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Sample records for striatal punches obtained

  1. Computer Data Punch Cards

    CERN Multimedia

    Those card are printed with minimal layout aids for the formatting of FORTRAN programs, plus extra guidelines every ten columns suggesting a generic tabular data layout. A punch card is a piece of stiff paper that can be used to contain digital information represented by the presence or absence of holes in predefined positions. Punched cards were used for specialized unit record machines, organized into semiautomatic data processing systems, used punched cards for data input, output, and storage. Furthermore many new digital computers started to used punched cards.

  2. Paper Punch Tape

    CERN Multimedia

    Physicists coded and recorded their programs through series of holes on punch paper tape or on punched cards. It was popular in the 1970s due to its high throughput speed and low cost, paper tape was one of the original data storage methods for computers. Information was encoded in the distinct pattern of holes punched in the paper; the paper itself was oiled to facilitate being run through the reading mechanism and to prevent tears due to brittleness. Though the paper was cheap, it had low storage capacity (only a few dozen kilobytes per roll) and the machinery involved in punching the holes was quite expensive. Higher capacity alternatives, such as magnetic tape, has get developped.

  3. NCDC Punched Card Reference Manuals

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Documentation for using and reading punched cards kept at the National Weather Records Center (NWRC, previous name for NCDC and NCEI). Many of these punched card...

  4. Small Punch Test Techniques for Irradiated Materials in Hot Cell

    International Nuclear Information System (INIS)

    Kim, Do Sik; Ahn, S. B.; Oh, W. H.; Yoo, B. O.; Choo, Y. S.

    2006-06-01

    Detailed procedures of the small punch test including the apparatus, the definition of small punch-related parameters, and the interpretation of results were presented. The testing machine should have a capability of the compressive loading and unloading at a given deflection level. The small punch specimen holder consists of an upper and lower die and clamping screws. The clamped specimen is deformed by using ball or spherical head punch. Two type of specimens with a circular and a square shape were used. The irradiated small punch specimen is made from the undamaged portion of the broken CVN bars or prepared by the irradiation of the specimen fabricated from the fresh materials. The heating and cooling devices should have the capability of the temperature control within ±2 .deg. C for the target value during the test. Based on the load-deflection data obtained from the small punch test. the empirical correlation between the small punch related parameters and a tensile properties such as 0.2% yield strength and ultimate tensile strength, fracture toughness, ductile-brittle transition temperature and creep properties determined from the standard test method is established and used to evaluate the mechanical properties of an irradiated materials. In addition, from the quantitative fractographic assessment of small punch test specimens, the relationship between the small punch energy and the quantity of ductile crack growth is obtained. Analytical formulations demonstrated good agreement with experimental load-deflection curves

  5. Measurement of tensile and fracture toughness properties using small punch test

    International Nuclear Information System (INIS)

    Chatterjee, S.; Shah Priti Kotak

    2005-05-01

    Small punch test wu carried out at room temperature on five different steels using 10 mm by 10 mm specimens of 0.4 mm thickness in a univesal testing machine. The tensile and fracture toughness properties of the five steels obtained from small punch test were compared with those obtained from the standard test method. The results (except in one steel) show that the tensile properties obtained from small punch test are in close proximity to those obtained ftom uni-axial tension test. The results also show that fracture toughness (Jic) properties obtained ftom small punch test are within ±20% of the corresponding values obtained using standard test procedures. (author)

  6. Meniscal shear stress for punching.

    Science.gov (United States)

    Tuijthof, Gabrielle J M; Meulman, Hubert N; Herder, Just L; van Dijk, C Niek

    2009-01-01

    Experimental determination of the shear stress for punching meniscal tissue. Meniscectomy (surgical treatment of a lesion of one of the menisci) is the most frequently performed arthroscopic procedure. The performance of a meniscectomy is not optimal with the currently available instruments. To design new instruments, the punching force of meniscal tissue is an important parameter. Quantitative data are unavailable. The meniscal punching process was simulated by pushing a rod through meniscal tissue at constant speed. Three punching rods were tested: a solid rod of Oslash; 3.00 mm, and two hollow tubes (Oslash; 3.00-2.60 mm) with sharpened cutting edges of 0.15 mm and 0.125 mm thick, respectively. Nineteen menisci acquired from 10 human cadaveric knee joints were punched (30 tests). The force and displacement were recorded from which the maximum shear stress was determined (average added with three times the standard deviation). The maximum shear stress for the solid rod was determined at 10.2 N/mm2. This rod required a significantly lower punch force in comparison with the hollow tube having a 0.15 mm cutting edge (plt;0.01). The maximum shear stress for punching can be applied to design instruments, and virtual reality training environments. This type of experiment is suitable to form a database with material properties of human tissue similar to databases for the manufacturing industry.

  7. Powder properties and compaction parameters that influence punch sticking propensity of pharmaceuticals.

    Science.gov (United States)

    Paul, Shubhajit; Taylor, Lisa J; Murphy, Brendan; Krzyzaniak, Joseph F; Dawson, Neil; Mullarney, Matthew P; Meenan, Paul; Sun, Changquan Calvin

    2017-04-15

    Punch sticking is a frequently occurring problem that challenges successful tablet manufacturing. A mechanistic understanding of the punch sticking phenomenon facilitates the design of effective strategies to solve punch sticking problems of a drug. The first step in this effort is to identify process parameters and particle properties that can profoundly affect sticking performance. This work was aimed at elucidating the key material properties and compaction parameters that influence punch sticking by statistically analyzing punch sticking data of 24 chemically diverse compounds obtained using a set of tooling with removable upper punch tip. Partial least square (PLS) analysis of the data revealed that particle surface area and tablet tensile strength are the most significant factors attributed to punch sticking. Die-wall pressure, ejection force, and take-off force also correlate with sticking, but to a lesser extent. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 21 CFR 882.4750 - Skull punch.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Skull punch. 882.4750 Section 882.4750 Food and... NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4750 Skull punch. (a) Identification. A skull punch is a device used to punch holes through a patient's skull to allow fixation of cranioplasty plates or...

  9. Analysis of the Strength on the Rotor Punching Sheet of Nuclear Reactor Cooling Medium Driving Motor

    Directory of Open Access Journals (Sweden)

    GE Bao-jun

    2017-02-01

    Full Text Available A strong stress is withstood by the rotor punching sheet during the running of nuclear reactor cooling medium driving motor. In order to study the strength on the rotor punching sheet and the influential factor of its stress,the rotor of driving motor was the research object, the three-dimensional rotor model of driving motor is established by the finite element method to obtain the Mires equivalent stress nephogram and check the rotor’s strength with setting parameters and constraints. According to different rotor speeds,the different average temperatures of rotor punching sheet and shaft and the different static magnitude of interference between rotor punching sheet and shaft,the research about how the contact pressure of matching surface between rotor punching sheet and shaft and the Mires equivalent stress are impacted is carried on. The results show that the maximum Miser equivalent stress value of rotor punching sheet emerges on the axial vents,the stress value is beyond the tensile limit of the materialand. The greater the static magnitude of interference and the smaller temperature difference of rotor punching sheet and shaft lead to the greater interface compressive stress of rotor punching sheet and shaft and the greater maximum Mires equivalent stress value of rotor punching sheet. The higher the rotor speed lead to the smaller interface compressive stress of rotor punching sheet and shaft and the greater equivalent stress value of rotor punching sheet.

  10. NCDC Punched Card Inventory - 1950s

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Index of foreign weather data available on punched cards held at the Joint Punched Card Library in Asheville NC, produced in the late 1950s, and also station/data...

  11. Lubricant test for punching and blanking

    DEFF Research Database (Denmark)

    Olsson, David Dam; Bay, Niels; Andreasen, Jan Lasson

    2003-01-01

    Punching/blanking is one of the tribologically wise most severe metal forming processes.Insu $cient lubrication leads to heavy pick-up of work piece material on the punch stem,bad tolerances and eventual breakdown of the punch due to excessive backstroke force,especially in case of tribologically...... of alternative lubricants the present paper describes a new lubricant test for punching....

  12. Moment Capacity of Timber Reinforced with Punched Metal Plate Fasteners

    DEFF Research Database (Denmark)

    Nielsen, Jacob; Ellegaard, Peter

    When designing timber trusses it is often found that the cross section controlling the dimensions of the top chord is located at a joint with a moment peak. However, the timber volume affected by the moment peak is rather limited and by embedding a punched metal plate in this area a reinforcement...... of the section is obtained, resulting in a more economic truss design. In order to develop design methods for sections with plate reinforcement, bending tests have been made. The timber is Swedish spruce of strength class K-18(S8) and K-24(S10) with a thickness of 45 mm. The punched metal plate is from Gang...

  13. Studies of lubricants and punch design in punching of stainless steel

    DEFF Research Database (Denmark)

    Olsson, David Dam; Bay, Niels; Andreasen, Jan Lasson

    2004-01-01

    Environmentally hazardous lubricants such as chlorinated paraffin oils are often applied in punching and blanking operations especially involving stainless steel workpiece materials. This is due to the fact that punching and blanking are among the tribologically most difficult forming operations...

  14. High-throughput sequencing of forensic genetic samples using punches of FTA cards with buccal swabs.

    Science.gov (United States)

    Kampmann, Marie-Louise; Buchard, Anders; Børsting, Claus; Morling, Niels

    2016-01-01

    Here, we demonstrate that punches from buccal swab samples preserved on FTA cards can be used for high-throughput DNA sequencing, also known as massively parallel sequencing (MPS). We typed 44 reference samples with the HID-Ion AmpliSeq Identity Panel using washed 1.2 mm punches from FTA cards with buccal swabs and compared the results with those obtained with DNA extracted using the EZ1 DNA Investigator Kit. Concordant profiles were obtained for all samples. Our protocol includes simple punch, wash, and PCR steps, reducing cost and hands-on time in the laboratory. Furthermore, it facilitates automation of DNA sequencing.

  15. Vibration Control of a High-Speed Precision Servo Numerically Controlled Punching Press: Multidomain Simulation and Experiments

    Directory of Open Access Journals (Sweden)

    Teng Xu

    2017-01-01

    Full Text Available A three-degree-of-freedom mathematical vibration model of a high-speed punching press was developed in order to explore the vibration modes of the punching press. A multidomain model of the punching press was established to predict the kinematic state during different conditions, as well as the effects of load fluctuation on the motor speed. Experimental measurements of the acceleration of the punching press were carried out. The results comparison reveals that the multidomain model is consistent with the vibration model and the experimental measurements. Modal analysis and structure modification of the punching press were conducted. The foundation at the base of the punching press was improved against excess of vibration. The effects of the dimensions of the foundation on the vibration were discussed with the aid of the multidomain model. Finally, proper foundation design, able to reduce the vibration, was obtained.

  16. Configurational phases in elastic foams under lengthscale-free punching

    Science.gov (United States)

    Sabuwala, Tapan; Dai, Xiangyu; Gioia, Gustavo

    2016-08-01

    We carry out experiments with brick-like specimens of elastic open-cell (EOC) foams of three relative densities. Individual specimens may be "tall" (height = width = depth) or "short" (2 height = width = depth). We place each specimen on a supporting plate and use a lengthscale-free (wedge-shaped or conical) punch to apply forces downward along the specimen's height. Regardless of the type of specimen, the force-penetration curves remain linear, for the wedge-shaped punch, or quadratic, for the conical punch, up to a sizable penetration commensurate with the smallest lengthscale of the specimen. After that there is an abrupt, all-but-discontinuous change in stiffness: if the specimen is tall, the stiffness drops; if the specimen is short, the stiffness shoots up. To analyze these curious experimental results, we posit that EOC foams can be found in either of two configurational phases, here termed the low-strain phase and the high-strain phase, which share a two-dimensional interface (a surface of strain discontinuity). The analysis may be outlined as follows. In the first part of an experiment, there obtains a "similarity regime" in which the penetration of the punch and the radius of the interface are the only prevailing lengthscales (because the punch is lengthscale free). In this case, it is possible to show that the force-penetration curve must be linear, or quadratic, depending on whether the punch be wedge-shaped or conical, respectively. This prediction of the analysis is consistent with the experiments. In time, the similarity regime breaks down when the interface reaches one of the specimen's boundaries distal to the tip of the punch. If the specimen is tall, the soft, stress-free lateral boundary is reached first, and the stiffness must drop; if the specimen is short, the hard boundary in contact with the supporting plate is reached first, and the stiffness must shoot up. These predictions too are consistent with the experiments. To provide direct

  17. Very heavy iron-punching concretes

    International Nuclear Information System (INIS)

    Dubois, F.

