an isotopic ratio of about two orders of magnitude higher. A distinct feature of the reconstructed radioactive plume was that it traveled with a speed of 12 cm s(-1), which we estimated and is consistent with the zonal speed in the Pacific. We coupled our (129)I results with the measurements from the June 2011 KOK cruise and we derived the levels of activity for (3)H and (137)Cs. On the USA West Coast, they did not exceed the international regulatory limits.

Neutron flux and power in RTP core-15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabir, Mohamad Hairie, E-mail: m-hairie@nuclearmalaysia.gov.my; Zin, Muhammad Rawi Md; Usang, Mark Dennis

PUSPATI TRIGA Reactor achieved initial criticality on June 28, 1982. The reactor is designed to effectively implement the various fields of basic nuclear research, manpower training, and production of radioisotopes. This paper describes the reactor parameters calculation for the PUSPATI TRIGA REACTOR (RTP); focusing on the application of the developed reactor 3D model for criticality calculation, analysis of power and neutron flux distribution of TRIGA core. The 3D continuous energy Monte Carlo code MCNP was used to develop a versatile and accurate full model of the TRIGA reactor. The model represents in detailed all important components of the core withmore » literally no physical approximation. The consistency and accuracy of the developed RTP MCNP model was established by comparing calculations to the available experimental results and TRIGLAV code calculation.« less

Fabrication and Testing of a Modular Micro-Pocket Fission Detector Instrumentation System for Test Nuclear Reactors

NASA Astrophysics Data System (ADS)

Reichenberger, Michael A.; Nichols, Daniel M.; Stevenson, Sarah R.; Swope, Tanner M.; Hilger, Caden W.; Roberts, Jeremy A.; Unruh, Troy C.; McGregor, Douglas S.

2018-01-01

Advancements in nuclear reactor core modeling and computational capability have encouraged further development of in-core neutron sensors. Measurement of the neutron-flux distribution within the reactor core provides a more complete understanding of the operating conditions in the reactor than typical ex-core sensors. Micro-Pocket Fission Detectors have been developed and tested previously but have been limited to single-node operation and have utilized highly specialized designs. The development of a widely deployable, multi-node Micro-Pocket Fission Detector assembly will enhance nuclear research capabilities. A modular, four-node Micro-Pocket Fission Detector array was designed, fabricated, and tested at Kansas State University. The array was constructed from materials that do not significantly perturb the neutron flux in the reactor core. All four sensor nodes were equally spaced axially in the array to span the fuel-region of the reactor core. The array was filled with neon gas, serving as an ionization medium in the small cavities of the Micro-Pocket Fission Detectors. The modular design of the instrument facilitates the testing and deployment of numerous sensor arrays. The unified design drastically improved device ruggedness and simplified construction from previous designs. Five 8-mm penetrations in the upper grid plate of the Kansas State University TRIGA Mk. II research nuclear reactor were utilized to deploy the array between fuel elements in the core. The Micro-Pocket Fission Detector array was coupled to an electronic support system which has been specially developed to support pulse-mode operation. The Micro-Pocket Fission Detector array composed of four sensors was used to monitor local neutron flux at a constant reactor power of 100 kWth at different axial locations simultaneously. The array was positioned at five different radial locations within the core to emulate the deployment of multiple arrays and develop a 2-dimensional measurement of

Utilization of thorium and U-ZrH1.6 fuels in various heterogeneous cores for TRIGA PUSPATI Reactor (RTP)

NASA Astrophysics Data System (ADS)

Damahuri, Abdul Hannan Bin; Mohamed, Hassan; Aziz Mohamed, Abdul; Idris, Faridah

2018-01-01

The use of thorium as nuclear fuel has been an appealing prospect for many years and will be great significance to nuclear power generation. There is an increasing need for more research on thorium as Malaysian government is currently active in the national Thorium Flagship Project, which was launched in 2014. The thorium project, which is still in phase 1, focuses on the research and development of the thorium extraction from mineral processing ore. Thus, the aim of the study is to investigate other alternative TRIGA PUSPATI Reactor (RTP) core designs that can fully utilize thorium. Currently, the RTP reactor has an average neutron flux of 2.797 x 1012 cm-2/s-1 and an effective multiplication factor, k eff, of 1.001. The RTP core has a circular array core configuration with six circular rings. Each ring consists of 6, 12, 18, 24, 30 or 36 U-ZrH1.6 fuel rods. There are three main type of uranium weight, namely 8.5, 12 and 20 wt.%. For this research, uranium zirconium hydride (U-ZrH1.6) fuel rods in the RTP core were replaced by thorium (ThO2) fuel rods. Seven core configurations with different thorium fuel rods placements were modelled in a 2D structure and simulated using Monte Carlo n-particle (MCNPX) code. Results show that the highest initial criticality obtained is around 1.35101. Additionally there is a significant discrepancy between results from previous study and the work because of the large estimated leakage probability of approximately 21.7% and 2D model simplification.

An investigation of reactivity effect due to inadvertent filling of the irradiation channels with water in NIRR-1 Nigeria Research Reactor-1.

PubMed

Iliyasu, U; Ibrahim, Y V; Umar, Sadiq; Agbo, S A; Jibrin, Y

2017-05-01

Investigation of reactivity variation due to flooding of the irradiation channels of Nigeria Research Reactor (NIRR-1) a low power miniature neutron source reactor (MNSR) located at the Centre for Energy Research and Training, Ahmadu Bello University, Zaria Nigeria using the MCNP code for High Enrich Uranium (HEU) and Low Enrich Uranium (LEU) core has been simulated in this present study. In this work, the excess reactivity worth of flooding HEU core for 1 inner, 2 inner, 3 inner, 4 inner and all inner are 0.318mk, 0.577mk, 0.318mk, 1.204mk and 1.503mk respectively, and outer irradiation channels are 0.119mk, 0.169mk, 0.348mk, 0.438mk and 0.418mk respectively, the highest excess reactivity result from flooding both inner and outer irradiation channels is 2.04mk (±1.72×10 -7 ), the excess reactivity for LEU core was 0.299mk, 0.568mk, 0.896mk, 1.195mk and 1.524mk in the inner irradiation channels, and the outer irradiation channels are 0.129mk, 0.189mk, 0.219mk, 0.269mk and 0.548mk where the highest excess reactivity was 1.942mk (±1.64×10 -7 ) resulting from flooding inner and outer irradiation channels. The reactivity induced by flooding of the irradiation channels of NIRR-1 with water is within design safety limit enshrined in Safety Analysis Report of NIRR-1. The results also compare well with literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cryostat system for investigation on new neutron moderator materials at reactor TRIGA PUSPATI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dris, Zakaria bin, E-mail: zakariadris@gmail.com; Centre for Nuclear Energy, Universiti Tenaga Nasional; Mohamed, Abdul Aziz bin

2016-01-22

A simple continuous flow (SCF) cryostat was designed to investigate the neutron moderation of alumina in high temperature co-ceramic (HTCC) and polymeric materials such as Teflon under TRIGA neutron environment using a reflected neutron beam from a monochromator. Cooling of the cryostat will be carried out using liquid nitrogen. The cryostat will be built with an aluminum holder for moderator within stainless steel cylinder pipe. A copper thermocouple will be used as the temperature sensor to monitor the moderator temperature inside the cryostat holder. Initial measurements of neutron spectrum after neutron passing through the moderating materials have been carried outmore » using a neutron spectrometer.« less

High Temperature Fuel Cladding Chemical Interactions Between TRIGA Fuels and 304 Stainless Steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez, Emmanuel; Keiser, Jr., Dennis D.; Forsmann, Bryan

High-temperature fuel-cladding chemical interactions (FCCI) between TRIGA (Training, Research, Isotopes, General Atomics) fuel elements and the 304 stainless steel (304SS) are of interest to develop an understanding of the fuel behavior during transient reactor scenarios. TRIGA fuels are composed of uranium (U) particles dispersed in a zirconium-hydride (Zr-H) matrix. In reactor, the fuel is encased in 304-stainless-steel (304SS) or Incoloy 800 clad tubes. At high temperatures, the fuel can readily interact with the cladding, resulting in FCCI. A number of FCCI can take place in this system. Interactions can be expected between the cladding and the Zr-H matrix, and/or betweenmore » the cladding and the U-particles. Other interactions may be expected between the Zr-H matrix and the U-particles. Furthermore, the fuel contains erbium-oxide (Er-O) additions. Interactions can also be expected between the Er-O, the cladding, the Zr-H and the U-particles. The overall result is that very complex interactions may take place as a result of fuel and cladding exposures to high temperatures. This report discusses the characterization of the baseline fuel microstructure in the as-received state (prior to exposure to high temperature), characterization of the fuel after annealing at 950C for 24 hours and the results from diffusion couple experiments carries out at 1000C for 5 and 24 hours. Characterization was carried out via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with sample preparation via focused ion beam in situ-liftout-technique.« less

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

PubMed

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.

Clinical physiology and mechanism of dizocilpine (MK-801)

PubMed Central

Somanathan, Ratnasamy

2010-01-01

Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3′-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and anti-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties. PMID:20716924

An approach to model reactor core nodalization for deterministic safety analysis

NASA Astrophysics Data System (ADS)

Salim, Mohd Faiz; Samsudin, Mohd Rafie; Mamat @ Ibrahim, Mohd Rizal; Roslan, Ridha; Sadri, Abd Aziz; Farid, Mohd Fairus Abd

2016-01-01

Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to be employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH1.6, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D® computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.

An approach to model reactor core nodalization for deterministic safety analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salim, Mohd Faiz, E-mail: mohdfaizs@tnb.com.my; Samsudin, Mohd Rafie, E-mail: rafies@tnb.com.my; Mamat Ibrahim, Mohd Rizal, E-mail: m-rizal@nuclearmalaysia.gov.my

Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to bemore » employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH{sub 1.6}, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D{sup ®} computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.« less

MK3TOOLS & NetCDF - storing VLBI data in a machine independent array oriented data format

NASA Astrophysics Data System (ADS)

Hobiger, T.; Koyama, Y.; Kondo, T.

2007-07-01

In the beginning of 2002 the International VLBI Service (IVS) has agreed to introduce a Platform-independent VLBI exchange format (PIVEX) which permits the exchange of observational data and stimulates the research across different analysis groups. Unfortunately PIVEX has never been implemented and many analysis software packages are still depending on prior processing (e.g. ambiguity resolution and computation of ionosphere corrections) done by CALC/SOLVE. Thus MK3TOOLS which handles MK3 databases without CALC/SOLVE being installed has been developed. It uses the NetCDF format to store the data and since interfaces exist for a variety of programming languages (FORTRAN, C/C++, JAVA, Perl, Python) it can be easily incorporated in existing and upcoming analysis software packages.

MK-2206 induces apoptosis of AML cells and enhances the cytotoxicity of cytarabine.

PubMed

Lu, Jeng-Wei; Lin, Yu-Min; Lai, Yen-Ling; Chen, Chien-Yuan; Hu, Chung-Yi; Tien, Hwei-Fang; Ou, Da-Liang; Lin, Liang-In

2015-07-01

Genetic alterations in the PI3K/AKT cascade have been linked to various human cancers including acute myeloid leukemia (AML) and have emerged to be promising targets for treatment. In this study, we explored the molecular mechanism and clinical implication of a specific allosteric AKT inhibitor, MK-2206, in the treatment of AML. Four leukemia cell lines, MV-4-11, MOLM-13, OCI/AML3, and U937, were used. Apoptosis and cell cycle distribution were determined by flow cytometry analysis. Expression of anti-apoptotic protein family and glycogen synthase kinase 3β (GSK3β) signaling was determined by western blotting. Drug combination effects of MK-2206 with cytarabine were evaluated by cell proliferation assay, and the combination index values were calculated by CompuSyn software. MK-2206 had no effect on normal peripheral blood mononuclear cells, but induced G1-phase arrest and apoptosis in leukemia cells. Among anti-apoptotic Bcl-2 family members, only myeloid cell leukemia-1 (Mcl-1) was significantly suppressed. Mcl-1 suppression by MK-2206 was closely associated with decreased GSK3β phosphorylation at Ser9, an event leads to GSK3β activation. Furthermore, the effect of MK-2206 on Mcl-1 downregulation was abolished by GSK3β inhibitor, lithium chloride and proteasome inhibitor, MG-132, suggesting that MK-2206 acted through a GSK3β-mediated, proteasome-dependent protein degradation. In addition, co-administration of MK-2206 with cytarabine could enhance the cytotoxic efficacy of cytarabine in leukemia cell lines. In conclusion, we have demonstrated that MK-2206 is an active agent in AML and its efficacy as in combination with cytarabine is implicated.

Exploring resistance mechanisms of HCV NS3/4A protease mutations to MK5172: insight from molecular dynamics simulations and free energy calculations.

PubMed

Guan, Yan; Sun, Huiyong; Pan, Peichen; Li, Youyong; Li, Dan; Hou, Tingjun

2015-09-01

Mutations at a number of key positions (Ala156, Asp168 and Arg155) of the HCV NS3/4A protease can induce medium to high resistance to MK5172. The emergence of the resistant mutations seriously compromises the antiviral therapy efficacy to hepatitis C. In this study, molecular dynamics (MD) simulations, free energy calculations and free energy decomposition were used to explore the interaction profiles of MK5172 with the wild-type (WT) and four mutated (R155K, D168A, D168V and A156T) HCV NS3/4A proteases. The binding free energies predicted by Molecular Mechanics/Generalized Born Solvent Area (MM/GBSA) are consistent with the trend of the experimental drug resistance data. The free energy decomposition analysis shows that the resistant mutants may change the protein-MK5172 interaction profiles, resulting in the unbalanced energetic distribution amongst the catalytic triad, the strand 135-139 and the strand 154-160. Moreover, umbrella sampling (US) simulations were employed to elucidate the unbinding processes of MK5172 from the active pockets of the WT HCV NS3/4A protease and the four mutants. The US simulations demonstrate that the dissociation pathways of MK5172 escaping from the binding pockets of the WT and mutants are quite different, and it is quite possible that MK5172 will be harder to get access to the correct binding sites of the mutated proteases, thereafter leading to drug resistance.

Preclinical Characterization of the Phosphodiesterase 10A PET Tracer [(11)C]MK-8193.

PubMed

Hostetler, Eric D; Fan, Hong; Joshi, Aniket D; Zeng, Zhizhen; Eng, Waisi; Gantert, Liza; Holahan, Marie; Meng, Xianjun; Miller, Patricia; O'Malley, Stacey; Purcell, Mona; Riffel, Kerry; Salinas, Cristian; Williams, Mangay; Ma, Bennett; Buist, Nicole; Smith, Sean M; Coleman, Paul J; Cox, Christopher D; Flores, Brock A; Raheem, Izzat T; Cook, Jacquelynn J; Evelhoch, Jeffrey L

2016-08-01

A positron emission tomography (PET) tracer for the enzyme phosphodiesterase 10A (PDE10A) is desirable to guide the discovery and development of PDE10A inhibitors as potential therapeutics. The preclinical characterization of the PDE10A PET tracer [(11)C]MK-8193 is described. In vitro binding studies with [(3)H]MK-8193 were conducted in rat, monkey, and human brain tissue. PET studies with [(11)C]MK-8193 were conducted in rats and rhesus monkeys at baseline and following administration of a PDE10A inhibitor. [(3)H]MK-8193 is a high-affinity, selective PDE10A radioligand in rat, monkey, and human brain tissue. In vivo, [(11)C]MK-8193 displays rapid kinetics, low test-retest variability, and a large specific signal that is displaced by a structurally diverse PDE10A inhibitor, enabling the determination of pharmacokinetic/enzyme occupancy relationships. [(11)C]MK-8193 is a useful PET tracer for the preclinical characterization of PDE10A therapeutic candidates in rat and monkey. Further evaluation of [(11)C]MK-8193 in humans is warranted.

Mk x Nk gated CMOS imager

NASA Astrophysics Data System (ADS)

Janesick, James; Elliott, Tom; Andrews, James; Tower, John; Bell, Perry; Teruya, Alan; Kimbrough, Joe; Bishop, Jeanne

2014-09-01

Our paper will describe a recently designed Mk x Nk x 10 um pixel CMOS gated imager intended to be first employed at the LLNL National Ignition Facility (NIF). Fabrication involves stitching MxN 1024x1024x10 um pixel blocks together into a monolithic imager (where M = 1, 2, . .10 and N = 1, 2, . . 10). The imager has been designed for either NMOS or PMOS pixel fabrication using a base 0.18 um/3.3V CMOS process. Details behind the design are discussed with emphasis on a custom global reset feature which erases the imager of unwanted charge in ~1 us during the fusion ignition process followed by an exposure to obtain useful data. Performance data generated by prototype imagers designed similar to the Mk x Nk sensor is presented.

Interaction of ( sup 3 H)MK-801 with multiple states of the N-methyl-D-aspartate receptor complex of rat brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Javitt, D.C.; Zukin, S.R.

1989-01-01

N-Methyl-D-aspartate (N-Me-D-Asp) and phencyclidine receptors interactively mediate central nervous system processes including psychotomimetic effects of drugs as well as neurodegenerative, cognitive, and developmental events. To elucidate the mechanism of this interaction, effects of N-Me-D-Asp agonists and antagonists and of glycine-like agents upon binding of the radiolabeled phencyclidine receptor ligand ({sup 3}H)MK-801 were determined in rat brain. Scatchard analysis revealed two discrete components of ({sup 3}H)MK-801 binding after 4 hr of incubation. Incubation in the presence of L-glutamate led to an increase in apparent densities but not in affinities of both components of ({sup 3}H)MK-801 binding as well as conversion ofmore » sites from apparent low to high affinity. Incubation in the presence of combined D-serine and L-glutamate led to an increase in the apparent density of high-affinity ({sup 3}H)MK-801 binding compared with incubation in the presence of either L-glutamate or D-serine alone. These data support a model in which phencyclidine receptor ligands bind differentially to closed as well as open conformations of the N-Me-D-Asp receptor complex and in which glycine-like agents permit or facilitate agonist-induced conversion of N-Me-D-Asp receptors from closed to open conformations.« less

MAPKAP kinase 2 (MK2)-dependent and independent models of blister formation in pemphigus vulgaris

PubMed Central

Mao, Xuming; Li, Hong; Sano, Yasuyo; Gaestel, Matthias; Park, Jin Mo; Payne, Aimee S.

2013-01-01

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by autoantibodies to the keratinocyte adhesion protein desmoglein (Dsg) 3. Previous studies suggest that PV pathogenesis involves p38 mitogen activated protein kinase-dependent and -independent pathways. However, p38 is a difficult protein to study and therapeutically target because it has four isoforms and multiple downstream effectors. In the current study, we identify MAPKAP kinase 2 (MK2) as a downstream effector of p38 signaling in PV and describe MK2-dependent and -independent mechanisms of blister formation using passive transfer of human anti-Dsg IgG4 mAbs to neonatal mice. In human keratinocytes, PV mAbs activate MK2 in a dose-dependent manner. MK2 is also activated in human pemphigus skin blisters, causing translocation of MK2 from the nucleus to the cytosol. Small molecule inhibition of MK2 and silencing of MK2 expression block PV mAb-induced Dsg3 endocytosis in human keratinocytes. Additionally, small molecule inhibition and genetic deletion of p38α and MK2 inhibit spontaneous, but not induced, suprabasal blisters by PV mAbs in mouse passive transfer models. Collectively, these data suggest that MK2 is a key downstream effector of p38 that can modulate PV autoantibody pathogenicity. MK2 inhibition may be a valuable adjunctive therapy for control of pemphigus blistering. PMID:23657501

The present situations and perspectives on utilization of research reactors in Thailand

NASA Astrophysics Data System (ADS)

Chongkum, Somporn

2002-01-01

The Thai Research Reactor 1/Modification 1, a TRIGA Mark III reactor, went critical on November 7, 1977. It has been playing a central role in the development of both Office of Atomic Energy for Peace (OAEP) and nuclear application in Thailand. It has a maximum power of 2 MW (thermal) at steady state and a pulsing capacity of 2000 MW. The highest thermal neutron flux at a central thimber is 1×10 13 n/cm 2/s, which is extensively utilized for radioisotope production, neutron activation analysis and neutron beam experiments, i.e. neutron scattering, prompt gamma analysis and neutron radiography. Following the nuclear technological development, the OAEP is in the process of establishing the Ongkharak Nuclear Research Center (ONRC). The center is being built in Nakhon Nayok province, 60 km northeast of Bangkok. The centerpiece of the ONRC is a multipurpose 10 MW TRIGA research reactor. Facilities are included for the production of radioisotopes for medicine, industry and agriculture, neutron transmutation doping of silicon, and neutron capture therapy. The neutron beam facilities will also be utilized for applied research and technology development as well as training in reactor operations, performance of experiments and reactor physics. This paper describes a recent program of utilization as well as a new research reactor for enlarging the perspectives of its utilization in the future.

Vertical stratification in the distribution of demersal fishes along the walls of the La Jolla and Scripps submarine canyons, California, USA

NASA Astrophysics Data System (ADS)

Smith, Joshua G.; Lindholm, James

2016-08-01

The geographic distributions of many coastal marine fish assemblages are strongly driven by habitat features, particularly among demersal fishes that live along the seafloor. Ecologists have long recognized the importance of characterizing fish habitat associations, especially where spatial management is under consideration. However, little is known about fish distributions and habitat suitability in unique demersal habitats such as submarine canyons. The active continental margin of the California coast is cut by eight submarine canyons, several of which extend from the shore to the deep abyssal plain. We sampled the demersal fish assemblages in two of those canyons: (1) the Scripps submarine canyon in the San-Diego-Scripps State Marine Conservation Area (SMCA) and (2) the La Jolla canyon in the Matlahuayl State Marine Reserve (SMR) to gain insight into both the distributions and habitat associations of demersal fishes in canyons. A remotely operated vehicle was used to conduct 21 vertically oriented transects along the canyon walls in depths ranging from 20 to 300 m. Species composition was assessed in three depth-stratified zones (100 m per zone) along the canyon walls. Species richness, abundance, and attributes of the surrounding canyon habitat structure (slope and benthic terrain ruggedness) were quantified. Three distinct assemblage groupings were identified, which comprised 35 species of demersal fishes from 17 families. Among all factors analyzed in this study, depth, slope, and ruggedness were strong explanatory variables of patterns of species richness and abundance; however, the relationship between depth and assemblage structure was non-linear. The greatest number of species was observed in the mid depth-stratified zone. These trends suggest that variation in canyon dynamics across depth strata may facilitate distinct assemblage groupings of demersal fishes, which can in turn be used to better manage these unique habitats.

Targeting Aurora Kinase with MK-0457 Inhibits Ovarian Cancer Growth

PubMed Central

Lin, Yvonne G.; Immaneni, Anand; Merritt, William M.; Mangala, Lingegowda S.; Kim, SeungWook; Shahzad, Mian M.K.; Tsang, Yvonne T.M.; Armaiz-Pena, Guillermo N.; Lu, Chunhua; Kamat, Aparna A.; Han, Liz Y.; Spannuth, WhitneyA.; Nick, Alpa M.; Landen, Charles N.; Wong, Kwong K.; Gray, Michael J.; Coleman, Robert L.; Bodurka, Diane C.; Brinkley, William R.; Sood, Anil K.

2009-01-01

Purpose The Aurora kinase family plays pivotal roles in mitotic integrity and cell cycle.We sought to determine the effects of inhibiting Aurora kinase on ovarian cancer growth in an orthotopic mouse model using a small molecule pan-Aurora kinase inhibitor, MK-0457. Experimental Design We examined cell cycle regulatory effects and ascertained the therapeutic efficacy of Aurora kinase inhibition both alone and combined with docetaxel using both in vitro and in vivo ovarian cancer models. Results In vitro cytotoxicity assays with HeyA8 and SKOV3ip1 cells revealed >10-fold greater docetaxel cytotoxicity in combination with MK-0457. After in vivo dose kinetics were determined using phospho-histone H3 status, therapy experiments with the chemosensitive HeyA8 and SKOV3ip1as well as the chemoresistant HeyA8-MDR and A2780-CP20 models showed that Aurora kinase inhibition alone significantly reduced tumor burden compared with controls (P values < 0.01). Combination treatment with docetaxel resulted in significantly improved reduction in tumor growth beyond that afforded by docetaxel alone (P ≤ 0.03). Proliferating cell nuclear antigen immunohistochemistry revealed that MK-0457 alone and in combination with docetaxel significantly reduced cellular proliferation (P values < 0.001). Compared with controls, treatment with MK-0457 alone and in combination with docetaxel also significantly increased tumor cell apoptosis by ∼3-fold (P < 0.01). Remarkably, compared with docetaxel monotherapy, MK-0457 combined with docetaxel resulted in significantly increased tumor cell apoptosis. Conclusions Aurora kinase inhibition significantly reduces tumor burden and cell proliferation and increases tumor cell apoptosis in this preclinical orthotopic model of ovarian cancer. The role of Aurora kinase inhibition in ovarian cancer merits further investigation in clinical trials. PMID:18765535

Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of ( sup 3 H)dopamine from striatal slices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowyer, J.F.; Scallet, A.C.; Holson, R.R.

1991-04-01

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 ({sup 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{sup 2}{sup +} present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated ({sup 3}H)dopamine and ({sup 3}H)metabolite (tritium) release of 3 to 6 and 12 to 16%more » of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg{sup 2}{sup +} 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{sup 2}{sup +} 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{sup 2}{sup +} present, 1 mM glutamine increased glutamate release and induced the release of ({sup 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%.« less

TRIGA MARK-II source term

DOE Office of Scientific and Technical Information (OSTI.GOV)

Usang, M. D., E-mail: mark-dennis@nuclearmalaysia.gov.my; Hamzah, N. S., E-mail: mark-dennis@nuclearmalaysia.gov.my; Abi, M. J. B., E-mail: mark-dennis@nuclearmalaysia.gov.my

ORIGEN 2.2 are employed to obtain data regarding γ source term and the radio-activity of irradiated TRIGA fuel. The fuel composition are specified in grams for use as input data. Three types of fuel are irradiated in the reactor, each differs from the other in terms of the amount of Uranium compared to the total weight. Each fuel are irradiated for 365 days with 50 days time step. We obtain results on the total radioactivity of the fuel, the composition of activated materials, composition of fission products and the photon spectrum of the burned fuel. We investigate the differences ofmore » results using BWR and PWR library for ORIGEN. Finally, we compare the composition of major nuclides after 1 year irradiation of both ORIGEN library with results from WIMS. We found only minor disagreements between the yields of PWR and BWR libraries. In comparison with WIMS, the errors are a little bit more pronounced. To overcome this errors, the irradiation power used in ORIGEN could be increased a little, so that the differences in the yield of ORIGEN and WIMS could be reduced. A more permanent solution is to use a different code altogether to simulate burnup such as DRAGON and ORIGEN-S. The result of this study are essential for the design of radiation shielding from the fuel.« less

MK-801 increases locomotor activity in a context-dependent manner in zebrafish.

PubMed

Tran, Steven; Muraleetharan, Arrujyan; Fulcher, Niveen; Chatterjee, Diptendu; Gerlai, Robert

2016-01-01

Zebrafish have become a popular animal model for behavioral neuroscience with an increasing number of studies examining the effects of pharmacological compounds targeting the brain. Exposure to MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist has been shown to increase locomotor activity in zebrafish. However, others have failed to replicate this finding as several contradicting studies report no changes in locomotor activity following exposure to similar doses. In the current study we reconcile these behavioral reports by demonstrating that zebrafish do not exhibit changes in locomotor activity during exposure to non-sedative doses of MK-801. Interestingly, zebrafish do exhibit significant increases in locomotion if pre-treated with MK-801 followed by subsequent testing in a novel environment, which suggests the effects of MK-801 are context-dependent. In addition, we examine the potential role of the dopaminergic system in mediating MK-801's locomotor stimulant effect by quantifying the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the brains of zebrafish following a 30 min exposure to 10 μM of MK-801 (the dose found to induce the largest increase in locomotor activity). Our findings indicate that the MK-801-induced increase in locomotor activity is not accompanied by changes in whole-brain levels of dopamine or DOPAC. Overall, our results suggest that MK-801's context-dependent locomotor stimulant effect may be independent of whole-brain dopaminergic activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles.

PubMed

Hostetler, Eric D; Walji, Abbas M; Zeng, Zhizhen; Miller, Patricia; Bennacef, Idriss; Salinas, Cristian; Connolly, Brett; Gantert, Liza; Haley, Hyking; Holahan, Marie; Purcell, Mona; Riffel, Kerry; Lohith, Talakad G; Coleman, Paul; Soriano, Aileen; Ogawa, Aimie; Xu, Serena; Zhang, Xiaoping; Joshi, Elizabeth; Della Rocca, Joseph; Hesk, David; Schenk, David J; Evelhoch, Jeffrey L

2016-10-01

A PET tracer is desired to help guide the discovery and development of disease-modifying therapeutics for neurodegenerative diseases characterized by neurofibrillary tangles (NFTs), the predominant tau pathology in Alzheimer disease (AD). We describe the preclinical characterization of the NFT PET tracer 18 F-MK-6240. In vitro binding studies were conducted with 3 H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs. Immunohistochemistry for phosphorylated tau was performed on human brain slices for comparison with 3 H-MK-6240 binding patterns on adjacent brain slices. PET studies were performed with 18 F-MK-6240 in monkeys to evaluate tracer kinetics and distribution in the brain. 18 F-MK-6240 monkey PET studies were conducted after dosing with unlabeled MK-6240 to evaluate tracer binding selectivity in vivo. The 3 H-MK-6240 binding pattern was consistent with the distribution of phosphorylated tau in human AD brain slices. 3 H-MK-6240 bound with high affinity to human AD brain cortex homogenates containing abundant NFTs but bound poorly to amyloid plaque-rich, NFT-poor AD brain homogenates. 3 H-MK-6240 showed no displaceable binding in the subcortical regions of human AD brain slices and in the hippocampus/entorhinal cortex of non-AD human brain homogenates. In monkey PET studies, 18 F-MK-6240 displayed rapid and homogeneous distribution in the brain. The 18 F-MK-6240 volume of distribution stabilized rapidly, indicating favorable tracer kinetics. No displaceable binding was observed in self-block studies in rhesus monkeys, which do not natively express NFTs. Moderate defluorination was observed as skull uptake. 18 F-MK-6240 is a promising PET tracer for the in vivo quantification of NFTs in AD patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Comparative neurobiological effects of ibogaine and MK-801 in rats.

PubMed

Baumann, M H; Rothman, R B; Ali, S F

2000-05-01

Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors.

Inhibition of the protein kinase MK-2 protects podocytes from nephrotic syndrome-related injury

PubMed Central

Pengal, Ruma; Guess, Adam J.; Agrawal, Shipra; Manley, Joshua; Ransom, Richard F.; Mourey, Robert J.; Smoyer, William E.

2011-01-01

While mitogen-activated protein kinase (MAPK) activation has been implicated in the pathogenesis of various glomerular diseases, including nephrotic syndrome (NS), its specific role in podocyte injury is not known. We hypothesized that MK-2, a downstream substrate of p38 MAPK, mediates the adverse effects of this pathway and that inhibition of MK-2 would protect podocytes from NS-related injury. Using cultured podocytes, we analyzed 1) the roles of MK-2 and p38 MAPK in puromycin aminonucleoside (PAN)-induced podocyte injury; 2) the ability of specific MK-2 and p38 MAPK inhibitors to protect podocytes against injury; 3) the role of serum albumin, known to induce podocyte injury, in activating p38 MAPK/MK-2 signaling; and 4) the role of p38 MAPK/MK-2 signaling in the expression of Cox-2, an enzyme associated with podocyte injury. Treatment with protein kinase inhibitors specific for both MK-2 (C23, a pyrrolopyridine-type compound) or p38 MAPK (SB203580) reduced PAN-induced podocyte injury and actin cytoskeletal disruption. Both inhibitors reduced baseline podocyte p38 MAPK/MK-2 signaling, as measured by the degree of phosphorylation of HSPB1, a downstream substrate of MK-2, but exhibited disparate effects on upstream signaling. Serum albumin activated p38 MAPK/MK-2 signaling and induced Cox-2 expression, and these responses were blocked by both inhibitors. Given the critical importance of podocyte injury to both NS and other progressive glomerular diseases, these data suggest an important role for p38 MAPK/MK-2 signaling in podocyte injury and identify MK-2 inhibition as a promising potential therapeutic strategy to protect podocytes in various glomerular diseases. PMID:21613416

Conference Eighth International Symposium on Blood Substitutes

DTIC Science & Technology

2001-04-01

Dept. of Bioengin, 0412 Japan University of California, San eishun(mn.waseda.ac.ip Diego 9500 Gilman Drive, John Frangos , Ph.D. La Jolla, CA 92093...Ph.D. La Jolla, CA 92093 Professor of Physiology and frangos @bioeng.ucsd.edu Medicine McGill University 3655 Drummond Street Montreal, Quebec, CANADA...Break 1050 1-2 Fabry 1050 V-3 Kerger 1100 1110 1-3 Manjufa P4Tsuchida 1105 V-4 Kim 1120 V-5 Kingma1130 I-4 Kramer 1130 P5 Frangos 1135 V-6 Pittman 1150

The synergistic effect of treatment with triptolide and MK-801 in the rat neuropathic pain model

PubMed Central

Wang, Jian; Qiao, Yu; Yang, Ri-Sheng; Zhang, Chun-Kui; Wu, Huang-Hui; Lin, Jia-Ji; Zhang, Ting

2017-01-01

Triptolide (T10), an active component of Tripterygium wilfordii Hook F, is reported to have potent anti-inflammatory and analgesic effects. Additionally, MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, can reduce glutamate toxicity and has a significant analgesic effect on chronic pain. In this study, we tested the possible synergistic analgesic ability by intrathecal administration of T10 and MK-801 for the treatment of neuropathic pain. Single T10 (3, 10, or 30 µg/kg), MK-801 (10, 30, or 90 µg/kg), or a combination of them were intrathecally administrated in rats with spinal nerve ligation. We found that single administration of T10 caused a slow-acting but long-term analgesic effect, while single administration of MK-801 caused a fast-acting but short-term effect. Administration of their combination showed obviously synergic analgesia and the 1:3 ratio of T10 to MK-801 reached the peak effect. Furthermore, application of T10 and/or MK-801 significantly inhibited the activation of microglia and astrocyte and phosphorylation of STAT3 and NR2B in the spinal dorsal horn induced by chronic neuropathic pain. Our data suggest that the combination of T10 and MK-801 may be a potentially novel strategy for treatment of neuropathic pain. PMID:29166839

Johnson noise measurements of a 3.1 k Ω resistor at mK temperatures using a SQUID-based circuit

NASA Astrophysics Data System (ADS)

Shingla, Vidhi; Kleinbaum, Ethan; Csáthy, Gábor

The measurement of Johnson noise of resistors of the order of a k Ω at mK temperatures is a difficult task. Such a measurement is not possible with room temperature amplifiers since the typical amplifier noise exceeds the Johnson noise. Such measurements are, however, possible with circuits based on cooled High Electron Mobility Transistors (HEMTs). We present an alternative circuit for such measurements which is based on a dc SQUID. We demonstrate that our circuit does not contribute appreciable noise to the Johnson noise of a 3 . 1 k Ω resistor down to 16 mK, enabling therefore Johnson noise thermometry. This work was supported by the NSF Grant DMR-1505866.

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

PubMed Central

Yoo, Seung-Jun; Cho, Bongki; Lee, Deokho; Son, Gowoon; Lee, Yeong-Bae; Soo Han, Hyung; Kim, Eunjoo; Moon, Chanil; Moon, Cheil

2017-01-01

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain–blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have

Status of the TRIGA-LASER experiment

NASA Astrophysics Data System (ADS)

Gorges, C.; Kaufmann, S.; Geppert, Ch.; Krämer, J.; Sánchez, R.; Nörtershäuser, W.

2017-11-01

We report on the newly developed control system called TRITON and the new data acquisition called TILDA as well as on improved isotope shift measurements of the isotopes 40,42,44,48Ca in the 4 s 2S1/2 → 4 p 2P3/2 (D2) transition at the TRIGA-LASER experiment in Mainz using collinear laser spectroscopy. Well known isotope shift measurements in the 4 s 2S1/2 → 4 p 2P1/2 (D1) transition act as calibration points to reduce the uncertainties in the D2-line to provide reference values for the determination of nuclear charge radii and quadrupole moments of neutron rich calcium isotopes at COLLAPS.

Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.

1989-01-01

The effect of a number of antemortem and postmortem factors on ({sup 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 ({sup 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.

High-intensity power-resolved radiation imaging of an operational nuclear reactor.

PubMed

Beaumont, Jonathan S; Mellor, Matthew P; Villa, Mario; Joyce, Malcolm J

2015-10-09

Knowledge of the neutron distribution in a nuclear reactor is necessary to ensure the safe and efficient burnup of reactor fuel. Currently these measurements are performed by in-core systems in what are extremely hostile environments and in most reactor accident scenarios it is likely that these systems would be damaged. Here we present a compact and portable radiation imaging system with the ability to image high-intensity fast-neutron and gamma-ray fields simultaneously. This system has been deployed to image radiation fields emitted during the operation of a TRIGA test reactor allowing a spatial visualization of the internal reactor conditions to be obtained. The imaged flux in each case is found to scale linearly with reactor power indicating that this method may be used for power-resolved reactor monitoring and for the assay of ongoing nuclear criticalities in damaged nuclear reactors.

Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Tomohito; Momoi, Kanae; Hosoyamada, Makoto

2008-03-15

Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-{sup mk}/{sub mk} mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl{sub 2} aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation,more » while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.« less

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

PubMed

Chen, XiuXiu; Gong, LiHua; Ou, RongYing; Zheng, ZhenZhen; Chen, JinYan; Xie, FengFeng; Huang, XiaoXiu; Qiu, JianGe; Zhang, WenJi; Jiang, QiWei; Yang, Yang; Zhu, Hua; Shi, Zhi; Yan, XiaoJian

2016-03-01

Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroprotective effects of MK-801 against traumatic brain injury in immature rats.

PubMed

Sönmez, Ataç; Sayın, Oya; Gürgen, Seren Gülşen; Çalişir, Meryem

2015-06-15

Traumatic brain injury (TBI) is a major health problem in pediatric ages and also has major social, economic, and emotional outcomes, with diverse sequelae in many spheres of everyday life. We aimed to investigate the effect of MK-801, a competitive NMDA receptor antagonist, on hippocampal damage and behavioral deficits on 10-day-old rat pups subjected to contusion injury. The aims of the present study were to determine: (i) the short term effects of MK-801 on hippocampal BDNF, NGF and NMDA receptor immunoreactivity and neuron density in hippocampus (ii) long term effects of MK-801 on cognitive dysfunction following TBI in the immature rats. MK-801, was injected intraperitoneally at the doses of 1mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining, BDNF, NGF and NMDAR receptor immunohistochemistry on P10 day and behavioral alterations were evaluated using elevated plus maze and novel object recognition tests two months after the trauma. Histopathological and immunohistochemical evaluations showed that treatment with a single dose of 1mg/kg MK-801 (i.p.) significantly ameliorated the trauma induced hippocampal neuron loss and decreased BDNF, NGF and NMDAR expressions in CA1, CA3 and DG hippocampal brain regions. Additionally, treatment with MK-801 ameliorated anxiety and hippocampus dependent memory of animals subjected to trauma. These results show that acute treatment of MK-801 has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in immature rats. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons.

PubMed

Wen, Xianjie; Lai, Xiaohong; Li, Xiaohong; Zhang, Tao; Liang, Hua

2016-12-01

In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK II α , CaMK II β , CaMK II δ , CaMK II γ , can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK II β , CaMK II δ , CaMK II g mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A compact cryogen-free platform operating at 1 K or 50 mK

NASA Astrophysics Data System (ADS)

Matthews, A. J.; Patton, M.; Marsh, T.; van der Vliet, H.

2018-03-01

We report the design and performance characteristics of a compact cryogen-free platform. The system is based around a continuous 1 K pot which operates using a small (10 m3 h‑1) room temperature circulation pump. The pot cools an experimental plate to ≈ 1.2 K, and has a cooling capacity of 100 mW at a temperature ≈ 1.9 K. Cooling the pot from room temperature to < 2 K takes around 12 hours. The temperature range of the platform can be lowered to < 50 mK with the addition of a small dilution refrigerator, using the 1 K pot as a pre-cooling stage for the circulating 3He. The dilution stage has a typical (continuous) cooling capacity of 30 µW at 100 mK (300 µW at 250 mK) and is designed to operate with just 3 litres of (NTP) 3He.

Prunella vulgaris attenuates prepulse inhibition deficit and attention disruption induced by MK-801 in mice.

PubMed

Park, Se Jin; Jeon, Se Jin; Dela Peña, Ike C; Lee, Hyung Eun; Kim, Dong Hyun; Kim, Jong Min; Lee, Young Woo; Jung, Jun Man; Shin, Bum Young; Lee, Seungheon; Cheong, Jae Hoon; Shin, Chan Young; Jang, Dae Sik; Ryu, Jong Hoon

2013-12-01

Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it has been traditionally used to treat inflammation or hypertension. In the present study, we investigated the effects of the ethanolic extract of the spikes of Prunella vulgaris var. lilacina (EEPV) on dizocilpine (MK-801)-induced schizophrenia-like phenotype behaviors such as the disruption of prepulse inhibition and attention deficits in mice. We also determined the effect of EEPV on MK-801-induced alterations in phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, phospho-glycogen synthase kinase 3-β, and phosphorylated cAMP response element-binding protein levels in the cortex and hippocampus of mice. MK-801-induced prepulse inhibition deficits were ameliorated by the administration of EEPV, as shown in the acoustic startle response test. Furthermore, EEPV attenuated the MK-801-induced attention deficits in the water finding test. We also found that EEPV attenuated the increased phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, or phospho-glycogen synthase kinase 3-β levels induced by MK-801 in the cortex but not in the hippocampus. These results suggest that EEPV could be useful for treating schizophrenia because EEPV ameliorates prepulse inhibition disruption and attention deficits induced by MK-801. Copyright © 2013 John Wiley & Sons, Ltd.

Two-dimensional superconductivity at a Mott insulator/band insulator interface LaTiO3/SrTiO3.

PubMed

Biscaras, J; Bergeal, N; Kushwaha, A; Wolf, T; Rastogi, A; Budhani, R C; Lesueur, J

2010-10-05

Transition metal oxides show a great variety of quantum electronic behaviours where correlations often have an important role. The achievement of high-quality epitaxial interfaces involving such materials gives a unique opportunity to engineer artificial structures where new electronic orders take place. One of the most striking result in this area is the recent observation of a two-dimensional electron gas at the interface between a strongly correlated Mott insulator LaTiO(3) and a band insulator SrTiO(3). The mechanism responsible for such a behaviour is still under debate. In particular, the influence of the nature of the insulator has to be clarified. In this article, we show that despite the expected electronic correlations, LaTiO(3)/SrTiO(3) heterostructures undergo a superconducting transition at a critical temperature T(c)(onset)~300 mK. We have found that the superconducting electron gas is confined over a typical thickness of 12 nm and is located mostly on the SrTiO(3) substrate.

TRIGA Mark II nuclear reactor facility. Final report, 1 July 1980--30 June 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, B.C.

1997-05-01

This report is a final culmination of activities funded through the Department of Energy`s (DOE) University Reactor Sharing Program, Grant DE-FG02-80ER10273, during the period 1 July 1980 through 30 June 1995. Progress reports have been periodically issued to the DOE, namely the Reactor Facility Annual Reports C00-2082/2219-7 through C00-2082/10723-21, which are contained as an appendix to this report. Due to the extent of time covered by this grant, summary tables are presented. Table 1 lists the fiscal year financial obligations of the grant. As listed in the original grant proposals, the DOE grant financed 70% of project costs, namely themore » total amount spent of these projects minus materials costs and technical support. Thus the bulk of funds was spent directly on reactor operations. With the exception of a few years, spending was in excess of the grant amount. As shown in Tables 2 and 3, the Reactor Sharing grant funded a immense number of research projects in nuclear engineering, geology, animal science, chemistry, anthropology, veterinary medicine, and many other fields. A list of these users is provided. Out of the average 3000 visitors per year, some groups participated in classes involving the reactor such as Boy Scout Merit Badge classes, teacher`s workshops, and summer internships. A large number of these projects met the requirements for the Reactor Sharing grant, but were funded by the University instead.« less

The Bonn MK IV Correlator Project

NASA Astrophysics Data System (ADS)

Alef, W.; Graham, D. A.; Zensus, J. A.; Müskens, A.; Schlüter, W.

2000-05-01

We describe the present status of the VLBI correlator in Bonn. The old MK III correlator has been made Y2K compliant, but it is expected to be taken out of operation this year. We report our first experience with the new MK IV correlator, jointly operated by the MPIfR and the BKG, as well as our short-term and long-term plans, both with respect to astronomical and geodetic requirements.

Upgrade of Irradiation Test Capability of the Experimental Fast Reactor Joyo

NASA Astrophysics Data System (ADS)

Sekine, Takashi; Aoyama, Takafumi; Suzuki, Soju; Yamashita, Yoshioki

2003-06-01

The JOYO MK-II core was operated from 1983 to 2000 as fast neutron irradiation bed. In order to meet various requirements for irradiation tests for development of FBRs, the JOYO upgrading project named MK-III program was initiated. The irradiation capability in the MK-III core will be about four times larger than that of the MK-II core. Advanced irradiation test subassemblies such as capsule type subassembly and on-line instrumentation rig are planned. As an innovative reactor safety system, the irradiation test of Self-Actuated Shutdown System (SASS) will be conducted. In order to improve the accuracy of neutron fluence, the core management code system was upgraded, and the Monte Carlo code and Helium Accumulation Fluence Monitor (HAFM) were applied. The MK-III core is planned to achieve initial criticality in July 2003.

Retention of Electronic Conductivity in LaAlO3/SrTiO3 Nanostructures Using a SrCuO2 Capping Layer

NASA Astrophysics Data System (ADS)

Aurino, P. P.; Kalabukhov, A.; Borgani, R.; Haviland, D. B.; Bauch, T.; Lombardi, F.; Claeson, T.; Winkler, D.

2016-08-01

The interface between two wide band-gap insulators, LaAlO3 and SrTiO3 (LAO/STO) offers a unique playground to study the interplay and competitions between different ordering phenomena in a strongly correlated two-dimensional electron gas. Recent studies of the LAO/STO interface reveal the inhomogeneous nature of the 2DEG that strongly influences electrical-transport properties. Nanowires needed in future applications may be adversely affected, and our aim is, thus, to produce a more homogeneous electron gas. In this work, we demonstrate that nanostructures fabricated in the quasi-2DEG at the LaAlO3/SrTiO3 interface, capped with a SrCuO2 layer, retain their electrical resistivity and mobility independent of the structure size, ranging from 100 nm to 30 μ m . This is in contrast to noncapped LAO/STO structures, where the room-temperature electrical resistivity significantly increases when the structure size becomes smaller than 1 μ m . High-resolution intermodulation electrostatic force microscopy reveals an inhomogeneous surface potential with "puddles" of a characteristic size of 130 nm in the noncapped samples and a more uniform surface potential with a larger characteristic size of the puddles in the capped samples. In addition, capped structures show superconductivity below 200 mK and nonlinear current-voltage characteristics with a clear critical current observed up to 700 mK. Our findings shed light on the complicated nature of the 2DEG at the LAO/STO interface and may also be used for the design of electronic devices.

EM61 MK2 Cart Data Collection and Analysis

DTIC Science & Technology

2011-06-01

number. 1. REPORT DATE JUN 2011 2 . REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE EM61 MK2 Cart Data Collection and Analysis... 2   1.3  REGULATORY DRIVERS... 2   1.3.1  OBJECTIVE OF THE ADVISORY GROUP .......................................................... 2   2.0  TECHNOLOGY

High-intensity power-resolved radiation imaging of an operational nuclear reactor

PubMed Central

Beaumont, Jonathan S.; Mellor, Matthew P.; Villa, Mario; Joyce, Malcolm J.

2015-01-01

Knowledge of the neutron distribution in a nuclear reactor is necessary to ensure the safe and efficient burnup of reactor fuel. Currently these measurements are performed by in-core systems in what are extremely hostile environments and in most reactor accident scenarios it is likely that these systems would be damaged. Here we present a compact and portable radiation imaging system with the ability to image high-intensity fast-neutron and gamma-ray fields simultaneously. This system has been deployed to image radiation fields emitted during the operation of a TRIGA test reactor allowing a spatial visualization of the internal reactor conditions to be obtained. The imaged flux in each case is found to scale linearly with reactor power indicating that this method may be used for power-resolved reactor monitoring and for the assay of ongoing nuclear criticalities in damaged nuclear reactors. PMID:26450669

MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea

PubMed Central

Chen, Yanfeng; Yang, Wenzhao; Zhang, Xiaobo; Yang, Shu; Peng, Gao; Wu, Ting; Zhou, Yueping; Huang, Caihong; Reinach, Peter S.; Li, Wei; Liu, Zuguo

2016-01-01

MK2 activation by p38 MAPK selectively induces inflammation in various diseases. We determined if a MK2 inhibitor (MK2i), improves cornea wound healing by inhibiting inflammation caused by burning rat corneas with alkali. Our study, for the first time, demonstrated that MK2i inhibited alkali burn-induced MK2 activation as well as rises in inflammation based on: a) blunting rises in inflammatory index, inflammatory cell infiltration, ED1+ macrophage and PMN+ neutrophil infiltration; b) suppressing IL-6 and IL-1β gene expression along with those of macrophage inflammatory protein-1α (MIP-1α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); c) reducing angiogenic gene expression levels and neovascularization (NV) whereas anti-angiogenic PEDF levels increased. In addition, this study found that MK2i did not affect human corneal epithelial cell (HCEC) proliferation and migration and had no detectable side effects on ocular surface integrity. Taken together, MK2i selectively inhibited alkali burn-induced corneal inflammation by blocking MK2 activation, these effects have clinical relevance in the treatment of inflammation related ocular surface diseases. PMID:27329698

Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABA(A) alpha2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers.

PubMed

de Haas, S L; de Visser, S J; van der Post, J P; Schoemaker, R C; van Dyck, K; Murphy, M G; de Smet, M; Vessey, L K; Ramakrishnan, R; Xue, L; Cohen, A F; van Gerven, J M A

2008-01-01

The use of non-selective gamma-aminobutyric acid (GABA) enhancers, such as benzodiazepines in the treatment of anxiety disorders is still widespread but hampered by unfavourable side effects. some of these may be associated with binding properties to certain subtypes of the GABA(A) receptor that are unnecessary for therapeutic effects. MK-0343 was designed to be a less sedating anxiolytic, based on reduced efficacy at the alpha1 subtype and significant efficacy at alpha2 and alpha3 subtypes of the GABA(A) receptor. This paper is a double-blind, four-way cross-over (n = 12) study to investigate the effects of MK-0343 (0.25 and 0.75 mg) in comparison to placebo and an anxiolytic dose (2 mg) of the non-selective agonist lorazepam. Effects were measured by eye movements, body sway, Visual Analogue scales (VAS) and memory tests. Lorazepam impaired saccadic peak velocity (SPV), VAs alertness scores, postural stability and memory and increased saccadic latency and inaccuracy. MK-0343 0.75 mg was equipotent with lorazepam as indicated by SPV (-42.4 deg/s), saccadic latency (0.02 s) and VAS alertness scores (1.50 ln mm), while effects on memory and postural stability were smaller. MK-0343 0.25 mg only affected postural stability to a similar extent as MK-0343 0.75 mg. The effect profile of MK-0343 0.75 mg is different from the full agonist lorazepam, which could reflect the selective actions of this compound. Although less effect on VAS alertness was expected, diminished effects on memory and postural stability were present. Clinical studies in anxiety patients should show whether this dose of MK-0343 is therapeutically effective with a different side-effect profile.

In Vitro Characterization of MK-1439, a Novel HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor

PubMed Central

Feng, Meizhen; Falgueyret, Jean-Pierre; Tawa, Paul; Witmer, Marc; DiStefano, Daniel; Li, Yuan; Burch, Jason; Sachs, Nancy; Lu, Meiqing; Cauchon, Elizabeth; Campeau, Louis-Charles; Grobler, Jay; Yan, Youwei; Ducharme, Yves; Côté, Bernard; Asante-Appiah, Ernest; Hazuda, Daria J.; Miller, Michael D.

2014-01-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for treating human immunodeficiency type 1 virus (HIV-1)-infected patients. MK-1439 is a novel NNRTI with a 50% inhibitory concentration (IC50) of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. Selectivity and cytotoxicity studies confirmed that MK-1439 is a highly specific NNRTI with minimum off-target activities. In the presence of 50% normal human serum (NHS), MK-1439 showed excellent potency in suppressing the replication of WT virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively. MK-1439 exhibited similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses). In addition, the susceptibility of a broader array of clinical NNRTI-associated mutant viruses (a total of 96 viruses) to MK-1439 and other benchmark NNRTIs was investigated. The results showed that the mutant profile of MK-1439 was superior overall to that of efavirenz (EFV) and comparable to that of etravirine (ETR) and rilpivirine (RPV). Furthermore, E138K, Y181C, and K101E mutant viruses that are associated with ETR and RPV were susceptible to MK-1439 with a fold change (FC) of <3. A two-drug in vitro combination study indicated that MK-1439 acts nonantagonistically in the antiviral activity with each of 18 FDA-licensed drugs for HIV infection. Taken together, these in vitro data suggest that MK-1439 possesses the desired properties for further development as a new antiviral agent. PMID:24379202

A continuous dry 300 mK cooler for THz sensing applications.

PubMed

Klemencic, G M; Ade, P A R; Chase, S; Sudiwala, R; Woodcraft, A L

2016-04-01

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 (3)He cooling systems. This closed dry system uses only 5 l of (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.

Modifications to the NRAD Reactor, 1977 to present

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weeks, A.A.; Pruett, D.P.; Heidel, C.C.

1986-01-01

Argonne National Laboratory-West, operated by the University of Chicago, is located near Idaho Falls, ID, on the Idaho National Engineering laboratory Site. ANL-West performs work in support of the Liquid Metal Fast Breeder Reactor Program (LMFBR) sponsored by the United States Department of Energy. The NRAD reactor is located at the Argonne Site within the Hot Fuel Examination Facility/North, a large hot cell facility where both non-destructive and destructive examinations are performed on highly irradiated reactor fuels and materials in support of the LMFBR program. The NRAD facility utilizes a 250-kW TRIGA reactor and is completely dedicated to neutron radiographymore » and the development of radiography techniques. Criticality was first achieved at the NRAD reactor in October of 1977. Since that time, a number of modifications have been implemented to improve operational efficiency and radiography production. This paper describes the modifications and changes that significantly improved operational efficiency and reliability of the reactor and the essential auxiliary reactor systems.« less

T-cell immunotherapy for human MK-1-expressing tumors using a fusion protein of the superantigen SEA and anti-MK-1 scFv antibody.

PubMed

Ueno, Aruto; Arakawa, Fumiko; Abe, Hironori; Matsumoto, Hisanobu; Kudo, Toshio; Asano, Ryutaro; Tsumoto, Kohei; Kumagai, Izumi; Kuroki, Motomu; Kuroki, Masahide

2002-01-01

The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we constructed a recombinant fusion protein of SEA and the single-chain variable fragment (scFv) of the FU-MK-1 antibody, which recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas. We employed recombinant DNA techniques to fuse recombinant mutant SEA to an scFv antibody derived from FU-MK-1 and the resulting fusion protein (SEA/FUscFv) was produced by a bacterial expression system, purified with a metal-affinity column, and characterized for its MK-1-binding specificity and its antitumor activity. The SEA/FUscFv fusion protein retained the reactivity with MK-1-expressing tumor cells, introduced a specific cytotoxicity of lymphokine-activated killer T-cells to the tumor cells, and consequently suppressed the tumor growth in a SCID mouse xenograft model. This genetically engineered SEA/FUscFv fusion protein may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.

MK-STYX, a Catalytically Inactive Phosphatase Regulating Mitochondrially Dependent Apoptosis ▿

PubMed Central

Niemi, Natalie M.; Lanning, Nathan J.; Klomp, Jeff A.; Tait, Stephen W.; Xu, Yong; Dykema, Karl J.; Murphy, Leon O.; Gaither, L. Alex; Xu, H. Eric; Furge, Kyle A.; Green, Douglas R.; MacKeigan, Jeffrey P.

2011-01-01

Evasion of apoptosis is a significant problem affecting an array of cancers. In order to identify novel regulators of apoptosis, we performed an RNA interference (RNAi) screen against all kinases and phosphatases in the human genome. We identified MK-STYX (STYXL1), a catalytically inactive phosphatase with homology to the mitogen-activated protein kinase (MAPK) phosphatases. Despite this homology, MK-STYX knockdown does not significantly regulate MAPK signaling in response to growth factors or apoptotic stimuli. Rather, RNAi-mediated knockdown of MK-STYX inhibits cells from undergoing apoptosis induced by cellular stressors activating mitochondrion-dependent apoptosis. This MK-STYX phenotype mimics the loss of Bax and Bak, two potent guardians of mitochondrial apoptotic potential. Similar to loss of both Bax and Bak, cells without MK-STYX expression are unable to release cytochrome c. Proapoptotic members of the BCL-2 family (Bax, Bid, and Bim) are unable to trigger cytochrome c release in MK-STYX-depleted cells, placing the apoptotic deficiency at the level of mitochondrial outer membrane permeabilization (MOMP). MK-STYX was found to localize to the mitochondria but is neither released from the mitochondria upon apoptotic stress nor proximal to the machinery currently known to control MOMP, indicating that MK-STYX regulates MOMP using a distinct mechanism. PMID:21262771

The MK VI - A second generation attitude control system

NASA Astrophysics Data System (ADS)

Meredith, P. J.

1986-10-01

The MK VI, a new multipurpose attitude control system for the exoatmospheric attitude control of sounding rocket payloads, is described. The system employs reprogrammable microcomputer memory for storage of basic control logic and for specific mission event control data. The paper includes descriptions of MK VI specifications and configuration; sensor characteristics; the electronic, analog, and digital sections; the pneumatic system; ground equipment; the system operation; and software. A review of the MK VI performance for the Comet Halley flight is presented. Block diagrams are included.

A continuous dry 300 mK cooler for THz sensing applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemencic, G. M., E-mail: Georgina.Klemencic@astro.cf.ac.uk; Ade, P. A. R.; Sudiwala, R.

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 ofmore » a far infrared camera.« less

MK-801-Treated Oligodendrocytes as a Cellular Model to Study Schizophrenia.

PubMed

Brandão-Teles, Caroline; Martins-de-Souza, Daniel; Guest, Paul C; Cassoli, Juliana S

2017-01-01

Glutamate is the most important excitatory neurotransmitter in the brain. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is found both in neurons and glial cells such as oligodendrocytes, which have been shown to be dysfunctional in schizophrenia. For this reasons, the oligodendrocyte MO3.13 cell line has been used to study glutamatergic dysfunction as a model of schizophrenia using the NMDA receptor antagonists such as MK-801 to block receptor function. Here, we describe a comprehensive protocol for culturing and carrying out proteomic analyses of MK-801-treated MO3.13 cells as a means of identifying potential new biomarkers and targets for drug discovery in schizophrenia research.

Northrop TRIGA facility decommissioning plan versus actual results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, F.W.

1986-01-01

This paper compares the TRIGA facility decontamination and decommissioning (D and D) plan to the actual results and discusses key areas where operational activities were impacted by the final US Nuclear Regulatory Commission approved D and D plan. A discussion of fuel transport, release criteria, and release survey plans is included.

Background studies for the MINER Coherent Neutrino Scattering reactor experiment

NASA Astrophysics Data System (ADS)

Agnolet, G.; Baker, W.; Barker, D.; Beck, R.; Carroll, T. J.; Cesar, J.; Cushman, P.; Dent, J. B.; De Rijck, S.; Dutta, B.; Flanagan, W.; Fritts, M.; Gao, Y.; Harris, H. R.; Hays, C. C.; Iyer, V.; Jastram, A.; Kadribasic, F.; Kennedy, A.; Kubik, A.; Lang, K.; Mahapatra, R.; Mandic, V.; Marianno, C.; Martin, R. D.; Mast, N.; McDeavitt, S.; Mirabolfathi, N.; Mohanty, B.; Nakajima, K.; Newhouse, J.; Newstead, J. L.; Ogawa, I.; Phan, D.; Proga, M.; Rajput, A.; Roberts, A.; Rogachev, G.; Salazar, R.; Sander, J.; Senapati, K.; Shimada, M.; Soubasis, B.; Strigari, L.; Tamagawa, Y.; Teizer, W.; Vermaak, J. I. C.; Villano, A. N.; Walker, J.; Webb, B.; Wetzel, Z.; Yadavalli, S. A.

2017-05-01

The proposed Mitchell Institute Neutrino Experiment at Reactor (MINER) experiment at the Nuclear Science Center at Texas A&M University will search for coherent elastic neutrino-nucleus scattering within close proximity (about 2 m) of a 1 MW TRIGA nuclear reactor core using low threshold, cryogenic germanium and silicon detectors. Given the Standard Model cross section of the scattering process and the proposed experimental proximity to the reactor, as many as 5-20 events/kg/day are expected. We discuss the status of preliminary measurements to characterize the main backgrounds for the proposed experiment. Both in situ measurements at the experimental site and simulations using the MCNP and GEANT4 codes are described. A strategy for monitoring backgrounds during data taking is briefly discussed.

Evolution of magnetism in LnCuGa3 (Ln = La-Nd, Sm-Gd) studied via μSR and specific heat

NASA Astrophysics Data System (ADS)

Graf, M. J.; Hettinger, J. D.; Nemeth, K.; Dally, R.; Baines, C.; Subbarao, U.; Peter, S. C.

2017-12-01

Muon spin rotation/relaxation (μSR) and specific heat measurements are presented for polycrystalline LnCuGa3, with Ln = La-Nd, and Sm-Gd. All materials undergo magnetic ordering transitions, apart from non-magnetic LaCuGa3, and PrCuGa3, which shows the onset of short range correlations below 3 K but no long-range magnetic order down to T = 25 mK. While magnetic order in the Ce and Nd compounds is incommensurate with the lattice, the order is commensurate for the Sm and Eu compounds. The strong damping in GdCuGa3 prevents us from determining the nature of magnetism in that system. SmCuGa3 exhibits two precessional frequencies, which appear at different temperatures, suggesting inhomogeneous magnetic ordering or a second magnetic/structural phase transition.

76 FR 2947 - Notice of Final Federal Agency Actions on Proposed Highway in California

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-18

...) from State Route 52 (SR-52) to La Jolla Village Drive. Two high occupancy vehicle (HOV) lanes (one in each direction) from La Jolla Village Drive to just north of Mira Mesa Boulevard (Blvd). The project.... Pending Federal actions include: 401 Water Quality Certification from the Regional Water Quality Control...

Reactor Physics Scoping and Characterization Study on Implementation of TRIGA Fuel in the Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jennifer Lyons; Wade R. Marcum; Mark D. DeHart

2014-01-01

The Advanced Test Reactor (ATR), under the Reduced Enrichment for Research and Test Reactors (RERTR) Program and the Global Threat Reduction Initiative (GTRI), is conducting feasibility studies for the conversion of its fuel from a highly enriched uranium (HEU) composition to a low enriched uranium (LEU) composition. These studies have considered a wide variety of LEU plate-type fuels to replace the current HEU fuel. Continuing to investigate potential alternatives to the present HEU fuel form, this study presents a preliminary analysis of TRIGA® fuel within the current ATR fuel envelopes and compares it to the functional requirements delineated by themore » Naval Reactors Program, which includes: greater than 4.8E+14 fissions/s/g of 235U, a fast to thermal neutron flux ratio that is less than 5% deviation of its current value, a constant cycle power within the corner lobes, and an operational cycle length of 56 days at 120 MW. Other parameters outside those put forth by the Naval Reactors Program which are investigated herein include axial and radial power profiles, effective delayed neutron fraction, and mean neutron generation time.« less

Heat transfer at a sapphire - indium interface in the 30 mK - 300 mK temperature range

NASA Astrophysics Data System (ADS)

Liberadzka, J.; Koettig, T.; Bremer, J.; van der Post, C. C. W.; ter Brake, H. J. M.

2017-02-01

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 particles should be reduced. Therefore a Penning trap, which is used to trap antiprotons and create antihydrogen, will be placed on a mixing chamber of an especially designed dilution refrigerator. The trap consists of 10 electrodes, which need to be electrically insulated, but thermally anchored. To ensure that the trap remains at a temperature below 100 mK, the heat transfer at the metallic-dielectric boundary is investigated. A copper - indium - sapphire - indium - copper sandwich setup was mounted on the CERN Cryolab dilution refrigerator. Keeping the mixing chamber at a constant low temperature in the range of 30 mK to 300 mK, steady-state measurements with indium in normal conducting and superconducting states have been performed. Obtained results along with a precise description of our setup are presented.

Swertisin ameliorates pre-pulse inhibition deficits and cognitive impairment induced by MK-801 in mice.

PubMed

Oh, Hee Kyong; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Eunji; Park, Se Jin; Kim, Ha Neul; Jung, Won Yong; Cheong, Jae Hoon; Jang, Dae Sik; Ryu, Jong Hoon

2017-02-01

Swertisin, a plant-derived C-glucosylflavone, is known to have antidiabetic, anti-inflammatory and antioxidant effects. In the present study, we investigated in mice the effects of swertisin on glutamatergic dysfunction induced by dizocilpine (MK-801), a non-competitive N-methyl-D-aspartate receptor antagonist. In the Acoustic Startle Response test, their MK-801-induced (given 0.2 mg/kg i.p.) pre-pulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg p.o.). In the Novel Object Recognition Test, the recognition memory impairments that were induced by MK-801 (0.2 mg/kg, given i.p.) were also reversed by administration of swertisin (30 mg/kg p.o.). In addition, swertisin normalized the MK-801-induced elevation of phosphorylation levels of Akt and GSK-3β signaling molecules in the prefrontal cortex. These results indicated that swertisin may be useful in managing the symptoms of schizophrenia, including sensorimotor gating disruption and cognitive impairment, and that these behavioral outcomes may be related to Akt-GSK-3β signaling in the prefrontal cortex.

ORIGEN2 calculations supporting TRIGA irradiated fuel data package

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmittroth, F.A.

ORIGEN2 calculations were performed for TRIGA spent fuel elements from the Hanford Neutron Radiography Facility. The calculations support storage and disposal and results include mass, activity,and decay heat. Comparisons with underwater dose-rate measurements were used to confirm and adjust the calculations.

SAFARI engineering model 50 mK cooler

NASA Astrophysics Data System (ADS)

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.

Calculation to experiment comparison of SPND signals in various nuclear reactor environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbot, Loic; Radulovic, Vladimir; Fourmentel, Damien

2015-07-01

In the perspective of irradiation experiments in the future Jules Horowitz Reactor (JHR), the Instrumentation Sensors and Dosimetry Laboratory of CEA Cadarache (France) is developing a numerical tool for SPND design, simulation and operation. In the frame of the SPND numerical tool qualification, dedicated experiments have been performed both in the Slovenian TRIGA Mark II reactor (JSI) and very recently in the French CEA Saclay OSIRIS reactor, as well as a test of two detectors in the core of the Polish MARIA reactor (NCBJ). A full description of experimental set-ups and neutron-gamma calculations schemes are provided in the first partmore » of the paper. Calculation to experiment comparison of the various SPNDs in the different reactors is thoroughly described and discussed in the second part. Presented comparisons show promising final results. (authors)« less

78 FR 39769 - National Register of Historic Places; Notification of Pending Nominations and Related Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... Chautauqua Blvd., Los Angeles, 13000513 Community Clubhouse, 1200 N. Vista St., West Hollywood, 13000510... Study House No. 23A, (Case Study House Program MPS) 2342 Rue de Anne, La Jolla, 13000520 Case Study House No. 23C, (Case Study House Program MPS) 2339 Rue de Anne, La Jolla, 13000521 Ventura County Case...

Testing of a Transport Cask for Research Reactor Spent Fuel - 13003

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourao, Rogerio P.; Leite da Silva, Luiz; Miranda, Carlos A.

2013-07-01

Since the beginning of the last decade three Latin American countries that operate research reactors - Argentina, Brazil and Chile - have been joining efforts to improve the regional capability in the management of spent fuel elements from the TRIGA and MTR reactors operated in the region. A main drive in this initiative, sponsored by the International Atomic Energy Agency, is the fact that no definite solution regarding the back end of the research reactor fuel cycle has been taken by any of the participating country. However, any long-term solution - either disposition in a repository or storage away frommore » reactor - will involve at some stage the transportation of the spent fuel through public roads. Therefore, a licensed cask that provides adequate shielding, assurance of subcriticality, and conformance to internationally accepted safety, security and safeguards regimes is considered a strategic part of any future solution to be adopted at a regional level. As a step in this direction, a packaging for the transport of irradiated fuel for MTR and TRIGA research reactors was designed by the tri-national team and a half-scale model equipped with the MTR version of the internal basket was constructed in Argentina and Brazil and tested in Brazil. Three test campaigns have been carried out so far, covering both normal conditions of transportation and hypothetical accident conditions. After failing the tests in the first two test series, the specimen successfully underwent the last test sequence. A second specimen, incorporating the structural improvements in view of the previous tests results, will be tested in the near future. Numerical simulations of the free drop and thermal tests are being carried out in parallel, in order to validate the computational modeling that is going to be used as a support for the package certification. (authors)« less

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

PubMed

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.

Clinical physiology and mechanism of dizocilpine (MK-801): electron transfer, radicals, redox metabolites and bioactivity.

PubMed

Kovacic, Peter; Somanathan, Ratnasamy

2010-01-01

Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3'-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and ant-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties.