    1966-01-01

    The present report deals with all the heavy iron-punching concretes, metallic wastes produced by the transformation industry. After a detailed description of the physical properties of metallic aggregates, a classification of heavy mortars is given, into three main categories: steel-shot grouts d = 5,3 - 6; steel-shot grouts mixed with a mineral d = 3,7 - 4,2; injection heavy grouts d = 3,5 - 4. The following chapter describes iron-punching concretes the most used in the atomic industry: iron-punching concretes mixed with cast-iron - iron-punching concretes mixed with magnetite; iron-punching concretes mixed with barite; iron-punching concretes mixed with limonite; iron-punching concretes mixed with boron. The compositions of these concretes are given together with their physical and mechanical characteristics. Numerous diagrams make it possible to find rapidly the proportions of the constituents of these concretes as a function of the required density. Technical advice and specifications are given in an appendix together with a bibliography of these heavy concretes. (author) [fr

  18. Effect of mid-thickness rebar mesh on the behavior and punching shear strength of interior slab–column connection

    Directory of Open Access Journals (Sweden)

    Ahmed Ibrahim

    2016-12-01

    The obtained results indicate that, the proposed shear reinforcement system has a positive effect in the enhancement of both the punching shear capacity and the strain energy of interior slab–column connection of both normal and high strength concrete. The general finite element software ANSYS can be used successfully to simulate the punching shear behavior of reinforced concrete flat plates.

  19. Recent progress in shear punch testing

    International Nuclear Information System (INIS)

    Hamilton, M.L.; Toloczko, M.B.; Lucas, G.E.

    1994-09-01

    The shear punch test was developed in response to the needs of the materials development community for small-scale mechanical properties tests. Such tests will be of great importance when a fusion neutron simulation device is built, since such a device is expected to have a limited irradiation volume. The shear punch test blanks a circular disk from a fixed sheet metal specimen, specifically a TEM disk. Load-displacement data generated during the test can be related to uniaxial tensile properties such as yield and ultimate strength. Shear punch and tensile tests were performed at room temperature on a number of unirradiated aluminum, copper, vanadium, and stainless steel alloys and on several irradiated aluminum alloys. Recent results discussed here suggest that the relationship between shear punch strength and tensile strength varies with alloy class, although the relationship determined for the unirradiated condition remains valid for the irradiated aluminum alloys

  20. Single maximal versus combination punch kinematics.

    Science.gov (United States)

    Piorkowski, Barry A; Lees, Adrian; Barton, Gabor J

    2011-03-01

    The aim of this study was to determine the influence of punch type (Jab, Cross, Lead Hook and Reverse Hook) and punch modality (Single maximal, 'In-synch' and 'Out of synch' combination) on punch speed and delivery time. Ten competition-standard volunteers performed punches with markers placed on their anatomical landmarks for 3D motion capture with an eight-camera optoelectronic system. Speed and duration between key moments were computed. There were significant differences in contact speed between punch types (F(2,18,84.87) = 105.76, p = 0.001) with Lead and Reverse Hooks developing greater speed than Jab and Cross. There were significant differences in contact speed between punch modalities (F(2,64,102.87) = 23.52, p = 0.001) with the Single maximal (M+/- SD: 9.26 +/- 2.09 m/s) higher than 'Out of synch' (7.49 +/- 2.32 m/s), 'In-synch' left (8.01 +/- 2.35 m/s) or right lead (7.97 +/- 2.53 m/s). Delivery times were significantly lower for Jab and Cross than Hook. Times were significantly lower 'In-synch' than a Single maximal or 'Out of synch' combination mode. It is concluded that a defender may have more evasion-time than previously reported. This research could be of use to performers and coaches when considering training preparations.

  1. Relationship between strain and central deflection in small punch creep specimens

    International Nuclear Information System (INIS)

    Yang Zhen; Wang Zhiwen

    2003-01-01

    Acquiring information about creep strain directly from small punch creep tests is difficult because the deformation behaviour of the small punch specimen is complicated. A routine is suggested in the present paper to treat this problem indirectly. Based on a finite element analysis, it is proposed that the relationship of central deflection δ to central creep strain ε c of a specimen subjected to creep can be represented approximately by the relationship of central deflection δ to central (elastic-plastic) strain ε of a specimen not subjected to creep. With this hypothesis, the δ∼ε c relation of the small punch creep specimen is obtained by resorting to a rigid-plastic membrane stretch forming model. Finally, small punch creep test results are used to evaluate creep strain and creep strain rate by taking advantage of this δ∼ε c relation

  2. Small punch test evaluation methods for material characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Janča, Adam, E-mail: adam.janca@fjfi.cvut.cz; Siegl, Jan, E-mail: jan.siegl@fjfi.cvut.cz; Haušild, Petr, E-mail: petr.hausild@fjfi.cvut.cz

    2016-12-01

    The Small Punch Test (SPT) is one of the most widespread mechanical testing methods using miniaturized specimens. The paper presented deals with the time independent SPT, in which a flat specimen is bent by means of a (hemi)spherical punch moving at a constant velocity. The main goal is to relate the measured data to deformation processes taking place during specimen loading. Understanding of such relations is crucial for characterizing a material using any non-standardized experimental procedure. Using enhanced instrumentation, not only traditional load-displacement or load-deflection curves could be obtained, but also specimen thinning could be continuously measured and evaluated. Five alloys having a broad range of mechanical properties were tested. The results obtained were evaluated using both traditional and newly proposed methods and they were correlated with results of the conventional tensile test. The methods proposed seem to lead to a universal correlation between SPT results and tensile characteristics. - Highlights: • The newly proposed methodology significantly improved results of SPT. • Plastic deformation starts inside the specimen from the very beginning of loading. • Specimen thinning = punch displacement−specimen deflection. • Material response to loading is well illustrated by the novel load-thinning curve.

  3. Parsing Heterogeneous Striatal Activity

    Directory of Open Access Journals (Sweden)

    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  4. Development of small punch tests for ductile-brittle transition temperature measurement of temper embrittled Ni-Cr steels

    International Nuclear Information System (INIS)

    Baik, J.M.; Kameda, J.; Buck, O.

    1983-01-01

    Small punch tests were developed to determine the ductile-brittle transition temperature of nickel-chromium (Ni-Cr) steels having various degrees of temper embrittlement and various microstructures. It was found that the small punch test clearly shows the ductile-brittle transition behavior of the temper-embrittled steels. The measured values were compared with those obtained from Charpy impact and uniaxial tensile tests. The effects of punch tip shape, a notch, and the strain rate on the ductile-brittle transition behavior were examined. It was found that the combined use of a notch, high strain rates, and a small punch tip strongly affects the ductile-brittle transition behavior. Considerable variations in the data were observed when the small punch tests were performed on coarse-grained steels. Several factors controlling embrittlement measurements of steels are discussed in terms of brittle fracture mechanisms

  5. Data on treatment of sewage wastewater by electrocoagulation using punched aluminum electrode and characterization of generated sludge

    Directory of Open Access Journals (Sweden)

    Vinita Khandegar

    2018-06-01

    Full Text Available The electrocoagulation setup must be optimized in order to design an economically feasible process. Therefore, in this work, the effect of the punched aluminum electrode on the performance of the electrocoagulation (EC has been investigated. A series of experiments were performed for treatment of sewage wastewater using plane electrode and compare with punched electrodes. Effect of contact time, voltage, electrode spacing and stirring speed has been optimized for removal of Biochemical oxygen demand (BOD and Total dissolved solids (TDS. It was observed that the performance of electrocoagulation process increased using punched electrode. Also, the less operating cost noticed in punched electrode as compared to a plane electrode for (70–80% removal of BOD and TDS. These data would be useful in designing of an EC reactor to obtain high removal efficiency at low energy consumption. Keywords: Electrocoagulation, Sewage wastewater, Aluminum, Plane, Punched electrode

  6. Punch Biopsy Results in Misdiagnosis of Pilomatrixoma

    Directory of Open Access Journals (Sweden)

    Metin Temel

    2017-03-01

    Full Text Available Punch biopsy results in misdiagnosis of clinically unsuspected giant pilomatrixoma located over the parotid gland. This study presents a case of pilomatrixoma that was misdiagnosed as a malignant epithelial tumor using punch biopsy. A 25-year-old male was admitted to our clinic for the evaluation of a mass measuring 7×8×8 cm located over the parotid gland. The patient had previously undergone punch biopsy at another clinic because of a lesion in the parotid gland. Punch biopsy revealed a malignant epithelial tumor. The patient underwent excisional biopsy at our clinic. After the biopsy, the residual skin defect was treated using full-thickness skin grafts. The facial nerve and parotid gland were preserved during the biopsy. Histopathological examination of the excisional biopsy material revealed pilomatrixoma. Punch biopsy may result in misdiagnosis of skin lesions in the parotid gland. A differential diagnosis for benign tumors such as pilomatrixoma is essential prior to an aggressive surgical intervention of the parotid gland.

  7. Shear punch tests performed using a new low compliance test fixture

    International Nuclear Information System (INIS)

    Toloczko, M.B.; Kurtz, R.J.; Hasegawa, A.; Abe, K.

    2002-01-01

    Based on a recent finite element analysis (FEA) study performed on the shear punch test technique, it was suggested that compliance in a test frame and fixturing which is quite acceptable for uniaxial tensile tests, is much too large for shear punch tests. The FEA study suggested that this relatively large compliance was masking both the true yield point and the shape of the load versus displacement trace obtained in shear punch tests. The knowledge gained from the FEA study was used to design a new shear punch test fixture which more directly measures punch tip displacement. The design of this fixture, the traces obtained from this fixture, and the correlation between uniaxial yield stress and shear yield stress obtained using this fixture are presented here. In general, traces obtained from the new fixture contain much less compliance resulting in a trace shape which is more similar in appearance to a corresponding uniaxial tensile trace. Due to the more direct measurement of displacement, it was possible to measure yield stress at an offset shear strain in a manner analogous to yield stress measurement in a uniaxial tensile test. The correlation between shear yield and uniaxial yield was altered by this new yield measurement technique, but the new correlation was not as greatly improved as was suggested would occur from the FEA study

  8. A solution for the narrow rectangular punch

    NARCIS (Netherlands)

    Panek, C.F.; Kalker, J.J.

    1977-01-01

    This paper considers the problem of a rectangular flat ended punch acting on an elastic half-space. An approximate solution is generated through application of the elastic line integral equations. The results produced by this method are then compared with another approximate solution already

  9. Damage modeling in Small Punch Test specimens

    DEFF Research Database (Denmark)

    Martínez Pañeda, Emilio; Cuesta, I.I.; Peñuelas, I.

    2016-01-01

    . Furthermore,Gurson-Tvergaard-Needleman model predictions from a top-down approach are employed to gain insightinto the mechanisms governing crack initiation and subsequent propagation in small punch experiments.An accurate assessment of micromechanical toughness parameters from the SPT...