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

PubMed Central

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

Role of Major NMDA or AMPA Receptor Subunits in MK-801 Potentiation of Ethanol Intoxication

PubMed Central

Palachick, Benjamin; Chen, Yi-Chyan; Enoch, Abigail J.; Karlsson, Rose-Marie; Mishina, Masayoshi; Holmes, Andrew

2008-01-01

Background The glutamate system plays a major role in mediating EtOH’s effects on brain and behavior, and is implicated in the pathophysiology of alcohol-related disorders. N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 (dizocilpine) interact with EtOH at the behavioral level, but the molecular basis of this interaction is unclear. Methods We first characterized the effects of MK-801 treatment on responses to the ataxic (accelerating rotarod), hypothermic and sedative/hypnotic effects of acute EtOH administration in C57BL/6J and 129/SvImJ inbred mice. Effects of another NMDAR antagonist, phencyclidine, on EtOH-induced sedation/hypnosis were also assessed. Gene knockout of the NMDAR subunit NR2A or L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate GluR1 or pharmacological antagonism of the NMDAR subunit NR2B (via Ro 25-6981) was employed to examine whether inactivating any one of these glutamate signaling molecules modified MK-801’s effect on EtOH-related behaviors. Results MK-801 markedly potentiated the ataxic effects of 1.75 g/kg EtOH and the sedative/hypnotic effects of 3.0 g/kg EtOH, but not the hypothermic effects of 3.0 g/kg EtOH, in C57BL/6J and 129/SvImJ mice. Phencyclidine potentiated EtOH-induced sedation/hypnosis in both inbred strains. Neither NR2A nor GluR1 KO significantly altered basal EtOH-induced ataxia, hypothermia, or sedation/hypnosis. Ro 25-6981 modestly increased EtOH-induced sedation/hypnosis. The ability of MK-801 to potentiate EtOH-induced ataxia and sedation/hypnosis was unaffected by GluR1 KO or NR2B antagonism. NR2A KO partially reduced MK-801 + EtOH-induced sedation/hypnosis, but not ataxia or hypothermia. Conclusions Data confirm a robust and response-specific potentiating effect of MK-801 on sensitivity to EtOH’s intoxicating effects. Inactivation of three major components of glutamate signaling had no or only partial impact on the ability of MK-801 to potentiate behavioral sensitivity to EtOH. Further

Extending the maximum operation time of the MNSR reactor.

PubMed

Dawahra, S; Khattab, K; Saba, G

2016-09-01

An effective modification to extend the maximum operation time of the Miniature Neutron Source Reactor (MNSR) to enhance the utilization of the reactor has been tested using the MCNP4C code. This modification consisted of inserting manually in each of the reactor inner irradiation tube a chain of three polyethylene-connected containers filled of water. The total height of the chain was 11.5cm. The replacement of the actual cadmium absorber with B(10) absorber was needed as well. The rest of the core structure materials and dimensions remained unchanged. A 3-D neutronic model with the new modifications was developed to compare the neutronic parameters of the old and modified cores. The results of the old and modified core excess reactivities (ρex) were: 3.954, 6.241 mk respectively. The maximum reactor operation times were: 428, 1025min and the safety reactivity factors were: 1.654 and 1.595 respectively. Therefore, a 139% increase in the maximum reactor operation time was noticed for the modified core. This increase enhanced the utilization of the MNSR reactor to conduct a long time irradiation of the unknown samples using the NAA technique and increase the amount of radioisotope production in the reactor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nuclear mass inventory, photon dose rate and thermal decay heat of spent research reactor fuel assemblies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pond, R.B.; Matos, J.E.

1996-05-01

As part of the Department of Energy`s spent nuclear fuel acceptance criteria, the mass of uranium and transuranic elements in spent research reactor fuel must be specified. These data are, however, not always known or readily determined. It is the purpose of this report to provide estimates of these data for some of the more common research reactor fuel assembly types. The specific types considered here are MTR, TRIGA and DIDO fuel assemblies. The degree of physical protection given to spent fuel assemblies is largely dependent upon the photon dose rate of the spent fuel material. These data also, aremore » not always known or readily determined. Because of a self-protecting dose rate level of radiation (dose rate greater than 100 ren-x/h at I m in air), it is important to know the dose rate of spent fuel assemblies at all time. Estimates of the photon dose rate for spent MTR, TRIGA and DIDO-type fuel assemblies are given in this report.« less

Validation of light water reactor calculation methods and JEF-1-based data libraries by TRX and BAPL critical experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paratte, J.M.; Pelloni, S.; Grimm, P.

1991-04-01

This paper analyzes the capability of various code systems and JEF-1-based nuclear data libraries to compute light water reactor lattices by comparing calculations with results from thermal reactor benchmark experiments TRX and BAPL and with previously published values. With the JEF-1 evaluation, eigenvalues are generally well predicted within 8 mk (1 mk = 0.001) or less by all code systems, and all methods give reasonable results for the measured reaction rate ratios within, or not too far from, the experimental uncertainty.

[Analgesic effects of ionotropic glutamate receptor antagonists MK-801 and NBQX on collagen-induced arthritis rats].

PubMed

Zhu, H; Zhu, R; Deng, Z D; Feng, Y C; Shen, H L

2016-12-18

The ionotropic glutamate receptorantagonists include two types: MK-801, antagonist of N-methyl-D-asparticacid (NMDA) receptor, and NBQX, antagonist of non-NMDA receptor.The above-mentioned ionotropic antagonists can block the glutamate and its corresponding receptor binding to produce analgesic effect. The objective of this research was to study two antagonists in analgesic effect on rat behavior,as well as to investigate the down-regulation and up-regulation of cyclooxygenase-2 (COX-2) and Janus-activated kinase (Jak3) in collagen-induced arthritis (CIA) rat serum and tissue fluid after the application of these antagonists, that is, the effect on molecular biology. This study used the ionotropic glutamate receptors as the target and established CIA rat model. Vivo studies were used to observe changes in behavior and molecular biology of the CIA rat.Behavioral assessment includedmechanical allodynia and joint swelling in the CIA rat,where themechanical allodynia was measured using the paw-withdrawal threshold (PWT) with VonFrey filaments according to the "Up-Down" method,and the drainage volume was used to assess joint swelling. Then the blood samples taken from the heart of the rat and the tissue homogenate were collected to detect the down-regulation and up-regulation of COX-2 and Jak3 in the serum and tissue fluid after the antagonists wereused. Using MK-801, NBQX alone or using the combination of these two antagonists,these three methods all could alleviate pain(P<0.01).The analgesic effect lasted more than 24 h.Both antagonists reached the peak of analgesia at the end of 4 hours post-injection. NBQX had stronger analgesic effect than MK-801 (P<0.05).Whether alone or combined use of these two antagonists,could not change the CIA rats' swelling of the joint (P>0.05). MK-801 could decrease the expression of COX-2 (P<0.01).At the same time, NBQX did not have this effect (P>0.05). Using MK-801, NBQX alone or combination of these two antagonists could not affect the

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keana, J.F.W.; Scherz, M.W.; Quarum, M.

1988-01-01

A (/sup 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 (/sup 3/H)-gas and subsequent purification of the radioactive product by reversed-phase high performance liquid chromatography (RP-HPLC). This resulted in pure (+) (/sup 3/H)MK-801 with a specific radioactivity of 97 Ci/mmol. The (+) (/sup 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 glutamatemore » and N-methyl-D-aspartate (NMDA). Drugs that interact with the PCP receptor block this channel. The (+) (/sup 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.« less

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

PubMed

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.

The pharmacokinetics and disposition of MK-0524, a Prosglandin D2 Receptor 1 antagonist, in rats, dogs and monkeys.

PubMed

Chang, S W; Reddy, V; Pereira, T; Dean, B J; Xia, Y-Q; Seto, C; Franklin, R B; Karanam, B V

2007-05-01

MK-0524 is a potent, selective and orally active Prosglandin D(2) Receptor 1 (DP(1)) antagonist currently under clinical development for the treatment of niacin-induced flushing. Experiments to study the pharmacokinetics, metabolism and excretion of MK-0524 were conducted in rats, dogs and monkeys. MK-0524 displayed linear kinetics and rapid absorption following an oral dose. Following intravenous (i.v.) administration of MK-0524 to rats and dogs (1 and 5 mg/kg), the mean Cl(p) was approximately 2 and approximately 6 ml/min/kg, the T(1/2) was approximately 7 and approximately 13 h and the Vd(ss) was approximately 1 and approximately 5 L/kg, respectively. In monkeys dosed i.v. at 3 mg/kg, the corresponding values were 8 ml/min/kg, 3 h and 1 L/kg, respectively. Following oral dosing of MK-0524 to rats (5, 25 and 100 mg/kg), dogs (5 mg/kg) and monkeys (3 mg/kg), the absorption was rapid with the mean C(max) occurring between 1 and 4 h. Absolute oral bioavailability values in rats, dogs and monkeys were 50, 70 and 8%, respectively. The major circulating metabolite was the acyl glucuronide of MK-0524 (M2), with ratios of glucuronide to the parent aglycone being highest in the monkey followed by dog and rat. In bile duct-cannulated rats and dogs, MK-0524 was eliminated primarily via acyl glucuronidation followed by biliary excretion of the acyl glucuronide, M2, the major drug-related entity in bile.

Preliminary study on new configuration with LEU fuel assemblies for the Dalat nuclear research reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Lam Pham; Vinh Vinh Le; Ton Nghiem Huynh

2008-07-15

The fuel conversion of the Dalat Nuclear Research Reactor (DNRR) is being realized. The DNRR is a pool type research reactor which was reconstructed from the 250 kW TRIGA- MARK II reactor. The reconstructed reactor attained its nominal power of 500 kW in February 1984. According to the results of design and safety analyses performed by the joint study between RERTR Program at Argonne National Laboratory (ANL) and Vietnam Atomic Energy Commission (VAEC) the mixed core of irradiated HEU and new LEU WWR-M2 fuel assemblies will be created soon. This paper presents the results of preliminary study on new configurationmore » with only LEU fuel assemblies for the DNRR. The codes MCNP, REBUS and VARI3D are used to calculate neutron flux performance in irradiation positions and kinetics parameters. The idea of change of Beryllium rod reloading enables to get working configuration assured shutdown margin, thermal-hydraulic safety and increase in thermal neutron flux in neutron trap at the center of DNRR active core. (author)« less

Group II Metabotropic Glutamate Receptor Agonist Ameliorates MK801-Induced Dysfunction of NMDA Receptors via the Akt/GSK-3β Pathway in Adult Rat Prefrontal Cortex

PubMed Central

Xi, Dong; Li, Yan-Chun; Snyder, Melissa A; Gao, Ruby Y; Adelman, Alicia E; Zhang, Wentong; Shumsky, Jed S; Gao, Wen-Jun

2011-01-01

Pharmacological intervention targeting mGluRs has emerged as a potential treatment for schizophrenia, whereas the mechanisms involved remain elusive. We explored the antipsychotic effects of an mGluR2/3 agonist in the MK-801 model of schizophrenia in the rat prefrontal cortex. We found that the mGluR2/3 agonist LY379268 effectively recovered the disrupted expression of NMDA receptors induced by MK-801 administration. This effect was attributable to the direct regulatory action of LY379268 on NMDA receptors via activation of the Akt/GSK-3β signaling pathway. As occurs with the antipsychotic drug clozapine, acute treatment with LY379268 significantly increased the expression and phosphorylation of NMDA receptors, as well as Akt and GSK-3β. Physiologically, LY379268 significantly enhanced NMDA-induced current in prefrontal neurons and a GSK-3β inhibitor occluded this effect. In contrast to the widely proposed mechanism of modulating presynaptic glutamate release, our results strongly argue that mGluR2/3 agonists modulate the function of NMDA receptors through postsynaptic actions and reverse the MK-801-induced NMDA dysfunction via the Akt/GSK-3β pathway. This study provides novel evidence for postsynaptic mechanisms of mGluR2/3 in regulation of NMDA receptors and presents useful insights into the mechanistic actions of mGluR2/3 agonists as potential antipsychotic agents for treating schizophrenia. PMID:21326193

Effect of the Angiotensin I Converting Enzyme Inhibitor, MK-421, on Experimentally Induced Drinking

NASA Technical Reports Server (NTRS)

Fregley, Melvin J.; Fater, Dennis C.; Greenleaf, John E.

1982-01-01

MK-421, the ethyl ester maleate salt of N-(S)-1-(ethoxycarbonyl)-3-phenyl-propyl- Ala-L-Pro, is an angiotensin I converting enzyme inhibitor. An initial objective was to determine whether MK-421, administered at 0, 2.5, 5.0, 10.0, 20.0 and 40.0 mg/kg, ip to 96 female rats 15 min prior to administration of the beta-adrenergic agonist, isoproterenol (25 microgram/kg, ip), would inhibit the drinking induced by isoproterenol during 2 h after its administration. The water intake induced by isoproterenol was inhibited significantly by 2.5 mg MK-421/kg. When a similar experiment was performed using Angiotensin I (AI) (200 microgram/kg, ip) as the dipsogenic agent, MK-421 (5 mg/kg, ip), administered 15 min prior to AI, inhibited significantly both the dipsogenic and the diuretic effect of AI. However, administration of angiotensin II (AII, 200 microgram/kg, ip) 15 min after MK-421 (5mg/kg) was accompanied by a water intake that did not differ from AII alone. The drink induced by ip administration of 1.0 m NaCl solution (1% of body wt, ip) was not inhibited by administration of MK-421 (5 mg/kg) 15 min prior to allowing access to water while the drink induced by a 24 h dehydration was partially inhibited. Thus, the drinks induced by administraition of either isoproterenol or AI are dependent on formation of AII. That induced by dehydration is partially dependent, while that induced by hypertonic siilinc is independent of the formation of AII.

Periventricular anteroventral third ventricle lesions diminish the pressor response produced by systemic injection of the N-methyl-D-aspartate receptor antagonist MK-801

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Beltz, T. G.; Lewis, S. J.; Johnson, A. K.

1999-01-01

This study examined whether electrolytic ablation of the periventricular anteroventral third ventricle (AV3V) would affect the increases in mean arterial blood pressure (MAP) and heart rate (HR) in conscious rats produced by systemic injection of the centrally acting N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801; 250 microgram/kg, i.v.). MK-801 produced a smaller increase in MAP in rats with AV3V lesions than in sham-lesion rats (+36+/-2% vs. +52+/-5%, respectively, P<0.05). In contrast, MK-801 produced similar increases in HR in the AV3V- and sham-lesion rats (+28+/-3% vs. +22+/-4%, respectively, P>0.05). These findings demonstrate that the MK-801-induced pressor response is dependent upon the integrity of the AV3V region, whereas the MK-801-induced tachycardia is not. Copyright 1999 Elsevier Science B.V.

Analytic representations of mK , FK, mη, and Fη in two loop S U (3 ) chiral perturbation theory

NASA Astrophysics Data System (ADS)

Ananthanarayan, B.; Bijnens, Johan; Friot, Samuel; Ghosh, Shayan

2018-06-01

In this work, we consider expressions for the masses and decay constants of the pseudoscalar mesons in S U (3 ) chiral perturbation theory. These involve sunset diagrams and their derivatives evaluated at p2=mP2 (P =π , K , η ). Recalling that there are three mass scales in this theory, mπ, mK and mη, there are instances when the finite part of the sunset diagrams do not admit an expression in terms of elementary functions, and have therefore been evaluated numerically in the past. In a recent publication, an expansion in the external momentum was performed to obtain approximate analytic expressions for mπ and Fπ, the pion mass and decay constant. We provide fully analytic exact expressions for mK and mη, the kaon and eta masses, and FK and Fη, the kaon and eta decay constants. These expressions, calculated using Mellin-Barnes methods, are in the form of double series in terms of two mass ratios. A numerical analysis of the results to evaluate the relative size of contributions coming from loops, chiral logarithms as well as phenomenological low-energy constants is presented. We also present a set of approximate analytic expressions for mK, FK, mη and Fη that facilitate comparisons with lattice results. Finally, we show how exact analytic expressions for mπ and Fπ may be obtained, the latter having been used in conjunction with the results for FK to produce a recently published analytic representation of FK/Fπ.

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

PubMed

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.

The effects of low dose MK-801 administration on NMDAR dependent executive functions in pigeons.

PubMed

Gökhan, Nurper; Neuwirth, Lorenz S; Meehan, Edward F

2017-05-01

An avian analogue of human fronto-executive dysfunction was used to study the long-term effects of a repeated low dose of MK-801. MK-801 is known to selectively antagonize the excitatory N-methyl-d-aspartate receptors (NMDA R ) and indirectly impair inhibitory related processes (GABA- AR ). First, eight pigeons were divided into two groups, receiving either 0.15mg/kg MK-801 or saline (i.p.) 1-hour prior to each session. Thirty 90-min sessions of a Differential Reinforcement of Low Rate of Response (DRL-10s) schedule were run over 3-months. Both overall number of responses and efficiency were unaffected by treatment, establishing a sub-threshold motoric dose. Then, another eight pigeons, treated identically, were given an operant visual discrimination task. Results demonstrated impairment of the fronto-striatal function of both excitatory and inhibitory processes in the MK-801 group during the entire 3-months. A 30-session treatment cross-over showed that the Saline-to-MK-801 group was unaffected, whereas the MK-801-to-Saline group exhibited rapid recovery of inhibitory control, however excitatory control did not fully recover. Together, these results suggested that the NMDA R system is involved in the acquisition of excitatory learning, but only in the expression of inhibitory learning. Our findings were discussed in terms of the value of avian models in translational research. Furthermore, our results were examined within the context of the NIH Research Domain of Criteria initiative and the role of NMDA R disruption, which underlie executive dysfunction in various neuropsychiatric disorders. Finally, our findings suggested that the potential long-term effects of the clinical and recreational use of NMDA R antagonists require further study. Copyright © 2017 Elsevier Inc. All rights reserved.

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

DTIC Science & Technology

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

Calcium and ZmCCaMK are involved in brassinosteroid-induced antioxidant defense in maize leaves.

PubMed

Yan, Jingwei; Guan, Li; Sun, Yue; Zhu, Yuan; Liu, Lei; Lu, Rui; Jiang, Mingyi; Tan, Mingpu; Zhang, Aying

2015-05-01

Brassinosteroids (BRs) have been shown to enhance stress tolerance by inducing antioxidant defense systems. However, the mechanisms of BR-induced antioxidant defense in plants remain to be determined. In this study, the role of calcium (Ca(2+)) and maize calcium/calmodulin-dependent protein kinase (CCaMK), ZmCCaMK, in BR-induced antioxidant defense, and the relationship between ZmCCaMK and Ca(2+) in BR signaling were investigated. BR treatment led to a significant increase in cytosolic Ca(2+) concentration in protoplasts from maize mesophyll, and Ca(2+) was shown to be required for BR-induced antioxidant defense. Treatment with BR induced increases in gene expression and enzyme activity of ZmCCaMK in maize leaves. Transient overexpression and silencing of ZmCCaMK in maize protoplasts demonstrated that ZmCCaMK was required for BR-induced antioxidant defense. The requirement for CCaMK was further investigated using a loss-of-function mutant of OsCCaMK, the orthologous gene of ZmCCaMK in rice. Consistent with the findings in maize, BR treatment could not induce antioxidant defense in the rice OsCCAMK mutant. Furthermore, Ca(2+) was required for BR-induced gene expression and activation of ZmCCaMK, while ZmCCaMK was shown to enhance the BR-induced increase in cytosolic Ca(2+) concentration. Moreover, our results also showed that ZmCCaMK and H2O2 influenced each other. These results indicate that Ca(2+) works together with ZmCCaMK in BR-induced antioxidant defense, and there are two positive feedback loops between Ca(2+) or H2O2 and ZmCCaMK in BR signaling in maize. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice.

PubMed

Mutlu, Oguz; Ulak, Güner; Celikyurt, Ipek Komsuoglu; Akar, Füruzan Yildiz; Erden, Faruk; Tanyeri, Pelin

2011-10-01

We investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on visual recognition memory using the novel object recognition (NOR) test in naive and MK-801-treated animals. The effects of drug treatment on locomotion and anxiety were also determined using the open field test. Male Balb-c mice were treated with olanzapine (0.2, 0.4 and 0.6 mg/kg; i.p.), sertindole (0.63, 1.3 and 2.5mg/kg; s.c.) or clozapine (0.5 and 1mg/kg; i.p.), and cognitive deficits were induced by MK-801 (0.2mg/kg; i.p.) administration. Olanzapine treatment decreased the ratio index in the NOR test, whereas sertindole and clozapine had no effect in naive mice. MK-801-induced cognitive impairment was reversed by treatment with olanzapine, sertindole or clozapine. While olanzapine, sertindole and clozapine had no effect on the anxiety of naive mice as determined by the open field test, MK-801 significantly increased the total distance traveled, time spent in the center zone and the velocity of the animals. MK-801-induced effects on locomotion and anxiety in the open field test were reversed by olanzapine, sertindole or clozapine treatment. The results of the present study demonstrated that olanzapine, sertindole and clozapine improved cognition in MK-801 treated mice, and indicate that these drugs have a potential to improve cognition in schizophrenia. Copyright © 2011 Elsevier Inc. All rights reserved.

Quasi-Square Hole with Optimum Shape in an Infinite Plate Subjected to In-Plane Loading. Optimization of Inner and Outer Boundaries of Beams and Plates with Holes,

DTIC Science & Technology

1982-04-01

Division 045 Administracion Naval Ship Resarc; and Development 14114 (Technical Library) Structures Research Division Center Langley Research Center...Virginia 23607 university of California. San Diego Dr. J. L. Swedlow Department of Applied Mechanics Carnegie-Mellon University La Jolla, California...Batdorf Keman AviDyne Suite 220 University of California Division of Kaman La Jolla, California 92037 School of Engineering Sciences Corporation and

A Novel Strategy for Isolation, Molecular and Functional Characterization of Embryonic Mammary Stem Cells Using Molecular Genetics and Microfluidic Sorting

DTIC Science & Technology

2008-06-01

Geoffrey M. Wahl, Ph.D. CONTRACTING ORGANIZATION: The Salk Institute for Biological Studies La Jolla, CA 92037-1099...PERFORMING ORGANIZATION REPORT NUMBER The Salk Institute for Biological Studies La Jolla, CA 92037-1099 9. SPONSORING...validated the use of a micro- volume cell sorter ( Celula , Inc.). This instrument is capable of sorting as few as 150 GFP positive cells from a sample

Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blizzard, Timothy A.; Chen, Helen; Kim, Seongkon

2014-02-01

β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem’s activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.

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

PubMed Central

2014-01-01

Background 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. Methods 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. Results 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. Conclusion MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity. Trial registration ClinicalTrials.gov: NCT00848718. PMID:24387695

MK-801 increases the baseline level of anxiety in mice introduced to a spatial memory task without prior habituation.

PubMed

Ennaceur, A; Michalikova, S; van Rensburg, R; Chazot, P L

2011-01-01

C57BL/6J mice were introduced to a nine arm radial maze without prior habituation and trained in the acquisition of a working memory task in 16 sessions, one session per day. In this maze mice need to climb onto an upward inclined bridge in order to reach and cross onto an arm. They received in each session an i.p. injection of MK-801 (0.1 mg/kg) 30 min before training or immediately after training. MK-801 pre-treated mice made significantly more entries onto the bridges, fewer entries onto the arms and took significantly longer time to make a first arm visit compared to saline and MK-801 post-treated mice during the first 3 session blocks (4 sessions per block). These results indicate that MK-801 induced anxiety which was extended throughout the first 3 session blocks. MK-801 pre-treated mice made also significantly more errors and required more sessions to reach the criterion compared to saline and MK-801 post-treated mice. Administration of MK-801 after training did not affect the acquisition of the task. The present results indicate that MK-801 pre-treatment impaired the acquisition of a spatial task and this can be accounted for by its effect on the baseline level of anxiety which was elevated. The introduction of mice to the acquisition of the task without prior habituation demonstrates that a drug treatment can affect learning and memory by increasing and/or prolonging anxiety. Such effect may be confounded with learning and memory performance and not detected with pre-habituation training procedures, particularly when the number of sessions is determined a-priori. Copyright © 2011 Elsevier Ltd. All rights reserved.

[The reasons why 13 MK1 attachment were re-fabricated and some methods for improvement].

PubMed

Wu, Zhi-hong; Zhang, Xue-jun; Zhao, Jun

2013-12-01

To investigate the reasons why 13 MK1 attachment were re-fabricated and to suggest some improvement methods. Mechanics and denture production technology were reviewed in 13 cases with MK1 attachment denture to determine the causes of failure. In some cases, MK1 attachments were poorly designed, while in other cases problems were found during denture design and production process due to limited experiences at the initial stage. MK1 attachments were re-done based on the specific cause and the outcome was good after 1-1.5 years of follow-up. When using MK1 attachment, prosthodontists should be familiar with the characteristics and indications of MK1 attachment. Meanwhile, we should strengthen doctor-patient communication and follow up patients timely to improve the success rate of MK1 attached denture repair.

MK-801-induced locomotor activity in long-sleep x short-sleep recombinant inbred mouse strains: correlational analysis with low-dose ethanol and provisional quantitative trait loci.

PubMed

Zahniser, N R; Negri, C A; Hanania, T; Gehle, V M

1999-11-01

Low doses of the N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (dizocilpine) or ethanol increase locomotor activity to a lesser extent in long-sleep (LS), than in short-sleep (SS), mice. LS mice also have fewer brain [3H]MK-801 binding sites than SS mice. In this study, LSXSS recombinant inbred (RI) mice were used to investigate whether different NMDAR densities contribute to differential MK-801 activation and whether common genes are involved in initial sensitivity to MK-801-and ethanol-induced activation. Locomotor activity was measured for 90 min after saline or MK-801 injection. Quantitative autoradiographic analysis of [3H]MK-801 binding was used to measure densities of NMDARs in seven brain regions. The ethanol (1-2 g/kg) activation scores from Erwin and colleagues (1997) were used for correlational analysis, as was their method for quantitative trait loci (QTL) analysis. Both saline and MK-801 (0.3 mg/kg, given intraperitoneally) induced a continuum of locomotor responses across the LSXSS RI strains. There was a 4-fold range of MK-801 difference scores (MK-801 score-saline baseline), with the RI 9 and RI 4 strains representing low and high responders, respectively. Dose-response experiments with these two strains confirmed that 0.3 mg/kg MK-801 produced significant activation, similar to previous results with LS and SS mice. However, unlike previous LS/SS results, lower densities of NMDARs were not observed in the RI 9 than in the RI 4 mouse brains. No significant genetic correlations were observed between MK-801-induced and ethanol-induced responses in the LSXSS RI mice. Two provisional MK-801 activation QTLs were identified (p < 0.01) on chromosomes 11 and 19, neither in common with those mapped for ethanol activation. Different densities of brain NMDARs are unlikely to account for the differential activation of LSXSS RI mice by MK-801. Additionally, in the RI mice either separate sets of genes regulate low dose MK-801- and ethanol

Antiviral Activity of MK-4965, a Novel Nonnucleoside Reverse Transcriptase Inhibitor▿

PubMed Central

Lai, Ming-Tain; Munshi, Vandna; Touch, Sinoeun; Tynebor, Robert M.; Tucker, Thomas J.; McKenna, Philip M.; Williams, Theresa M.; DiStefano, Daniel J.; Hazuda, Daria J.; Miller, Michael D.

2009-01-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are the mainstays of therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, the effectiveness of NNRTIs can be hampered by the development of resistance mutations which confer cross-resistance to drugs in the same class. Extensive efforts have been made to identify new NNRTIs that can suppress the replication of the prevalent NNRTI-resistant viruses. MK-4965 is a novel NNRTI that possesses both diaryl ether and indazole moieties. The compound displays potency at subnanomolar concentrations against wild-type (WT), K103N, and Y181C reverse transcriptase (RT) in biochemical assays. MK-4965 is also highly potent against the WT virus and two most prevalent NNRTI-resistant viruses (viruses that harbor the K103N or the Y181C mutation), against which it had 95% effective concentrations (EC95s) of <30 nM in the presence of 10% fetal bovine serum. The antiviral EC95 of MK-4965 was reduced approximately four- to sixfold when it was tested in 50% human serum. Moreover, MK-4965 was evaluated with a panel of 15 viruses with NNRTI resistance-associated mutations and showed a superior mutant profile to that of efavirenz but not to that of etravirine. MK-4965 was similarly effective against various HIV-1 subtypes and viruses containing nucleoside reverse transcriptase inhibitor or protease inhibitor resistance-conferring mutations. A two-drug combination study showed that the antiviral activity of MK-4965 was nonantagonistic with each of the 18 FDA-licensed drugs tested vice versa in the present study. Taken together, these in vitro data show that MK-4965 possesses the desired properties for further development as a new NNRTI for the treatment of HIV-1 infection. PMID:19289522

Effect of the glucocorticoid receptor antagonist RU486 on MK-801 induced behavioural sensitisation

PubMed Central

Lefevre, Emilia M.; Medley, Gregory A.; Reeks, Timothy; Alexander, Suzy; Burne, Thomas H. J.; Eyles, Darryl W.

2017-01-01

Stress is known to modulate sensitisation to repeated psychostimulant exposure. However, there is no direct evidence linking glucocorticoids and sensitisation achieved by repeated administration of the NMDA receptor antagonist MK-801. We tested the hypothesis that co-administration of RU486, a glucocorticoid receptor (GR) antagonist, prior to repeated daily MK-801 injections would block the expression of locomotor sensitisation due to its dual effects on corticosterone and dopamine. We employed a repeated MK-801 administration locomotor sensitisation paradigm in male Sprague Dawley rats. RU486 or a dimethyl sulfoxide (DMSO) vehicle was co-administered with MK-801 or saline during the induction phase. Subsequent to withdrawal, rats were challenged with MK-801 alone to test for the expression of sensitisation. In a separate cohort of rats, plasma corticosterone levels were quantified from blood samples taken on the 1st, 4th and 7th day of induction and at expression. One day after challenge, nucleus accumbens tissue levels of dopamine and its metabolites DOPAC and HVA were measured. During the induction phase, RU486 progressively enhanced locomotor sensitisation to MK-801. RU486 and MK-801 both showed stimulatory effects on corticosterone levels and this was further augmented when given in combination. Contrary to our hypothesis, RU486 did not block the expression of locomotor sensitisation to MK-801 and actually increased levels of dopamine, DOPAC and HVA in nucleus accumbens tissue. Our results showed that RU486 has augmentative rather than inhibitory effects on MK-801-induced sensitisation. This study indicates a divergent role for glucocorticoids in sensitisation to MK-801 compared to sensitisation with other psychostimulants. PMID:28430805

The CSIRO Mk3L climate system model v1.0 coupled to the CABLE land surface scheme v1.4b: evaluation of the control climatology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Jiafu; Phipps, S.J.; Pitman, A.J.

The CSIRO Mk3L climate system model, a reduced-resolution coupled general circulation model, has previously been described in this journal. The model is configured for millennium scale or multiple century scale simulations. This paper reports the impact of replacing the relatively simple land surface scheme that is the default parameterisation in Mk3L with a sophisticated land surface model that simulates the terrestrial energy, water and carbon balance in a physically and biologically consistent way. An evaluation of the new model s near-surface climatology highlights strengths and weaknesses, but overall the atmospheric variables, including the near-surface air temperature and precipitation, are simulatedmore » well. The impact of the more sophisticated land surface model on existing variables is relatively small, but generally positive. More significantly, the new land surface scheme allows an examination of surface carbon-related quantities including net primary productivity which adds significantly to the capacity of Mk3L. Overall, results demonstrate that this reduced-resolution climate model is a good foundation for exploring long time scale phenomena. The addition of the more sophisticated land surface model enables an exploration of important Earth System questions including land cover change and abrupt changes in terrestrial carbon storage.« less

Platelets, neutrophils, and vasoconstriction after arterial injury by angioplasty in pigs: effects of MK-886, a leukotriene biosynthesis inhibitor

PubMed Central

Provost, Patrick; Borgeat, Pierre; Merhi, Yahye

1998-01-01

Leukotrienes constitute a class of potent bioactive mediators known to play a pivotal role in inflammation. Since their biosynthesis has been shown to be enhanced by platelet-neutrophil interactions, leukotrienes may be involved in these interactions and the arterial response to injury. Therefore, we investigated the effects of the selective leukotriene biosynthesis inhibitor 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid (MK-886) on the acute thrombotic and vasomotor responses after arterial injury by angioplasty.Carotid arterial injury was produced by balloon dilatation in control (molecusol vehicle; n=10) and treated (MK-886, 10 mg kg−1, i.v.; n=9) pigs. The acute thrombotic reaction following deep arterial wall injury was quantified with 51Cr labelled platelets and 111In labelled neutrophils, and the vasomotor response was determined angiographically.Platelet deposition at the site of deep arterial wall injury averaged 56.4±11.0×106 platelets cm−2 in the control group, and was significantly reduced to 18.2±3.8×106 platelets cm−2 (P<0.005) by treatment with MK-886. Neutrophil deposition was also decreased by MK-886, from 242.8±36.8 to 120.9±20.3×103 neutrophils cm−2 (P<0.01). MK-886-treated animals had a significant decrease in the postangioplasty vasoconstrictive response at the site of endothelial injury distally, from 37.5±3.1% in the control group to 13.5±2.5% (P<0.001).The effects of MK-886 were associated with a profound inhibition of ex vivo leukotriene B4 (LTB4) synthesis in blood stimulated by the calcium ionophore A23187 and a significant reduction of neutrophil aggregation in whole blood (P<0.01), whereas neutrophil superoxide anion production, serum thromboxane B2 and platelet aggregation in whole blood were not influenced.The relevant effects of MK-886 are primarily related to inhibition of neutrophil function and suggest an important modulatory role for leukotrienes in the

MK-801 (Dizocilpine) Regulates Multiple Steps of Adult Hippocampal Neurogenesis and Alters Psychological Symptoms via Wnt/β-Catenin Signaling in Parkinsonian Rats.

PubMed

Singh, Sonu; Mishra, Akanksha; Srivastava, Neha; Shukla, Shubha

2017-03-15

Adult hippocampal neurogenesis is directly involved in regulation of stress, anxiety, and depression that are commonly observed nonmotor symptoms in Parkinson's disease (PD). These symptoms do not respond to pharmacological dopamine replacement therapy. Excitotoxic damage to neuronal cells by N-methyl-d-aspartate (NMDA) receptor activation is also a major contributing factor in PD development, but whether it regulates hippocampal neurogenesis and nonmotor symptoms in PD is yet unexplored. Herein, for the first time, we studied the effect of MK-801, an NMDA receptor antagonist, on adult hippocampal neurogenesis and behavioral functions in 6-OHDA (6-hydroxydopamine) induced rat model of PD. MK-801 treatment (0.2 mg/kg, ip) increased neural stem cell (NSC) proliferation, self-renewal capacity, long-term survival, and neuronal differentiation in the hippocampus of rat model of PD. MK-801 potentially enhanced long-term survival, improved dendritic arborization of immature neurons, and reduced 6-OHDA induced neurodegeneration via maintaining the NSC pool in hippocampus, leading to decreased anxiety and depression-like phenotypes in the PD model. MK-801 inhibited glycogen synthase kinase-3β (GSK-3β) through up-regulation of Wnt-3a, which resulted in the activation of Wnt/β-catenin signaling leading to enhanced hippocampal neurogenesis in PD model. Additionally, MK-801 treatment protected the dopaminergic (DAergic) neurons in the nigrostriatal pathway and improved motor functions by increasing the expression of Nurr-1 and Pitx-3 in the PD model. Therefore, MK-801 treatment serves as a valuable tool to enhance hippocampal neurogenesis in PD, but further studies are needed to revisit the role of MK-801 in the neurodegenerative disorder before proposing a potential therapeutic candidate.

Nature of superconductor-insulator transition at LaAlO{sub 3}/SrTiO{sub 3} interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohanta, N., E-mail: nmohanta@phy.iitkgp.ernet.in; Taraphder, A.; Centre for Theoretical Studies, Indian Institute of Technology Kharagpur, W. B. 721302

2015-05-15

The two-dimensional electron liquid, at the interface between two band insulators LaAlO{sub 3} and SrTiO{sub 3}, exhibits novel, unconventional superconductivity below 200 mK. One of the remarkable properties of the two-dimensional superconductor is its fantastic tunability by external parameters such as gate-voltage or magnetic field. We study the superconductor to insulator transition induced by gate-voltage by employing a self-consistent, mean-field Bogoliubov-de Gennes treatment based on an effective model. We show that the non-monotonic behaviour of the superconductivity with respect to gate-voltage is intrinsically due to the Rashba spin-orbit coupling. With increasing gate-voltage both the electron concentration and Rashba spin-orbit splittingmore » increases. Elevated electron filling boosts superconductivity whereas enhanced spin-orbit splitting annihilates electron-pairing. The non-monotonicity is a result of this competition. The device application of the superconductor-insulator transition in this interface is discussed.« less

The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish.

PubMed

da Silva, Raquel Bohrer; Siebel, Anna Maria; Bonan, Carla Denise

2015-12-01

Depression is a serious disease characterized by low mood, anhedonia, loss of interest in daily activities, appetite and sleep disturbances, reduced concentration, and psychomotor agitation. There is a growing interest in NMDA antagonists as a promising target for the development of new antidepressants. Considering that purinergic and dopaminergic systems are involved in depression and anxiety states, we characterized the role of these signaling pathways on MK-801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at the doses of 5, 10, 15, or 20μM during 15, 30, or 60min spent longer time in the top area of aquariums in comparison to control group, indicating an anxiolytic/antidepressant effect induced by this drug. Animals treated with MK-801 spent longer time period at top area until 2 (5μM MK-801) and 4 (20μM MK-801) hours after treatment, returning to basal levels from 24h to 7days after exposure. Repeated MK-801 treatment did not induce cumulative effects, since animals treated daily during 7days had the same behavioral response pattern observed since the first until the 7th day. In order to investigate the effects of adenosine A1 and A2A receptor antagonist and agonist and the influence of modulation of adenosine levels on MK-801 effects, we treated zebrafish with caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI during 30min before MK-801 exposure. The non-specific adenosine receptor antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH 23390) did not change the behavioral alterations induced by MK-801. Our findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are mediated through adenosine A1 receptor activation

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

PubMed

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.

Spectral Classification in the MK System of 167 Northern HD Stars

NASA Astrophysics Data System (ADS)

Jensen, K. S.

1981-09-01

Spectral classifications in the MK system of 167 northern HD stars are presented. The spectra (102 A/mm at Hγ, width 0.60 mm) are from objective prism plates obtained with the Schmidt telescope of the CUO, Brorfelde. Most of the stars have no previous MK classification.

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

PubMed

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

2016-07-01

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 (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).

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

PubMed Central

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

Experiences in utilization of research reactors in Yugoslavia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Copic, M.; Gabrovsek, Z.; Pop-Jordanov, J.

1971-06-15

The nuclear institutes in Yugoslavia possess three research reactors. Since 1958, two heavy-water reactors have been in operation at the 'Boris Kidric' Institute, a zero-power reactor RB and a 6. 5-MW reactor RA. At the Jozef Stefan Institute, a 250-kW TRIGA Mark II reactor has been operating since 1966. All reactors are equipped with the necessary experimental facilities. The main activities based on these reactors are: (1) fundamental research in solid-state and nuclear physics; (2) R and D activities related to nuclear power program; and (3) radioisotope production. In fundamental physics, inelastic neutron scattering and diffraction phenomena are studied bymore » means of the neutron beam tubes and applied to investigations of the structures of solids and liquids. Valuable results are also obtained in n - γ reaction studies. Experiments connected with the fuel -element development program, owing to the characteristics of the existing reactors, are limited to determination of the fuel element parameters, to studies on the purity of uranium, and to a small number of capsule irradiations. All three reactors are also used for the verification of different methods applied in the analysis of power reactors, particularly concerning neutron flux distributions, the optimization of reactor core configurations and the shielding effects. An appreciable irradiation space in the reactors is reserved for isotope production. Fruitful international co-operation has been established in all these activities, on the basis of either bilateral or multilateral arrangements. The paper gives a critical analysis of the utilization of research reactors in a developing country such as Yugoslavia. The investments in and the operational costs of research reactors are compared with the benefits obtained in different areas of reactor application. The impact on the general scientific, technological and educational level in the country is also considered. In particular, an attempt is made ro

NMDA receptor antagonist MK-801 reduces neuronal damage and preserves learning and memory in a rat model of traumatic brain injury.

PubMed

Han, Rui-Zhang; Hu, Jin-Jia; Weng, Yuan-Chi; Li, Ding-Feng; Huang, Yi

2009-12-01

NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury (TBI). The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Forty Sprague-Dawley rats (weighing approximately 200 g) were randomized into 5 groups (n = 8 in each group): control group, model group, low-dose group (MK-801 0.5 mg/kg), middle-dose group (MK-801 2 mg/kg), and high-dose group (MK-801 10 mg/kg). TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase (nNOS)-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.

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

PubMed

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 < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables. Superficial 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.

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

PubMed

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.

Integrated Array and 3-Component Processing Using a Seismic Microarray

DTIC Science & Technology

1991-05-31

VA 22091 Pasadena, CA 91125 Mr. William J. Best Prof. F. A. Dahlen 907 Westwood Drive Geological and Geophysical Sciences Vienna, VA 22180 Princeton...Station S-CUBED University of California A Division of Maxwell Laboratory Berkeley, CA 94720 P.O. Box 1620 La Jolla, CA 92038-1 60 2 Prof. William ...Geosciences Building #77 University of Arizona Tucson, AZ 85721 Dr. William Wortman Mission Research Corporation 8560 Cinderbed Rd. Suite # 700

Negative modulation of α5 GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion

PubMed Central

Stamenić, Tamara Timić; Joksimović, Srdjan; Biawat, Poonam; Stanković, Tamara; Marković, Bojan; Cook, James M; Savić, Miroslav M

2016-01-01

Reportedly, negative modulation of α5 GABAA receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5 and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of α5 GABAA receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-D-aspartate – receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of α5 GABAA receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia. PMID:26105958

Negative modulation of α₅ GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion.

PubMed

Timić Stamenić, Tamara; Joksimović, Srdjan; Biawat, Poonam; Stanković, Tamara; Marković, Bojan; Cook, James M; Savić, Miroslav M

2015-09-01

Reportedly, negative modulation of α5 GABAA receptors may improve cognition in normal and pharmacologically-impaired animals, and such modulation has been proposed as an avenue for treatment of cognitive symptoms in schizophrenia. This study assessed the actions of PWZ-029, administered at doses (2, 5, and 10 mg/kg) at which it reached micromolar concentrations in brain tissue with estimated free concentrations adequate for selective modulation of α5 GABAA receptors, in three cognitive tasks in male Wistar rats acutely treated with the noncompetitive N-methyl-d-aspartate receptor antagonist, MK-801 (0.1 mg/kg), as well in tests of locomotor activity potentiated by MK-801 (0.2 mg/kg) or amphetamine (0.5 mg/kg). In a hormetic-like manner, only 5 mg/kg PWZ-029 reversed MK-801-induced deficits in novel object recognition test (visual recognition memory), whereas in the Morris water maze, the 2 mg/kg dose of PWZ-029 exerted partial beneficial effects on spatial learning impairment. PWZ-029 did not affect recognition memory deficits in social novelty discrimination procedure. Motor hyperactivity induced with MK-801 or amphetamine was not preventable by PWZ-029. Our results show that certain MK-801-induced memory deficits can be ameliorated by negative modulation of α5 GABAA receptors, and point to the need for further elucidation of their translational relevance to cognitive deterioration in schizophrenia. © The Author(s) 2015.

The rate of decay of fresh fission products from a nuclear reactor

NASA Astrophysics Data System (ADS)

Dolan, David J.

Determining the rate of decay of fresh fission products from a nuclear reactor is complex because of the number of isotopes involved, different types of decay, half-lives of the isotopes, and some isotopes decay into other radioactive isotopes. Traditionally, a simplified rule of 7s and 10s is used to determine the dose rate from nuclear weapons and can be to estimate the dose rate from fresh fission products of a nuclear reactor. An experiment was designed to determine the dose rate with respect to time from fresh fission products of a nuclear reactor. The experiment exposed 0.5 grams of unenriched Uranium to a fast and thermal neutron flux from a TRIGA Research Reactor (Lakewood, CO) for ten minutes. The dose rate from the fission products was measured by four Mirion DMC 2000XB electronic personal dosimeters over a period of six days. The resulting dose rate following a rule of 10s: the dose rate of fresh fission products from a nuclear reactor decreases by a factor of 10 for every 10 units of time.

White matter injuries induced by MK-801 in a mouse model of schizophrenia based on NMDA antagonism.

PubMed

Xiu, Yun; Kong, Xiang-Ru; Zhang, Lei; Qiu, Xuan; Chao, Feng-Lei; Peng, Chao; Gao, Yuan; Huang, Chun-Xia; Wang, San-Rong; Tang, Yong

2014-08-01

The etiology of schizophrenia (SZ) is complex and largely unknown. Neuroimaging and postmortem studies have suggested white matter disturbances in SZ. In the present study, we tested the white matter deficits hypothesis of SZ using a mouse model of SZ induced by NMDA receptor antagonist MK-801. We found that mice with repeated chronic MK-801 administration showed increased locomotor activity in the open field test, less exploration of a novel environment in the hole-board test, and increased anxiety in the elevated plus maze but no impairments were observed in coordination or motor function on accelerating rota-rod. The total white matter volume and corpus callosum volume in mice treated with MK-801 were significantly decreased compared to control mice treated with saline. Myelin basic protein and 2', 3'-cyclic nucleotide 3'-phosphodiesterase were also significantly decreased in the mouse model of SZ. Furthermore, we observed degenerative changes of myelin sheaths in the mouse model of SZ. These results provide further evidence of white matter deficits in SZ and indicate that the animal model of SZ induced by MK-801 is a useful model to investigate mechanisms underlying white matter abnormalities in SZ. Copyright © 2014 Wiley Periodicals, Inc.

Testing of 100 mK bolometers for space applications

NASA Technical Reports Server (NTRS)

Murray, A. G.; Ade, P. A. R.; Bhatia, R. S.; Griffin, M. J.; Maffei, B.; Nartallo, R.; Beeman, J. W.; Bock, J.; Lange, A.; DelCastillo, H.

1996-01-01

Electrical and optical performance data are presented for a prototype 100 mK spider-web bolometer operating under very low photon backgrounds. These data are compared with the bolometer theory and are used to estimate the expected sensitivity of such a detector used for low background space astronomy. The results demonstrate that the sensitivity and speed of response requirements of the bolometer instruments proposed for these missions can be met by 100 mK spider-web bolometers using neutron transmutation doped germanium as the temperature sensitive element.

Medial Prefrontal Administration of MK-801 Impairs T-maze Discrimination Reversal Learning in Weanling Rats

PubMed Central

Watson, Deborah J.; Stanton, Mark E.

2009-01-01

Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats [1, 16, 34, 55]. Systemic administration of MK-801, an NMDA receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA receptor antagonism in this effect is not known in either adult or young animals. This set of studies showed that mPFC NMDA receptors are specifically involved in T-maze discrimination reversal in weanling rats. In Experiment 1, 26-day-old rats (P26) demonstrated a dose-dependent impairment following bilateral mPFC administration of either 2.5 or 5.0 µg MK-801 or saline (vehicle) during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but 4 groups of rats received bilateral mPFC infusions during acquisition only (MK-SAL), reversal only (SAL-MK), both phases (MK-MK) or neither phase (SAL-SAL). MK-801 impaired performance only when infused during reversal. This suggests that NMDA receptor antagonism in the mPFC is selectively involved in reversal learning during development and this may account for the previously reported effects of systemic MK-801 on T-maze discrimination reversal in weanling rats. PMID:19643149

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

PubMed Central

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 (p<0.05) and these deficits were blocked by treatment with olanzapine (p<0.05) but not haloperidol. The administration of MK-801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p<0.01), which was prevented by treatment with olanzapine (p<0.05) but not haloperidol. Conclusion These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis. PMID:27489382

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

PubMed Central

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

Co-administration of MK-801 and morphine attenuates neuropathic pain in rat.

PubMed

Hamidi, Gholam Ali; Manaheji, Homa; Janahmadi, Mahyar; Noorbakhsh, Sayed Mohammad; Salami, Mahmoud

2006-07-30

Partial peripheral nerve injury often leads to chronic pain states, including allodynia and hyperalgesia. The purpose of this study was to investigate the involvement of the N-methyl-D-aspartate and opioid receptors in the behavioural responses following chronic constriction nerve injury (CCI). The animals were injected a combination of MK-801 (0.3 mg/kg, 20 min before, and 6 h after the operation) and morphine (8 mg/kg, 30 min prior to the operation) and were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after CCI. Compound action potentials were also recorded from the injured nerve 2 weeks post-operation to indicate nerve injury state electrophysiologically. Our results indicate that the CCI model importantly influences the behavioural responses to both the thermal and mechanical stimulations. Also, the pre-emptive co-administration of MK-801 and morphine has suppressive effects on the cold allodynia but a slight alleviation on the mechano-allodynia and heat hyperalgesia.

75 FR 4493 - Natural Resources Defense Council; Denial of Petition for Rulemaking

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... NRC continues to license the civilian use of HEU to fuel seven existing research and test reactors... predicts that the three HEU-fueled TRIGA-type research reactors at Oregon State University, the University...) is scheduled for conversion to LEU but notes that the newer and larger LEU-fueled TRIGA facility at...

Manned Certification Tests of the Modernized MK 16 MOD 1

DTIC Science & Technology

2013-11-01

CERTIFICATION TESTS OF THE MODERNIZED MK 16 MOD 1 Authors: D. E . Warkander, Ph.D. D. J. Doolette, Ph.D...PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dan E . Warkander; David J. Doolette; Paul C. Algra 5d. PROJECT NUMBER 5e. TASK NUMBER 10-08 5f. WORK UNIT...electronics must be turned on when calibrating the secondary display. 11 REFERENCES 1. R. P. Layton , Unmanned Evaluation of the Modernized MK 16 MOD

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

PubMed

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.

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

PubMed

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.

Determination of SPEAR-1 Rocket Body Potential during High-Voltage Experiments

DTIC Science & Technology

1990-06-01

California at San Diego La Jolla, CA 92093 10 . Dr. C. E. McIlwain Center for Astrophysics and Space Science University of California at San Diego La Jolla...Postgraduate School 39 Naval Postgraduate School 6c. ADDRESS (City, S:are, and ZIP Code) 7b. ADDRESS (Ciy, State, and ZIP Code) Monterey. CA 93943-5000...Monterey. CA 93943-5000 8a. NAME OF FUNDING.SPONSORING 80. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable

On Learning the Past Tenses of English Verbs.

DTIC Science & Technology

1985-10-01

RD-AI164 233 ON LEARING THE PAST TENSES OF ENGLISH YERBS(U) vi1 r CALIFORNIA UNIV SAN DIEGO LA JOLLA INST FOR COGNITIVE SCIENCE D E RUMELNART ET AL... COGNITIVE SCIENCE O I$FE13Me~ 0C*" INSTITUTE FOR COGNITIVE SCIENCE UNIVERSITY OF CALIFORNIA, SAN DIEGO LA JOLLA, CALIFORNIA 92093 - *~-’~7...8507 . *** David E. Rurneihart James L. McClelland Institute for Cognitive Science Department of Psychology University of Calif ornia. San Diego

An Expert System for Classifying Stars on the MK Spectral Classification System

NASA Astrophysics Data System (ADS)

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

2013-01-01

We will describe an expert computer system designed to classify stellar spectra on the MK Spectral Classification system employing methods similar to those of humans who make direct comparison with the MK classification standards. Like an expert human classifier, MKCLASS first comes up with a rough spectral type, and then refines that type by direct comparison with MK standards drawn from a standards library using spectral criteria appropriate to the spectral class. Certain common spectral-type peculiarities can also be detected by the program. The program is also capable of identifying WD spectra and carbon stars and giving appropriate (but currently approximate) spectral types on the relevant systems. We will show comparisons between spectral types (including luminosity types) performed by MKCLASS and humans. The program currently is capable of competent classifications in the violet-green region, but plans are underway to extend the spectral criteria into the red and near-infrared regions. Two standard libraries with resolutions of 1.8 and 3.6Å are now available, but a higher-resolution standard library, using the new spectrograph on the Vatican Advanced Technology Telescope, is currently under preparation. Once that library is available, MKCLASS and the spectral libraries will be made available to the astronomical community.

Performance oriented packaging testing of nine Mk 3 Mod 0 signal containers in PPP-B-621 wood box for packing group II solid hazardous materials. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Libbert, K.J.

1992-10-01

A PPP-B-621 wood box containing nine Mk 3 Mod 0 Signal containers was tested for conformance to Performance Oriented Packaging criteria established by Code of Federal Regulations Title 49 CFR. The container was tested with a gross weight of 123.3 pounds (56 kilograms) and met all requirements.

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

PubMed

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.

A CAMAC based real-time noise analysis system for nuclear reactors

NASA Astrophysics Data System (ADS)

Ciftcioglu, Özer

1987-05-01

A CAMAC based real-time noise analysis system was designed for the TRIGA MARK II nuclear reactor at the Institute for Nuclear Energy, Istanbul. The input analog signals obtained from the radiation detectors are introduced to the system through CAMAC interface. The signals converted into digital form are processed by a PDP-11 computer. The fast data processing based on auto/cross power spectral density computations is carried out by means of assembly written FFT algorithms in real-time and the spectra obtained are displayed on a CAMAC driven display system as an additional monitoring device. The system has the advantage of being software programmable and controlled by a CAMAC system so that it is operated under program control for reactor surveillance, anomaly detection and diagnosis. The system can also be used for the identification of nonstationary operational characteristics of the reactor in long term by comparing the noise power spectra with the corresponding reference noise patterns prepared in advance.

N-(2-Mercaptoethyl)-1,3-Propanediamine (WR-1065) Protects Thymocytes from Programed Cell Death

DTIC Science & Technology

1992-03-15

and most characteristic biohemical marker for apoptosts is calcium lontophores stimulate a suicide process in nuclear DNA fragmentation Into...1065 the dephosphory- exposed to -7-radiation. dexamethazone. or calcium lated form of WR-2721 and generally considered to be Ionophore A23187. WR...33258 fluorochrome was purchased from Calbiochem-Rehring. La Jolla, CA: Dexameth- azone and calcium lonophore A23 187 were purchased from Sigmatos

Determining Pu-239 content by resonance transmission analysis using a filtered reactor beam.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klann, R. T.

A novel technique has been developed at Argonne National Laboratory to determine the {sup 239}Pu content in EBR-II blanket elements using resonance transmission analysis (RTA) with a filtered reactor beam. The technique uses cadmium and gadolinium filters along with a {sup 239}Pu fission chamber to isolate the 0.3 eV resonance in {sup 239}Pu. In the energy range from 0.1 to 0.5 eV, the total microscopic cross-section of {sup 239}Pu is significantly larger than the cross-sections of {sup 238}U and {sup 235}U. This large difference in cross-section allows small amounts of {sup 239}Pu to be detected in uranium samples. Tests usingmore » a direct beam from a 250 kW TRIGA reactor have been performed with stacks of depleted uranium and {sup 239}Pu foils. Preliminary measurement results are in good agreement with the predicted results up to about two weight percent of {sup 239}Pu in the sample. In addition, measured {sup 239}Pu masses were in agreement with actual sample masses with uncertainties less than 3.8 percent.« less

Cosmogenic Production of Be-7 and Be-10 in Water Targets

NASA Technical Reports Server (NTRS)

Nishiizumi, K.; Finkel, R. C.; Klein, J.; Kohl, C. P.

1996-01-01

We have measured Be-10(t(sub 1/2) = 1.5 x 10(exp 6) years) and Be-7 (t(sub 1/2) = 53.28 days) concentrations in water targets exposed for 1 to 2 years at Echo Lake, Colorado (elevation = 3246 m) and at La Jolla, California (140 m). Neutron monitor data were used to normalize the measured concentrations in order to calculate production rates equivalent to the cosmic ray flux averaged over four solar cycles (43 years). The Be-7 production rates thus obtained correspond to 6.03 +/- 0.07 x 10(exp -6) atom/g.O/s at Echo Lake and 5.06 +/- 0.20 x 10(exp -7) atom/g.O/ s at La Jolla. The Be-10 production rates correspond to 3.14 +/- 0.18 x 10(exp -6) atom/g.O/s at Echo Lake and 2.68 +/- 0.47 x 10(exp -7) atom/g.O/s at La Jolla. When compared with Be-10 production rates determined in Be-10-saturated rocks from the Antarctic and with theoretical calculations based on meteorite and lunar sample data, we find that the million-year average production rate is about 14 - 17% greater than the present production rate averaged over the last four solar cycles. Comparison with production rates determined by measuring glacially polished rocks from the Sierra Nevada in California indicates that average production (based on a revised 13,000-year deglaciation age and a geographic latitude correction) is a about 11% greater than the average over the last four solar cycles. The measured Be-10/Be-7 production ratio in oxygen is 0.52 +/- 0.03 at Echo Lake and 0.55 +/- 0.07 at La Jolla.

Antipsychotic drugs prevent the motor hyperactivity induced by psychotomimetic MK-801 in zebrafish (Danio rerio).

PubMed

Seibt, Kelly Juliana; Oliveira, Renata da Luz; Zimmermann, Fernanda Francine; Capiotti, Katiúcia Marques; Bogo, Maurício Reis; Ghisleni, Gabriele; Bonan, Carla Denise

2010-12-25

Glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), elicit schizophrenia-like symptoms in humans and a behavioral syndrome in rodents, characterized by hyperlocomotion and stereotyped actions, which is antagonized by antipsychotic drugs. Animal models of schizophrenia have been established and used for the development of new antipsychotic drugs. In this work we characterized the behavioral effects of MK-801 and investigated the effect of typical and atypical antipsychotic treatments on locomotor activity as well on the hyperlocomotion induced by MK-801 in zebrafish. MK-801 (20 microM) increased the locomotor behavior as measured by the number of line crossings, distance traveled, and the mean speed in the tank test after 15, 30, and 60 min of exposure. All tested antipsychotics counteracted MK-801-induced hyperactivity on all parameters analyzed and at doses that, given alone, had no effect on spontaneous locomotor activity. The results suggest a similar profile between typical and atypical antipsychotics in the reversal of locomotor disorders induced by MK-801. Moreover, an anxiolytic effect was verified at 30 and 60 min of MK-801 exposure, which was not reversed by antipsychotics tested in this work. In addition, olanzapine, which alone caused an anxiolytic response, when given with MK-801 potentiated the latter's effect on anxiety. In this work we demonstrated the value of the zebrafish, a simple to use animal model, in developing some behavioral features observed in schizophrenia, which may indicate a new approach for drug screening. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allwörden, H. von; Ruschmeier, K.; Köhler, A.

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 chambersmore » 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).« less

Delayed Gamma Measurements in Different Nuclear Research Reactors Bringing Out the Importance of the Delayed Contribution in Gamma Flux Calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fourmentel, D.; Radulovic, V.; Barbot, L.

Neutron and gamma flux levels are key parameters in nuclear research reactors. In Material Testing Reactors, such as the future Jules Horowitz Reactor, under construction at the French Alternative Energies and Atomic Energy Commission (CEA Cadarache, France), the expected gamma flux levels are very high (nuclear heating is of the order of 20 W/g at 100 MWth). As gamma rays deposit their energy in the reactor structures and structural materials it is important to take them into account when designing irradiation devices. There are only a few sensors which allow measurements of the nuclear heating ; a recent development atmore » the CEA Cadarache allows measurements of the gamma flux using a miniature ionization chamber (MIC). The measured MIC response is often compared with calculation using modern Monte Carlo (MC) neutron and photon transport codes, such as TRIPOLI-4 and MCNP6. In these calculations only the production of prompt gamma rays in the reactor is usually modelled thus neglecting the delayed gamma rays. Hence calculations and measurements are usually in better accordance for the neutron flux than for the gamma flux. In this paper we study the contribution of delayed gamma rays to the total MIC signal in order to estimate the systematic error in gamma flux MC calculations. In order to experimentally determine the delayed gamma flux contributions to the MIC response, we performed gamma flux measurements with CEA developed MIC at three different research reactors: the OSIRIS reactor (MTR - 70 MWth at CEA Saclay, France), the TRIGA MARK II reactor (TRIGA - 250 kWth at the Jozef Stefan Institute, Slovenia) and the MARIA reactor (MTR - 30 MWth at the National Center for Nuclear Research, Poland). In order to experimentally assess the delayed gamma flux contribution to the total gamma flux, several reactor shut down (scram) experiments were performed specifically for the purpose of the measurements. Results show that on average about 30 % of the MIC signal is

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

PubMed Central

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

TRIGA: Telecommunications Protocol Processing Subsystem Using Reconfigurable Interoperable Gate Arrays

NASA Technical Reports Server (NTRS)

Pang, Jackson; Pingree, Paula J.; Torgerson, J. Leigh

2006-01-01

We present the Telecommunications protocol processing subsystem using Reconfigurable Interoperable Gate Arrays (TRIGA), a novel approach that unifies fault tolerance, error correction coding and interplanetary communication protocol off-loading to implement CCSDS File Delivery Protocol and Datalink layers. The new reconfigurable architecture offers more than one order of magnitude throughput increase while reducing footprint requirements in memory, command and data handling processor utilization, communication system interconnects and power consumption.

On the development of radiation tolerant surveillance camera from consumer-grade components

NASA Astrophysics Data System (ADS)

Klemen, Ambrožič; Luka, Snoj; Lars, Öhlin; Jan, Gunnarsson; Niklas, Barringer

2017-09-01

In this paper an overview on the process of designing a radiation tolerant surveillance camera from consumer grade components and commercially available particle shielding materials is given. This involves utilization of Monte-Carlo particle transport code MCNP6 and ENDF/B-VII.0 nuclear data libraries, as well as testing the physical electrical systems against γ radiation, utilizing JSI TRIGA mk. II fuel elements as a γ-ray sources. A new, aluminum, 20 cm × 20 cm × 30 cm irradiation facility with electrical power and signal wire guide-tube to the reactor platform, was designed and constructed and used for irradiation of large electronic and optical components assemblies with activated fuel elements. Electronic components to be used in the camera were tested against γ-radiation in an independent manner, to determine their radiation tolerance. Several camera designs were proposed and simulated using MCNP, to determine incident particle and dose attenuation factors. Data obtained from the measurements and MCNP simulations will be used to finalize the design of 3 surveillance camera models, with different radiation tolerances.

SNAP 10A FS-3 reactor performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hawley, J.P.; Johnson, R.A.

1966-08-15

SNAP 10FS-3 was the first flight-qualified SNAP reactor system to be operated in a simulated space environment. Prestart-up qualification testing, automatic start-up, endurance period performance, extended operation test and reactor shutdown are described as they affected, or were affected by, overall reactor performance. Performance of the reactor control system and the diagnostic instrumentation is critically evaluted.

3D-Stereoscopic Analysis of Solar Active Region Loops. 2; SoHo/EIT Observations at Temperatures of 1.5-2.5 MK

NASA Technical Reports Server (NTRS)

Aschwanden, Markus J.; Alexander, David; Hurlburt, Neal; Newmark, Jeffrey S.; Neupert, Werner M.; Klimchuk, J. A.; Gary, G. Allen

1999-01-01

In this paper we study the three-dimensional (3D) structure of hot (T(sub e) approximately equals 1.5 - 2.5 MK) loops in solar active region NOAA 7986, observed on 1996 August 30 with the Extreme-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SoHO). This complements a first study on cooler (T(sub e) approximately equals 1.0 - 1.5 MK) loops of the same active region, using the same method of Dynamic Stereoscopy to reconstruct the 3D geometry. We reconstruct the 3D-coordinates x(s), y(s), z(s), the density n(sub e)(s), and temperature profile T(sub e)(s) of 35 individual loop segments (as function of the loop coordinate s) using EIT 195 A and 284 A images. The major findings are: (1) All loops are found to be in hydrostatic equilibrium, in the entire temperature regime of T(sub e) = 1.0 - 2.5 MK; (2) The analyzed loops have a height of 2-3 scale heights, and thus only segments extending over about one vertical scale height have sufficient emission measure contrast for detection; (3) The temperature gradient over the lowest scale height is of order dT/ds is approximately 1 - 4 K/km; (4) The radiative loss rate is found to exceed the conductive loss rate by about two orders or magnitude, making thermal conduction negligible to explain the temperature structure of the loops; (5) A steady-state can only be achieved when the heating rate E(sub H) matches the radiative loss rate in hydrostatic equilibrium, requiring a heat deposition length lambda(sub H) of the half density scale height lambda, predicting a scaling law with the loop base pressure, EH varies as p(sub 0 exp 2). This favors coronal heating mechanisms that operate near the loop footpoints; (6) We find a reciprocal correlation between the loop pressure p(sub 0) and loop length L, i.e. p(sub 0) varies as 1/L, implying a scaling law of the steady-state requirement with loop length, i.e. E(sub H ) varies as 1/L(exp 2). The heating rate shows no correlation with the loop

Age-related differential sensitivity to MK-801-induced locomotion and stereotypy in C57BL/6 mice

PubMed Central

Qi, Chunting; Zou, Hong; Zhang, Ruizhong; Zhao, Guoping; Jin, Meilei; Yu, Lei

2009-01-01

Psychomotor effects elicited by systemic administration of the noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) represent perturbation of glutamatergic pathways, providing an animal model for psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two main psychomotor behaviors induced by MK-801. This study compared MK-801-induced hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month old), in order to determine how the aging process may influence these behaviors. The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK-801 impacted the aged mice more pronouncedly than the young mice, as both hyperlocomotion and stereotypy were increased significantly more in the aged mice relative to the young mice. These results suggest an age-related increase in MK-801 sensitivity in mice. PMID:18053981

Enhanced Low-Enriched Uranium Fuel Element for the Advanced Test Reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pope, M. A.; DeHart, M. D.; Morrell, S. R.

2015-03-01

Under the current US Department of Energy (DOE) policy and planning scenario, the Advanced Test Reactor (ATR) and its associated critical facility (ATRC) will be reconfigured to operate on low-enriched uranium (LEU) fuel. This effort has produced a conceptual design for an Enhanced LEU Fuel (ELF) element. This fuel features monolithic U-10Mo fuel foils and aluminum cladding separated by a thin zirconium barrier. As with previous iterations of the ELF design, radial power peaking is managed using different U-10Mo foil thicknesses in different plates of the element. The lead fuel element design, ELF Mk1A, features only three fuel meat thicknesses,more » a reduction from the previous iterations meant to simplify manufacturing. Evaluation of the ELF Mk1A fuel design against reactor performance requirements is ongoing, as are investigations of the impact of manufacturing uncertainty on safety margins. The element design has been evaluated in what are expected to be the most demanding design basis accident scenarios and has met all initial thermal-hydraulic criteria.« less

Age specific effect of MK-801 on hypoxic body temperature regulation in rats.

PubMed

Baig, Mirza Shafiulla; Joseph, Vincent

2008-02-01

Hypoxic exposure produces a consistent decrease of rectal temperature (Tb), which is recognized as a potent protective response. While some of the neural mechanisms underlying this response have recently been described, it remains poorly known how these mechanisms evolve during post-natal development. We recently reported that in rat pups NMDA glutamate receptor limits Tb drop upon hypoxic exposure, an effect that has not been reported by others in adult rats. Accordingly, we tested the hypothesis that the implication of NMDA receptors on temperature control during hypoxic exposure evolves during development. To this aim, we evaluated the hypoxic (30 min - 12% O(2)) responses of Tb, metabolic rate, and ventilation in rats after injection of vehicle, or the NMDA receptor antagonist MK-801, at different ages (post-natal days 4, 10, 20 and 2-3 month-old - P4, P10, P20 and P60). MK-801 amplified the magnitude of the hypoxic-induced Tb drop in P4, P10 and P20 rats, but this effect was not apparent in adults. In P20 rats MK-801 tripled the hypoxic induced Tb drop, which was 0.5 degrees C in control and 1.4 degrees C in treated rats (p<0.0001). This effect was specific to temperature regulation, and was not accompanied by similar changes of other recorded parameters. MK-801 induced a significant decrease of the hypoxic ventilatory response in adults only. We conclude that NMDA glutamate receptor acts as a counter-regulatory factor that limits the hypoxic-induced drop of rectal temperature during post-natal development in rats.

Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK-6577 in baboons.

PubMed

Zheng, Ming-Qiang; Lin, Shu-Fei; Holden, Daniel; Naganawa, Mika; Ropchan, Jim R; Najafzaden, Soheila; Kapinos, Michael; Tabriz, Mike; Carson, Richard E; Hamill, Terence G; Huang, Yiyun

2016-03-01

Glycine transporter type-1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [(11) C]GSK931145, and [(18) F]MK-6577, in baboons. Two baboons were imaged with [(11) C]GSK931145 and [(18) F]MK-6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [(11) C]GSK931145 and [(18) F]MK-6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ∼ 30% of parent at 30 min post-injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [(18) F]MK-6577 displayed higher uptake and faster kinetics than [(11) C]GSK931145. Time activity curves were well described by the two-tissue compartment model. Regional volume of distribution (VT ) values were higher for [(18) F]MK-6577 than [(11) C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of VT estimates between tracers indicated higher specific binding for [(18) F]MK-6577 than [(11) C]GSK931145, consistent with higher regional binding potential (BPND ) values of [(18) F]MK-6577 calculated using VT from the baseline scans and non-displaceable distribution volume (VND ) derived from blocking studies. [(18) F]MK-6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [(11) C]GSK931145. © 2016 Wiley Periodicals, Inc.

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

PubMed Central

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

Poussée de maladie de Kaposi et élévation du CA 19-9: penser à la tuberculose!

PubMed Central

Ajili, Faida; Hariz, Héla; Souissi, Asmahen; Abid, Rim; Boussetta, Najeh; Laabidi, Besma; Battikh, Riadh; Louzir, Bassem; Othmani, Salah

2013-01-01

La maladie de Kaposi (MK) est une entité pathologique qui peut survenir chez les patients VIH positifs et dans le cadre d'une immunodépression, d'origine tuberculeuse très rarement. On décrit le cas d'une MK chez un patient VIH négatif au décours d'une tuberculose. Nous rapportons le cas d'un patient âgé de 81 ans, VIH négatif, ayant présenté deux nodules angiomateux de l'avant bras gauche dont la biopsie cutanée était en faveur d'une MK. L’évolution était marquée 2 mois plus tard, par l'apparition de placards angiomateux extensifs des deux membres supérieurs et d'adénopathies cervicales jugulo-carotidiennes bilatérales. La biopsie ganglionnaire était en faveur d'une tuberculose ganglionnaire. Par ailleurs, il avait un taux sérique élevé des CA 19-9. La régression de l’étendue des lésions au niveau des membres supérieurs et la normalisation du taux sérique des CA 19-9 ont été obtenues sous traitement anti-tuberculeux. Chez les patients atteints d'une MK avec une élévation des CA 19-9, il faut penser à la tuberculose. PMID:24711871

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roychowdhury, Anita; Center for Nanophysics and Advanced Materials, Department of Physics, University of Maryland, College Park, Maryland 20740; Gubrud, M. A.

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 viamore » 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.« less

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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.

D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats.