  10. Optimization of fruit punch using mixture design.

    Science.gov (United States)

    Kumar, S Bharath; Ravi, R; Saraswathi, G

    2010-01-01

    A highly acceptable dehydrated fruit punch was developed with selected fruits, namely lemon, orange, and mango, using a mixture design and optimization technique. The fruit juices were freeze dried, powdered, and used in the reconstitution studies. Fruit punches were prepared according to the experimental design combinations (total 10) based on a mixture design and then subjected to sensory evaluation for acceptability. Response surfaces of sensory attributes were also generated as a function of fruit juices. Analysis of data revealed that the fruit punch prepared using 66% of mango, 33% of orange, and 1% of lemon had highly desirable sensory scores for color (6.00), body (5.92), sweetness (5.68), and pleasantness (5.94). The aroma pattern of individual as well as combinations of fruit juices were also analyzed by electronic nose. The electronic nose could discriminate the aroma patterns of individual as well as fruit juice combinations by mixture design. The results provide information on the sensory quality of best fruit punch formulations liked by the consumer panel based on lemon, orange, and mango.

  11. Novel uses of skin biopsy punches in dermatosurgery

    Directory of Open Access Journals (Sweden)

    Deepak S Hurkudli

    2015-01-01

    Full Text Available The skin punch or surgical punch is an instrument which is used almost exclusively by dermatologists. It is a circular hollow blade attached to a pencil-like handle ranging in size from 0.5 to 10 mm. It is available as a disposable, reusable, and automated instrument. The punch can be used as a diagnostic, therapeutic, and cosmetic tool in dermatology. We have used punch as a diagnostic, therapeutic, and cosmetic tool in our dermatosurgery practice in our hospital. Various original research articles, text book publications, and review articles were studied and compiled. Techniques used by various authors and our own experiences with punch have been described. This article aims at providing the novel usefulness of skin biopsy punch in dermatology as the basic punch surgery is quick and easy to learn. Complications such as bleeding and infection are minimal.

  12. Frictionless contact of a rigid punch indenting a transversely isotropic elastic layer

    Directory of Open Access Journals (Sweden)

    Rajesh Patra

    2016-03-01

    Full Text Available This article is concerned with the study of frictionless contact between a rigid punch and a transversely isotropic elastic layer. The rigid punch is assumed to be axially symmetric and is being pressed towards the layer by an applied concentrated load. The layer is resting on a rigid base and is assumed to be ufficiently thick in comparison with the amount of indentation by the rigid punch. The relationship between the applied load $P$ and the contact area is obtained by solving the mathematically formulated problem through use of Hankel transform of different order. Effect of indentation on the distribution of normal stress at the surface as well as the relationship between the applied load and the area of contact have been shown graphically.

  13. Love-type wave propagation in a pre-stressed viscoelastic medium influenced by smooth moving punch

    Science.gov (United States)

    Singh, A. K.; Parween, Z.; Chatterjee, M.; Chattopadhyay, A.

    2015-04-01

    In the present paper, a mathematical model studying the effect of smooth moving semi-infinite punch on the propagation of Love-type wave in an initially stressed viscoelastic strip is developed. The dynamic stress concentration due to the punch for the force of a constant intensity has been obtained in the closed form. Method based on Weiner-hopf technique which is indicated by Matczynski has been employed. The study manifests the significant effect of various affecting parameters viz. speed of moving punch associated with Love-type wave speed, horizontal compressive/tensile initial stress, vertical compressive/tensile initial stress, frequency parameter, and viscoelastic parameter on dynamic stress concentration due to semi-infinite punch. Moreover, some important peculiarities have been traced out and depicted by means of graphs.

  14. Small punch creep test: A promising methodology for high temperature plant components life evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tettamanti, S. [CISE SpA, Milan (Italy); Crudeli, R. [ENEL SpA, Milan (Italy)

    1998-12-31

    CISE and ENEL are involved for years in a miniaturization creep methodology project to obtain similar non-destructive test with the same standard creep test reliability. The goal can be reached with `Small punch creep test` that collect all the requested characteristics; quasi nondestructive disk specimens extracted both on external or internal side of components, than accurately machined and tested on little and cheap apparatus. CISE has developed complete creep small punch procedure that involved peculiar test facility and correlation`s law comparable with the more diffused isostress methodology for residual life evaluation on ex-serviced high temperature plant components. The aim of this work is to obtain a simple and immediately applicable relationship useful for plant maintenance managing. More added work is need to validate the Small Punch methodology and for relationship calibration on most diffusion high temperature structural materials. First obtained results on a comparative work on ASTM A355 P12 ex-serviced pipe material are presented joint with a description of the Small Punch apparatus realized in CISE. (orig.) 6 refs.

  15. Small punch creep test: A promising methodology for high temperature plant components life evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tettamanti, S [CISE SpA, Milan (Italy); Crudeli, R [ENEL SpA, Milan (Italy)

    1999-12-31

    CISE and ENEL are involved for years in a miniaturization creep methodology project to obtain similar non-destructive test with the same standard creep test reliability. The goal can be reached with `Small punch creep test` that collect all the requested characteristics; quasi nondestructive disk specimens extracted both on external or internal side of components, than accurately machined and tested on little and cheap apparatus. CISE has developed complete creep small punch procedure that involved peculiar test facility and correlation`s law comparable with the more diffused isostress methodology for residual life evaluation on ex-serviced high temperature plant components. The aim of this work is to obtain a simple and immediately applicable relationship useful for plant maintenance managing. More added work is need to validate the Small Punch methodology and for relationship calibration on most diffusion high temperature structural materials. First obtained results on a comparative work on ASTM A355 P12 ex-serviced pipe material are presented joint with a description of the Small Punch apparatus realized in CISE. (orig.) 6 refs.

  16. Investigating the effect of tablet thickness and punch curvature on density distribution using finite elements method.

    Science.gov (United States)

    Diarra, Harona; Mazel, Vincent; Busignies, Virginie; Tchoreloff, Pierre

    2015-09-30

    Finite elements method was used to study the influence of tablet thickness and punch curvature on the density distribution inside convex faced (CF) tablets. The modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous calcium phosphate and microcrystalline cellulose) by using Drucker-Prager Cap model in Abaqus(®) software. The parameters of the model were obtained from experimental tests. Several punch shapes based on industrial standards were used. A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with a diameter of 8mm were chosen. Different tablet thicknesses were studied at a constant compression force. The simulation of the compaction of CF tablets with increasing thicknesses showed an important change on the density distribution inside the tablet. For smaller thicknesses, low density zones are located toward the center. The density is not uniform inside CF tablets and the center of the 2 faces appears with low density whereas the distribution inside FF tablets is almost independent of the tablet thickness. These results showed that FF and CF tablets, even obtained at the same compression force, do not have the same density at the center of the compact. As a consequence differences in tensile strength, as measured by diametral compression, are expected. This was confirmed by experimental tests. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Analysis of Pick-Up Development in Punching

    DEFF Research Database (Denmark)

    Olsson, David Dam; Bay, Niels; Andreasen, Jan Lasson

    2002-01-01

    The development of pick-up of work piece material on the punch surface with increasing number of strokes during punching of stainless steel sheet is investigated applying Scanning Electron Microscopy (SEM), 3D roughness mapping and measurements of the backstroke force. It is found that pick...

  18. Development of lubricant test for punching and blanking

    DEFF Research Database (Denmark)

    Olsson, David Dam

    2001-01-01

    The background for development of new lubricants Requirements to lubricant test for punching Methods of evaluating lubricants Test equipment developed at DTU Conclusion.......The background for development of new lubricants Requirements to lubricant test for punching Methods of evaluating lubricants Test equipment developed at DTU Conclusion....

  19. Applying a punch with microridges in multistage deep drawing processes.

    Science.gov (United States)

    Lin, Bor-Tsuen; Yang, Cheng-Yu

    2016-01-01

    The developers of high aspect ratio components aim to minimize the processing stages in deep drawing processes. This study elucidates the application of microridge punches in multistage deep drawing processes. A microridge punch improves drawing performance, thereby reducing the number of stages required in deep forming processes. As an example, the original eight-stage deep forming process for a copper cylindrical cup with a high aspect ratio was analyzed by finite element simulation. Microridge punch designs were introduced in Stages 4 and 7 to replace the original punches. In addition, Stages 3 and 6 were eliminated. Finally, these changes were verified through experiments. The results showed that the microridge punches reduced the number of deep drawing stages yielding similar thickness difference percentages. Further, the numerical and experimental results demonstrated good consistency in the thickness distribution.

  20. Cone penetrometer tests and HydroPunch sampling: A screening technique for plume definition

    International Nuclear Information System (INIS)

    Smolley, M.; Kappmeyer, J.C.

    1991-01-01

    Cone penetrometer tests and HydroPunch sampling were used to define the extent of volatile organic compounds in ground water. The investigation indicated that the combination of the these techniques is effective for obtaining ground water samples for preliminary plume definition. HydroPunch samples can be collected in unconsolidated sediments and the analytical results obtained from these samples are comparable to those obtained from adjacent monitoring wells. This sampling method is a rapid and cost-effective screening technique for characterizing the extent of contaminant plumes in soft sediment environments. Use of this screening technique allowed monitoring wells to be located at the plume boundary, thereby reducing the number of wells installed and the overall cost of the plume definition program

  1. Research on the Visual Processing System of the Punch Press

    Directory of Open Access Journals (Sweden)

    Sun Xuan

    2016-01-01

    Full Text Available Most of raw materials of small hardware processing for plate scraps, and it’s realized through the manual operation of ordinary punch, which way has the low production efficiency and the high labor intensity. In order to improve the automation level of production, developing and designing of a visual processing system for punch press manipulator which based on the MFC tools of Visual Studio software platform. Through the image acquisition and image processing, get the information about the board to be processed, such as shape, length, the center of gravity position and pose, and providing relevant parameters for positioning gripping and placing into the punch table positioning of the feeding manipulator and automatic programming of punching machine, so as to realize the automatic operation about press feeding and processing.

  2. Interaction between a punch and an arbitrary crack or inclusion in a transversely isotropic half-space

    Science.gov (United States)

    Fabrikant, I.; Karapetian, E.; Kalinin, S. V.

    2018-02-01

    We consider the problem of an arbitrary shaped rigid punch pressed against the boundary of a transversely isotropic half-space and interacting with an arbitrary flat crack or inclusion, located in the plane parallel to the boundary. The set of governing integral equations is derived for the most general conditions, namely the presence of both normal and tangential stresses under the punch, as well as general loading of the crack faces. In order to verify correctness of the derivations, two different methods were used to obtain governing integral equations: generalized method of images and utilization of the reciprocal theorem. Both methods gave the same results. Axisymmetric coaxial case of interaction between a rigid inclusion and a flat circular punch both centered along the z-axis is considered as an illustrative example. Most of the final results are presented in terms of elementary functions.

  3. Cost Optimization on Energy Consumption of Punching Machine Based on Green Manufacturing Method at PT Buana Intan Gemilang

    Directory of Open Access Journals (Sweden)

    Prillia Ayudia

    2017-01-01

    Full Text Available PT Buana Intan Gemilang is a company engaged in textile industry. The curtain textile production need punching machine to control the fabric process. The operator still works manually so it takes high cost of electrical energy consumption. So to solve the problem can implement green manufacturing on punching machine. The method include firstly to identify the color by classifying the company into the black, brown, gray or green color categories using questionnaire. Secondly is improvement area to be optimized and analyzed. Improvement plan at this stage that is focusing on energy area and technology. Thirdly is process applies by modifying the technology through implementing automation system on the punching machine so that there is an increase of green level on the process machine. The result obtained after implement the method can save cost on electrical energy consumption in the amount of Rp 1.068.159/day.

  4. Countering Stryker’s Punch: Algorithmically Filling the Black Hole

    OpenAIRE

    Michael J. Bennett

    2017-01-01

    Two current digital image editing programs are examined in the context of filling in missing visual image data from hole-punched United States Farm Security Administration (FSA) negatives. Specifically, Photoshop's Content-Aware Fill feature and GIMP's Resynthesizer plugin are evaluated and contrasted against comparable images. A possible automated workflow geared towards large scale editing of similarly hole-punched negatives is also explored. Finally, potential future research based upon th...