PubMed

Karasawa, Jun-Ichi; Hashimoto, Kenji; Chaki, Shigeyuki

2008-01-10

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5 mg/kg, i.p.) but not haloperidol (0.03, 0.1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with D-serine at 800 mg/kg (i.p.) or NFPS (0.3, 1 mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

3D-Stereoscopic Analysis of Solar Active Region Loops: I: SoHo/EIT Observations at Temperatures of 1.0-1.5 MK

NASA Technical Reports Server (NTRS)

Aschwanden, Markus J.; Newmark, Jeff; Delaboudiniere, Jean-Pierre; Neupert, Werner M.; Portier-Fozzani, Fabrice; Gary, G. Allen; Zucker, Arik

1998-01-01

The three-dimensional (3D) structure of solar active region NOAA 7986 observed on 1996 August 30 with the Extrem-ultraviolet Imaging Telescope (EIT) onboard the Solar and Heliospheric Observatory (SoHO) is analyzed. We develop a new method of Dynamic Stereoscopy to reconstruct the 3D geometry of dynamically changing loops, which allows us to determine the orientation of the loop plane with respect to the line-of-sight, a prerequisite to correct properly for projection effects in 3D loop models. With this method and the filter-ratio technique applied to EIT 171 A and 195 A images we determine the 3D coordinates (x(s), y(s), z(s)), the loop width) w(s), the electron density n(sub e)(s), and the electron temperature T(sub e)(s) as function of the loop length s for 30 loop segments. Fitting the loop densities with an exponential density model n(sub e)(h) we find that the so inferred scale height temperatures, T(sub e)(sup lambda) = 1.22 +/- 0.23 MK, match closely the EIT filter-ratio temperatures, T(sub e)(sup FIT) = 1.21 +/- 0.06 MK. We conclude that these rather large-scale loops (with heights of h approx. equals 50 - 200 Mm) that dominate EIT 171 A images are close to thermal equilibrium. Most of the loops show no significant thickness variation w(s), but many exhibit a trend of increasing temperature (dT/ds greater than 0) above the footpoint.

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

NASA Astrophysics Data System (ADS)

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.

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

PubMed

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.

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

PubMed Central

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

Dopaminergic system in CA1 modulates MK-801 induced anxiolytic-like responses.

PubMed

Zarrindast, Mohammad Reza; Nasehi, Mohammad; Pournaghshband, Mahnaz; Yekta, Batool Ghorbani

2012-11-01

Today, there is relatively no debate on the notion that NMDA receptor antagonist agents in the hippocampus induce anxiolytic-like effects through distinct mechanisms. There is also a bulk of studies showing the involvement of the dopaminergic system in NMDA induced behaviors. Thus, on the basis of the involvement of dopaminergic system in anxiety-related behaviors, the present study aimed to investigate the involvement of the dorsal hippocampal (CA1) dopaminergic system in anxiolytic-like responses induced by MK801 (NMDA receptor antagonist) in male Wistar rats. We used the elevated plus maze to test anxiety. This apparatus has widely been employed to test parameters of anxiety-related behaviors including the open arm time percentage (%OAT), open arm entries percentage (%OAE), locomotor activity, grooming (the rat rubs its face), rearing (the rat maintains an erect posture) and defecation (the number of boli defection). The data showed that, intra-CA1 injection of MK801 (2 μg/rat) increases %OAT and %OAE but not other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, sole intra-CA1 injection of SCH23390, dopamine D1 receptor antagonist, (0.25, 0.5 and 1 μg/rat) and sulpiride, dopamine D2 receptor antagonist, (0.25,0.5 and 0.75 μg/rat) did not alter anxiety-like behaviors. Co-administration of subthreshold doses of SCH23390 (0.5 μg/rat) and MK801 (0.5 g/rat), induced anxiolytic-like behaviors. Furthermore, intra-CA1 administration of different doses of sulpiride (0.12, 0.5 and 0.75 μg/rat), 5 min before the injection of an effective dose of MK801 (2 μg/rat), decreased %OAT and %OAE, however did not alter other exploratory behaviors induced by MK801. Our results suggested a modulatory effect of the CA1 dopaminergic system on the anxiolytic-like effects induced by MK801.

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

PubMed Central

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

Metal-Insulator Transitions in Epitaxial LaVO(3) and LaTiO(3) Films

DTIC Science & Technology

2012-08-01

epitaxial films of LaVO3 and LaTiO3 can exhibit metallicity though their bulk counterparts are Mott insulators. When LaTiO3 films are compressively...secondarily to interface electronic reconstruction at the LaTiO3 /SrTiO3 interface. However, when LaVO3 films are compressively strained on SrTiO3...ABSTRACT We have demonstrated that epitaxial films of LaVO3 and LaTiO3 can exhibit metallicity though their bulk counterparts are Mott insulators. When

NMDA antagonist MK801 recreates auditory electrophysiology disruption present in autism and other neurodevelopmental disorders.

PubMed

Saunders, John A; Gandal, Michael J; Roberts, Timothy P; Siegel, Steve J

2012-10-01

Autism is a highly disabling neurodevelopmental disorder characterized by social deficits, language impairment, and repetitive behaviors. There are few effective biological treatments for this disorder, partly due to the lack of translational biomarkers. However, recent data suggest that autism has reliable electrophysiological endophenotypes, along with evidence that some deficits may be caused by NMDA receptor (NMDAR) dysfunction. Similarly, the NMDAR antagonist MK801 has been used in behavioral animal models of autism. Since MK801 has also been used as a model of schizophrenia, this paper examines the independent and overlapping ways in which MK801 recreates the electrophysiogical changes present in both diseases. Mouse EEG was recorded in response to auditory stimuli after either vehicle or MK801 and the dose-response relationship for each measure was determined. ERP component amplitude and latency analysis was performed along with time-frequency analysis of gamma frequency inter-trial coherence and evoked power. Evoked gamma power and ITC were decreased by MK801 at the highest dose. P1, N1 latency and gamma baseline power were increased in dose dependent fashion following MK801. There were no amplitude changes in P1 or N1. MK801 caused alterations in evoked gamma activity, gamma ITC, gamma baseline power, P1 and N1 latency similar to findings in autism. These data provide evidence indicating that NMDAR dysfunction may contribute to deficits specific to autism and some that overlap with other disorders such as schizophrenia. Such observations could be important for developing novel therapeutics, as electrophysiological endophenotypes associate with functional measures and may provide early biomarkers for efficacy in clinical trials. Copyright © 2012. Published by Elsevier B.V.

Permeation of Polymethoxyflavones into the Mouse Brain and Their Effect on MK-801-Induced Locomotive Hyperactivity.

PubMed

Okuyama, Satoshi; Miyazaki, Kohei; Yamada, Rie; Amakura, Yoshiaki; Yoshimura, Morio; Sawamoto, Atsushi; Nakajima, Mitsunari; Furukawa, Yoshiko

2017-02-24

Accumulating data have indicated that citrus polymethoxyflavones (PMFs) have the ability to affect brain function. In the present study, we showed that 3,5,6,7,8,3',4'-heptamethoxy- flavone (HMF) given intraperitoneally to mice was immediately detected in the brain and that the permeability of the brain tissues to it was significantly higher than that of other citrus PMFs (nobiletin, tangeretin, and natsudaidain). The permeation of these PMFs into the brain well correlated with their abilities to suppress MK-801-induced locomotive hyperactivity, suggesting that HMF had the ability to act directly in the brain. We also obtained data suggesting that the suppressive effect of HMF on MK-801-induced locomotive hyperactivity was mediated by phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the hippocampus.

The TRIGA Reactor Facility at the Armed Forces Radiobiology Research Institute: A Simplified Technical Description.

DTIC Science & Technology

1986-05-01

COUNT Technical FROM_ TO May 1986 20 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18. SUBJECT TERMS iConitinue on reverse if neceasary and identify by...Reactor, Modes of Operation, The AFRRI Reactor, Exposure Facilities, and Cerenkov Radiation. I- 20 DISTRISUTIONIAVAILABILITY OF ABSTRACT 21. ABSTRACT...6 Exposure Facilities 12 Cerenkov Radiation 17 Acoessiofl For NTIS GRA&I DT.C TABUnamnnounced [] UusnriOfltond -. By IZ Distribution/ Availability

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

PubMed

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.

Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

PubMed

Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

2016-09-15

Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Uncooled IR imager with 5-mK NEDT

NASA Astrophysics Data System (ADS)

Amantea, Robert; Knoedler, C. M.; Pantuso, Francis P.; Patel, Vipulkumar; Sauer, Donald J.; Tower, John R.

1997-08-01

The bi-material concept for room-temperature infrared imaging has the potential of reaching an NE(Delta) T approaching the theoretical limit because of its high responsivity and low noise. The approach, which is 100% compatible with silicon IC foundry processing, utilizes a novel combination of surface micromachining and conventional integrated circuits to produce a bimaterial thermally sensitive element that controls the position of a capacitive plate coupled to the input of a low noise MOS amplifier. This approach can achieve the high sensitivity, the low weight, and the low cost necessary for equipment such as helmet mounted IR viewers and IR rifle sights. The pixel design has the following benefits: (1) an order of magnitude improvement in NE(Delta) T due to extremely high sensitivity and low noise, (2) low cost due to 100% silicon IC compatibility, (3) high image quality and increased yield due to ability to do offset and sensitivity corrections on the imager, pixel-by-pixel; (4) no cryogenic cooler and no high vacuum processing; and (5) commercial applications such as law enforcement, home security, and transportation safety. Two designs are presented. One is a 50 micrometer pixel using silicon nitride as the thermal isolation element that can achieve 5 mK NE(Delta) T; the other is a 29 micrometer pixel using silicon carbide that provides much higher thermal isolation and can achieve 10 mK NE(Delta) T.

Pharmacokinetic and pharmacodynamic interaction between the lipoxygenase inhibitor MK-0591 and the cyclooxygenase inhibitor ibuprofen in man.

PubMed

Depré, M; Van Hecken, A; Verbesselt, R; De Lepeleire, I; Schwartz, J; Porras, A; Larson, P; Lin, C; De Schepper, P J

1998-01-01

Twelve healthy male subjects participated in a double-blind, placebo-controlled, randomized, three-period, crossover study to investigate the safety, tolerability, biochemical activity and pharmacokinetics of ibuprofen, a cyclooxygenase inhibitor and MK-0591, a 5-lipoxygenase inhibitor, given as single entities and in combination. Each subject received for three consecutive 8-day periods, separated by 1 week washout, each of the following treatments: ibuprofen 600 mg three times a day with 125 mg MK-0591 twice a day, ibuprofen 600 mg three times a day with placebo for MK-0591 and MK-0591 125 mg twice a day with placebo for ibuprofen. Cyclooxygenase inhibition was measured by platelet thromboxane (TxB2) generation test, and 5-lipoxygenase inhibition was measured by urinary leukotriene E4 excretion and ex vivo LTB4 generation in calcium-ionophore-stimulated blood. TxB2 suppression on day 8 by ibuprofen was not affected by concomitant treatment with MK-0591. MK-0591 alone had no effect on TxB2 generation. Leukotriene biosynthesis was inhibited by more than 90% by MK-0591 alone and by combined treatment, while ibuprofen alone had no effect. Coadministration appears to affect the pharmacokinetics of MK-0591 (decrease of area under the plasma concentration-vs-time curve [AUC] and maximum plasma concentrations [Cmax]) and of ibuprofen (increase of AUC and half-lives of elimination (t1/2) of the (S)-enantiomer, increase of t1/2 the (R)-enantiomer). Combined treatment had no effect on creatinine clearance nor on the number and intensity of the reported adverse experiences.

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

PubMed

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 (P<0.001 and P=0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social 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.

Development and Evaluation of a Monte Carlo Code System for Analysis of Ionization Chamber Responses,

DTIC Science & Technology

1987-07-01

ft. ft 3 ORNL/TM- 10196 INTERNAL DISTRIBUTION 1. F. S. Alsmiller 32. R. T. Santoro 2. R. G. Alsmiller, Jr. 33. M. S. Smith 3. D. E. Bartine 34. J. S...W. Armstrong, Science Applications, Inc., P.O. Box 2807, La Jolla, CA 92038. 57. Miguel Awschalom, National Accelerator Laboratory, P. 0. Box 500

Benzothiophene inhibitors of MK2. Part 2: Improvements in kinase selectivity and cell potency

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, David R.; Meyers, Marvin J.; Kurumbail, Ravi G.

2010-10-01

Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

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

PubMed

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 < 0.05. A significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. 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.

Material properties of perovskites in the quasi-ternary system LaFeO3-LaCoO3-LaNiO3

NASA Astrophysics Data System (ADS)

Tietz, F.; Arul Raj, I.; Ma, Q.; Baumann, S.; Mahmoud, A.; Hermann, R. P.

2016-05-01

An overview is presented on the variation of electrical conductivity, oxygen permeation, and thermal expansion coefficient as a function of the composition of perovskites in the quasi-ternary system LaFeO3-LaCoO3-LaNiO3. Powders of thirteen nominal perovskite compositions were synthesized under identical conditions by the Pechini method. The powder X-ray diffraction data of two series, namely La(Ni0.5Fe0.5)1-xCoxO3 and LaNi0.5-xFexCo0.5O3, are presented after the powders had been sintered at 1100 °C for 6 h in air. The measurements revealed a rhombohedral structure for all compositions except LaNi0.5Fe0.5O3 for which 60% rhombohedral and 40% orthorhombic phase was found. The maximum DC electrical conductivity value of the perovskites at 800 °C was 1229 S cm-1 for the composition LaCoO3 and the minimum was 91 S cm-1 for the composition LaCo0.5Fe0.5O3. The oxygen permeation of samples with promising conductivities at 800 °C was one order of magnitude lower than that of La0.6Sr0.4Co0.8Fe0.2O3 (LSCF). The highest value of 0.017 ml cm-2 min-1 at 950 °C was obtained with LaNi0.5Co0.5O3. The coefficients of thermal expansion varied in the range of 13.2×10-6 K-1 and 21.9×10-6 K-1 for LaNi0.5Fe0.5O3 and LaCoO3, respectively. 57Fe Mössbauer spectroscopy was used as probe for the oxidation states, local environment and magnetic properties of iron ions as a function of chemical composition. The substitution had a great influence on the chemical properties of the materials.

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

PubMed Central

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

Intra-Accumbens Injection of a Dopamine Aptamer Abates MK-801-Induced Cognitive Dysfunction in a Model of Schizophrenia

PubMed Central

Holahan, Matthew R.; Madularu, Dan; McConnell, Erin M.; Walsh, Ryan; DeRosa, Maria C.

2011-01-01

Systemic administration of the noncompetitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. The present work investigated the ability of a dopamine-binding DNA aptamer to regulate these MK-801-induced cognitive deficits when injected into the nucleus accumbens. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar pressing response. Two control groups were also included that did not receive MK-801. Data revealed that injection of Tris buffer or the random oligonucleotide sequence into the nucleus accumbens prior to treatment with MK-801 did not reduce the MK-801-induced extinction deficit. Animals continued to press at a high rate over the entire course of the extinction session. Injection of the dopamine aptamer reversed this MK-801-induced elevation in lever pressing to levels as seen in rats not treated with MK-801. Tests for activity showed that the aptamer did not impair locomotor activity. Results demonstrate the in vivo utility of DNA aptamers as tools to investigate neurobiological processes in preclinical animal models of mental health disease. PMID:21779401

Quantifying the electronic reconstruction in LaTiO3/LaNiO3/(LaAlO3)3 heterostructures using RIXS

NASA Astrophysics Data System (ADS)

Fabbris, Gilberto; Disa, Ankit S.; Ismail-Beigi, Sohab; Walker, Frederick J.; Ahn, Charles H.; Pelliciari, Jonathan; Huang, Yaobo; Schmitt, Thorsten; Xu, Lei; Hozoi, Liviu; van den Brink, Jeroen; Dean, Mark

A novel approach for manipulating the 3d state in transition metal oxide heterostructures has emerged with the growth of trilayer nickelate LaTiO3/LaNiO3/(LaAlO3)3 (LTNAO). This heterostructure induces a striking reconstruction of the LaNiO3 electronic structure, which is due to a combination of charge transfer from Ti's 3d state and octahedral elongation along the c axis. We use resonant inelastic x-ray scattering (RIXS) experiments at Ni L2,3 and O K edges to spectroscopically resolve the LTNAO electronic structure. Surprisingly, our results show that the octahedral elongation generates minor changes in crystal fields at Ni's 3d state compared to bulk LaNiO3. Instead, heterostructuring creates an anisotropic reconstruction of the Ni 3d - O 2p hybridization. The x2-y2 orbital is significantly more hybridized with O p, leading to a 3z2-r2/x2-y2 hole ratio of ~0.55 and large orbital polarization as measured by x-ray absorption spectroscopy. This work establishes RIXS as an ultra-sensitive probe of complex oxide heterostructures. Work at BNL was supported by the US Department of Energy under Award No DEAC02-98CH10886 and under Early Career Award No 20878.

Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment.

PubMed

Lins, Brittney R; Phillips, Anthony G; Howland, John G

2015-12-01

New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder. The objective of the present studies was to test the effects of the D- and L-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats. We also assessed effects of the typical antipsychotic haloperidol as a comparator compound. MK-801 (0.05, 0.1, 0.15, and 0.2 mg/kg), D- and L-govadine (0.3, 1.0, and 3.0 mg/kg), and haloperidol (0.05, 0.1, and 0.25 mg/kg) were administered acutely to rats well trained on the PAL task in touchscreen-equipped operant conditioning chambers. Acute MK-801 impaired performance of PAL in a dose-dependent manner by reducing accuracy and increasing correction trials. L-Govadine (1.0 mg/kg), but not D-govadine, blocked the disruptive effects of MK-801 (0.15 mg/kg) on PAL. Haloperidol failed to affect the MK-801-induced disruption of PAL. Higher doses of L-govadine and haloperidol dramatically impaired performance of the task which confounded interpretation of cognitive outcomes. L-Govadine appears unique in its ability to improve performance of the MK-801-induced impairment in the PAL task. This behavioral effect may relate the ability of L-govadine to antagonize dopamine D2 receptors while also promoting dopamine efflux. Future research should further characterize the role of the dopamine system in the rodent PAL task to elucidate the mechanisms of its pro-cognitive effects.

A multiple drug fatality involving MK-801 (dizocilpine), a mimic of phencyclidine.

PubMed

Mozayani, Ashraf; Schrode, Paul; Carter, Joye; Danielson, Terry J

2003-04-23

MK-801 (dizocilpine) is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) family of glutamate receptors in the central nervous system. It is an anticonvulsant and also shares several pharmacological properties with phencyclidine and ketamine. It is not observed routinely as a substance of abuse. The deceased, a 45-year-old white male, obtained MK-801 surreptitiously in an attempt to treat a self-diagnosed depression. He was discovered the next morning, unresponsive on the bathroom floor. An empty bottle, labeled to contain 25mg of MK-801, was found near the body. The autopsy was performed at the Joseph A Jachimczyk Forensic Center, Houston, TX. Body weight at autopsy was 88kg. Lungs were edematous and congested (right: 775g; left 700g). The heart had proportionate chambers and was otherwise unremarkable. The kidneys (right: 220g; left 225g) were smooth surfaced. The brain (1550g) was congested and without trauma. Microscopic evaluation of the heart, kidneys and lungs showed normal histology and confirmed pulmonary congestion and edema. Samples of heart blood, liver, bile, vitreous humor, stomach contents and urine were collected at autopsy. There were 550ml of stomach contents. Drugs in blood were screened by EMIT II Plus immunoassay procedures and by gas chromatography/mass spectrometry (GC/MS) of an organic solvent extract of basified blood. Alcohol was determined by gas chromatography with headspace injection. MK-801, benzodiazepines and alcohol were detected in blood. Amounts of MK-801 present in blood, bile, liver, vitreous humor and urine were 0.15, 0.29, 0.92, less than 0.1 and 0.36 mg/l (kg), respectively. The cause of death was benzodiazepine, dizocilpine and ethanol toxicity and the manner accidental.

Assay development and case history of a 32K-biased library high-content MK2-EGFP translocation screen to identify p38 mitogen-activated protein kinase inhibitors on the ArrayScan 3.1 imaging platform.

PubMed

Trask, Oscar J; Baker, Audrey; Williams, Rhonda Gates; Nickischer, Debra; Kandasamy, Ramani; Laethem, Carmen; Johnston, Patricia A; Johnston, Paul A

2006-01-01

This chapter describes the conversion and assay development of a 96-well MK2-EGFP translocation assay into a higher density 384-well format high-content assay to be screened on the ArrayScan 3.1 imaging platform. The assay takes advantage of the well-substantiated hypothesis that mitogen-activated protein kinase-activating protein kinase-2 (MK2) is a substrate of p38 MAPK kinase and that p38-induced phosphorylation of MK-2 induces a nucleus-to-cytoplasm translocation. This chapter also presents a case history of the performance of the MK2-EGFP translocation assay, run as a "high-content" screen of a 32K kinase-biased library to identify p38 inhibitors. The assay performed very well and a number of putative p38 inhibitor hits were identified. Through the use of multiparameter data provided by the nuclear translocation algorithm and by checking images, a number of compounds were identified that were potential artifacts due to interference with the imaging format. These included fluorescent compounds, or compounds that dramatically reduced cell numbers due to cytotoxicity or by disrupting cell adherence. A total of 145 compounds produced IC(50) values <50.0 muM in the MK2-EGFP translocation assay, and a cross target query of the Lilly-RTP HTS database confirmed their inhibitory activity against in vitro kinase targets, including p38a. Compounds were confirmed structurally by LCMS analysis and profiled in cell-based imaging assays for MAPK signaling pathway selectivity. Three of the hit scaffolds identified in the MK2-EGFP translocation HCS run on the ArrayScan were selected for a p38a inhibitor hit-to-lead structure activity relationship (SAR) chemistry effort.

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

PubMed Central

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

Cannabidiol Affects MK-801-Induced Changes in the PPI Learned Response of Capuchin Monkeys (Sapajus spp.).

PubMed

Saletti, Patricia G; Maior, Rafael S; Barros, Marilia; Nishijo, Hisao; Tomaz, Carlos

2017-01-01

There are several lines of evidence indicating a possible therapeutic action of cannabidiol (CBD) in schizophrenia treatment. Studies with rodents have demonstrated that CBD reverses MK-801 effects in prepulse inhibition (PPI) disruption, which may indicate that CBD acts by improving sensorimotor gating deficits. In the present study, we investigated the effects of CBD on a PPI learned response of capuchin monkeys ( Sapajus spp.). A total of seven monkeys were employed in this study. In Experiment 1, we evaluated the CBD (doses of 15, 30, 60 mg/kg, i.p.) effects on PPI. In Experiment 2, the effects of sub-chronic MK-801 (0.02 mg/kg, i.m.) on PPI were challenged by a CBD pre-treatment. No changes in PPI response were observed after CBD-alone administration. However, MK-801 increased the PPI response of our animals. CBD pre-treatment blocked the PPI increase induced by MK-801. Our findings suggest that CBD's reversal of the MK-801 effects on PPI is unlikely to stem from a direct involvement on sensorimotor mechanisms, but may possibly reflect its anxiolytic properties.

Introduction to D-He(3) fusion reactors

NASA Technical Reports Server (NTRS)

Vlases, G. C.; Steinhauer, L. C.

1989-01-01

A review and evaluation of D-He(3) fusion reactor technology is presented. The advantages and disadvantages of the D-He(3) and D-T reactor cycles are outlined and compared. In addition, the general design features of D-He(3) tokamaks and field reversed configuration (FRC) reactors are described and the relative merits of each are compared. It is concluded that both tokamaks and FRC's offer certain advantages, and that the ultimate decision as to which to persue for terrestrial power generation will depend heavily on how the physics performance of each of them develops over the next few years. It is clear that the D-He(3) fuel cycle offers marked advantages over the D-T cycle. Although the physics requirements for D-He(3) are more demanding, the overwhelming advantages resulting from the two order of magnitude reduction of neutron flux are expected to lead to a shorter time to commercialization than for the D-T cycle.

Introduction to D-He(3) fusion reactors

NASA Astrophysics Data System (ADS)

Vlases, G. C.; Steinhauer, L. C.

1989-07-01

A review and evaluation of D-He(3) fusion reactor technology is presented. The advantages and disadvantages of the D-He(3) and D-T reactor cycles are outlined and compared. In addition, the general design features of D-He(3) tokamaks and field reversed configuration (FRC) reactors are described and the relative merits of each are compared. It is concluded that both tokamaks and FRC's offer certain advantages, and that the ultimate decision as to which to persue for terrestrial power generation will depend heavily on how the physics performance of each of them develops over the next few years. It is clear that the D-He(3) fuel cycle offers marked advantages over the D-T cycle. Although the physics requirements for D-He(3) are more demanding, the overwhelming advantages resulting from the two order of magnitude reduction of neutron flux are expected to lead to a shorter time to commercialization than for the D-T cycle.

Dissociable effects of the noncompetitive NMDA receptor antagonists ketamine and MK-801 on intracranial self-stimulation in rats

PubMed Central

Hillhouse, Todd M.; Porter, Joseph H.; Negus, S. Stevens

2014-01-01

Rationale The noncompetitive NMDA antagonist ketamine produces rapid antidepressant effects in treatment-resistant patients suffering from major depressive and bipolar disorders. However, abuse liability is a concern. Objectives This study examined abuse-related effects of keta-mine using intracranial self-stimulation (ICSS) in rats. The higher-affinity NMDA antagonist MK-801 and the monoamine reuptake inhibitor cocaine were examined for comparison. Methods Male Sprague Dawley rats were implanted with electrodes targeting the medial forebrain bundle and trained to respond to brain stimulation under a frequency–rate ICSS procedure. The first experiment compared the potency and time course of ketamine (3.2–10.0 mg/kg) and MK-801 (0.032–0.32 mg/kg). The second experiment examined effects of repeated dosing with ketamine (3.2–20.0 mg/kg/day) and acute cocaine (10.0 mg/kg). Results Following acute administration, ketamine (3.2–10 mg/kg) produced only dose- and time-dependent depressions of ICSS and failed to produce an abuse-related facilitation of ICSS at any dose or pretreatment time. In contrast, MK-801 (0.032–0.32 mg/kg) produced a mixed profile of rate-increasing and rate-decreasing effects; ICSS facilitation was especially prominent at an intermediate dose of 0.18 mg/kg. Repeated dosing with ketamine produced dose-dependent tolerance to the rate-decreasing effects of ketamine (10.0 and 18.0 mg/kg) but failed to unmask expression of ICSS facilitation. Termination of ketamine treatment failed to produce withdrawal-associated decreases in ICSS. As reported previously, 10.0 mg/kg cocaine facilitated ICSS. Conclusions The dissociable effects of ketamine and MK-801 suggest differences in the pharmacology of these nominally similar NMDA antagonists. Failure of ketamine to facilitate ICSS contrasts with other evidence for the abuse liability of ketamine. PMID:24522331

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.

PubMed

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.

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

DTIC Science & Technology

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurumaji, A.; McCulloch, J.

1989-12-01

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 inmore » 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.« less

Integrating Marine Observatories into a System-of-Systems: Messaging in the US Ocean Observatories Initiative

DTIC Science & Technology

2010-06-01

Woods Hole, MA 02543, USA 3 Raytheon Intelligence and Information Systems, Aurora , CO 80011, USA 4 Scripps Institution of Oceanography, La Jolla...Amazon.com, Amazon Web Services for the Amazon Elastic Compute Cloud ( Amazon EC2). http://aws.amazon.com/ec2/. [4] M. Arrott, B. Demchak, V. Ermagan, C

Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice.

PubMed

Melo-Thomas, L; Gil-Martínez, A L; Cuenca, L; Estrada, C; Gonzalez-Cuello, A; Schwarting, R K; Herrero, M T

2018-03-01

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment. Copyright © 2018 Elsevier B.V. All rights reserved.

MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex.

PubMed

Cui, Xiaoying; Lefevre, Emilia; Turner, Karly M; Coelho, Carlos M; Alexander, Suzy; Burne, Thomas H J; Eyles, Darryl W

2015-02-01

Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists. The aims of the present study were twofold, firstly to examine whether a single dose of dizocilpine maleate (MK-801) could induce long-term behavioural sensitisation and secondly to examine DA release in the PFC of sensitised rats. Behavioural sensitisation was assessed by measuring locomotion after drug exposure. DA release in the PFC was measured using freely moving microdialysis. We show that a single dose of MK-801 can induce sensitisation to subsequent MK-801 exposure in a high percentage of rats (66 %). Furthermore, rats sensitised to MK-801 have altered DA release and turnover in the PFC compared with non-sensitised rats. Schizophrenia patients have been postulated to have 'endogenous sensitisation' to psychostimulants. MK-801-induced sensitised rats, in particular when compared with non-sensitised rats, provide a useful model for studying PFC dysfunction in schizophrenia.

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

PubMed Central

Bagley, Mark C.; Baashen, Mohammed; Chuckowree, Irina; Dwyer, Jessica E.; Kipling, David; Davis, Terence

2015-01-01

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. PMID:26046488

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

PubMed

Bagley, Mark C; Baashen, Mohammed; Chuckowree, Irina; Dwyer, Jessica E; Kipling, David; Davis, Terence

2015-06-03

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.

Digitized neutron imaging with high spatial resolution at a low power research reactor: I. Analysis of detector performance

NASA Astrophysics Data System (ADS)

Zawisky, M.; Hameed, F.; Dyrnjaja, E.; Springer, J.

2008-03-01

Imaging techniques provide an indispensable tool for investigation of materials. Neutrons, due to their specific properties, offer a unique probe for many aspects of condensed matter. Neutron imaging techniques present a challenging experimental task, especially at a low power research reactor. The Atomic Institute with a 250 kW TRIGA MARK II reactor looks back at a long tradition in neutron imaging. Here we report on the advantages gained in a recent upgrade of the imaging instrument including the acquisition of a thin-plate scintillation detector, a single counting micro-channel plate detector, and an imaging plate detector in combination with a high resolution scanner. We analyze the strengths and limitations of each detector in the field of neutron radiography and tomography, and demonstrate that high resolution digitized imaging down to the 50 μm scale can be accomplished with weak beam intensities of 1.3×10 5 n/cm 2 s, if appropriate measures are taken for the inevitable extension of measurement times. In a separate paper we will present some promising first results from the fields of engineering and geology.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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

Material properties of perovskites in the quasi-ternary system LaFeO 3–LaCoO 3–LaNiO 3

DOE PAGES

Tietz, F.; Arul Raj, I.; Ma, Q.; ...

2016-02-02

We present an overview on the variation of electrical conductivity, oxygen permeation, oxygen surface exchange and thermal expansion coefficient as a function of the composition of perovskites in the quasi-ternary system LaFeO 3–LaCoO 3–LaNiO 3. Powders of thirteen nominal perovskite compositions were synthesized under identical conditions by the Pechini method. The powder X-ray diffraction data of two series, namely La(Ni 0.5Fe 0.5) 1-xCo xO 3 and LaNi 0.5- xFe xCo 0.5O 3, are presented after the powders had been sintered at 1100 C for 6 h in air. The measurements revealed a rhombohedral structure for all compositions except LaNi 0.5Femore » 0.5O 3 for which 60% rhombohedral and 40% orthorhombic phase was found. Moreover, the maximum DC electrical conductivity value of the perovskites at 800 C was 1229 S cm-1 for the composition LaCoO 3 and the minimum was 91 S cm-1 for the composition LaCo 0.5Fe 0.5O 3. The oxygen permeation of samples with promising conductivities at 800 C was one order of magnitude lower than that of La 0.6Sr 0.4Co 0.8Fe 0.2O 3 (LSCF). The highest value of 0.017 ml cm -2 min-1 at 950 C was obtained with LaNi 0.5Co 0.5O 3. The coefficients of thermal expansion varied in the range of 13.2 x 10 -6 K -1 and 21.9 x 10 -6 K -1 for LaNi 0.5Fe 0.5O 3 and LaCoO 3, respectively. 57Fe M ssbauer spectroscopy was used as probe for the oxidation states, local environment and magnetic properties of iron ions as a function of chemical composition. Ultimately, the substitution had a great influence on the chemical properties of the materials.« less

Enhanced photocatalytic hydrogen production from water-ethanol solution by Ruthenium doped La-NaTaO3

NASA Astrophysics Data System (ADS)

Husin, H.; Alam, P. N.; Zaki, M.; Sofyana; Jakfar; Husaini; Hasfita, F.

2018-04-01

The photocatalytic hydrogen production from ethanol aqueous solution, with the use ruthenium doped La-NaTaO3 has been investigated. Ruthenium doped La-NaTaO3 catalysts are prepared by impregnation method. The catalysts are by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The Ru co-catalyst demonstrated from the TEM image shows a good dispersion on the surface of La-C-NaTaO3 with an average particle size between 4-5 nm. The photocatalytic reaction is carried out in a closed reactor with a gas circulation system. The catalytic activity of La-NaTaO3 improved markedly (6.6 times from pure water) when Ru is loaded onto its surface. The hydrogen production is notably enhanced in the presence of ethanol as electron donors. This result is much higher when compared with the rate of hydrogen production in the sample without co- catalysts about 9.4 times higher after Ru deposition from ethanol aqueous solution. Increasing the production of hydrogen on the Ru/La-NaTaO3 closely related to the decrease in recombination between electron-hole pairs.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Sharon M.; Patton, Bradley D.

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 ofmore » 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.« less

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

PubMed

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.

The Modeling of Drop-Containing Turbulent Eddies

DTIC Science & Technology

1989-11-01

gouttes denses. tandis que la twile do la grappe n’est pas un facteur limitant pour Ies grappes dilubes. On discuto des implications pratiques de ces...Conference, La Jolla, CA, July 9-12, 1989 VIII. SCIENTIFIC PERSONNEL SUPPORTED BY THE PROJECT AND DEGREES AWARDED DURING THE CONTRACT PERIOD. J. Bellan K. G...V + r )t(A1. 3) 4rd y, (t) = d Setting ’T - , = const in (A1. la ) and assuming that Yv <<l we find the equation for the wall Ywa d boundary, 37 Y =Y.Ua

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

PubMed Central

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

[Vitamin K metabolism. Menaquinone-4 (MK-4) formation from ingested VK analogues and its potent relation to bone function].

PubMed

Komai, Michio; Shirakawa, Hitoshi

2007-11-01

Phylloquinone (vitamin K(1) = VK(1)) and the menaquinones (MK-n, or vitamin K(2) = VK(2)) are naturally occurring forms of VK. Most of the menaquinone series are synthesized by microorganisms, but we have reported that MK-4 is usual in being synthesized by the conversion of orally ingested VK(1) or MK-n in the major tissues of germfree rats and mice which lack their intestinal microflora. This result led us to deny 1960's Martius' hypothesis that described the participation of bacterial enzyme of the intestinal flora to this conversion. VK acts as a cofactor in the posttranslational synthesis of gamma-carboxyglutamic acid (Gla) from glutamic acid (Glu) residues in the nascent Gla-protein molecule. Therefore, VK is essential for blood coagulation (various clotting factors) and bone structure (as osteocalcin [OC = BGP] and matrix Gla-protein [MGP] in mammals. In addition to the liver, VK is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4, and it has been reported that MK-4 itself has specific biological activities in these tissues beside Gla-protein formation. However, the physiological role of MK-4 in these organs has not been fully understood yet. Recently MK-4 has been attracted the attention of researchers due to its activities such as apoptotic activity on the osteoclast cells and leukemia cells, SXR/PXR ligand, and so on. We further review the potent important physiological role of MK-4 in the bone as well as other major tissues.

Pebble Bed Reactors Design Optimization Methods and their Application to the Pebble Bed Fluoride Salt Cooled High Temperature Reactor (PB-FHR)

NASA Astrophysics Data System (ADS)

Cisneros, Anselmo Tomas, Jr.

The Fluoride salt cooled High temperature Reactor (FHR) is a class of advanced nuclear reactors that combine the robust coated particle fuel form from high temperature gas cooled reactors, direct reactor auxillary cooling system (DRACS) passive decay removal of liquid metal fast reactors, and the transparent, high volumetric heat capacitance liquid fluoride salt working fluids---flibe (33%7Li2F-67%BeF)---from molten salt reactors. This combination of fuel and coolant enables FHRs to operate in a high-temperature low-pressure design space that has beneficial safety and economic implications. In 2012, UC Berkeley was charged with developing a pre-conceptual design of a commercial prototype FHR---the Pebble Bed- Fluoride Salt Cooled High Temperature Reactor (PB-FHR)---as part of the Nuclear Energy University Programs' (NEUP) integrated research project. The Mark 1 design of the PB-FHR (Mk1 PB-FHR) is 236 MWt flibe cooled pebble bed nuclear heat source that drives an open-air Brayton combine-cycle power conversion system. The PB-FHR's pebble bed consists of a 19.8% enriched uranium fuel core surrounded by an inert graphite pebble reflector that shields the outer solid graphite reflector, core barrel and reactor vessel. The fuel reaches an average burnup of 178000 MWt-d/MT. The Mk1 PB-FHR exhibits strong negative temperature reactivity feedback from the fuel, graphite moderator and the flibe coolant but a small positive temperature reactivity feedback of the inner reflector and from the outer graphite pebble reflector. A novel neutronics and depletion methodology---the multiple burnup state methodology was developed for an accurate and efficient search for the equilibrium composition of an arbitrary continuously refueled pebble bed reactor core. The Burnup Equilibrium Analysis Utility (BEAU) computer program was developed to implement this methodology. BEAU was successfully benchmarked against published results generated with existing equilibrium depletion codes VSOP

Therapeutic effect of the NMDA antagonist MK-801 on low-level laser induced retinal injury

NASA Astrophysics Data System (ADS)

Yan, W.-H.; Wu, J.; Chen, P.; Dou, J.-T.; Pan, C.-Y.; Mu, Y.-M.; Lu, J.-M.

2009-03-01

The aim of this article was to explore the mechanism of injury in rat retina after constant low-level helium-neon (He-Ne) laser exposure and therapeutic effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on laser-induced retinal injury. He-Ne laser lesions were created in the central retina of adult Wistar Kyoto rats and were followed immediately by intraperitoneal injection of MK-801 (2 mg/kg) or saline, macroscopical and microscopical lesion were observed by funduscope and light microscope. Ultrastructural changes of the degenerating cells were examined by electron microscopy. Photoreceptor apoptosis was evaluated by TdT-mediated dUTP nick end-labeling (TUNEL). mRNA levels were measured by in situ hybridization and NMDA receptor expression was determined by immunohistochemistry. Laser induced damage was histologically quantified by image-analysis morphometry. Electroretinograms (ERGs) were recorded at different time point after the cessation of exposure to constant irradiation. There was no visible bleeding, exudation or necrosis under funduscope. TUNEL and electron microscopy showed photoreceptor apoptosis after irradiation. MK-801-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after exposure to laser. In situ hybridization (ISH) showed that the NMDAR mRNA level of MK-801-treated rats decreased in the inner plexiform layer 6 h after the cessation of exposure to constant irradiation when compared with that of saline-treated rats. So did Immunohistochemistry (IHC). Electroretinogram showed that b-wave amplitudes of MK-801-treated group were higher than that of saline-treated group after laser exposure. These findings suggest that Low level laser may cause the retinal pathological changes under given conditions. High expression of NMDAR is one of the possible mechanisms causing experimental retinal laser injury of rats. MK-801 exhibits the therapeutic effect due to promote the

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1990-02-01

The phencyclidine analogue ({sup 3}H)(1-(2-thienyl)cyclohexyl)piperidine ({sup 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 {sup 3}H-TCP binding in brain closely parallels that of ({sup 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 {sup 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 themore » 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 {sup 3}H-TCP binding in hypoxic-ischemic brain was relatively preserved and there were no interhemispheric asymmetries in {sup 3}H-TCP binding densities. In addition, in three unoperated rats decapitated 24 hours after MK-801 treatment, {sup 3}H-TCP binding was reduced by 15-35%; similar bilateral suppression of {sup 3}H-TCP binding was detected in MK-801-treated ligates. Our data indicate that {sup 3}H-TCP autoradiography can be used to assay the efficacy of neuroprotective agents in this experimental model of perinatal stroke.« less

Application of Regional Arrays in Seismic Verification Research

DTIC Science & Technology

1990-08-31

Hill, MA 02167 P.O. Box 1620 La Jolla, CA 92038-1620 Dr. Richard LaCoss Prof. William Menke MIT-Lincoln Laboratory L amront-Doherty -- dogical b ser t...LWH of Columbia University Hanscom AFB, MA 01731-5000 Palisades, NY 10964 3 Dr. Lorraine Wolf GLILWH Hanscom AFB, MA 01731-5000 Dr. William Wortman... William J. Best Prof. Robert W. Clayton 907 Westwood Drive Seismological Laboratory Vienna, VA 22180 Division of Geological & Planetary Sciences

Effects of cholinergic system of dorsal hippocampus of rats on MK-801 induced anxiolytic-like behavior.

PubMed

Zarrindast, Mohammad Reza; Nasehi, Mohammad; Piri, Morteza; Heidari, Negar

2011-11-14

Some investigations have shown that the glutamate receptors play a critical role in cognitive processes such as learning and anxiety. The possible involvement of the cholinergic system of the dorsal hippocampus in the anxiolytic-like response induced by MK-801, NMDA receptor antagonist, was investigated in the present study. Male Wistar rats were used in the elevated plus maze apparatus to test the parameters: open arm time (%OAT), open arm entries (%OAE), close arm time (%CAT), close arm entries (%CAE) and other exploratory behaviors (locomotor activity, grooming, rearing and defecation) of anxiety-like response. The data indicated that intra-CA1 administration of MK-801 increased %OAT (2μg/rat) and %OAE (1 and 2μg/rat) while decreased %CAT and %CAE and did not alter other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, intra-hippocampal injections of mecamylamine, a cholinergic receptor antagonists (2μg/rat) and scopolamine (4μg/rat), by themselves, 5min before testing, increased %OAT and %OAE but decreased %CAT and %CAE and did not alter locomotor activity and other exploratory behaviors, suggesting an anxiolytic-like effect. On the other hand, intra-CA1 co-administration of an ineffective dose of scopolamine (3μg/rat), but not mecamylamine (1μg/rat), with an ineffective dose of MK-801 (0.5μg/rat) increased %OAT and %OAE and decreased %CAT and %CAE. The data may indicate the possible involvement of the cholinergic system of the CA1 in the anxiolytic-like response induced by MK-801. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

78 FR 14352 - Notice of Approved Class III Tribal Gaming Ordinances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... Rancheria of California 20. Bois Forte Band of the Minnesota Chippewa Tribe 21. Buena Vista Rancheria of Me... Chippewa Indians 116. LaJolla Band of Luiseno Indians 117. La Posta Band of Mission Indians 118. Las Vegas...

MK-801 reduces sensitivity to Müller-Lyer's illusion in capuchin monkeys.

PubMed

Jacobsen, M E; Barros, M; Maior, R S

2017-01-01

The Müller-Lyer's illusion (MLI) is a visual illusion in which the presence of contextual cues (i.e., the orientation of arrowheads) changes the perception of the length of straight lines. An altered sensitivity to the MLI has been proposed as a marker for the progression of perceptual deficits in schizophrenia. Since dizocilpine (MK-801), a noncompetitive antagonist of the NMDA glutamate receptor, induces schizophrenic-like sensory impairments, it may have potential value for investigating the neurochemical basis of the perceptual changes in schizophrenia. Here we tested the effects of MK-801 on the perception of the MLI in a nonhuman primate. Five capuchin monkeys Sapajus spp. were trained on a MLI task using a touch screen monitor. After training, the Point of Subjective Equality (PSE; i.e., the minimum difference in length between two lines which the subject can distinguish) was determined for each subject. Then, during 12 consecutive days, we evaluated changes in PSE in response to vehicle, MK-801 (5.6μg/kg, i.m.) and a no-treatment protocol (post- test). Each of these was given as a single daily treatment, on four consecutive days. Results showed that MK-801 increased the monkeys' performance in the MLI task, suggesting that NMDA receptor modulation reduces sensitivity to this illusion, similar to prodromal stage in schizophrenia patients. The MLI protocol may thus be used in nonhuman primates to screen potential antipsychotic drugs for early stages of this disease. Copyright © 2016 Elsevier B.V. All rights reserved.

A simple and quantitative liquid culture system to measure megakaryocyte growth using highly purified CFU-MK.

PubMed

Miyazaki, H; Horie, K; Shimada, Y; Kokubo, A; Maeda, E; Inoue, H; Kato, T

1995-10-01

A new and quantitative liquid culture system has been developed to measure the production of megakaryocytes from megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]). The system uses as a target population a glycoprotein (Gp) IIb/IIIa+ subpopulation of rat bone marrow cells previously demonstrated to be highly enriched for CFU-MK. GpIIb/IIIa+ cells were cultured at 5 x 10(4) cells/mL (10(4) cells/well) with test samples in 96-well tissue culture plates for 4 days at 37 degrees C. During the final 3 hours of incubation, the cells were pulsed with [14C]5-hydroxytryptamine creatinine sulfate (14C-serotonin). After incubation, the plates were washed and the cell pellets were lysed with Triton-X 100. The cell lysate was infiltrated into a commercially available solid scintillator and dried, and radioactivity was measured. In this assay system, rat interleukin-3 (IL-3) was found to be the most potent among known cytokines tested. Murine granulocyte-macrophage colony-stimulating factor (GM-CSF), human erythropoietin (Epo), human IL-6, and murine stem cell factor (SCF) each alone stimulated megakaryocyte growth but were much less active than rat IL-3. Plasma of rats rendered thrombocytopenic by injection of monoclonal antirat platelet GpIIb/IIIa antibody exhibited significant activity, and the active protein fractions partially purified from the plasma showed much higher activity, but normal rat plasma had no effect. This liquid culture system allows the measurement of a large number of test samples--including a wide variety of cytokines and unknown growth factors, alone or in combinations--and provides a simple method for evaluating the early proliferative events involving CFU-MK in the megakaryocyte differentiation pathway.

Neutron and electron diffraction studies of La(Zn1/2Ti1/2)O3 perovskite.

PubMed

Ubic, Rick; Hu, Yi; Abrahams, Isaac

2006-08-01

The crystallography and microwave dielectric properties of La(Zn(1/2)Ti(1/2))O(3) (LZT) ceramics prepared via the mixed-oxide route were investigated in this study. While samples were largely single phase, small amounts of ZnO impurity were detected in sintered pellets. Observed reflections in electron and neutron diffraction patterns indicate that the symmetry of LZT is P2(1)/n. The B site is ordered on {110} or pseudocubic {111}, but the presence of the pseudocubic 1/2(111) reflection is in itself insufficient to indicate the existence of such order. Rietveld refinements of the neutron diffraction data yield an excellent fit for such a model. The structure is highly twinned, with variants related through common {211} composition planes and 90 degrees rotations about <011>. The microwave dielectric properties measured were epsilon(r) = 34, Qf = 36,090 and tau(f) = -70 MK(-1).

FRASS: the web-server for RNA structural comparison

PubMed Central

2010-01-01

Background The impressive increase of novel RNA structures, during the past few years, demands automated methods for structure comparison. While many algorithms handle only small motifs, few techniques, developed in recent years, (ARTS, DIAL, SARA, SARSA, and LaJolla) are available for the structural comparison of large and intact RNA molecules. Results The FRASS web-server represents a RNA chain with its Gauss integrals and allows one to compare structures of RNA chains and to find similar entries in a database derived from the Protein Data Bank. We observed that FRASS scores correlate well with the ARTS and LaJolla similarity scores. Moreover, the-web server can also reproduce satisfactorily the DARTS classification of RNA 3D structures and the classification of the SCOR functions that was obtained by the SARA method. Conclusions The FRASS web-server can be easily used to detect relationships among RNA molecules and to scan efficiently the rapidly enlarging structural databases. PMID:20553602

76 FR 62839 - Notice of Inventory Completion: University of Colorado Museum, Boulder, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-11

...; Bridgeport Paiute Indian Colony of California; Buena Vista Rancheria of Me-Wuk Indians of California; Burns... Indians of the Stewarts Point Rancheria, California; Klamath Tribes, Oregon; La Jolla Band of Luiseno Indians, California; La Posta Band of Diegueno Mission Indians of the La Posta Indian Reservation...

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

NASA Astrophysics Data System (ADS)

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.

Dissociable effects of the d- and l- enantiomers of govadine on the disruption of prepulse inhibition by MK-801 and apomorphine in male Long-Evans rats.

PubMed

Lins, Brittney R; Marks, Wendie N; Phillips, Anthony G; Howland, John G

2017-04-01

The search for novel antipsychotic drugs to treat schizophrenia is driven by the poor treatment efficacy, serious side effects, and poor patient compliance of current medications. Recently, a class of compounds known as tetrahydroprotoberberines, which includes the compound d,l -govadine, have shown promise in preclinical rodent tests relevant to schizophrenia. To date, the effect of govadine on prepulse inhibition (PPI), a test for sensorimotor gating commonly used to assess the effects of putative treatments for schizophrenia, has not been determined. The objective of the present study was to determine the effects of each enantiomer of govadine ( d - and l -govadine) on PPI alone and its disruption by the distinct pharmacological compounds apomorphine and MK-801. Male Long-Evans rats were treated systemically with d - or l -govadine and apomorphine or MK-801 prior to PPI. The PPI paradigm employed here included parametric manipulations of the prepulse intensity and the interval between the prepulse and pulse. Acute MK-801 (0.15 mg/kg) significantly increased the startle response to startle pulses alone, while both MK-801 and apomorphine (0.2 mg/kg) significantly increased reactivity to prepulse-alone trials. Both MK-801 and apomorphine disrupted PPI. In addition, d -govadine alone significantly disrupted PPI in the apomorphine experiment. Pretreatment with l -, but not d -, govadine (1.0 mg/kg) blocked the effect of apomorphine and MK-801 on PPI. Treatment of rats with l -govadine alone (0.3, 1.0, 3.0 mg/kg) also dose-dependently increased PPI. Given the high affinity of l -govadine for dopamine D2 receptors, these results suggest that further testing of l -govadine as an antipsychotic is warranted.

Evaluation of Neutron Radiography Reactor LEU-Core Start-Up Measurements

DOE PAGES

Bess, John D.; Maddock, Thomas L.; Smolinski, Andrew T.; ...

2014-11-04

Benchmark models were developed to evaluate the cold-critical start-up measurements performed during the fresh core reload of the Neutron Radiography (NRAD) reactor with Low Enriched Uranium (LEU) fuel. Experiments include criticality, control-rod worth measurements, shutdown margin, and excess reactivity for four core loadings with 56, 60, 62, and 64 fuel elements. The worth of four graphite reflector block assemblies and an empty dry tube used for experiment irradiations were also measured and evaluated for the 60-fuel-element core configuration. Dominant uncertainties in the experimental k eff come from uncertainties in the manganese content and impurities in the stainless steel fuel claddingmore » as well as the 236U and erbium poison content in the fuel matrix. Calculations with MCNP5 and ENDF/B-VII.0 neutron nuclear data are approximately 1.4% (9σ) greater than the benchmark model eigenvalues, which is commonly seen in Monte Carlo simulations of other TRIGA reactors. Simulations of the worth measurements are within the 2σ uncertainty for most of the benchmark experiment worth values. The complete benchmark evaluation details are available in the 2014 edition of the International Handbook of Evaluated Reactor Physics Benchmark Experiments.« less

Evaluation of Neutron Radiography Reactor LEU-Core Start-Up Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bess, John D.; Maddock, Thomas L.; Smolinski, Andrew T.

Benchmark models were developed to evaluate the cold-critical start-up measurements performed during the fresh core reload of the Neutron Radiography (NRAD) reactor with Low Enriched Uranium (LEU) fuel. Experiments include criticality, control-rod worth measurements, shutdown margin, and excess reactivity for four core loadings with 56, 60, 62, and 64 fuel elements. The worth of four graphite reflector block assemblies and an empty dry tube used for experiment irradiations were also measured and evaluated for the 60-fuel-element core configuration. Dominant uncertainties in the experimental k eff come from uncertainties in the manganese content and impurities in the stainless steel fuel claddingmore » as well as the 236U and erbium poison content in the fuel matrix. Calculations with MCNP5 and ENDF/B-VII.0 neutron nuclear data are approximately 1.4% (9σ) greater than the benchmark model eigenvalues, which is commonly seen in Monte Carlo simulations of other TRIGA reactors. Simulations of the worth measurements are within the 2σ uncertainty for most of the benchmark experiment worth values. The complete benchmark evaluation details are available in the 2014 edition of the International Handbook of Evaluated Reactor Physics Benchmark Experiments.« less

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

PubMed

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.

Design and Testing of 100 mK High-voltage Electrodes for AEgIS

NASA Astrophysics Data System (ADS)

Derking, J. H.; Liberadzka, J.; Koettig, T.; Bremer, J.

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 about 100 mK to reduce its random vertical velocity. This is obtained by mounting a Penning trap consisting of multiple high-voltage electrodes on the mixing chamber of a dilution refrigerator with cooling capacity of 100 μW at 50 mK. A design of the high-voltage electrodes is made and experimentally tested at operating conditions. The high-voltage electrodes are made of sapphire with four gold sputtered electrode sectors on it. The electrodes have a width of 40 mm, a height of 18 mm and a thickness of 5.8 mm and for performance testing are mountedto the mixing chamber of a dilution refrigerator with a 250 μm thick indium foil sandwiched inbetween the two to increase the thermal contact. A static heat load of 120 nW applied to the top surface of the electrode results in a maximum measured temperature of 100 mK while the mixing chamber is kept at a constant temperature of 50 mK. The measured totalthermal resistivity lies in the range of 210-260 cm2 K4 W-1, which is much higher than expected from literature. Further research needs to be done to investigate this.

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

PubMed

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.

Helium-3 blankets for tritium breeding in fusion reactors

NASA Technical Reports Server (NTRS)

Steiner, Don; Embrechts, Mark; Varsamis, Georgios; Vesey, Roger; Gierszewski, Paul

1988-01-01

It is concluded that He-3 blankets offers considerable promise for tritium breeding in fusion reactors: good breeding potential, low operational risk, and attractive safety features. The availability of He-3 resources is the key issue for this concept. There is sufficient He-3 from decay of military stockpiles to meet the International Thermonuclear Experimental Reactor needs. Extraterrestrial sources of He-3 would be required for a fusion power economy.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, J.X.; Xu, X.J.; Aldskogius, H.

1991-08-01

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 temperaturemore » 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.« less

STS-42 Commander Grabe uses DTO 653 MK1 Rowing Machine on OV-103's middeck

NASA Technical Reports Server (NTRS)

1992-01-01

STS-42 Commander Ronald J. Grabe exercises using MK1 Rowing Machine on the middeck of Discovery, Orbiter Vehicle (OV) 103. Grabe is using the exercise device as part of Development Test Objective (DTO) 653, Evaluation of MK1 Rowing Machine. The forward lockers appear at Grabe's right and the sleep station behind him.

3D-QSAR and Molecular Docking Studies on Derivatives of MK-0457, GSK1070916 and SNS-314 as Inhibitors against Aurora B Kinase

PubMed Central

Zhang, Baidong; Li, Yan; Zhang, Huixiao; Ai, Chunzhi

2010-01-01

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. PMID:21151441

3D-QSAR and molecular docking studies on derivatives of MK-0457, GSK1070916 and SNS-314 as inhibitors against Aurora B kinase.

PubMed

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.

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

PubMed

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.

Evidence for involvement of nitric oxide and GABAB receptors in MK-801- stimulated release of glutamate in rat prefrontal cortex

PubMed Central

Roenker, Nicole L.; Gudelsky, Gary A.; Ahlbrand, Rebecca; Horn, Paul S.; Richtand, Neil M.

2012-01-01

Systemic administration of NMDA receptor antagonists elevates extracellular glutamate within prefrontal cortex. The cognitive and behavioral effects of NMDA receptor blockade have direct relevance to symptoms of schizophrenia, and recent studies demonstrate an important role for nitric oxide and GABAB receptors in mediating the effects of NMDA receptor blockade on these behaviors. We sought to extend those observations by directly measuring the effects of nitric oxide and GABAB receptor mechanisms on MK-801-induced glutamate release in the prefrontal cortex. Systemic MK-801 injection (0.3 mg/kg) to male Sprague-Dawley rats significantly increased extracellular glutamate levels in prefrontal cortex, as determined by microdialysis. This effect was blocked by pretreatment with the nitric oxide synthase inhibitor L-NAME (60 mg/kg). Reverse dialysis of the nitric oxide donor SNAP (0.5 – 5 mM) directly into prefrontal cortex mimicked the effect of systemic MK-801, dose-dependently elevating cortical extracellular glutamate. The effect of MK-801 was also blocked by systemic treatment with the GABAB receptor agonist baclofen (5 mg/kg). In combination, these data suggest increased nitric oxide formation is necessary for NMDA antagonist-induced elevations of extracellular glutamate in the prefrontal cortex. Additionally, the data suggest GABAB receptor activation can modulate the NMDA antagonist-induced increase in cortical glutamate release. PMID:22579658

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.

PubMed

Che, Huan-Yong; Guo, Hang-Yuan; Si, Xu-Wei; You, Qiao-Ying; Lou, Wei-Ying

2014-01-01

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy.

The neuroprotective effects of MK-801 on the induction of microgyria by freezing injury to the newborn rat neocortex.

PubMed

Rosen, G D; Sigel, E A; Sherman, G F; Galaburda, A M

1995-11-01

Four-layered microgyria is associated with many developmental disorders, including mental retardation, epilepsy, and developmental dyslexia. Freezing lesions to the newborn rodent neocortex result in the formation of four-layered microgyria. Previous research had suggested this type of injury acts as an hypoxic/ischemic event to the developing cortical plate. The current study examines the effectiveness of the non-competitive N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) in protecting against freezing injury to the newborn rat cortical plate. Three groups of rats received freezing injury to the cortical plate on the first day of life (postnatal day 1). Two groups were treated with MK-801 (1 or 2 mg/kg) 0.5 h before the lesion and 6 and 14 h after, while one group received saline injections. A fourth group received MK-801 injections, but did not have a freezing lesion. The volume of neocortical abnormality was determined for all three groups in rats killed after postnatal day 7. Treatment with the higher dose of MK-801 (3 x 2 mg/kg) dramatically reduced the effects of freezing injury but also resulted in over 50% mortality in both lesioned and unlesioned groups. Animals in the lesioned group, however, had a decreased volume of abnormal cortex, and there were fewer animals with microsulci than in the untreated group. This is the first demonstration of a significant anatomical neuroprotective effect in newborns leading to a reduction of cortical malformation.

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

PubMed

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

Test of a prototype neutron spectrometer based on diamond detectors in a fast reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osipenko, M.; Ripani, M.; Ricco, G.

2015-07-01

A prototype of neutron spectrometer based on diamond detectors has been developed. This prototype consists of a {sup 6}Li neutron converter sandwiched between two CVD diamond crystals. The radiation hardness of the diamond crystals makes it suitable for applications in low power research reactors, while a low sensitivity to gamma rays and low leakage current of the detector permit to reach good energy resolution. A fast coincidence between two crystals is used to reject background. The detector was read out using two different electronic chains connected to it by a few meters of cable. The first chain was based onmore » conventional charge-sensitive amplifiers, the other used a custom fast charge amplifier developed for this purpose. The prototype has been tested at various neutron sources and showed its practicability. In particular, the detector was calibrated in a TRIGA thermal reactor (LENA laboratory, University of Pavia) with neutron fluxes of 10{sup 8} n/cm{sup 2}s and at the 3 MeV D-D monochromatic neutron source named FNG (ENEA, Rome) with neutron fluxes of 10{sup 6} n/cm{sup 2}s. The neutron spectrum measurement was performed at the TAPIRO fast research reactor (ENEA, Casaccia) with fluxes of 10{sup 9} n/cm{sup 2}s. The obtained spectra were compared to Monte Carlo simulations, modeling detector response with MCNP and Geant4. (authors)« less

Preparation and quantification of radioactive particles for tracking hydrodynamic behavior in multiphase reactors.

PubMed

Yunos, Mohd Amirul Syafiq Mohd; Hussain, Siti Aslina; Yusoff, Hamdan Mohamed; Abdullah, Jaafar

2014-09-01

Radioactive particle tracking (RPT) has emerged as a promising and versatile technique that can provide rich information about a variety of multiphase flow systems. However, RPT is not an off-the-shelf technique, and thus, users must customize RPT for their applications. This paper presents a simple procedure for preparing radioactive tracer particles created via irradiation with neutrons from the TRIGA Mark II research reactor. The present study focuses on the performance evaluation of encapsulated gold and scandium particles for applications as individual radioactive tracer particles using qualitative and quantitative neutron activation analysis (NAA) and an X-ray microcomputed tomography (X-ray Micro-CT) scanner installed at the Malaysian Nuclear Agency. Copyright © 2014 Elsevier Ltd. All rights reserved.

Highstand fans in the California borderland: the overlooked deep-water depositional systems

USGS Publications Warehouse

Covault, Jacob A.; Normark, William R.; Romans, Brian W.; Graham, Stephan A.

2007-01-01

Contrary to widely used sequence-stratigraphic models, lowstand fans are only part of the turbidite depositional record; our analysis reveals that a comparable volume of coarse-grained sediment has been deposited in California borderland deep-water basins regardless of sea level. Sedimentation rates and periods of active sediment transport have been determined for deep-water canyon-channel systems contributing to the southeastern Gulf of Santa Catalina and San Diego Trough since 40 ka using an extensive grid of high-resolution and deep-penetration seismic-reflection data. A regional seismic-reflection horizon (40 ka) has been correlated across the study area using radiocarbon age dates from the Mohole borehole and U.S. Geological Survey piston cores. This study focused on the submarine fans fed by the Oceanside, Carlsbad, and La Jolla Canyons, all of which head within the length of the Ocean-side littoral cell. The Oceanside Canyon–channel system was active from 45 to 13 ka, and the Carlsbad system was active from 50 (or earlier) to 10 ka. The La Jolla system was active over two periods, from 50 (or earlier) to 40 ka, and from 13 ka to the present. One or more of these canyon-channel systems have been active regardless of sea level. During sea-level fluctuation, shelf width between the canyon head and the littoral zone is the primary control on canyon-channel system activity. Highstand fan deposition occurs when a majority of the sediment within the Oceanside littoral cell is intercepted by one of the canyon heads, currently La Jolla Canyon. Since 40 ka, the sedimentation rate on the La Jolla highstand fan has been >2 times the combined rates on the Oceanside and Carlsbad lowstand fans.

MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.

PubMed

Thomas, David M; Kuhn, Donald M

2005-07-19

Methamphetamine causes long-term toxicity to dopamine nerve endings of the striatum. Evidence is emerging that microglia can contribute to the neuronal damage associated with disease, injury, or inflammation, but their role in methamphetamine-induced neurotoxicity has received relatively little attention. Lipopolysaccharide (LPS) and the neurotoxic HIV Tat protein, which cause dopamine neuronal toxicity after direct infusion into brain, cause activation of cultured mouse microglial cells as evidenced by increased expression of intracellular cyclooxygenase-2 and elevated secretion of tumor necrosis factor-alpha. MK-801, a non-competitive NMDA receptor antagonist that is known to protect against methamphetamine neurotoxicity, prevents microglial activation by LPS and HIV Tat. Dextromethorphan, an antitussive agent with NMDA receptor blocking properties, also prevents microglial activation. In vivo, MK-801 and dextromethorphan reduce methamphetamine-induced activation of microglia in striatum and they protect dopamine nerve endings against drug-induced nerve terminal damage. The present results indicate that the ability of MK-801 and dextromethorphan to protect against methamphetamine neurotoxicity is related to their common property as blockers of microglial activation.

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

PubMed Central

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

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

PubMed

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

2013-11-01

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 Mg(2+) is also present. In the presence of Mg(2+), 50% recovery from MK-801 blockade is achieved after 10' of 100 μM NMDA, or 30' of 15 μM NMDA exposure. In Mg(2+)-free medium, NMDA-induced MK-801 dissociation was found to be much slower. Memantine, another PCP-site antagonist, could substitute for Mg(2+) 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 Mg(2+) 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 Mg(2+) 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'. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Involvement of the CA1 GABAA receptors in MK-801-induced anxiolytic-like effects: an isobologram analysis.

PubMed

Naseri, Mohammad-Hasan; Hesami-Tackallou, Saeed; Torabi-Nami, Mohammad; Zarrindast, Mohammad-Reza; Nasehi, Mohammad

2014-06-01

There seems to be a close relationship between hippocampal N-methyl-D-aspartic acid (NMDA) and GABAA receptors with respect to the modulation of behavior that occurs in the CA1 region of the hippocampus. This study investigated the possible involvement of the CA1 GABAA receptors in anxiolytic-like effects induced by (+)-MK-801 (a noncompetitive antagonist of the NMDA subtype of the glutamate receptor). Male Wistar rats were subjected to the elevated plus-maze apparatus and open arm time (%OAT), and open arm entries (%OAE) for anxiety-related behaviors, and closed arm entries that correspond to the locomotor activity were assessed. An intra-CA1 injection of (+)-MK-801 (2 μg/rat) and muscimol (0.5 μg/rat; a GABAA receptor agonist) increased %OAT and %OAE by themselves while not altering the closed arm entries, indicating an anxiolytic-like effect of these drugs. Injection of bicuculline (0.1, 0.25, and 0.5 μg/rat; a GABAA receptor antagonist) did not alter any of the anxiety-related parameters. An intra-CA1 injection of a subthreshold dose of muscimol (0.1 μg/rat) or bicuculline (0.5 μg/rat), 5 min before injection of subthreshold and effective doses of (+)-MK-801 (0.5, 1 and 2 μg/rat), increased and decreased the anxiolytic-like effect of (+)-MK-801, respectively. The isobologram analysis of these findings suggested a synergistic anxiety-like effect of intra-CA1 (+)-MK-801 and muscimol. In conclusion, the CA1 GABAA receptors appear to be involved in anxiolytic-like behaviors induced by (+)-MK-801.

GPR40 partial agonist MK-2305 lower fasting glucose in the Goto Kakizaki rat via suppression of endogenous glucose production

PubMed Central

Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Bunzel, Michelle; Cao, Jin; Souza, Sarah; Thomas-Fowlkes, Brande; Di Salvo, Jerry; Weinglass, Adam B.; Li, Xiaoyan; Myers, Robert W.; Knagge, Kevin; Carrington, Paul E.; Hagmann, William K.

2017-01-01

GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized. To determine the mechanism(s) mediating these changes in glucose metabolism, we measured the absolute contribution of precursors to glucose production in the presence or absence of MK-2305. MK-2305 treatment resulted in decreased endogenous glucose production (EGP) driven primarily through changes in gluconeogenesis from substrates entering at the TCA cycle. The decrease in EGP was not likely due to a direct effect on the liver, as isolated perfused liver studies showed no effect of MK-2305 ex vivo and GPR40 is not expressed in the liver. Taken together, our results suggest MK-2305 treatment increases glucose stimulated insulin secretion (GSIS), resulting in changes to hepatic substrate handling that improve glucose homeostasis in the diabetic state. Importantly, these data extend our understanding of the underlying mechanisms by which GPR40 partial agonists reduce hyperglycemia. PMID:28542610

ITER Plasma at Ion Cyclotron Frequency Domain: The Fusion Alpha Particles Diagnostics Based on the Stimulated Raman Scattering of Fast Magnetosonic Wave off High Harmonic Ion Bernstein Modes

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander

2014-10-01

A novel method for alpha particle diagnostics is proposed. The theory of stimulated Raman scattering, SRS, of the fast wave and ion Bernstein mode, IBM, turbulence in multi-ion species plasmas, (Stefan University Press, La Jolla, CA, 2008). is utilized for the diagnostics of fast ions, (4)He (+2), in ITER plasmas. Nonlinear Landau damping of the IBM on fast ions near the plasma edge leads to the space-time changes in the turbulence level, (inverse alpha particle channeling). The space-time monitoring of the IBM turbulence via the SRS techniques may prove efficient for the real time study of the fast ion velocity distribution function, spatial distribution, and transport. Supported by Nikola Tesla Labs., La Jolla, CA 92037.

Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801

NASA Astrophysics Data System (ADS)

Trujillo, Keith A.; Akil, Huda

1991-01-01

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.

STS-42 Commander Grabe uses DTO 653 MK1 Rowing Machine on OV-103's middeck

NASA Image and Video Library

1992-01-30

STS042-05-037 (30 Jan 1992) --- Astronaut Ronald J. Grabe, STS-42 commander, exercises using MK1 Rowing Machine on the middeck of Discovery, Orbiter Vehicle (OV) 103. Grabe is using the exercise device as part of Development Test Objective (DTO) 653, Evaluation of MK1 Rowing Machine. The forward lockers appear at Grabe's right and the sleep station behind him.

On-and-off chip cooling of a Coulomb blockade thermometer down to 2.8 mK

NASA Astrophysics Data System (ADS)

Palma, M.; Scheller, C. P.; Maradan, D.; Feshchenko, A. V.; Meschke, M.; Zumbühl, D. M.

2017-12-01

Cooling nanoelectronic devices below 10 mK is a great challenge since thermal conductivities become very small, thus creating a pronounced sensitivity to heat leaks. Here, we overcome these difficulties by using adiabatic demagnetization of both the electronic leads and the large metallic islands of a Coulomb blockade thermometer. This reduces the external heat leak through the leads and also provides on-chip refrigeration, together cooling the thermometer down to 2.8 ± 0.1 mK. We present a thermal model which gives a good qualitative account and suggests that the main limitation is heating due to pulse tube vibrations. With better decoupling, temperatures below 1 mK should be within reach, thus opening the door for μK nanoelectronics.

Resurfacing the Jodrell Bank Mk II radio telescope

NASA Astrophysics Data System (ADS)

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.

Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats.

PubMed

Zhu, Min-xia; Lu, Chao; Xia, Chun-mei; Qiao, Zhong-wei; Zhu, Da-nian

2014-12-01

Excitotoxicity and cytotoxic edema are the two major factors resulting in neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream signal molecular of N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to control the flux of water. In a previous study, we had reported that pretreatment of simvastatin protected the cerebrum from ischemia and reperfusion injury by decreasing neurological deficit score and infarct area (Zhu et al. PLoS One 7:e51552, 2012). The present study used a middle cerebral artery occlusion (MCAO) model to further explore the pleiotropic effect of simvastatin via CaMK II and AQP4. The results showed that simvastatin reduced degenerated cells and brain edema while decreasing the protein expressions of phosphor-CaMK II and AQP4, and increasing the ratios of Bcl-2/Bax, which was independent of cholesterol-lowering effect. Immunocomplexes formed between the subunit of NMDARs-NR3A and AQP4 were detected for the first time. It was concluded that simvastatin could protect the cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the expressions of phosphor-CaMK II and AQP4, and that the interaction between NR3A and AQP4 might provide the base for AQP4 involving in the signaling pathways mediated by NMDARs.