  5. Prediction of effects of punch shapes on tableting failure by using a multi-functional single-punch tablet press

    Directory of Open Access Journals (Sweden)

    Takashi Osamura

    2017-09-01

    Full Text Available We previously determined “Tableting properties” by using a multi-functional single-punch tablet press (GTP-1. We proposed plotting “Compactability” on the x-axis against “Manufacturability” on the y-axis to allow visual evaluation of “Tableting properties”. Various types of tableting failure occur in commercial drug production and are influenced by the amount of lubricant used and the shape of the punch. We used the GTP-1 to measure “Tableting properties” with different amounts of lubricant and compared the results with those of tableting on a commercial rotary tableting machine. Tablets compressed with a small amount of lubricant showed bad “Manufacturability”, leading to sticking of powder on punches. We also tested various punch shapes. The GTP-1 correctly predicted the actual tableting results for all punch shapes. With punches that were more likely to cause tableting failure, our system predicted the effects of lubricant quantity in the tablet formulation and the occurrence of sticking in the rotary tableting machine.

  6. Dysregulation of striatal projection neurons in Parkinson's disease.

    Science.gov (United States)

    Beck, Goichi; Singh, Arun; Papa, Stella M

    2018-03-01

    The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

  7. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P fetal rat lateral ganglionic...

  8. Repetitive forging (RF) using inclined punches as a new bulk severe plastic deformation method

    Energy Technology Data Exchange (ETDEWEB)

    Babaei, A. [Department of Mechanical Engineering, University College of Engineering, University of Tehran, Tehran 11155-4563 (Iran, Islamic Republic of); Faraji, G., E-mail: ghfaraji@ut.ac.ir [Department of Mechanical Engineering, University College of Engineering, University of Tehran, Tehran 11155-4563 (Iran, Islamic Republic of); Department of Engineering Design and Manufacture, University of Malaya, 50603 Kuala Lumpur (Malaysia); Mashhadi, M.M. [Department of Mechanical Engineering, University College of Engineering, University of Tehran, Tehran 11155-4563 (Iran, Islamic Republic of); Hamdi, M. [Department of Engineering Design and Manufacture, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2012-12-15

    A new bulk severe plastic deformation method based on repetitive forging (RF) using inclined punches is proposed. This process consists of two half cycles. In the first half cycle, a square cross section deforms to parallelogram by forging with two inclined punches, and the parallelogram cross section is forged back to square using two flat punches in the second half cycle. This method was applied to commercially pure copper and significant grain refinement was achieved after four passes of RF. The results showed that significant improvement in the mechanical properties was obtained. Notable increase of yield and ultimate strengths corresponding to 358 MPa and 381 MPa after four passes of RF from the initial values of 121 MPa and 230.5 MPa is detectable. Microhardness increases to about 100 Hv after four passes of RF from the initial value of 53 Hv. Finite element (FE) results illustrate that RF is able to impose extremely high plastic strains to the materials. In the RF process, the processed samples have the same dimensions and geometry as those of the initial sample without any waste material and there is no need for back pressure.

  9. Using Teamcenter engineering software for a successive punching tool lifecycle management

    Science.gov (United States)

    Blaga, F.; Pele, A.-V.; Stǎnǎşel, I.; Buidoş, T.; Hule, V.

    2015-11-01

    The paper presents studies and researches results of the implementation of Teamcenter (TC) integrated management of a product lifecycle, in a virtual enterprise. The results are able to be implemented also in a real enterprise. The product was considered a successive punching and cutting tool, designed to materialize a metal sheet part. The paper defines the technical documentation flow (flow of information) in the process of constructive computer aided design of the tool. After the design phase is completed a list of parts is generated containing standard or manufactured components (BOM, Bill of Materials). The BOM may be exported to MS Excel (.xls) format and can be transferred to other departments of the company in order to supply the necessary materials and resources to achieve the final product. This paper describes the procedure to modify or change certain dimensions of sheet metal part obtained by punching. After 3D and 2D design, the digital prototype of punching tool moves to following lifecycle phase of the manufacturing process. For each operation of the technological process the corresponding phases are described in detail. Teamcenter enables to describe manufacturing company structure, underlying workstations that carry out various operations of manufacturing process. The paper revealed that the implementation of Teamcenter PDM in a company, improves efficiency of managing product information, eliminating time working with search, verification and correction of documentation, while ensuring the uniqueness and completeness of the product data.

  10. Shear punch and microhardness tests for strength and ductility measurements

    International Nuclear Information System (INIS)

    Lucas, G.E.; Odette, G.R.; Sheckherd, J.W.

    1983-01-01

    In response to the requirements of the fusion reactor materials development program for small-scale mechanical property tests, two techniques have been developed, namely ball microhardness and shear punch tests. The ball microhardness test is based on the repeated measurement at increasing loads of the chordal diameter of an impression made by a spherical penetrator. A correlation has been developed to predict the constitutive relation of the test material from these data. In addition, the indentation pile-up geometry can be analyzed to provide information on the homogeneity of plastic flow in the test material. The shear punch test complements the microhardness test. It is based on blanking a circular disk from a fixed sheet metal specimen. The test is instrumented to provide punch load-displacement data, and these data can be used to determine flow properties of the test material such as yield stress, ultimate tensile strength, work-hardening exponent, and reduction of area

  11. Blanking Clearance and Punch Velocity Effects on The Sheared Edge Characteristic in Micro-Blanking of Commercially Pure Copper Sheet

    OpenAIRE

    Didin Zakaria Lubis; Ichsan Ristiawan

    2017-01-01

    This study aims to identify the influences between clearance and punch velocity on the part edge quality of blanked parts. Experiments have been conducted using material copper, punch-die clearance and punch velocity variations. In order to determine the reachable punch-die clearance and punch velocity required for blanking. The quality of the part-edge characteristics shows that higher punch velocity and decreases clearance value can improve the part-edge quality, resulting in smaller burr h...

  12. Measuring the force of punches using an accelerometric punching bag - Relationship between force of punches and power of jump - An example of application of the modern information technology in sport

    Science.gov (United States)

    Pilewska, Wiesława; Buśko, Krzysztof; Nikolaidis, Pantelis Theodoros

    2017-11-01

    The main aim of the study was to design a new system to measure punching forces in boxers. In addition, the study examined whether there were any relationship between force of punches and power of jump. A total of 9 boxers (age: 17.5±1.2 years, body height: 174.1±8.1 cm, body mass: 73.9±11.8 kg) participated in the study. The punching bag was equipped with acceleration transducers and gyroscopes embedded in a cylinder covered with a layer to absorb shock as well as a set of colour signal diodes. Value of the punching bag's acceleration was used for calculating: strike force; the punching location on the bag; and time of a strike. The relative error of force calculation was 3%; the relative error in acceleration measurement was less than 1%. The maximal straight of rear and lead punching forces were 1702.4±497.8 N and 1262.0±417.7 N in boxers, respectively. Strong correlations were found between the punching force and power of lower limbs developed for the ACMJ, CMJ and SPJ jump. Height of rise of the body mass centre and punching force correlated insignificantly. Based on these findings, it was concluded that the modified punching bag is a good diagnostic tool for combat sports. The measurement of power during the jump may be a good diagnostic test in boxers.

  13. Recent developments in small punch testing: Applications at elevated temperatures

    Czech Academy of Sciences Publication Activity Database

    Dymáček, Petr

    2016-01-01

    Roč. 86, DEC (2016), s. 25-33 ISSN 0167-8442 R&D Projects: GA MŠk(CZ) LQ1601 Institutional support: RVO:68081723 Keywords : Small punch test * Creep rupture * Stress relaxation Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.659, year: 2016

  14. A Semiotics of Cartoons in Two Nigerian Newspapers: The Punch ...

    African Journals Online (AJOL)

    The paper explores the semiotics of cartoons using selected samples from The punch and The Guardian, newspapers based in Nigeria. It seeks to bridge the gap between semiotics and the act of cartooning. It also attempts to show the relationship between the cartoons and the semiotic resources employed. It analyses how ...

  15. Moving Griffith crack in an orthotropic strip with punches at boundary faces

    Directory of Open Access Journals (Sweden)

    S. Mukherjee

    2005-01-01

    Full Text Available Integral transform technique is employed to solve the elastodynamic problem of steady-state propagation of a Griffith crack centrally situated along the midplane of orthotropic strip of finite thickness 2h and subjected to point loading with centrally situated moving punches under constant pressure along the boundaries of the layer. The problem is reduced to the solution of a pair of simultaneous singular integral equations with Cauchy-type singularities which have finally been solved through the finite Hilbert transform technique. For large h, analytical expression for the stress intensity factor at the crack tip is obtained. Graphical plots of the numerical results are also presented.

  16. Control of striatal signaling by G protein regulators

    Directory of Open Access Journals (Sweden)

    Keqiang eXie

    2011-08-01

    Full Text Available Signaling via heterotrimeric G proteins plays a crucial role in modulating the responses of striatal neurons that ultimately shape core behaviors mediated by the basal ganglia circuitry, such as reward valuation, habit formation and movement coordination. Activation of G-protein-coupled receptors (GPCRs by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes and protein kinases. Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling pathways and cellular responses with unique profiles but common molecular mechanisms. Studies over the last decade have revealed that the extent and duration of GPCR signaling are controlled by a conserved protein family named Regulator of G protein Signaling (RGS. RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this review, we discuss the progress made in understanding the roles of RGS proteins in controlling striatal G protein signaling and providing integration and selectivity of signal transmission. We review evidence on the formation of a macromolecular complex between RGS proteins and other components of striatal signaling pathways, their molecular regulatory mechanisms and impacts on GPCR signaling in the striatum obtained from biochemical studies and experiments involving genetic mouse models. Special emphasis is placed on RGS9-2, a member of the RGS family that is highly enriched in the striatum and plays critical roles in drug addiction and motor control.

  17. Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem.

    Science.gov (United States)

    Laker-Oketta, Miriam O; Wenger, Megan; Semeere, Aggrey; Castelnuovo, Barbara; Kambugu, Andrew; Lukande, Robert; Asirwa, F Chite; Busakhala, Naftali; Buziba, Nathan; Diero, Lameck; Wools-Kaloustian, Kara; Strother, Robert Matthew; Bwana, Mwebesa; Muyindike, Winnie; Amerson, Erin; Mbidde, Edward; Maurer, Toby; Martin, Jeffrey

    2015-01-01

    Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic's essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

  18. Characterization of Rubbers from Spherical Punch - Plate Indentation Tests

    Directory of Open Access Journals (Sweden)

    Florina Carmen Ciornei

    2016-12-01

    Full Text Available Rubber plates with different compositions and hardness were tested by continuous indentation, using a spherical punch and hysteretic phenomenon was evidenced. The experimental data interpolation with polynomial functions is accurate and permits estimation of the lost work during loading cycles. The interpolation by power law functions is more convenient by using less parameters and having a form accepted in literature. From the rubbers tested, two were considered to present good damping properties.

  19. Design of punching shear for prestressed slabs with unbonded tendons on internal columns

    Directory of Open Access Journals (Sweden)

    L. A. R. Luchi

    Full Text Available ABSTRACT This paper is related to the punching shear in prestressed slabs with unbonded tendons for interior columns calculated by the codes ABNT NBR 6118:2007, ABNT NBR 6118:2014, EN 1992-1-1:2004 e ACI 318-11. To calculate the punching shear resistance the formulations of the NBR 6118:07, effective until April/2014, did not consider the compression of the concrete in the plane of the slab, due to prestressing. Just the inclined components of some tendons were considered for total load applied relief, but this fact did not generate a significant difference, compared to reinforced concrete, because the inclination angle is very close to zero. The American and European provisions consider a portion related to the compression of the concrete in the planeof the slab. Differences in the results obtained by the four design codes will be exposed, showing that the EC2:04 and the NBR6118:14 achieved the best results.