Experiment for search for sterile neutrino at SM-3 reactor

NASA Astrophysics Data System (ADS)

Serebrov, A. P.; Ivochkin, V. G.; Samoylov, R. M.; Fomin, A. K.; Zinoviev, V. G.; Neustroev, P. V.; Golovtsov, V. L.; Gruzinsky, N. V.; Solovey, V. A.; Cherniy, A. V.; Zherebtsov, O. M.; Martemyanov, V. P.; Zinoev, V. G.; Tarasenkov, V. G.; Aleshin, V. I.; Petelin, A. L.; Pavlov, S. V.; Izhutov, A. L.; Sazontov, S. A.; Ryazanov, D. K.; Gromov, M. O.; Afanasiev, V. V.; Matrosov, L. N.; Matrosova, M. Yu.

2016-11-01

In connection with the question of possible existence of sterile neutrino the laboratory on the basis of SM-3 reactor was created to search for oscillations of reactor antineutrino. A prototype of a neutrino detector with scintillator volume of 400 l can be moved at the distance of 6-11 m from the reactor core. The measurements of background conditions have been made. It is shown that the main experimental problem is associated with cosmic radiation background. Test measurements of dependence of a reactor antineutrino flux on the distance from a reactor core have been made. The prospects of search for oscillations of reactor antineutrino at short distances are discussed.

Neuropeptide S attenuates neuropathological, neurochemical and behavioral changes induced by the NMDA receptor antagonist MK-801

PubMed Central

Okamura, Naoe; Reinscheid, Rainer K.; Ohgake, Shintaro; Iyo, Masaomi; Hashimoto, Kenji

2009-01-01

Neuropeptide S (NPS) and its cognate receptor were reported to mediate anxiolytic-like and arousal effects. NPS receptors are predominantly expressed in the brain, especially in limbic structures, including amygdala, olfactory nucleus, subiculum and retrosplenial cortex. In contrast, the NPS precursor is expressed in only a few brainstem nuclei where it is co-expressed with various excitatory transmitters, including glutamate. The current study investigates interactions of the NPS system with glutamatergic neurotransmission. It has been suggested that dysfunctions in glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA) receptors might be involved in the pathophysiology of schizophrenia since NMDA receptor antagonists, such as MK-801, have been shown to induce psychotic-like behavior in humans and animal models. Also, MK-801 is known to produce histological changes such as cytoplasmic vacuoles in retrosplenial cortex neurons where NPS receptors are highly expressed. In this study we show that NPS is able to alleviate neuropathological, neurochemical and behavioral changes produced by NMDA receptor antagonists. NPS treatment attenuated MK-801-induced vacuolization in the rat retrosplenial cortex in a dose dependent manner that can be blocked by an NPS receptor-selective antagonist. NPS also suppressed MK-801-induced increases of extracellular acetylcholine levels in the retrosplenial cortex. In the prepulse inhibition (PPI) assay, animals pretreated with NPS recovered significantly from MK-801-induced disruption of PPI. Our study suggests that NPS may have protective effects against the neurotoxic and behavioral changes produced by NMDA receptor antagonists and that NPS receptor agonists may elicit antipsychotic effects. PMID:19576911

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

PubMed Central

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.

2014-01-01

Purpose 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 60mg on alternate days (QOD). Due to a long half-life (60-80h), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Experimental Design Patients with advanced cancers were enrolled onto 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. Results Seventy-one patients were enrolled; 38 patients had 60mg MK-2206 QOD, while 33 received MK-2206 at 90mg, 135mg, 150mg, 200mg, 250mg, and 300mg QW. The QW MK-2206 MTD was established at 200mg following dose-limiting rash at 250mg and 300mg. 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. Conclusions MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200mg QW is currently used in phase II MK-2206 monotherapy and combination studies. PMID:25239610

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 spectralmore » 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.« less

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

PubMed Central

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

Calculation and Experiment of Adding Top Beryllium Shims for Iran MNSR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebadati, Javad; Rezvanifard, Mehdi; Shahabi, Iraj

2006-07-01

Miniature Neutron Source Reactor which is called MNSR were put into operation on June 1994 in Esfahan Nuclear Technology Center (ENTC). At that time the excess reactivity at the cold condition was 3.85 mk. After 7 years of operation and fuel consumption the reactivity was reduced to 2.90 mk. To compensate this reduction and upgrade the reactor, Beryllium Shim were used at the top of the core. This paper discusses the steps for this accurate and sensitive task. Finally a layer of 1.5 mm Beryllium were added to restore the reactor life. (authors)

76 FR 58471 - Endangered Species; File No. 15634

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

... NMFS Southwest Fisheries Science Center (SWFSC), 3333 N. Torrey Pines Ct., La Jolla, CA 92037...; weigh; flipper and passive integrated transponder tag; ultrasound; tissue, blood, cloacal swab and fat...

Impairment of the Anterior Thalamic Head Direction Cell Network Following Administration of the NMDA antagonist MK-801

PubMed Central

Housh, Adam A.; Berkowitz, Laura E.; Ybarra, Isaac; Kim, Esther U.; Lee, Brian R.; Calton, Jeffrey L.

2014-01-01

Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure. The animals were then administered MK-801 at a dose of .05 mg/kg or 0.1 mg/kg, or isotonic saline, and cells were re-examined for changes in directional specificity and landmark control. While the cells showed no changes in directional specificity and landmark control following administration of saline or the lower dose of MK-801, the higher dose of MK-801 caused a dramatic attenuation of the directional signal, characterized by decreases in peak firing rates, signal to noise, and directional information content. While the greatly attenuated directional specificity of cells in the high dose condition usually remained stable relative to the landmarks within the recording enclosure, a few cells in this condition exhibited unstable preferred directions within and between recording sessions. Our results are discussed relative to the possibility that the findings explain the effects of MK-801 on the acquisition and performance of spatial tasks. PMID:25307435

Hydrogen production from water-glucose solution over NiO/La-NaTaO3 photocatalyst

NASA Astrophysics Data System (ADS)

Mardian, R.; Husin, H.; Pontas, K.; Zaki, M.; Asnawi, T. M.; Ahmadi

2018-03-01

This paper reports the evaluation of La-NaTaO3 photocatalyst performance in producing hydrogen from water-glucose solution. The main goal of the studies is to investigate the influence of glucose as a sacrificial reagent on the photocatalytic efficiency in water splitting reactions under ultraviolet (UV) irradiation. Photocatalyst has been fabricated via sol-gel method and being confirmed using x-ray diffraction (XRD) and scanning electron microscopy (SEM). Nickel loaded La-NaTaO3 photocatalyst are prepared by impregnation method. It was observed that the prepared photocatalysts displayed particle sizes in the 30-250 nm range with orthorhombic structure. Their photocatalytic activity for hydrogen production via water splitting was conducted in a Pyrex glass reactor under UV light irradiation. The aqueous solution contained glucose employed as a renewable organic scavenger. A significant improvement in hydrogen production was observed in glucose-water mixtures and NiO loaded photocatalyst. The prepared La-NaTaO3 showed that the highest activity for hydrogen generation of 35.1 mmol h-1.g-1 was obtained at 0.10 mol.L-1 glucose and 0.3 wt.% NiO. This suggests the important role played by the glucose as electron donor and loading nickel on La-NaTaO3 as a cocatalyst increasing electron storage and suppressing electron-hole recombination.

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

PubMed Central

Kavitha, Alapati; Vijayalakshmi, Muvva

2012-01-01

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. PMID:22619604

A study on L-asparaginase of Nocardia levis MK-VL_113.

PubMed

Kavitha, Alapati; Vijayalakshmi, Muvva

2012-01-01

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1991-04-01

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 {sup 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 amore » 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.« less

Subchronic MK-801 treatment and post-weaning social isolation in rats: differential effects on locomotor activity and hippocampal long-term potentiation.

PubMed

Ashby, Donovan M; Habib, Diala; Dringenberg, Hans C; Reynolds, James N; Beninger, Richard J

2010-09-01

Subchronic NMDA receptor antagonist treatment and post-weaning social isolation are two animal models of schizophrenia symptoms. However, behavioral and physiological changes following a combination of these two procedures have not been investigated. Thus, we examined effects of a novel, "double hit" model combining these two treatments, comparing them to standard models involving only NMDA antagonist treatment or social isolation. Male, Sprague-Dawley rats were either group-housed or maintained in social isolation (starting at postnatal day [PD] 21 and continuing throughout the study). Each housing condition was further subdivided into two groups, receiving either subchronic treatment with either saline or MK-801 (0.5mg/kg, i.p., 2xday for seven days starting at PD 56). Post-weaning social isolation increased locomotor activity (assessed at PD 70) in response to a novel environment and an acute amphetamine injection, while subchronic MK-801 increased only amphetamine induced locomotor activity. Subsequent electrophysiological experiments (under urethane anesthesia) assessing changes in plasticity of hippocampal synapses showed that subchronic MK-801 treatment resulted in an increase in long-term potentiation in area CA1 in response to high frequency stimulation of the contralateral CA3 area, while housing condition had no effect. No other changes in hippocampal electrophysiology (input-output curves, paired-pulse facilitation) were observed. These data are the first to demonstrate an enhancement in hippocampal long-term plasticity in vivo following subchronic MK-801 administration, an effect that may be related to the well-characterized changes in glutamatergic and GABAergic systems seen after subchronic NMDA receptor blockade. That lack of additive or synergistic effects in the "double hit model" suggests that combining isolation and subchronic MK-801 treatment does not necessarily produce greater behavioral or physiological dysfunction than that seen with either

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

PubMed

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.

La interstitial defect-induced insulator-metal transition in the oxide heterostructures LaAl O3 /SrTi O3

NASA Astrophysics Data System (ADS)

Zhou, Jun; Yang, Ming; Feng, Yuan Ping; Rusydi, Andrivo

2017-11-01

Perovskite oxide interfaces have attracted tremendous research interest for their fundamental physics and promising all-oxide electronic applications. Here, based on first-principles calculations, we propose a surface La interstitial promoted interface insulator-metal transition in LaAl O3 /SrTi O3 (110). Compared with surface oxygen vacancies, which play a determining role on the insulator-metal transition of LaAl O3 /SrTi O3 (001) interfaces, we find that surface La interstitials can be more experimentally realistic and accessible for manipulation and more stable in an ambient atmospheric environment. Interestingly, these surface La interstitials also induce significant spin-splitting states with a Ti dy z/dx z character at a conducting LaAl O3 /SrTi O3 (110) interface. On the other hand, for insulating LaAl O3 /SrTi O3 (110) (<4 unit cells LaAl O3 thickness), a distortion between La (Al) and O atoms is found at the LaAl O3 side, partially compensating the polarization divergence. Our results reveal the origin of the metal-insulator transition in LaAl O3 /SrTi O3 (110) heterostructures, and also shed light on the manipulation of the superior properties of LaAl O3 /SrTi O3 (110) for different possibilities in electronic and magnetic applications.

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

PubMed

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.

The Scripps Research Institute (La Jolla, CA)

DOEpatents

Schultz, Peter G.; Wang, Lei

2010-01-05

The invention provides proteins attached to solid supports, and methods of preparing such solid support-bound proteins are provided. The proteins are attached to solid supports by means of an unnatural amino acid incorporated into the protein, which unnatural amino acid includes a reactive group that can react with a second reactive group that is attached to a solid support.

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

PubMed Central

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

Additive effect of combined application of magnesium and MK-801 on analgesic action of morphine.

PubMed

Bujalska-Zadrożny, Magdalena; Duda, Kamila

2014-01-01

As previously reported, magnesium ions (Mg(2+)) administered in relatively low doses markedly potentiated opioid analgesia in neuropathic pain, in which the effectiveness of opioids is limited. Considering that Mg(2+) behaves like an N-methyl-D-aspartate receptor antagonist, the effect of this ion on the analgesic action of morphine was compared with that of MK-801. Acute pain was evoked by mechanical or thermal stimuli, whereas neuropathic hyperalgesia was induced by streptozotocin (STZ) administration. Magnesium sulphate (40 mg/kg i.p.) or MK-801 (0.05 mg/kg s.c.) administered alone did not modify the nociceptive threshold to acute stimuli or the streptozotocin hyperalgesia but significantly augmented the analgesic action of morphine (5 mg/kg i.p.). Furthermore, if these drugs (i.e. magnesium sulphate and MK-801) were applied concomitantly, a clear additive effect on the analgesic action of morphine occurred in both models of pain. Possible explanations of these observations are discussed. © 2014 S. Karger AG, Basel.

77 FR 36571 - Endangered Species; Receipt of Applications for Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-19

.... III. Permit Applications A. Endangered Species Applicant: Southwest Fisheries Science Center, La Jolla... applicants each request a permit to import the sport- hunted trophy of one male bontebok (Damaliscus pygargus...

Compositional and gate tuning of the interfacial conductivity in LaAlO3/LaTiO3/SrTiO3 heterostructures

NASA Astrophysics Data System (ADS)

Hosoda, Masayuki; Bell, Christopher; Hikita, Yasuyuki; Hwang, Harold Y.

2013-03-01

We investigate the effect of LaTiO3 insertion at the interface between LaAlO3 and TiO2 terminated {100} SrTiO3 for a series of LaAlO3 and LaTiO3 thicknesses. A clear increase of the carrier density was observed while the Hall mobility was largely unchanged. In structures with LaAlO3 thickness ˜3 unit cells, close to the critical thickness for conductivity, as little as 0.25 unit cells of LaTiO3 drives an insulator-to-metal transition. These samples show a strong dependence of the conductivity on voltage with electrostatic back-gating, which can be understood in a two-carrier picture, and dominated by the change in carrier density at the interface.

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

PubMed

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 < 0.05. The induction time was shorter, reduction in MAP was detected, more dobutamine was given and HR and CI were higher after DET+MK, while SVR was higher with DET. Arterial oxygen tension and Pa O2 /FiO2 (40 minutes after induction), DO2 and venous partial pressure of oxygen (40 and 60 minutes after induction) were higher with DET+MK. Plasma 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

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

PubMed

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.

The tumor suppressor gene TUSC2 (FUS1) sensitizes NSCLC to the AKT inhibitor MK2206 in LKB1-dependent manner.

PubMed

Meng, Jieru; Majidi, Mourad; Fang, Bingliang; Ji, Lin; Bekele, B Nebiyou; Minna, John D; Roth, Jack A

2013-01-01

TUSC2-defective gene expression is detected in the majority of lung cancers and is associated with worse overall survival. We analyzed the effects of TUSC2 re-expression on tumor cell sensitivity to the AKT inhibitor, MK2206, and explored their mutual signaling connections, in vitro and in vivo. TUSC2 transient expression in three LKB1-defective non-small cell lung cancer (NSCLC) cell lines combined with MK2206 treatment resulted in increased repression of cell viability and colony formation, and increased apoptotic activity. In contrast, TUSC2 did not affect the response to MK2206 treatment for two LKB1-wild type NSCLC cell lines. In vivo, TUSC2 systemic delivery, by nanoparticle gene transfer, combined with MK2206 treatment markedly inhibited growth of tumors in a human LKB1-defective H322 lung cancer xenograft mouse model. Biochemical analysis showed that TUSC2 transient expression in LKB1-defective NSCLC cells significantly stimulated AMP-activated protein kinase (AMPK) phosphorylation and enzymatic activity. More importantly, AMPK gene knockdown abrogated TUSC2-MK2206 cooperation, as evidenced by reduced sensitivity to the combined treatment. Together, TUSC2 re-expression and MK2206 treatment was more effective in inhibiting the phosphorylation and kinase activities of AKT and mTOR proteins than either single agent alone. In conclusion, these findings support the hypothesis that TUSC2 expression status is a biological variable that potentiates MK2206 sensitivity in LKB1-defective NSCLC cells, and identifies the AMPK/AKT/mTOR signaling axis as an important regulator of this activity.

Starmind: A Fuzzy Logic Knowledge-Based System for the Automated Classification of Stars in the MK System

NASA Astrophysics Data System (ADS)

Manteiga, M.; Carricajo, I.; Rodríguez, A.; Dafonte, C.; Arcay, B.

2009-02-01

Astrophysics is evolving toward a more rational use of costly observational data by intelligently exploiting the large terrestrial and spatial astronomical databases. In this paper, we present a study showing the suitability of an expert system to perform the classification of stellar spectra in the Morgan and Keenan (MK) system. Using the formalism of artificial intelligence for the development of such a system, we propose a rules' base that contains classification criteria and confidence grades, all integrated in an inference engine that emulates human reasoning by means of a hierarchical decision rules tree that also considers the uncertainty factors associated with rules. Our main objective is to illustrate the formulation and development of such a system for an astrophysical classification problem. An extensive spectral database of MK standard spectra has been collected and used as a reference to determine the spectral indexes that are suitable for classification in the MK system. It is shown that by considering 30 spectral indexes and associating them with uncertainty factors, we can find an accurate diagnose in MK types of a particular spectrum. The system was evaluated against the NOAO-INDO-US spectral catalog.

The Influence of the CB1 Receptor Ligands on the Schizophrenia-Like Effects in Mice Induced by MK-801.

PubMed

Kruk-Slomka, Marta; Budzynska, Barbara; Slomka, Tomasz; Banaszkiewicz, Izabela; Biala, Grazyna

2016-11-01

A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia. We provoked psychosis-like effects in mice by an acute administration of NMDA receptor antagonist, MK-801 (0.1-0.6 mg/kg). An acute administration of MK-801 induced psychotic symptoms, manifested in the increase in locomotor activity (hyperactivity), measured in actimeters, as well as the memory impairment, assessed in the passive avoidance task. We revealed that an acute injection of CB1 receptor agonist, oleamide (5-20 mg/kg), had no influence on the short- and long-term memory-related disturbances, as well as on the hyperlocomotion in mice, provoking by an acute MK-801. In turn, an amnestic effects or hyperactivity induced by an acute MK-801 was attenuated by an acute administration of AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist. The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice. Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.

Spectral Weight Redistribution in ( LaNiO 3 ) n / ( LaMnO 3 ) 2 Superlattices from Optical Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Pietro, P.; Hoffman, J.; Bhattacharya, A.

2015-04-01

We have studied the optical properties of four (LaNiO3)(n)/(LaMnO3)(2) superlattices (SL) (n = 2, 3, 4, 5) on SrTiO3 substrates. We have measured the reflectivity at temperatures from 20 to 400 K, and extracted the optical conductivity through a fitting procedure based on a Kramers-Kronig consistent Lorentz-Drude model. With increasing LaNiO3 thickness, the SLs undergo an insulator-to-metal transition (IMT) that is accompanied by the transfer of spectral weight from high to low frequency. The presence of a broad midinfrared band, however, shows that the optical conductivity of the (LaNiO3)(n)/(LaMnO3)(2) SLs is not a linear combination of the LaMnO3 and LaNiO3more » conductivities. Our observations suggest that interfacial charge transfer leads to an IMT due to a change in valence at the Mn and Ni sites.« less

Behavioral performance altering effects of MK-801 in zebrafish (Danio rerio)

PubMed Central

Sison, Margarette; Gerlai, Robert

2011-01-01

MK-801, a non-competitive NMDA-R antagonist, has been utilized in the analysis of mammalian learning and memory. The zebrafish is a novel vertebrate study species that has been proposed for the analysis of the mechanisms of learning and memory. Although learning paradigms have been developed for this species, psychopharmacological characterization of its behavioral responses is rudimentary. Before one attempts the analysis of the effects of MK-801 on learning and memory in zebrafish, one needs to know whether this drug affects motor function, perception and/or motivation, factors that may influence performance in learning tasks. Here we conduct dose response analyses investigating the effects of 0, 2, 20 and 100 µM MK-801 administered 24 hours or 30 minutes before the behavioral test, or during the test. We analyze responses in the open tank to measure motor and posture patterns, in the light dark paradigm to evaluate visual perception, and in a group preference task to attempt to quantify motivation. Our results show a significant performance alteration only in the highest (100 µM) dose groups. These fish spent more time on the bottom of their tank, showed elevated erratic movement, increased their clockwise and counterclockwise turning frequency, and reduced the time spent near a shoal stimulus, behavioral alterations that also depended upon the timing of drug administration. Thus, using the current delivery procedures and outbred zebrafish population, the highest dose that may not lead to significant performance deficits is 20 µM, a concentration we propose to use in a future learning study in zebrafish. PMID:21333690

EphB4 Receptor Tyrosine Kinase in Prostate Cancer

DTIC Science & Technology

2011-09-01

San Diego, La Jolla, CA, USAAbbreviations: MAP kinase, mitogen-activated prote tidylinositol 4,5-bisphosphate; PI(3,4,5)P3, phosphatid PI3K...okadaic acid (MP Biomedicals, 150 μM stock in DMSO), LY294002, PD98059, rapamycin (see previous section), dasatinib (LC Laboratories; 50 μM stock in DMSO...the phosphatase inhibitor tautomycin, which preferentially inhibits PP1 over PP2A. The cells were stimulated and analyzed as in (D). (F) Okadaic acid

MiR-137 inhibited inflammatory response and apoptosis after spinal cord injury via targeting of MK2.

PubMed

Gao, Lin; Dai, Chenfei; Feng, Zhiping; Zhang, Lixin; Zhang, Zhiqiang

2018-04-01

Spinal cord injuries are common and troublesome disorder, which is mediated by various signal pathways and mechanisms. MK2 is also involved in numerous inflammatory diseases including spinal cord injury. The role of microRNA-137 (miR-137) and its detailed working mechanism in spinal cord injuries remain unclear. In the present study, we found that an elevated MK2 but a decreased miR-137 was expressed in serum specimens of patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Meanwhile, we suggested that upregulation of miR-137 could inhibit the expression of TNF-α and IL-6, two markers of inflammatory response after SCI, and apoptosis in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Furthermore, we verified that MK2 was a direct target of miR-137 thorough a constructed luciferase assay. Even further, we elucidated that miR-137 could suppress the inflammatory response and apoptosis via negative regulation of MK2. Finally, through an animal model trial performed using mice, we demonstrated the protective effect of how miR-137 works on inflammatory response and apoptosis after spinal cord injury. Considering all the forementioned, our findings revealed that miR-137 inhibited inflammatory response and apoptosis after spinal cord injury via the targeting of MK2. The outcomes of the present study might indicate a new target in molecular treatment of SCI. © 2017 Wiley Periodicals, Inc.

Designing Secure Systems on Reconfigurable Hardware

DTIC Science & Technology

2008-07-01

Jeff White Department of Electrical and Computer Engineering University of California, Santa Barbara Santa Barbara, CA 93106 {nick callegari,valamehr...ece.ucsb.edu, jdwhite08@engineering.ucsb.edu Ryan Kastner Department of Computer Science and Engineering University of California, San Diego La Jolla...Transactions on Design Automation of Electronic Systems (TODAES), Vol. 13, No. 3, July 2008, 1-24 14. ABSTRACT see report 15. SUBJECT TERMS 16

TNF-alpha-induced c-Fos generation in the nucleus of the solitary tract is blocked by NBQX and MK-801.

PubMed

Emch, G S; Hermann, G E; Rogers, R C

2001-11-01

Previous studies have shown that identified neurons of the nucleus of the solitary tract (NST) are excited by the cytokine tumor necrosis factor-alpha (TNF-alpha). Vagal afferent connections with the NST are predominantly glutaminergic. Therefore, we hypothesized that TNF-alpha effects on NST neurons may be via modulation of glutamate neurotransmission. The present study used activation of the immediate early gene product c-Fos as a marker for neuronal activation in the NST. c-Fos expression was evaluated after microinjections of TNF-alpha in the presence or absence of either the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX) or the N-methyl-D- aspartate (NMDA) antagonist MK-801. To assess the specificity of the interaction between TNF-alpha and glutamate, c-Fos expression was also evaluated after injection of oxytocin (OT) (which has a direct excitatory effect in this area of the brain stem) in the presence and absence of NBQX or MK-801. c-Fos labeling was significantly increased in the NST after TNF-alpha exposure. Coinjection of either NBQX or MK-801 with TNF-alpha prevented significant c-Fos induction in the NST. Microinjections of OT also induced significant NST c-Fos elevation, but this expression was unaffected by coinjection of either antagonist with OT. These data lead us to conclude that TNF-alpha activation of NST neurons depends on glutamate and such an interaction is not generalized to all agonists that act on the NST.

The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma.

PubMed

Pokorny, Jenny L; Calligaris, David; Gupta, Shiv K; Iyekegbe, Dennis O; Mueller, Dustin; Bakken, Katrina K; Carlson, Brett L; Schroeder, Mark A; Evans, Debra L; Lou, Zhenkun; Decker, Paul A; Eckel-Passow, Jeanette E; Pucci, Vincenzo; Ma, Bennett; Shumway, Stuart D; Elmquist, William F; Agar, Nathalie Y R; Sarkaria, Jann N

2015-04-15

Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in glioblastoma multiforme (GBM) xenograft models alone and in combination with radiation and/or temozolomide. In vitro MK-1775 efficacy alone and in combination with temozolomide, and the impact on DNA damage, was analyzed by Western blotting and γH2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI)-MS imaging. GBM22 (IC50 = 68 nmol/L) was significantly more sensitive to MK-1775 compared with five other GBM xenograft lines, including GBM6 (IC50 >300 nmol/L), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with temozolomide in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with temozolomide, whereas in a flank model of GBM22, MK-1775 exhibited both single-agent and combinatorial activity with temozolomide. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared with heterotopic GBM22 tumors. Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. ©2015 American Association for Cancer Research.

The efficacy of the Wee1 inhibitor MK-1775 combined with temozolomide is limited by heterogeneous distribution across the blood-brain barrier in glioblastoma

PubMed Central

Pokorny, Jenny L.; Calligaris, David; Gupta, Shiv K.; Iyekegbe, Dennis O.; Mueller, Dustin; Bakken, Katrina K.; Carlson, Brett L.; Schroeder, Mark A.; Evans, Debra L.; Lou, Zhenkun; Decker, Paul A.; Eckel-Passow, Jeanette E.; Pucci, Vincenzo; Ma, Bennett; Shumway, Stuart D.; Elmquist, William; Agar, Nathalie Y.; Sarkaria, Jann N.

2015-01-01

Purpose Wee1 regulates key DNA damage checkpoints, and in this study, the efficacy of the Wee1 inhibitor MK-1775 was evaluated in GBM xenograft models alone and in combination with radiation and/or temozolomide (TMZ). Experimental design In vitro MK-1775 efficacy alone and in combination with TMZ, and the impact on DNA damage was analyzed by western blotting and γH2AX foci formation. In vivo efficacy was evaluated in orthotopic and heterotopic xenografts. Drug distribution was assessed by conventional mass spectrometry (MS) and matrix-assisted laser desorption/ionization (MALDI) -MS imaging. Results GBM22 (IC50 = 68 nM) was significantly more sensitive to MK-1775 compared to 5 other GBM xenograft lines including GBM6 (IC50 >300 nM), and this was associated with a significant difference in pan-nuclear γH2AX staining between treated GBM22 (81% cells positive) and GBM6 (20% cells positive) cells. However, there was no sensitizing effect of MK-1775 when combined with TMZ in vitro. In an orthotopic GBM22 model, MK-1775 was ineffective when combined with TMZ, while in a flank model of GBM22, MK-1775 exhibited both single agent and combinatorial activity with TMZ. Consistent with limited drug delivery into orthotopic tumors, the normal brain to whole blood ratio following a single MK-1775 dose was 5%, and MALDI-MS imaging demonstrated heterogeneous and markedly lower MK-1775 distribution in orthotopic as compared to heterotopic GBM22 tumors. Conclusions Limited distribution to brain tumors may limit the efficacy of MK-1775 in GBM. PMID:25609063

Dizocilpine (MK-801) arrests status epilepticus and prevents brain damage induced by Soman. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparenborg, S.; Brennecke, L.H.; Jaax, N.K.

1992-12-31

The involvement of the NMDA receptor in the neurotoxicity induced by soman, an organophosphorus compound which irreversibly inhibits cholinesterase, was studied in guinea pigs. The drug MK-801 (0.5, 1 or 5 mg/kg, i.p.) was given as a pretreatment before a convulsant dose of soman or as a post treatment (30, 100 or 300 micron g/kg, i.m.) 5 min after the development of soman-induced status epilepticus. Pyridostigmine, atropine and pralidoxime chloride were also given to each subject to counteract the lethality of soman. All subjects that were challenged with soman and given the vehicle for MK-801 (saline) exhibited severe convulsions andmore » electrographic seizure activity. Neuronal necrosis was found in the hippocampus, amygdala, thalamus and the pyriform and cerebral cortices of those subjects surviving for 48 hr. Pretreatment with 0.5 or 1 mg/kg doses of MK-801 did not prevent nor delay the onset of seizure activity but did diminish its intensity and led to its early arrest. At the largest dose (5 mg/kg), MK-801 completely prevented the development of seizure activity and brain damage. Post treatment with MK-801 prevented, arrested or reduced seizure activity, convulsions and neuronal necrosis in a dose-dependent manner. The NMDA receptor may play a more critical role in the spread and maintenance, rather than the initiation of cholinergically-induced seizure activity....Seizure-related brain damage, Organophosphorus compound, Nerve agent, Cholinesterase inhibition, Excitotoxicity, Guinea pig.« less

Characterization of the ERK homologue CpMK2 from the chestnut blight fungus Cryphonectria parasitica.

PubMed

Choi, Eun-Sil; Chung, Hea-Jong; Kim, Myoung-Ju; Park, Seung-Moon; Cha, Byeong-Jin; Yang, Moon-Sik; Kim, Dae-Hyuk

2005-05-01

The Cryphonectria parasitica gene cpmk2, which encodes a mitogen-activated protein kinase belonging to the yeast extracellular signalling-regulated kinase (YERK1) subfamily, was isolated and its biological function was examined. Disruption of cpmk2 resulted in impaired pigmentation and abolished conidiation. Growth defects were observed in the cpmk2 mutant grown on solid plates, but growth of the mutant appeared normal in liquid media, including EP complete and PD broth, suggesting that the cpmk2 gene is involved in sensing and responding to growth conditions. The mutant's production of laccase, as measured by the size of the coloured area produced on tannic-acid-supplemented plates, was significantly reduced compared with the wild-type, but the intensity of the coloured area was unchanged, suggesting that the reduced laccase activity was owing to reduced growth on solid media rather than transcriptional downregulation. A dramatic reduction observed in the canker area produced by the cpmk2 mutant compared with the wild-type, even more severe than that of a hypovirulent strain, can also be ascribed to defective growth on solid surfaces rather than to impairments in a virulence factor(s). Downregulation of the pheromone gene Mf2/1 was also observed in the mutant, indicating a possible explanation for the regulation of the pheromone precursor gene in filamentous fungi and suggesting the presence of the yeast-like pheromone-responsive pathway in C. parasitica. Immunoblot analyses revealed that the phosphorylation level of CpMK2 increased in both virus-free and virus-containing strains in liquid cultures of up to 5 days old and decreased in older cultures. Moreover, the CpMK2 phosphorylation level increased in both strains after transfer from liquid to solid medium. However, levels of phosphorylated CpMK2 were similar in the two strains, suggesting that CpMK2, unlike CpMK1, is not under the direct control of a hypovirus.

D-He-3 spherical torus fusion reactor system study

NASA Astrophysics Data System (ADS)

Macon, William A., Jr.

1992-04-01

This system study extrapolates present physics knowledge and technology to predict the anticipated characteristics of D-He3 spherical torus fusion reactors and their sensitivity to uncertainties in important parameters. Reference cases for steady-state 1000 MWe reactors operating in H-mode in both the 1st stability regime and the 2nd stability regime were developed and assessed quantitatively. These devices would a very small aspect ratio (A=1,2), a major radius of about 2.0 m, an on-axis magnetic field less than 2 T, a large plasma current (80-120 MA) dominated by the bootstrap effect, and high plasma beta (greater than O.6). The estimated cost of electricity is in the range of 60-90 mills/kW-hr, assuming the use of a direct energy conversion system. The inherent safety and environmental advantages of D-He3 fusion indicate that this reactor concept could be competitive with advanced fission breeder reactors and large-scale solar electric plants by the end of the 21st century if research and development can produce the anticipated physics and technology advances.

Trace elements study of high purity nanocrystalline silicon carbide (3C-SiC) using k0-INAA method

NASA Astrophysics Data System (ADS)

Huseynov, Elchin; Jazbec, Anze

2017-07-01

Silicon carbide (3C-SiC) nanoparticles have been irradiated by neutron flux (2×1013 n·cm-2·s-1) at TRIGA Mark II type research reactor. After neutron irradiation, the radioisotopes of trace elements in the nanocrystalline 3C-SiC were studied as time functions. The identification of isotopes which significantly increased the activity of the samples as a result of neutron radiation was carried out. Nanocrystalline 3C-SiC are synthesized by standard laser technique and the purity of samples was determined by the k0-based Instrumental Neutron Activation Analysis (k0-INAA) method. Trace elements concentration in the 3C-SiC nanoparticles were determined by the radionuclides of appropriate elements. The trace element isotopes concentration have been calculated in percentage according to k0-INAA method.

Fundamental approaches for analysis thermal hydraulic parameter for Puspati Research Reactor

NASA Astrophysics Data System (ADS)

Hashim, Zaredah; Lanyau, Tonny Anak; Farid, Mohamad Fairus Abdul; Kassim, Mohammad Suhaimi; Azhar, Noraishah Syahirah

2016-01-01

The 1-MW PUSPATI Research Reactor (RTP) is the one and only nuclear pool type research reactor developed by General Atomic (GA) in Malaysia. It was installed at Malaysian Nuclear Agency and has reached the first criticality on 8 June 1982. Based on the initial core which comprised of 80 standard TRIGA fuel elements, the very fundamental thermal hydraulic model was investigated during steady state operation using the PARET-code. The main objective of this paper is to determine the variation of temperature profiles and Departure of Nucleate Boiling Ratio (DNBR) of RTP at full power operation. The second objective is to confirm that the values obtained from PARET-code are in agreement with Safety Analysis Report (SAR) for RTP. The code was employed for the hot and average channels in the core in order to calculate of fuel's center and surface, cladding, coolant temperatures as well as DNBR's values. In this study, it was found that the results obtained from the PARET-code showed that the thermal hydraulic parameters related to safety for initial core which was cooled by natural convection was in agreement with the designed values and safety limit in SAR.

Measure of anxiety-related behaviors and hippocampal BDNF levels associated to the amnesic effect induced by MK-801 evaluated in the modified elevated plus-maze in rats.

PubMed

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

2015-08-01

Non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonists impair rodent cognition. Specifically, MK-801, the most potent NMDA-R antagonist, induces an amnesic effect on the modified elevated plus maze (mEPM) learning test in rodents, which reflects spatial long-term memory. However, alterations in anxiety-related behaviors could overlap this amnesic effect. Accumulated evidence supports the role of brain-derived neurotrophic factor (BDNF) in learning and memory processes and deficits in hippocampal BDNF function, which underlie cognitive impairments, have been extensively reported. Therefore, we investigated if changes in anxiety-related behaviors and hippocampal BDNF levels are related with the amnesic effect induced by MK-801 in the mEPM.Transfer latency (TL) as an index of spatial memory in the mEPM was used. TL1 was evaluated 30 min after saline/MK-801 injection (day 1, acquisition session) while learning/memory performance was measured 24 h later at TL2 (day 2, retention session). Also at TL2, two other experimental groups were added to measure the anxiety-related behaviors using the classic EPM and BDNF protein levels by ELISA. To evaluate if amnesia endures, an additional session was recorded on day 3 (TL3) and BDNF levels were measured.While TL1 was not significantly modified by MK-801, TL2 was increased compared to the control group indicating an amnesic effect. This effect was not mimicked by anxiety-related behaviors and it was associated to a significant attenuation of BDNF levels. During the third post-training day, the cognitive performance of MK-801-treated animals was improved and an increased BDNF protein expression in the hippocampus accompanied this change

Modelling of MOCVD Reactor: New 3D Approach

NASA Astrophysics Data System (ADS)

Raj, E.; Lisik, Z.; Niedzielski, P.; Ruta, L.; Turczynski, M.; Wang, X.; Waag, A.