  20. Optimal design of a main driving mechanism for servo punch press based on performance atlases

    Science.gov (United States)

    Zhou, Yanhua; Xie, Fugui; Liu, Xinjun

    2013-09-01

    The servomotor drive turret punch press is attracting more attentions and being developed more intensively due to the advantages of high speed, high accuracy, high flexibility, high productivity, low noise, cleaning and energy saving. To effectively improve the performance and lower the cost, it is necessary to develop new mechanisms and establish corresponding optimal design method with uniform performance indices. A new patented main driving mechanism and a new optimal design method are proposed. In the optimal design, the performance indices, i.e., the local motion/force transmission indices ITI, OTI, good transmission workspace good transmission workspace(GTW) and the global transmission indices GTIs are defined. The non-dimensional normalization method is used to get all feasible solutions in dimensional synthesis. Thereafter, the performance atlases, which can present all possible design solutions, are depicted. As a result, the feasible solution of the mechanism with good motion/force transmission performance is obtained. And the solution can be flexibly adjusted by designer according to the practical design requirements. The proposed mechanism is original, and the presented design method provides a feasible solution to the optimal design of the main driving mechanism for servo punch press.

  1. Development of a miniaturized bulge test (small punch test) for post-irradiation mechanical property evaluation

    International Nuclear Information System (INIS)

    Eto, Motokuni; Suzuki, Masahide; Nishiyama, Yutaka; Fukaya, Kiyoshi; Jitsukawa, Shiro; Misawa, Toshihei

    1993-01-01

    To examine the effectiveness of the small punch test for evaluating strength and toughness of irradiated ferritic steels, detailed procedures are described aiming at standardization of the test. The statistical approach to analysis of the SP energy as a function of temperature for evaluation of DBTT was also reviewed. The method was then applied to neutron-irradiated ferritic steels, which included F-82, F-82H, HT-9, and 2 1/4 Cr-1Mo steel. Fluence and irradiation temperatures ranged from 2 to 12 x 10 23 n/m 2 (E ≥ 1 MeV) and from 573 to 673 K, respectively. Comparison of parameters obtained from the small punch test with the properties measured by the conventional method indicated that: (a) the 0.2% offset stress and the ultimate tensile strength at room temperature can be correlated well with the parameters, P y /(t 0 ) 2 and P max /(t 0 ) 2 , respectively. Here, P y and P max are the loads corresponding to the yield and the maximum, and t 0 is the initial thickness of a specimen; (b) fracture toughness, J IC , can be evaluated using equivalent fracture strain, anti ε qf , and the previously established relationship between these values; and (c) DBTT measured by a Charpy test can be predicted from the results of temperature dependence of SP energy determined from the area under the load-deflection curve using a statistical analysis based on a Weibull distribution

  2. An inquiry into the semiquantitative parameters of striatal dopamine receptor imaging

    International Nuclear Information System (INIS)

    Cao Guoxiang; Tan Tianzhi; Kuang Anren; Liang Zhenglu

    1998-01-01

    Purpose: To inquire into the optimal striatal reference region for nonspecific IBZM uptake in brain dopamine receptor imaging. Methods: Using in vivo data from rats, the authors compared the results of 125 I-iodobenzamide ( 125 I-IBZM) striatal specific binding that were respectively obtained taking cerebellum and frontal cortex as striatal reference region of nonspecific uptake of ligand. Results: Radioiodination labelled IBZM bound stereoselectively and reversibly to striatal D2 receptors. Frontal cortex and cerebellum showed rapid uptake and rapid washout of ligand. When cerebellar uptake was used as a reference of nonspecific uptake in striatum, IBZM saturation could not be demonstrated. But when the frontal cortex was used as reference region, saturation could be demonstrated with B max = 44 pmol/g striatum tissue. The percentage of haloperidol replacement and the percentage of uptake difference between striatum and other brain regions which were derived from competitive inhibition experiments with a large does of spiperone or haloperidol, suggested that the cerebellar uptake underestimated nonspecific uptake in the striatum while frontal cortex was an appropriate reference region for nonspecific uptake of ligand in striatum. Conclusions: For the calculation of specific IBZM binding and other semiquantitative parameters of striatal dopamine D2 receptor imaging, frontal cortex would be the nonspecific reference region of choice

  3. Findings from the experience with the punch technique for auditory osseointegrated implants: A retrospective single center comparative study.

    Science.gov (United States)

    Bonilla, Alfonso; Magri, Carlos; Juan, Eulalia

    To compare the punch technique and linear incision with soft tissue reduction for the placement of auditory osseointegrated implants (AOI) and analyze results of osseointegration obtained with the punch technique as measured with the Implant Stability Quotient (ISQ). Case review of 34 patients who received auditory osseointegrated implants between January 2010 and July 2015 and were divided into two groups according to the surgical technique: 18 with the punch technique (PT) and 16 with the linear incision technique (LI). Minimum follow-up was four months (mean: 24 months; range 4-64 months). Included in the analysis were patient profiles and records of the demographic data, surgical indications, surgical technique, implant placement, surgical time, intraoperative complications, as well as postsurgical complications (Holgers classification) and implant stability quotients (ISQ). Use of larger abutments was significantly greater in the PT group (PT, 10mm; LI, 6mm, p<0.001). The PT technique resulted in a shorter procedure than the LI (PT, 20min; LI, 45min, p<0.001). Holgers classification scores identified significantly fewer skin complications one week after surgery for the PT group; however, only small differences were seen between the two groups at the one- and three-month control visits. As shown for our cohort, the punch technique for surgical placement of AOI is faster and presents fewer immediate postoperative complications when compared to the linear incision technique. The clinical application of the ISQ is a useful, easy method to demonstrate the status of osseointegration and, thus, the stability of the device. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  4. Effects of plyometric exercise training with external weights on punching ability of experienced amateur boxers.

    Science.gov (United States)

    Bruzas, Vidas; Kamandulis, Sigitas; Venckunas, Tomas; Snieckus, Audrius; Mockus, Pranas

    2018-03-01

    During competition, a boxer must continue to deliver high-impact punches despite increasing fatigue. It is unclear whether the effects of plyometric training using external weights are transferred to sport-specific movements such as punching. The aim of the study was to investigate the effects of a 4-week cycle of plyometric training with external weights on punching ability. The study involved eight male amateur boxers aged 22.3±2.5 years with at least 7 years of competitive experience. They performed 12 plyometric training sessions, each comprising eight exercises of various muscle groups performed at maximum movement velocity. Six drills were performed with external weights, and two drills were performed using the body weight as resistance. All exercises required coordination. The punching ability was tested at baseline and after the 4 weeks of training using the Kiktest-100 boxing bag. The force of single punches and the frequency of punches within a series did not change from before to after the 4 weeks, except for increased power in the rear-hand low punch (Pplyometric training with external weights did not change the maximum punching power or movement frequency significantly, but had a beneficial effect on punching power endurance in boxers.

  5. FORTRAN text correction with the CDC-1604-A console typewriter during reading a punched card program

    International Nuclear Information System (INIS)

    Kotorobaj, F.; Ruzhichka, Ya.; Stolyarskij, Yu.V.

    1977-01-01

    The paper describes FORTRAN text correction with the CDC 1604-A console typewriter during reading a punched card program. This method gives one more possibility of FORTRAN program correction during program's input to the CDC 1604-A computer. This essentially reduced the time necessary for punched card correction with other methods. Possibility of inputting desired number of punched cards one after another allows one writing small FORTRAN programs to computer core storage with simultaneous punching of the cards. The correction program has been written to the CDC 1604 COOP monitor

  6. Experimental and Numerical Simulation Research on Micro-Gears Fabrication by Laser Shock Punching Process

    OpenAIRE

    Huixia Liu; Jianwen Li; Zongbao Shen; Qing Qian; Hongfeng Zhang; Xiao Wang

    2015-01-01

    The aim of this paper is to fabricate micro-gears via laser shock punching with Spitlight 2000 Nd-YAG Laser, and to discuss effects of process parameters namely laser energy, soft punch properties and blank-holder on the quality of micro-gears deeply. Results show that dimensional accuracy is the best shocked at 1690 mJ. Tensile fracture instead of shear fracture is the main fracture mode under low laser energy. The soft punch might cause damage to punching quality when too high energy is emp...

  7. Small punch creep test in a 316 austenitic stainless steel

    Directory of Open Access Journals (Sweden)

    Saucedo-Muñoz, Maribel L.

    2015-03-01

    Full Text Available The small punch creep test was applied to evaluate the creep behavior of a 316 type austenitic stainless steel at temperatures of 650, 675 and 700 °C. The small punch test was carried out using a creep tester with a specimen size of 10×10×0.3 mm at 650, 675 and 700 °C using loads from 199 to 512 N. The small punch creep curves show the three stages found in the creep curves of the conventional uniaxial test. The conventional creep relationships which involve parameters such as creep rate, stress, time to rupture and temperature were followed with the corresponding parameters of small punch creep test and they permitted to explain the creep behavior in this steel. The mechanism and activation energy of the deformation process were the grain boundary sliding and diffusion, respectively, during creep which caused the intergranular fracture in the tested specimens.El ensayo de termofluencia por indentación se utilizó para evaluar el comportamiento a la termofluencia en un acero inoxidable austenítico 316. Este ensayo se realizó en una máquina de indentación con muestras de 10×10×0,3 mm a temperaturas de 650, 675 y 700 °C con cargas de 199 a 512 N. Las curvas de termofluencia del ensayo mostraron las tres etapas características observadas en el ensayo convencional de tensión. Asimismo, las principales relaciones de termofluencia entre parámetros como velocidad de termofluencia, esfuerzo, tiempo de ruptura y temperatura se observaron en los parámetros correspondientes al ensayo de indentación, lo que permitió caracterizar el comportamiento de termofluencia en este acero. El mecanismo y la energía de activación del proceso de deformación en la termofluencia corresponden al deslizamiento de los límites de grano y la difusión a través de los mismos, respectivamente, lo cual causó la fractura intergranular en las muestras ensayadas.

  8. Precision hole punching on composite fiber reinforced polymer panels

    Science.gov (United States)

    Abdullah, A. B.; Zain, M. S. M.; Chan, H. Y.; Samad, Z.

    2017-12-01

    Structural materials, such as composite panels, can only be assembled, and in most cases through the use of fasteners, which are fitted into the drilled holes. However, drilling is costly and time consuming, thus affecting productivity. This research aims to develop an alternative method to drilling. In this paper, the precision of the holes was measured and the effects of the die clearance to the areas around the holes were evaluated. Measurement and evaluation were performed based on the profile of the holes constructed using Alicona IFM, a 3D surface measurement technique. Results showed that punching is a potential alternative to drilling but still requires improvements.

  9. Shear Punch Testing of BOR-60 Irradiated TEM Specimens

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, Tarik A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Quintana, Matthew Estevan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Tobias J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-13

    As a part of the project “High Fidelity Ion Beam Simulation of High Dose Neutron Irradiation” an Integrated Research Program (IRP) project from the U.S. Department of Energy, Nuclear Energy University Programs (NEUP), TEM geometry samples of ferritic cladding alloys, Ni based super alloys and model alloys were irradiated in the BOR-60 reactor to ~16 dpa at ~370°C and ~400°C. Samples were sent to Los Alamos National Laboratory and subjected to shear punch testing. This report presents the results from this testing.

  10. Advanced Modelling of Trusses with Punched Metal Plate Fasteners

    DEFF Research Database (Denmark)

    Ellegaard, Peter; Nielsen, Jacob

    Most of the finite element programs for design of timber trusses with punched metal fasteners are based on models using beam and fictitious elements. Different models have been used for different types of joints. Common problems for all the models are how to calculate the forces in the nail groups...... and the plates and furthermore, how big 'the deformations in the joints are. By developing an advanced model that includes all parts of the joint, i.e. plate, nail groups and contact it is possible to give a better description of the joint. An advanced model with these properties is presented. The advanced model...

  11. Small Punch Tests applied to the nuclear industry

    International Nuclear Information System (INIS)

    Moreno, M.; Gongora, P.; Bertolino, G; Yawny, A.

    2012-01-01

    The interest on miniaturized specimen techniques for the characterization of the mechanical behavior of materials was strongly motivated in the early eighties by the different programs associated with the development of fusion reactor technology. The importance of such developments is obvious in the case of the nuclear industry where the limited space available, the presence of fluence gradients in large specimens, the concern about gamma heating and dose to personnel in post-irradiation testing have all been motivations for reducing specimen size. Testing of miniature specimen includes a wide spectrum of techniques such as tensile, instrumented micro-hardness, small punch, bend, fracture, impact and fatigue. Small Punch Testing (SPT) techniques use a spherical penetrator which deforms to failure a miniature disc shaped flat specimen (typically, 3-10 mm in diameter and 0.25-0.50 mm in thickness) supported on its outer rim. Analysis of load-displacement data recorded along the test is performed for the determination of the property of interest. The present work focuses on the characterization of the elastoplastic response of pure Al, ADN 420 structural steel and AISI 304L using SPT and its correlation with the associated standard uniaxial testing behavior. In addition, the sensitivity of the technique to the specific material under study and to different experimental parameters, i.e. specimen diameter and thickness, clearance or clamping force and friction between disc and dies have been assessed both experimentally and by performing simulations using the finite element method (author)

  12. Behavioral sensitivity of temporally modulated striatal neurons

    Directory of Open Access Journals (Sweden)

    George ePortugal

    2011-07-01

    Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

  13. The small punch assessment of toughness losses in low alloy steels

    Energy Technology Data Exchange (ETDEWEB)

    Bulloch, J.H. [ESB, Power Generation, Dublin (Ireland)

    1998-12-31

    The presentation deals at length with the relationship between the Small Punch, SP, test transition temperature Tsp, behaviour and those displayed by the conventional Charpy Fracture Appearance Transition Temperature, FATT, obtained from large test specimens. Essentially it was demonstrated that the total test temperature range trends could reasonably be described by a non-linear expression such as FATT varied inversely with the square of the Tsp. Finally when the Tsp against FATT trends were separated into different steel classes an encouraging picture emerged inasmuch that a reasonable amount of data exhibited good agreement with the predicted effects of grain size. Fractographic details were also discussed and strong effects of strain or loading rates were identified. (orig.) 19 refs.

  14. The small punch assessment of toughness losses in low alloy steels

    Energy Technology Data Exchange (ETDEWEB)

    Bulloch, J H [ESB, Power Generation, Dublin (Ireland)

    1999-12-31

    The presentation deals at length with the relationship between the Small Punch, SP, test transition temperature Tsp, behaviour and those displayed by the conventional Charpy Fracture Appearance Transition Temperature, FATT, obtained from large test specimens. Essentially it was demonstrated that the total test temperature range trends could reasonably be described by a non-linear expression such as FATT varied inversely with the square of the Tsp. Finally when the Tsp against FATT trends were separated into different steel classes an encouraging picture emerged inasmuch that a reasonable amount of data exhibited good agreement with the predicted effects of grain size. Fractographic details were also discussed and strong effects of strain or loading rates were identified. (orig.) 19 refs.

  15. Diagnostic accuracy of confocal microscopy imaging vs. punch biopsy for diagnosing and subtyping basal cell carcinoma

    NARCIS (Netherlands)

    Kadouch, D. J.; Leeflang, M. M.; Elshot, Y. S.; Longo, C.; Ulrich, M.; van der Wal, A. C.; Wolkerstorfer, A.; Bekkenk, M. W.; de Rie, M. A.

    2017-01-01

    BackgroundIn vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and

  16. High-throughput sequencing of forensic genetic samples using punches of FTA cards with buccal swabs

    DEFF Research Database (Denmark)

    Kampmann, Marie-Louise; Buchard, Anders; Børsting, Claus

    2016-01-01

    Here, we demonstrate that punches from buccal swab samples preserved on FTA cards can be used for high-throughput DNA sequencing, also known as massively parallel sequencing (MPS). We typed 44 reference samples with the HID-Ion AmpliSeq Identity Panel using washed 1.2 mm punches from FTA cards...

  17. Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia.

    Science.gov (United States)

    Horga, Guillermo; Cassidy, Clifford M; Xu, Xiaoyan; Moore, Holly; Slifstein, Mark; Van Snellenberg, Jared X; Abi-Dargham, Anissa

    2016-08-01

    Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication. To examine whether the pattern of brain connectivity across striatal subregions is abnormal in unmedicated patients with schizophrenia and whether this abnormality relates to psychotic symptoms and extrastriatal dopaminergic transmission. In this multimodal, case-control study, we obtained resting-state functional magnetic resonance imaging data from 18 unmedicated patients with schizophrenia and 24 matched healthy controls from the New York State Psychiatric Institute. A subset of these (12 and 17, respectively) underwent positron emission tomography with the dopamine D2 receptor radiotracer carbon 11-labeled FLB457 before and after amphetamine administration. Data were acquired between June 16, 2011, and February 25, 2014. Data analysis was performed from September 1, 2014, to January 11, 2016. Group differences in the striatal connectivity pattern (assessed via multivariable logistic regression) across striatal subregions, the association between the multivariate striatal connectivity pattern and extrastriatal baseline D2 receptor binding potential and its change after amphetamine administration, and the association between the multivariate connectivity pattern and the severity of positive symptoms evaluated with the Positive and Negative Syndrome Scale. Of the patients with schizophrenia (mean [SEM] age, 35.6 [11.8] years), 9 (50%) were male and 9

  18. Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

    International Nuclear Information System (INIS)

    Eells, J.T.; Dubocovich, M.L.

    1988-01-01

    The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [ 3 H]dopamine and [ 3 H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [ 3 H]dopamine and [ 3 H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [ 3 H]norepinephrine or [ 3 H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions

  19. Performance improvement in a tubular heat exchanger by punched delta-winglet vortex generators

    Science.gov (United States)

    Khanoknaiyakarn, C.; Promvonge, P.; Thianpong, C.; Skullong, S.

    2018-01-01

    A novel tubular heat exchanger incorporated with punched delta-winglet vortex generators (called perforated delta-winglet vortex generator, P-DWVG) is proposed for improving its thermal performance and energy saving. The P-DWVG elements are punched out from a straight tape having its width nearly equal to the tube diameter before insertion. The main aim at employing the P-DWVG insert is to produce counter-rotating vortices along the tube to promote turbulence intensity inside as well as to transport the cold fluid at the central core to the near-wall regions. The experiment was performed to study thermal behaviors in a uniform heat-fluxed tube inserted with P-DWVGs. The P-DWVGs with the attack angle of 45° were mounted periodically with three different blockage ratios (BR = 0.1, 0.2 and 0.3) and two pitch ratios (PR = 2 and 3). Air as the test fluid was varied to obtain turbulent airflow for Reynolds number (Re) in a range of 4,150-25,500. The experimental results show that the P-DWVG provides a considerable increase in the rate of heat transfer around 3.1-4.01 times whereas friction factor increases around 11.44- 34.23 times higher than the plain tube. To assess the real benefits of P-DWVGs, thermal performance factor (TEF) is examined and in the range of 1.39-1.48 where its maximum is at BR = 0.1 and PR = 2.

  20. Punch grafts to treat lower limb intractable sores

    Directory of Open Access Journals (Sweden)

    JÚLIO WILSON FERNANDES

    Full Text Available ABSTRACT Lower limb recurrent ulcers, usually caused by prolonged decubitus, trauma, diabetes or burns, may not heal with conventional clinical or surgical treatment. Frequently, laminated skin grafts do not integrate with the recipient layer, and the only alternatives are neighbor microsurgical flaps. These have higher morbidity and create secondary defects, to be corrected with skin grafts, when fasciocutaneous or miocutaneous segments are removed for the treatment of the primary defect. We describe the non-conventional use of punch grafts in the treatment of lower limb ulcers, when conventional skin laminated graft failed, without the use of flaps. Since this is a very successful technique, its use should be considered as a valuable alternative for the treatment of recurrent lower limb ulcers. It is a simple and easy-learned technique that may be used by different surgeons, even in remote places without correct specialized hospital facilities.

  1. John Punch, Scotist Holy War, and the Irish Catholic Revolutionary Tradition in the Seventeenth Century.

    Science.gov (United States)

    Campbell, Ian W

    2016-07-01

    During the 1640s, the Irish Franciscan theologian John Punch taught his theology students in Rome that war against Protestants was made just by their religion alone. Jesuits like Luis de Molina identified the holy war tradition in which Punch stood as a Scotist one, and insisted that the Scotists had confused the natural and supernatural spheres. Among Irishmen, Punch was unusual. The main Irish Catholic revolutionary tradition employed Jesuit and Thomist theory. They argued that the Stuarts had lost the right to rule Ireland for natural reasons, not supernatural ones; because the Stuarts were tyrants, not because they were Protestants.

  2. Blanking Clearance and Punch Velocity Effects on The Sheared Edge Characteristic in Micro-Blanking of Commercially Pure Copper Sheet

    Directory of Open Access Journals (Sweden)

    Didin Zakaria Lubis

    2017-11-01

    Full Text Available This study aims to identify the influences between clearance and punch velocity on the part edge quality of blanked parts. Experiments have been conducted using material copper, punch-die clearance and punch velocity variations. In order to determine the reachable punch-die clearance and punch velocity required for blanking. The quality of the part-edge characteristics shows that higher punch velocity and decreases clearance value can improve the part-edge quality, resulting in smaller burr height and rollover, and a larger shear zone. Furthermore, it could be observed that the part-edge quality improvement when blanking with high punch velocity is much more distinct for stele than for copper. According to blanking theory, this improvement was expected because copper have much higher heat conduction coefficients. Therefore, the heat dissipates faster and the desired stress relief effect does not take place to the same degree as for stele.

  3. Tensile properties of modified 9Cr-1Mo steel by shear punch testing and correlation with microstructures

    Energy Technology Data Exchange (ETDEWEB)

    Karthik, V., E-mail: karthik@igcar.gov.in [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamil Nadu 603102 (India); Laha, K.; Parameswaran, P.; Chandravathi, K.S.; Kasiviswanathan, K.V.; Jayakumar, T.; Raj, Baldev [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamil Nadu 603102 (India)

    2011-10-15

    Modified 9Cr-1Mo ferritic steel (P91) is subjected to a series of heat treatments consisting of soaking for 5 min at the selected temperatures in the range 973 K-1623 K (below Ac{sub 1} to above Ac{sub 4}) followed by oil quenching and tempering at 1033 K for 1 h to obtain different microstructural conditions. The tensile properties of the different microstructural conditions are evaluated from small volumes of material by shear punch test technique. A new methodology for evaluating yield strength, ultimate tensile strength and strain hardening exponent from shear punch test by using correlation equations without employing empirical constants is presented and validated. The changes in the tensile properties are related to the microstructural changes of the steel investigated by electron microscopic studies. The steel exhibits minimum strength and hardness when soaked between Ac{sub 1} and Ac{sub 3} (intercritical range) temperatures due to the replacement of original lath martensitic structure with subgrains. The finer martensitic microstructure produced in the steel after soaking at temperatures above Ac{sub 3} leads to a monotonic increase in hardness and strength with decreasing strain hardening exponent. For soaking temperatures above Ac{sub 4}, the hardness and strength of the steel increases marginally due to the formation of soft {delta} ferrite. - Highlights: > A methodology presented for computing tensile properties from shear punch test. > UTS and strain hardening estimated using extended analysis of blanking models. > The analysis methodology validated for different heat treated 9Cr-1Mo steel. > Changes in tensile properties of steel correlated with microstructures.