2014-04-01

The paper presents comparison of two different 3D models of vertical, rotating disc MOCVD reactor used for 3D GaN structure growth. The first one is based on the reactor symmetry, while the second, novel one incorporates only single line of showerhead nozzles. It is shown that both of them can be applied interchangeably regarding the phenomena taking place within the processing area. Moreover, the importance of boundary conditions regarding proper modelling of showerhead cooling and the significance of thermal radiation on temperature field within the modelled structure are presented and analysed. The last phenomenon is erroneously neglected in most of the hitherto studies.

PR-EDB: Power Reactor Embrittlement Database - Version 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jy-An John; Subramani, Ranjit

2008-03-01

The aging and degradation of light-water reactor pressure vessels is of particular concern because of their relevance to plant integrity and the magnitude of the expected irradiation embrittlement. The radiation embrittlement of reactor pressure vessel materials depends on many factors, such as neutron fluence, flux, and energy spectrum, irradiation temperature, and preirradiation material history and chemical compositions. These factors must be considered to reliably predict pressure vessel embrittlement and to ensure the safe operation of the reactor. Large amounts of data from surveillance capsules are needed to develop a generally applicable damage prediction model that can be used for industrymore » standards and regulatory guides. Furthermore, the investigations of regulatory issues such as vessel integrity over plant life, vessel failure, and sufficiency of current codes, Standard Review Plans (SRPs), and Guides for license renewal can be greatly expedited by the use of a well-designed computerized database. The Power Reactor Embrittlement Database (PR-EDB) is such a comprehensive collection of data for U.S. designed commercial nuclear reactors. The current version of the PR-EDB lists the test results of 104 heat-affected-zone (HAZ) materials, 115 weld materials, and 141 base materials, including 103 plates, 35 forgings, and 3 correlation monitor materials that were irradiated in 321 capsules from 106 commercial power reactors. The data files are given in dBASE format and can be accessed with any personal computer using the Windows operating system. "User-friendly" utility programs have been written to investigate radiation embrittlement using this database. Utility programs allow the user to retrieve, select and manipulate specific data, display data to the screen or printer, and fit and plot Charpy impact data. The PR-EDB Version 3.0 upgrades Version 2.0. The package was developed based on the Microsoft .NET framework technology and uses Microsoft Access

Pt nanoparticle on La0.02Na0.98TaO3 catalyst for hydrogen evolution from glycerol aqueous solution

NASA Astrophysics Data System (ADS)

Husin, Husni; Adisalamun, Sy, Yuliana; Asnawi, Teku Muhammad; Hasfita, Fikri

2017-01-01

Pt nanoparticles on La-doped sodium tantalum oxide (La0.02Na0.98TaO3), which acts as an active co-catalyst for H2 evolution under UV light irradiation was successfully synthesized by photo-deposition method. The La0.02Na0.98TaO3 photocatalyst was obtained by the reaction of La(NO3)2.3H2O, TaCl5, and NaOH at ambient temperature. The catalyst produced was characterized by a scanning electron microscope (SEM) and a high-resolution transmission electron microscope (HRTEM). SEM images of the La0.02Na0.98TaO3 sample showing that its particles size is ranging between 50-150 nm. The Pt particles are detected from HRTEM images is around 2-4 nm. The Pt/La0.02Na0.98TaO3 samples prepared were applied for photocatalytic H2 production at 30°C. The photocatalyst performance was evaluated for hydrogen production from water combining with glycerol as an electron donor (sacrificial reagent). The reactions were carried out in a closed reactor with a gas circulation system, illuminated with mercury (Hg) lamp. The experimental results show that the presence of glycerol in the systems can not only improve the efficiency of photocatalytic hydrogen generation but can also be decomposed to hydrogen efficiently. The photocatalytic activity of La0.02Na0.98TaO3 is significantly enhanced when Pt was loaded onto its crystalline surface.

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.

PubMed

Hurtubise, Jessica L; Marks, Wendie N; Davies, Don A; Catton, Jillian K; Baker, Glen B; Howland, John G

2017-01-01

The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients. The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment. SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task. Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials. These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.

Latin American Literatures and Cultures: Self and Society. Papers from the National Endowment for the Humanities Summer Institute (La Jolla, California, August 1996).

ERIC Educational Resources Information Center

Seabrook, John H., Ed.

1996-01-01

This special issue contains the following articles: (1) "Critiquing the Center: Rigoberta Menchu and Enrique Dussel" (Joseph R. Hoff); (2) "Caroline Maria De Jesus: A Testimonial Voice in the Wilderness" (Eva Bueno); (3) "Latin American Women's Voices: La Malinche to Rigoberta Menchu" (Ana Maria Romo de Mease); (4) "China in Borges''The Garden of…

The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion.

PubMed

Feistel, Stephan; Albrecht, Stephanie; Messlinger, Karl

2013-11-20

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are regarded as key mediators in migraine and other primary headaches. Migraineurs respond to infusion of nitroglycerin with delayed headaches, and inhibition of CGRP receptors has been shown to be effective in migraine therapy. In animal experiments nitrovasodilators like nitroglycerin induced increases in spinal trigeminal activity, which were reversed after inhibition of CGRP receptors. In the present study we asked if CGRP receptor inhibition can also prevent spinal trigeminal activity induced by nitroglycerin. In isoflurane anaesthetised rats extracellular recordings were made from neurons in the spinal trigeminal nucleus with meningeal afferent input. The non-peptide CGRP receptor inhibitor MK-8825 (5 mg/kg) dissolved in acidic saline (pH 3.3) was slowly infused into rats one hour prior to prolonged glyceryl trinitrate (nitroglycerin) infusion (250 μg/kg/h for two hours). After infusion of MK-8825 the activity of spinal trigeminal neurons with meningeal afferent input did not increase under continuous nitroglycerin infusion but decreased two hours later below baseline. In contrast, vehicle infusion followed by nitroglycerin was accompanied by a transient increase in activity. CGRP receptors may be important in an early phase of nitroglycerin-induced central trigeminal activity. This finding may be relevant for nitroglycerin-induced headaches.

Obsessive-compulsive personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Insomnia

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Illness anxiety disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Paranoid personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Avoidant personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Adjustment disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Dependent personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Antisocial personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Generalized anxiety disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Phobia - simple/specific

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Drug abuse

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Schizotypal personality disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic Psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Conversion disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Schizophrenia

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Agoraphobia

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Managing your depression - teens

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Panic disorder

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Personality disorders

MedlinePlus

... Updated by: Fred K. Berger, MD, addiction and forensic psychiatrist, Scripps Memorial Hospital, La Jolla, CA. Also ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Effects of MK-0941, a Novel Glucokinase Activator, on Glycemic Control in Insulin-Treated Patients With Type 2 Diabetes

PubMed Central

Meininger, Gary E.; Scott, Russell; Alba, Maria; Shentu, Yue; Luo, Edmund; Amin, Himal; Davies, Michael J.; Kaufman, Keith D.; Goldstein, Barry J.

2011-01-01

OBJECTIVE To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14. RESULTS At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were −0.8% and −37 mg/dL (−2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure. CONCLUSIONS In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure. PMID:21994424

X-ray absorption and magnetic circular dichroism of LaCoO3 , La0.7Ce0.3CoO3 , and La0.7Sr0.3CoO3 films: Evidence for cobalt-valence-dependent magnetism

NASA Astrophysics Data System (ADS)

Merz, M.; Nagel, P.; Pinta, C.; Samartsev, A.; v. Löhneysen, H.; Wissinger, M.; Uebe, S.; Assmann, A.; Fuchs, D.; Schuppler, S.

2010-11-01

Epitaxial thin films of undoped LaCoO3 , of electron-doped La0.7Ce0.3CoO3 , and of hole-doped La0.7Sr0.3CoO3 exhibit ferromagnetic order with a transition temperature TC≈84K , 23 K, and 194 K, respectively. The spin-state structure for these compounds was studied by soft x-ray magnetic circular dichroism and by near-edge x-ray absorption fine structure at the CoL2,3 and OK edges. It turns out that superexchange between Co3+ high-spin and Co3+ low-spin states is responsible for the ferromagnetism in LaCoO3 . For La0.7Ce0.3CoO3 the Co3+ ions are in a low-spin state and the spin and orbital moments are predominantly determined by a Co2+ high-spin configuration. A spin blockade naturally explains the low transition temperature and the insulating characteristics of La0.7Ce0.3CoO3 . For La0.7Sr0.3CoO3 , on the other hand, the magnetic moments in the epitaxial films originate from high-spin Co3+ and high-spin Co4+ states. Ferromagnetism is induced by t2g double exchange between the two high-spin configurations. For all systems, a strong magnetic anisotropy is observed, with the magnetic moments essentially oriented within the film plane.

Benchmark tests of JENDL-3.2 for thermal and fast reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takano, Hideki; Akie, Hiroshi; Kikuchi, Yasuyuki

1994-12-31

Benchmark calculations for a variety of thermal and fast reactors have been performed by using the newly evaluated JENDL-3 Version-2 (JENDL-3.2) file. In the thermal reactor calculations for the uranium and plutonium fueled cores of TRX and TCA, the k{sub eff} and lattice parameters were well predicted. The fast reactor calculations for ZPPR-9 and FCA assemblies showed that the k{sub eff} reactivity worths of Doppler, sodium void and control rod, and reaction rate distribution were in a very good agreement with the experiments.

Cross state-dependency of learning between tramadol and MK-801 in the mouse dorsal hippocampus: involvement of nitric oxide (NO) signaling pathway.

PubMed

Jafari-Sabet, Majid; Amiri, Shiva; Ataee, Ramin

2018-04-21

Tramadol, an atypical μ-opioid receptor agonist, as a psychoactive drug, is frequently abused by human beings. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help prevent drug addiction and relapse. Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al. Can J Physiol Pharmacol 96:45-50, 2018). To clarify the exact mechanisms involved, the activation of CA1 nitric oxide (NO) signaling pathway by L-arginine (a nitric oxide precursor) on the interaction between tramadol and MK-801 in memory retrieval was examined. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated and a single-trial step-down inhibitory avoidance apparatus was used for the assessment of memory retrieval. Post-training and/or pre-test microinjection of tramadol (0.5 and 1 μg/mouse) and/or a non-competitive NMDA receptor antagonist, MK-801 (0.25 and 0.5 μg/mouse), induced amnesia which were reversed when the same doses of the drugs were administered 24 h later in a pre-test session, suggesting tramadol state-dependent learning (SDL) and MK-801 SDL. The amnesia induced by post-training microinjection of tramadol (1 μg/mouse) was reversed by pre-test microinjection of MK-801 (0.25 and 0.5 μg/mouse). Pre-test microinjection of MK-801 (0.125 and 0.25 μg/mouse) with an ineffective dose of tramadol (0.25 μg/mouse) potentiated tramadol SDL. The amnesia induced by post-training microinjection of MK-801 (0.5 μg/mouse) was reversed by pre-test microinjection of tramadol (0.5 and 1 μg/mouse). Pre-test microinjection of tramadol (0.25 and 0.5 μg/mouse) with an ineffective dose of MK-801 (0.125 μg/mouse) potentiated MK-801 SDL. Pre-test microinjection of ineffective doses of L-arginine (0.125, 025, and 0.5 μg/mouse) improved amnesia

Structure of the β-form of human MK2 in complex with the non-selective kinase inhibitor TEI-L03090

PubMed Central

Fujino, Aiko; Fukushima, Kei; Kubota, Takaharu; Matsumoto, Yoshiyuki; Takimoto-Kamimura, Midori

2013-01-01

Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2), a serine/threonine kinase from the p38 mitogen-activated protein kinase signalling pathway, plays an important role in the production of TNF-α and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI-I01800 adopts an α-helical glycine-rich loop that is induced by the stable nonplanar conformer of TEI-I01800. To understand the mechanism of the structural change, the structure of MK2 bound to TEI-L03090, which lacks the key substituent found in TEI-I01800, was determined. MK2–TEI-L03090 has a β-sheet glycine-rich loop in common with other kinases, as predicted. This result suggests that a small compound can induce a drastic conformational change in the target protein structure and can be used to design potent and selective inhibitors. PMID:24316826

Vector space methods of photometric analysis. II - Refinement of the MK grid for B stars. III - The two components of ultraviolet reddening

NASA Technical Reports Server (NTRS)

Massa, D.

1980-01-01

This paper discusses systematic errors which arise from exclusive use of the MK system to determine reddening. It is found that implementation of uvby, beta photometry to refine the qualitative MK grid substantially reduces stellar mismatch error. A working definition of 'identical' ubvy, beta types is investigated and the relationship of uvby to B-V color excesses is determined. A comparison is also made of the hydrogen based uvby, beta types with the MK system based on He and metal lines. A small core correlated effective temperature luminosity error in the MK system for the early B stars is observed along with a breakdown of the MK luminosity criteria for the late B stars. The second part investigates the wavelength dependence of interstellar extinction in the ultraviolet wavelength range observed with the TD-1 satellite. In this study the sets of identical stars employed to find reddening are determined more precisely than in previous studies and consist only of normal, nonsupergiant stars. A multivariate analysis of variance techniques in an unbiased coordinate system is used for determining the wavelength dependence of reddening.

The Impact of CB2 Receptor Ligands on the MK-801-Induced Hyperactivity in Mice.

PubMed

Kruk-Slomka, Marta; Banaszkiewicz, Izabela; Biala, Grazyna

2017-04-01

It has been known that there is a relationship between cannabis use and schizophrenia-related symptoms; however, it can be a subject of controversy. The involvement of CB1 receptor ligands in the schizophrenia has already been revealed and confirmed. However, there is still lack of information concerning the role of CB2 receptors in the psychosis-like effects in mice and the further studies are needed.The aim of the present research was to study the role of the CB2 receptor ligands in the symptoms typical for schizophrenia. We provoked hyperlocomotion in mice which is analogous to positive psychosis-like effects in humans, by an acute administration of a NMDA receptor antagonist, MK-801 (0.3 and 0.6 mg/kg), a pharmacological model of schizophrenia. An acute administration of MK-801 induced the increase in locomotor activity (hyperactivity) in rodents, measured in actimeters.We revealed that an acute injection of CB2 receptor agonist JWH 133 at the dose range (0.05-1.0 mg/kg) and CB2 receptor antagonist, AM 630 at the dose range (0.1-1.0 mg/kg) decreased locomotion of mice. An acute injection of JWH 133 (2.0 mg/kg) and AM 630 (2.0 mg/kg) had no statistical significant influence on the locomotor activity of mice. However, an acute injection of both CB2 receptor ligands (agonist and antagonist), JWH 133, at the non-effective dose of 2.0 mg/kg and AM 630 at the non-effective dose of 2.0 mg/kg, potentiated the MK-801-induced hyperactivity.The present findings have confirmed that endocannabinoid system, not only via CB1, but also via CB2 receptors, may be involved in the schizophrenia-like responses, including hyperlocomotion in mice.

LaFe 0.9Ni 0.1O 3 perovskite catalyst with enhanced activity and coke-resistance for dry reforming of ethane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Baohuai; Yan, Binhang; Yao, Siyu

In this work, a LaFe 0.9Ni 0.1O 3 perovskite catalyst was evaluated for dry reforming of ethane (DRE), with two conventional oxide supported Ni catalysts (Ni/La 2O 3 and NiFe/La 2O 3) being used as references. LaFe 0.9Ni 0.1O 3 showed the best activity and high coke-/sintering-resistance. TEM, TGA, and Raman characterizations confirmed that the deactivation of Ni/La 2O 3 was owing to the growth of Ni particles and the accumulation of coke, although the formation of La 2O 2CO 3 was able to remove part of the coke during the reaction. The introduction of Fe-related species inhibited the cokemore » formation while decreased the activity due to the loss of active sites. A portion of Ni ions in the perovskite lattice could be reduced to form highly dispersed and stable Ni nanoparticles on the surface during the reaction and oxygen vacancies were left in the perovskite lattice. Pulse reactor studies revealed that the oxygen vacancies in the perovskite could facilitate the activation and dissociation of CO 2 to form CO and reactive oxygen species. Additionally, C 2H 6 was activated with the assistance of oxygen from the surface or subsurface of LaFe 0.9Ni 0.1O 3 to form CO, rather than directly dissociated to surface carbon species as observed over Ni/La 2O 3.« less

LaFe 0.9Ni 0.1O 3 perovskite catalyst with enhanced activity and coke-resistance for dry reforming of ethane

DOE PAGES

Zhao, Baohuai; Yan, Binhang; Yao, Siyu; ...

2017-12-29

In this work, a LaFe 0.9Ni 0.1O 3 perovskite catalyst was evaluated for dry reforming of ethane (DRE), with two conventional oxide supported Ni catalysts (Ni/La 2O 3 and NiFe/La 2O 3) being used as references. LaFe 0.9Ni 0.1O 3 showed the best activity and high coke-/sintering-resistance. TEM, TGA, and Raman characterizations confirmed that the deactivation of Ni/La 2O 3 was owing to the growth of Ni particles and the accumulation of coke, although the formation of La 2O 2CO 3 was able to remove part of the coke during the reaction. The introduction of Fe-related species inhibited the cokemore » formation while decreased the activity due to the loss of active sites. A portion of Ni ions in the perovskite lattice could be reduced to form highly dispersed and stable Ni nanoparticles on the surface during the reaction and oxygen vacancies were left in the perovskite lattice. Pulse reactor studies revealed that the oxygen vacancies in the perovskite could facilitate the activation and dissociation of CO 2 to form CO and reactive oxygen species. Additionally, C 2H 6 was activated with the assistance of oxygen from the surface or subsurface of LaFe 0.9Ni 0.1O 3 to form CO, rather than directly dissociated to surface carbon species as observed over Ni/La 2O 3.« less

Imaging the Morphotectonic Setting of Seismic Events and Their Propagation Paths: Methodology and Comparative Studies.

DTIC Science & Technology

1991-03-20

Suite 1212 California Institute of Technology Resron, VA 22091 Pasadena, CA 91125 Mr. William J. Best Prof. F. A. Dahlen 907 Westwood Drive...P.O. Box 1620 La Jolla, CA 92038-1620 2 Prof. William Menke Prof. Charles G. Sammis Lamont-Doherty Geological Observatory Center for Earth Sciences...Cruz, CA 95064 3, Prof. Terry C. Wallace Department of Geosciences Building #77 University of Arizona Tucson, AZ 85721 Dr. William Wortman Mission

Scattering of Regional Pn by Moho Topography

DTIC Science & Technology

1991-02-28

1212 California Institute of Technology Reston, VA 22091 Pasadena, CA 91125 Mr. William J. Best Prof. F. A. Dahlen 907 Westwood Drive Geological and...1620 La Jolla, CA 92038-1620 2 Prof. William Menke Prof. Charles G. Sammis Lamont-Doherty Geological Observatory Center for Earth Sciences of...95064 3 Prof. Terry C. Wallace Department of Geosciences Building #77 University of Arizona Tucson, AZ 85721 Dr. William Wortman Mission Research

High Frequency Array Studies of Long Range Lg Propagation and the Causes of Lg Blockage and Attenuation in the Eurasian Continental Craton. Volume 2

DTIC Science & Technology

1991-03-21

Drive, Suite 1212 California Institute of Technology Reston, VA 22091 Pasadena, CA 91125 Mr. William J. Best Prof. F. A. Dahlen 907 Westwood Drive...Box 1620 La Jolla, CA 92038-1620 2 Prof. William Menke Prof. Charles G. Sammis Lamont-Doherty Geological Observatory Center for Earth Sciences of...Cruz, CA 95064 3 Prof. Terry C. Wallace Department of Geosciences Building #77 University of Arizona Tucson, AZ 85721 Dr. William Wortman Mission

MK-801 and amphetamine result in dissociable profiles of cognitive impairment in a rodent paired associates learning task with relevance for schizophrenia.

PubMed

Talpos, John; Aerts, Nancy; Waddell, Jason; Steckler, Thomas

2015-11-01

Paired associates learning (PAL) has been suggested to be predictive of functional outcomes in first episode psychosis and of conversion from mild cognitive impairment to Alzheimer's disease. An automated touch screen-based rodent PAL (rPAL) task has been developed and is sensitive to manipulations of the dopaminergic and glutamatergic system. Accordingly, rPAL when used with pharmacological models of schizophrenia, like NMDA receptor blockade with MK-801 or dopaminergic stimulation with amphetamine, may have utility as a translational model of cognitive impairment in schizophrenia. The purpose of this study was to determine if amphetamine- and MK-801-induced impairment represent distinct models of cognitive impairment by testing their sensitivity to common antipsychotics and determine the relative contributions of D1 versus D2 receptors on performance of PAL. Rats were trained in rPAL and were then treated with MK-801, amphetamine, risperidone, haloperidol, quinpirole, SK-82958, or SCH-23390 alone and in combination. While both amphetamine and MK-801 caused clear impairments in accuracy, MK-801 induced a profound "perseverative" type behavior that was more pronounced when compared to amphetamine. Moreover, amphetamine-induced impairments, but not the effects of MK-801, could be reversed by antipsychotics as well as the D1 receptor antagonist SCH-23390, suggesting a role for both the D1 and D2 receptor in the amphetamine impairment model. These data suggest that amphetamine and MK-801 represent dissociable models of impairment in PAL, dependent on different underlying neurobiology. The ability to distinguish dopaminergic versus glutamatergic effects on performance in rPAL makes it a unique and useful tool in the modeling of cognitive impairments in schizophrenia.

Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628

PubMed Central

Stathis, Anastasios; Zucca, Emanuele; Bekradda, Mohamed; Gomez-Roca, Carlos; Delord, Jean-Pierre; de La Motte Rouge, Thibault; Uro-Coste, Emmanuelle; de Braud, Filippo; Pelosi, Giuseppe; French, Christopher A.

2016-01-01

The anti-neoplastic, pro-differentiative effects of bromodomain and extra-terminal (BET) bromodomain (BRD) inhibitors were initially discovered in NUT midline carcinoma (NMC), an aggressive subtype of squamous cancer driven by the BRD4-NUT fusion oncoprotein. BRD4-NUT blocks differentiation and maintains tumor growth through a potent chromatin modifying mechanism. OTX015/MK-8628, a novel oral BET inhibitor, targets BRD2/3/4/T with preclinical activity in NMC and several other tumor types, and is currently in clinical development. Antitumor activity was evaluated in four advanced stage NMC patients with confirmed BRD4-NUT fusions who were treated with 80 mg OTX015/MK-8628 once daily in a compassionate-use context. Two patients responded rapidly with tumor regression and symptomatic relief, and a third had meaningful disease stabilization with a minor metabolic response. The main side effects were mild to moderate gastrointestinal toxicity and fatigue, and reversible grade 3 thrombocytopenia. This is the first proof-of-concept evidence of clinical activity of a bromodomain inhibitor in targeting BRD4-NUT. PMID:26976114

Surfactant-free synthesis, luminescent properties, and drug-release properties of LaF3 and LaCO3F hollow microspheres.

PubMed

Lv, Ruichan; Gai, Shili; Dai, Yunlu; He, Fei; Niu, Na; Yang, Piaoping

2014-01-21

Uniform LaF3 and LaCO3F hollow microspheres were successfully synthesized through a surfactant-free route by employing La(OH)CO3 colloidal microspheres as a sacrificial template and NaBF4 as the fluorine source. The synthetic process consists of two steps: the preparation of a La(OH)CO3 precursor via a facile urea-based precipitation and the following formation of lanthanide fluoride hollow microspheres under aqueous conditions at low temperature (50 °C) and short reaction time (3 h), without using any surfactant and catalyst. The formation of hollow spheres with controlled size can be assigned to the Kirkendall effect. It is found that the phase and structure of the products can be simply tuned by changing the pH values of the solution. Time-dependent experiments were employed to study the possible formation process. N2 adsorption/desorption results indicate the mesoporous nature of LaF3 hollow spheres. Yb(3+)/Er(3+) (Ho(3+)) and Yb(3+)/Tm(3+)-doped LaF3 hollow spheres exhibit characteristic up-conversion (UC) emissions of Er(3+) (Ho(3+)) and Tm(3+) under 980 nm laser-diode excitation, and Ce(3+)/Tb(3+)-doped LaF3 and LaCO3F emit bright yellow-green and near-white light under UV irradiation, respectively. In particular, LaF3:Yb/Er and LaCO3F:Ce/Tb hollow microspheres exhibit obvious sustained and pH-dependent doxorubicin release properties. The luminescent properties of the carriers allow them to be tracked or monitored during the release or therapy process, suggesting their high potential in the biomedical field.

Development of imaging bolometers for magnetic fusion reactors (invited)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, Byron J.; Parchamy, Homaira; Ashikawa, Naoko

2008-10-15

Imaging bolometers utilize an infrared (IR) video camera to measure the change in temperature of a thin foil exposed to the plasma radiation, thereby avoiding the risks of conventional resistive bolometers related to electric cabling and vacuum feedthroughs in a reactor environment. A prototype of the IR imaging video bolometer (IRVB) has been installed and operated on the JT-60U tokamak demonstrating its applicability to a reactor environment and its ability to provide two-dimensional measurements of the radiation emissivity in a poloidal cross section. In this paper we review this development and present the first results of an upgraded version ofmore » this IRVB on JT-60U. This upgrade utilizes a state-of-the-art IR camera (FLIR/Indigo Phoenix-InSb) (3-5 {mu}m, 256x360 pixels, 345 Hz, 11 mK) mounted in a neutron/gamma/magnetic shield behind a 3.6 m IR periscope consisting of CaF{sub 2} optics and an aluminum mirror. The IRVB foil is 7 cmx9 cmx5 {mu}m tantalum. A noise equivalent power density of 300 {mu}W/cm{sup 2} is achieved with 40x24 channels and a time response of 10 ms or 23 {mu}W/cm{sup 2} for 16x12 channels and a time response of 33 ms, which is 30 times better than the previous version of the IRVB on JT-60U.« less

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

PubMed

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.

Possible involvement of nitric oxide (NO) signaling pathway in the antidepressant-like effect of MK-801(dizocilpine), a NMDA receptor antagonist in mouse forced swim test.

PubMed

Dhir, Ashish; Kulkarni, S K

2008-03-01

L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) is an important signaling pathway involved in depression. With this information, the present study aimed to study the involvement of this signaling pathway in the antidepressant-like action of MK-801 (dizocilpine; N-methyl-d-aspartate receptor antagonist) in the mouse forced-swim test. Total immobility period was recorded in mouse forced swim test for 6 min. MK-801 (5-25 microg/kg., ip) produced a U-shaped curve in reducing the immobility period. The antidepressant-like effect of MK-801 (10 microg/kg, ip) was prevented by pretreatment with L-arginine (750 mg/kg, ip) [substrate for nitric oxide synthase (NOS)]. Pretreatment of mice with 7-nitroindazole (7-NI) (25 mg/kg, ip) [a specific neuronal nitric oxide synthase inhibitor] produced potentiation of the action of subeffective dose of MK-801 (5 microg/kg, ip). In addition, treatment of mice with methylene blue (10 mg/kg, ip) [direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase] potentiated the effect of MK-801 (5 microg/kg, ip) in the forced-swim test. Further, the reduction in the immobility period elicited by MK-801 (10 microg/kg, ip) was also inhibited by pretreatment with sildenafil (5 mg/kg, ip) [phosphodiesterase 5 inhibitor]. The various modulators used in the study and their combination did not produce any changes in locomotor activity per se and in combination with MK-801. MK-801 however, at higher doses (25 microg/kg, ip) produced hyperlocomotion. The results demonstrated the involvement of nitric oxide signaling pathway in the antidepressant-like effect of MK-801 in mouse forced-swim test.

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

PubMed Central

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

MkMRCC, APUCC, APUBD calculations of didehydronated species: comparison among calculated through-bond effective exchange integrals for diradicals

NASA Astrophysics Data System (ADS)

Saito, Toru; Nishihara, Satomichi; Yamanaka, Shusuke; Kitagawa, Yasutaka; Kawakami, Takashi; Okumura, Mitsutaka; Yamaguchi, Kizashi

2010-10-01

Mukherjee's type of multireference coupled-cluster (MkMRCC), approximate spin-projected spin-unrestricted CC (APUCC), and AP spin-unrestricted Brueckner's (APUBD) methods were applied to didehydronated ethylene, allyl cation, cis-butadiene, and naphthalene. The focus is on descriptions of magnetic properties for these diradical species such as S-T gaps and diradical characters. Several types of orbital sets were examined as reference orbitals for MkMRCC calculations, and it was found that the change of orbital sets do not give significant impacts on computational results for these species. Comparison of MkMRCC results with APUCC and APUBD results show that these two types of methods yield similar results. These results show that the quantum spin corrected UCC and UBD methods can effectively account for both nondynamical and dynamical correlation effects that are covered by the MkMRCC methods. It was also shown that appropriately parameterized hybrid density functional theory (DFT) with AP corrections (APUDFT) calculations yielded very accurate data that qualitatively agree with those of MRCC and APUBD methods. This hierarchy of methods, MRCC, APUCC, and APUDFT, is expected to constitute a series of standard ab initio approaches towards radical systems, among which we could choose one of them, depending on the size of the systems and the required accuracy.

Metallic Borides, La 2 Re 3 B 7 and La 3 Re 2 B 5 , Featuring Extensive Boron–Boron Bonding

DOE PAGES

Bugaris, Daniel E.; Malliakas, Christos D.; Chung, Duck Young; ...

2016-01-26

We synthesized La 2Re 3B 7 and La 3Re 2B 5 in single-crystalline form from a molten La/Ni eutectic at 1000°C, in the first example of the flux crystal growth of ternary rare-earth rhenium borides. Both compounds crystallize in their own orthorhombic structure types, with La 2Re 3B 7 (space group Pcca) having lattice parameters a = 7.657(2) Å, b = 6.755(1) Å, and c = 11.617(2) Å, and La 3Re 2B 5 (space group Pmma) having lattice parameters a = 10.809(2) Å, b = 5.287(1) Å, and c = 5.747(1) Å. Furthermore, the compounds possess three-dimensional framework structures thatmore » are built up from rhenium boride polyhedra and boron-boron bonding. La 3Re 2B 5 features fairly common B 2 dumbbells, whereas La 2Re 3B 7 has unique one-dimensional subunits composed of alternating triangular B3 and trans-B4 zigzag chain fragments. Also observed in La 3Re 2B 5 is an unusual coordination of B by an octahedron of La atoms. Electronic band structure calculations predict that La 2Re 3B 7 is a semimetal, which is observed in the electrical resistivity data as measured on single crystals, with behavior obeying the Bloch-Grüneisen model and a room-temperature resistivity ρ300K of ~ 375 μΩ cm. The electronic band structure calculations also suggest that La 3Re 2B 5 is a regular metal.« less

Metallic Borides, La 2 Re 3 B 7 and La 3 Re 2 B 5 , Featuring Extensive Boron–Boron Bonding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bugaris, Daniel E.; Malliakas, Christos D.; Chung, Duck Young

We synthesized La 2Re 3B 7 and La 3Re 2B 5 in single-crystalline form from a molten La/Ni eutectic at 1000°C, in the first example of the flux crystal growth of ternary rare-earth rhenium borides. Both compounds crystallize in their own orthorhombic structure types, with La 2Re 3B 7 (space group Pcca) having lattice parameters a = 7.657(2) Å, b = 6.755(1) Å, and c = 11.617(2) Å, and La 3Re 2B 5 (space group Pmma) having lattice parameters a = 10.809(2) Å, b = 5.287(1) Å, and c = 5.747(1) Å. Furthermore, the compounds possess three-dimensional framework structures thatmore » are built up from rhenium boride polyhedra and boron-boron bonding. La 3Re 2B 5 features fairly common B 2 dumbbells, whereas La 2Re 3B 7 has unique one-dimensional subunits composed of alternating triangular B3 and trans-B4 zigzag chain fragments. Also observed in La 3Re 2B 5 is an unusual coordination of B by an octahedron of La atoms. Electronic band structure calculations predict that La 2Re 3B 7 is a semimetal, which is observed in the electrical resistivity data as measured on single crystals, with behavior obeying the Bloch-Grüneisen model and a room-temperature resistivity ρ300K of ~ 375 μΩ cm. The electronic band structure calculations also suggest that La 3Re 2B 5 is a regular metal.« less

IL-1β-induced and p38MAPK-dependent activation of the mitogen-activated protein kinase-activated protein kinase 2 (MK2) in hepatocytes: Signal transduction with robust and concentration-independent signal amplification

PubMed Central

Kulawik, Andreas; Engesser, Raphael; Ehlting, Christian; Raue, Andreas; Albrecht, Ute; Hahn, Bettina; Lehmann, Wolf-Dieter; Gaestel, Matthias; Klingmüller, Ursula; Häussinger, Dieter; Timmer, Jens; Bode, Johannes G.

2017-01-01

The IL-1β induced activation of the p38MAPK/MAPK-activated protein kinase 2 (MK2) pathway in hepatocytes is important for control of the acute phase response and regulation of liver regeneration. Many aspects of the regulatory relevance of this pathway have been investigated in immune cells in the context of inflammation. However, very little is known about concentration-dependent activation kinetics and signal propagation in hepatocytes and the role of MK2. We established a mathematical model for IL-1β-induced activation of the p38MAPK/MK2 pathway in hepatocytes that was calibrated to quantitative data on time- and IL-1β concentration-dependent phosphorylation of p38MAPK and MK2 in primary mouse hepatocytes. This analysis showed that, in hepatocytes, signal transduction from IL-1β via p38MAPK to MK2 is characterized by strong signal amplification. Quantification of p38MAPK and MK2 revealed that, in hepatocytes, at maximum, 11.3% of p38MAPK molecules and 36.5% of MK2 molecules are activated in response to IL-1β. The mathematical model was experimentally validated by employing phosphatase inhibitors and the p38MAPK inhibitor SB203580. Model simulations predicted an IC50 of 1–1.2 μm for SB203580 in hepatocytes. In silico analyses and experimental validation demonstrated that the kinase activity of p38MAPK determines signal amplitude, whereas phosphatase activity affects both signal amplitude and duration. p38MAPK and MK2 concentrations and responsiveness toward IL-1β were quantitatively compared between hepatocytes and macrophages. In macrophages, the absolute p38MAPK and MK2 concentration was significantly higher. Finally, in line with experimental observations, the mathematical model predicted a significantly higher half-maximal effective concentration for IL-1β-induced pathway activation in macrophages compared with hepatocytes, underscoring the importance of cell type-specific differences in pathway regulation. PMID:28223354

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

PubMed

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.

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

DTIC Science & Technology

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

Targeting Mitogen-activated Protein Kinase-activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts to Lead Small Molecule Inhibitors to Clinical Trials

PubMed Central

Fiore, Mario; Forli, Stefano; Manetti, Fabrizio