  4. Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Imis Dogan

    2015-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

  5. Effect of Punch Stroke on Deformation During Sheet Forming Through Finite Element

    Science.gov (United States)

    Akinlabi, Stephen; Akinlabi, Esther

    2017-08-01

    Forming is one of the traditional methods of making shapes, bends and curvature in metallic components during a fabrication process. Mechanical forming, in particular, employs the use of a punch, which is pressed against the sheet material to be deformed into a die by the application of an external force. This study reports on the finite element analysis of the effects of punch stroke on the resulting sheet deformation, which is directly a function of the structural integrity of the formed components for possible application in the automotive industry. The results show that punch stroke is directly proportional to the resulting bend angle of the formed components. It was further revealed that the developed plastic strain increases as the punch stroke increases.

  6. A new virtual instrument for estimating punch velocity in combat sports.

    Science.gov (United States)

    Urbinati, K S; Scheeren, E; Nohama, P

    2013-01-01

    For improving the performance in combat sport, especially percussion, it is necessary achieving high velocity in punches and kicks. The aim of this study was to evaluate the applicability of 3D accelerometry in a Virtual Instrumentation System (VIS) designed for estimating punch velocity in combat sports. It was conducted in two phases: (1) integration of the 3D accelerometer with the communication interface and software for processing and visualization, and (2) applicability of the system. Fifteen karate athletes performed five gyaku zuki type punches (with reverse leg) using the accelerometer on the 3rd metacarpal on the back of the hand. It was performed nonparametric Mann-Whitney U-test to determine differences in the mean linear velocity among three punches performed sequentially (p sport.

  7. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation

    International Nuclear Information System (INIS)

    Calvini, Piero; Rodriguez, Guido; Nobili, Flavio; Inguglia, Fabrizio; Mignone, Alessandro; Guerra, Ugo P.

    2007-01-01

    To design a novel algorithm (BasGan) for automatic segmentation of striatal 123 I-FP-CIT SPECT. The BasGan algorithm is based on a high-definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. A highly significant correlation was achieved between true binding potential and measured 123 I activity from the phantom. 123 I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co-registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. (orig.)

  8. Kinematics of self-initiated and reactive karate punches.

    Science.gov (United States)

    Martinez de Quel, Oscar; Bennett, Simon J

    2014-03-01

    This study investigated whether within-task expertise affects the reported asymmetry in execution time exhibited in reactive and self-initiated movements. Karate practitioners and no-karate practitioners were compared performing a reverse punch in reaction to an external stimulus or following the intention to produce a response (self-initiated). The task was completed following the presentation of a specific (i.e., life-size image of opponent) or general stimulus and in the presence of click trains or white noise. Kinematic analyses indicated reactive movement had shorter time to peak velocity and movement time, as well as greater accuracy than self-initiated movement. These differences were independent of participant skill level although peak velocity was higher in the karate practice group than in the no-karate practice group. Reaction time (RT) of skilled participants was facilitated by a specific stimulus. There was no effect on RT or kinematic variables of the different type of auditory cues. The results of this study indicate that asymmetry in execution time of reactive and self-initiated movement holds irrespective of within-task expertise and stimulus specificity. This could have implications for training of sports and/or relearning of tasks that require rapid and accurate movements to intercept/contact a target.

  9. Is effective mass in combat sports punching above its weight?

    Science.gov (United States)

    Lenetsky, Seth; Nates, Roy J; Brughelli, Matt; Harris, Nigel K

    2015-04-01

    The segmental and muscular complexity of the human body can result in challenges when examining the kinetics of impacts. To better understand this complexity, combat sports literature has selected effective mass as a measure of an athlete's inertial contribution to the momentum transfer during the impact of strikes. This measure helps to clarify the analysis of striking kinetics in combat sports. This paper will review: (1) effective mass as a concept and its usage as a measure of impact intensity in combat sports, (2) the neuromuscular pattern known as "double peak muscle activation" which has been theorized to help enhance initial hand velocity upon impact and joint stiffening during impact, (3) the methods and equations used to calculate effective mass, and (4) practitioner recommendations based on the literature. We will argue in this manuscript that the act of punching presents unique challenges to the current understanding of effective mass due to additional force application during impact. This review will improve the understanding of effective mass and its roles in effective striking serving to underpin future research into performance enhancement in striking based combat sports. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Analysis of potential factors influencing the relation between small punch and conventional creep test

    Czech Academy of Sciences Publication Activity Database

    Dymáček, Petr; Milička, Karel; Dobeš, Ferdinand

    2010-01-01

    Roč. 63, Spp. Issue (2010), s. 50-53 ISSN 0018-8069. [International Conference "Determination of Mechanical Properties of Materials by Small Punch and Other Miniature testing Techniques" /1./. Ostrava, 31.08.2010-02.09.2010] R&D Projects: GA AV ČR(CZ) IAA200410801 Institutional research plan: CEZ:AV0Z20410507 Keywords : creep * small punch test * chromium steel Subject RIV: JG - Metallurgy

  11. Punching influence on magnetic properties of the stator teeth of an induction motor

    International Nuclear Information System (INIS)

    Kedous-Lebouc, A.; Cornut, B.; Perrier, J.C.; Manfe, Ph.; Chevalier, Th.

    2003-01-01

    In order to study the effects of punching of electrical steel sheets, a suitable geometrical structure able to characterize the stator teeth behavior of an induction motor is proposed and validated. The influence of the punching on a fully processed M330-65A is then characterized. A spectacular degradation of loss and B(H) curves is observed. This leads to a perceptible increase of the no-load machine current

  12. Control program for punched paper tape for the PDP-8/1 computer

    International Nuclear Information System (INIS)

    German, U.

    1976-01-01

    A program was developed for the PDP-8/1 computer to control the punched paper tape supplied by the measuring instruments. Any departure from the program is detected by an optical reader which stops the tape and displays the error on an accumulator. This program which is suitable for large amounts of data punched on paper tape has been in use at the Beer-Sheva laboratories for detecting errors in the sample changing operation. (B.G.)

  13. Application of Small Punch Test for Estimation of Fracture Properties of Fe-Al Alloys

    Czech Academy of Sciences Publication Activity Database

    Dobeš, Ferdinand; Milička, Karel

    2010-01-01

    Roč. 63, Sp. Iss. (2010), s. 83-86 ISSN 0018-8069. [Determination of Mechanical Properties of Materials by Small Punch and Other Miniature Testing Techniques/1./. Ostrava, 31.08.2010-02.09.2010] R&D Projects: GA ČR GA106/08/1238 Institutional research plan: CEZ:AV0Z20410507 Keywords : small punch test * ductility * iron aluminides Subject RIV: JG - Metallurgy

  14. The Influence of a Padded Hand Wrap on Punching Force in Elite and Untrained Punchers

    Directory of Open Access Journals (Sweden)

    Andrew J. Galpin

    2015-10-01

    Full Text Available Punching is integral to success in combat sports, making it a frequent activity during practice/training. Improving safety of this activity benefits both the athlete and training partners. This study was designed to 1 test the precision and reliability of a commercially available striking device and 2 assess the influence of a novel padded hand wrap on punching force in elite and untrained punchers. Fourteen male professional boxers and mixed martial artists (PRO; age=29.2±5.6y; height=180.3±9.0cm; mass=87.1±17.9kg, winning %=73.8±13.8%, number of victories via knockout/technical knockout=35.6± 21.9% and 24 untrained male punchers (UNT; 27.6±6.9y, 177.6±18.3cm, 84.3±16.9kg wore a standardized boxing glove and performed 20 maximal punches (4 sets of 5 into a device designed to measure punching force. All participants performed, in a counterbalanced order, 2 sets of 5 with a standardized hand wrap and 2 sets of 5 with the same wrap plus an additional 1.2cm thick cylinder 4g foam-like pad (WRAP placed over the knuckles. PRO produced significantly more punching force than UNT, regardless of condition. Punching force was lower by 12.6% (p<0.05 for PRO and 8.9% (p<0.05 for UNT with WRAP (compared to no WRAP. These findings suggest WRAP significantly reduces punching force, which may be important for long-term safety of the puncher’s hand and/or the person receiving the strike. Keywords: safety, punching, striking, hitting, combat, pad

  15. Creep damage evaluation of low alloy steel weld joint by small punch creep testing

    International Nuclear Information System (INIS)

    Nishioka, Tomoya; Sawaragi, Yoshiatsu; Uemura, Hiromi

    2013-01-01

    The effect of sampling location on SPC (Small Punch Creep) tests were investigated for weld joints to establish evaluation method of Type IV creep behavior. The SPC specimen shape was 10mm diameter and 0.5mm thick round disc prepared from weld joints of 2.25Cr-1Mo low alloy steel. It was found that the center of SPC specimen should be 2mm apart from the weld interface as the recommended sampling location. Creep damage was imposed for large weld joint specimens by axial creep loading at 620degC, 52MPa with the interrupted time fraction of 0.34, 0.45, 0.64 and 0.82.SPC samples were prepared from those damaged specimens following the recommended way described in this paper. Among the various SPC tests conducted, good relationships were found for the test condition of 625degC, 200N. Namely, good relationships were obtained both between minimum deflection rate and creep life fraction, and between rupture time and creep life fraction. Consequently, creep life assessment of Type IV fracture by SPC tests could be well conducted using the sampling location and the test condition recommended in this paper. (author)

  16. Development of small specimen test techniques. Development of a remote controlled small punch testing apparatus

    International Nuclear Information System (INIS)

    Ohmi, Masao; Saito, Junichi; Ooka, Norikazu; Jitsukawa, Shiro; Hishinuma, Akimichi; Umino, Akira.

    1997-01-01

    An accelerator-driven deuterium-lithium (d-Li) stripping reaction-type neutron source, such as the International Fusion Materials Irradiation Facility (IFMIF) planned by the International Energy Agency is recognized as one of the most promising facility to obtain test environments of high-energy neutrons for fusion reactor materials development. The limitation on the available irradiation volume of the irradiation facility requires the development of the small specimen test techniques (SSTT). Application of SSTT to evaluate the degradation of various components in the light water reactor for the life extension is expected to be also quite beneficial. A remote-controlled testing machine for the Small Punch (SP) and miniaturized tensile tests was developed at the hot laboratory of the Japan Materials Testing Reactor (JMTR). The machine is designed for testing at temperatures ranging between 93 and 1,123 K to evaluate the temperature dependence of the strength of materials including the embrittlement at low temperatures and the softening at elevated temperatures. The tests are performed in a vacuum or in an inert gas environment. The machine has been installed in a hot cell and is being used for the round robin test program of the SP test method. The round robin test program is planned to identify the capability of the test method and to establish a standard test procedure. The configuration and the specifications of the test machine are introduced and the results of the SP tests are also shown. (author)

  17. Recommended practice for small punch (SP) testing of metallic materials (draft)

    International Nuclear Information System (INIS)

    Takahashi, Hideaki; Shoji, Tetsuo; Mao, Xinyuan

    1988-09-01

    This practice covers the determination of fracture toughness characteristics of metallic materials such as ductile to brittle transition temperature (SPDBTT) and elastic-plastic fracture toughness (J ICSP ) using miniature small punch (SP) specimens. Three kinds of specimens with different shape; 10 by 10 by 0.5 mm, 10 by 10 by 0.25 mm and φ3 by 0.25 mm, are selected as the standard SP specimens. Two types of fixture shall be respectively used for the 10 and φ3 specimens. The relationship between load and deflection during buldge tests shall be recorded from low to high temperatures. Following two parameters in relation to fracture toughness are obtained from analyses of load-deflection curves: (1) The SP energy is calculated from the area surrounded with load-deflection curves, which corresponds to the total energy consumed up to the fracture. (2) The equivalent fracture strain (ε-bar qf ) is calculated from the maximum deflection at fracture (δ*). The SPDBTT can be derived from temperature dependence of SP energy, and the J ICSP can be estimated from the rational correlation curve between ε-bar qf and J IC . (author)

  18. Evaluation of toughness degradation by small punch (SP) tests for neutron irradiated structural steels

    International Nuclear Information System (INIS)

    Misawa, Toshihei; Hamaguchi, Yoshikazu; Kimura, Akihiko; Eto, Motokuni; Suzuki, Masahide; Nakajima, Nobuya.

    1992-01-01

    The small punch (SP) test as one of the useful small specimen testing technique (SSTT) has been developed to evaluate the fracture toughness, ductile-brittle transition temperature (DBTT) and tensile properties for neutron irradiated structural materials. The SP tests using the miniaturized specimens of φ3 mm TEM disk and 10 mm 2 coupon were performed for six kinds of ferritic steels of F-82, F-82H, HT-9, JFMS, 2.25-1Mo and SQV2A. It was shown that the temperature dependence of SP fracture energies with scatter in miniaturized testing can give reliable information on the DBTT by use of the statistical analysis based on the Weibull distribution. A good correlation between the DBTT of the SP tests and that of the standard CVN test has been obtained for the various nuclear ferritic steels. The SP test was performed for cryogenic austenitic steels as a way of evaluating elastic-plastic fracture toughness, J IC , on the basis of a universal empirical relationship between J IC and SP equivalent fracture strain, ε-bar qf . The SP testing using the neutron irradiated specimens of 2.25Cr-1Mo, F-82, F-82H and HT-9 steels was successfully applied and presented the neutron radiation induced changes on the DBTT, fracture toughness and tensile properties. (author)

  19. On the correlation between minimum thickness and central deflection during small punch test

    International Nuclear Information System (INIS)

    Kumar, Pradeep; Chattopadhyay, J.; Dutta, B.K.

    2016-01-01

    Present paper deals with a detailed study on the correlation between minimum thickness (t/t_0) and central deflection (δ/t_0). Such data are obtained during the deformation of a small punch test of miniaturized specimen. Finite element studies have been carried out to investigate the effect of various parameters which are expected to influence this correlation. The parameters under consideration are material hardening, material yield stress, coefficient of friction and initial thickness of the specimen. It is shown that the correlation remains unaffected with respect to change in material parameters. Similarly, the coefficient of friction beyond 0.2 also does not affect the correlation. However, change in thickness has significant effect on the correlation. A modification has been suggested in the existing correlation to consider the influence of thickness change. The modified correlation is then used to calculate fracture toughness using the experimental results quoted in the literature. It is shown that the modified correlation improves the fracture toughness prediction considerably.

  20. Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

    Science.gov (United States)

    Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

    2017-01-01

    Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602

  1. Shear punch testing as a tool for evaluating welded pipeline steel

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, G.R.; Elwazri, A.; Varano, R.; Yue, S.; Jonas, J.J. [McGill Univ., Montreal, PQ (Canada). Dept. of Metals and Materials Engineering; Pokutylowicz, N. [ExxonMobil Research and Engineering Co., Annandale, NJ (United States)

    2005-07-01

    This study examined the mechanical properties across a welded joint in a 35 mm steel pipe. Results were compared with microhardness measurements. The chemical composition of the 4130 steel and welding wire included carbon, manganese, silicon, nickel, chromium and molybdenum. The thermal cycles experienced during welding can result in differences in the grain size, phase, composition and morphology of precipitates. These thermal cycles can upset the balance of high strength and good toughness in steels, producing poor toughness in the heat-affected zone (HAZ). In the shear punch test, a flat-ended cylindrical punch was used to produce a 3 mm diameter disk from a sheet specimen with a recommended thickness of 300 to 350 {mu}m. The shear punch test provided tensile property data with only a very small amount of material, which is ideal for testing welds. It also provides full tensile data (yield strength, ultimate tensile strength and elongation) which are not specifically provided by hardness testing. Shear punch techniques can also improve the across-weld resolution of tensile testing. The results showed that the changes in strength properties across the weld were consistent with the microhardness measurements. The change in elongation across the weld joint was successfully measured using the punch test method. The HAZ in the welded joint in this study had a good combination of high strength and ductility, while the weld bead had moderate strength and relatively low ductility. 7 refs., 1 tab., 9 figs.

  2. Flexural behaviour and punching shear of selfcompacting concrete ribbed slab reinforced with steel fibres

    Directory of Open Access Journals (Sweden)

    Ahmad Hazrina

    2017-01-01

    Full Text Available This paper investigates the effects of steel fibres as a replacement to the conventional reinforcement under flexural behaviour and punching shear in self-compacting (SCC ribbed slab reinforced with steel fibres. Four ribbed slabs with similar dimensions of 2.8 m length × 1.2 m width and 0.2m thickness were constructed. Two of the samples were considered as control samples (conventionally reinforced with reinforcement bars and welded mesh while another two samples were fully reinforced with 1% (80 kg/m3 volume of steel fibres incorporated to the SCC mix. For the flexural behaviour study, the ribbed slab samples were subjected to two line loads under four point bending. Meanwhile, for the punching shear analysis, the ribbed slab samples were subjected to a point load to simulate loading from the column. The analysis of the experimental results displayed that steel fibres incorporation had been found to effectively delay the first crack occurrence under both flexural and punching shear. The steel fibre replacement has been proven to be able to sustain up to 80% and 73% of the ultimate load resistance for flexural and punching shear, respectively, in comparison to conventionally reinforced ribbed slab structure. The visual observation carried out during the experiment exhibited similar failure mode for both steel fibre reinforced and control samples. This was observed for both flexural and punching shear samples. Overall, it can be concluded that the steel fibres had displayed a promising potential to effectively replace the conventional reinforcements.

  3. Experimental and Numerical Simulation Research on Micro-Gears Fabrication by Laser Shock Punching Process

    Directory of Open Access Journals (Sweden)

    Huixia Liu

    2015-07-01

    Full Text Available The aim of this paper is to fabricate micro-gears via laser shock punching with Spitlight 2000 Nd-YAG Laser, and to discuss effects of process parameters namely laser energy, soft punch properties and blank-holder on the quality of micro-gears deeply. Results show that dimensional accuracy is the best shocked at 1690 mJ. Tensile fracture instead of shear fracture is the main fracture mode under low laser energy. The soft punch might cause damage to punching quality when too high energy is employed. Appropriate thickness and hardness of soft punch is necessary. Silica gel with 200 µm in thickness is beneficial to not only homogenize energy but also propagate the shock wave. Polyurethane films need more energy than silica gel with the same thickness. In addition, blank-holders with different weight levels are used. A heavier blank-holder is more beneficial to improve the cutting quality. Furthermore, the simulation is conducted to reveal typical stages and the different deformation behavior under high and low pulse energy. The simulation results show that the fracture mode changes under lower energy.

  4. Striatal dysfunction in attention deficit and hyperkinetic disorder

    International Nuclear Information System (INIS)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

  5. Assessment of striatal & postural deformities in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

  6. Striatal dysfunction in attention deficit and hyperkinetic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

  7. Prefrontal cortex and striatal activation by feedback in Parkinson's disease

    NARCIS (Netherlands)

    Keitz, Martijn; Koerts, Janneke; Kortekaas, Rudie; Renken, Remco; de Jong, Bauke M.; Leenders, Klaus L.

    2008-01-01

    Positive feedbacks reinforce goal-directed behavior and evoke pleasure. in Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary

  8. Flat punch adhesion: transition from fracture-based to strength-limited pull-off

    International Nuclear Information System (INIS)

    Jiang, Yijie; Turner, Kevin T; Grierson, David S

    2014-01-01

    The adhesion of a cylindrical flat punch to a surface due to interatomic forces is a well-known problem that is important in many applications, including indentation experiments and the adhesion of fibrillar structures. Traditionally, the pull-off force has been related to the work of adhesion and punch geometry via the Kendall solution that uses a Griffith energy balance to assess crack propagation and pull-off. More recently, it has been shown that under certain conditions, notably at small punch diameters, the contact can behave in a ‘strength-limited’ fashion in which the interface separates uniformly rather than via crack propagation. Here, a Maugis-Dugdale-type analysis of power-law-shaped bodies in contact is used to examine the change in behaviour from the fracture-based Kendall solution to strength-limited pull-off for cylindrical flat punches. The transition from fracture-based to strength-limited behaviour is described in terms of a non-dimensional parameter that is similar to previous quantities used to describe the transition and is a function of the punch size, the elasticity of the contact, and the adhesion properties. The results of this relatively simple analysis compare favourably with results from more complex computational simulations. In addition, the results are used to develop a function that quantifies the transition between the Kendall solution and the strength-limited solution in order to facilitate interpretation of adhesion measurements in the transition regime between the two limits. Finally, the power-law analysis is used to assess the sensitivity of the transition to the exact shape of the punch. (paper)

  9. Development and validation of the small punch test for UHMWPE used in total joint replacements

    Energy Technology Data Exchange (ETDEWEB)

    Edidin, A.A. [Drexel Univ., Philadelphia, PA (United States). School of Biomedical Engineering, Science and Health Systems; Howmedica Osteonics Corp., Allendale, NJ (United States); Kurtz, S.M. [Drexel Univ., Philadelphia, PA (United States). School of Biomedical Engineering, Science and Health Systems; Thomas Jefferson Univ., Philadelphia, PA (United States). Dept. of Orthopaedic Surgery; Exponent, Inc., Philadelphia, PA (United States)

    2001-07-01

    In order to better understand the mechanical effects of oxidative degradation, improved oxidative stability and crosslinking on ultra-high molecular weight polyethylene (UHMWPE), a unique miniature specimen mechanical testing technique, known as the small punch test, was developed for evaluating total joint replacement components. The small punch test involves deforming a disk-shaped specimen having a thickness of 0.5 mm and a diameter of 6.4 mm. In addition to its small specimen size, the small punch test differs from conventional testing in that deformation of the UHMWPE specimen occurs under multiaxial loading conditions. Using the small punch test, we have traced the evolution of mechanical behavior in UHMWPE after natural (shelf-storage) and accelerated aging conditions. In addition, we have determined relationships between the mechanical behavior of UHMWPE and the biologically relevant wear debris volume generated in total hip replacements. The small punch test has also been used to investigate the effects of radiation crosslinking which has been shown to improve the wear performance in an in vitro hip simulator. However, the crosslinking and subsequent thermal processes used to improve the wear behavior may compromise the native mechanical behavior by changing the ductility and toughness of the UHMWPE bearing. The primary objective of this study was to investigate which tradeoffs exist related to the mechanical behavior associated with various clinically available types of highly crosslinked and thermally treated UHMWPE. We also review the development and validation of the small punch disk bend test and highlight its application to problems of clinical relevance in both hip and knee arthroplasty. (orig.)

  10. Numerical investigation by finite element simulation of the bail punch test: application to tempered martensitic steels

    International Nuclear Information System (INIS)

    Campitelli, E.; Spatig, P.; Bertsch, J.

    2007-01-01

    Full text of publication follows: Over the years, the small ball punch test technique has been used to evaluate conventional tensile properties of a variety of materials. The development and use of this type of small specimen techniques is indispensable for an efficient use of the limited irradiation volume of the future fusion material intense neutron source. Up to now, empirical correlations between features of the load-displacement curves of the ball punch test and the mechanical properties, such as the yield stress or the ultimate tensile stress, are established on materials in the unirradiated condition. These correlations are believed to be applicable to irradiated materials and they have been very often used to estimate the irradiation hardening. However, it is well known that the overall constitutive behavior of the materials is generally affected by neutron irradiation. Therefore, there is a need to quantify the effect of the constitutive behavior on the correlations. In this paper, we employ a 3D non-linear finite element model for the ball punch test to address these effects of the irradiation-induced changes on the ball punch test curve. We apply first the model on the tempered martensitic steel EUROFER97 in the unirradiated condition with variations in the post-yield behavior, either in the low strain domain ( 10%). The effects on the ball punch test load deflection curve are outlined. Second, we study the effects of the irradiation hardening on the same constitutive behaviors as those used for the unirradiated condition. We show that that the usual correlations must be considered with great care on irradiated materials since strong variation on the strain-hardening may lead to erroneous estimation of the irradiation hardening. We also propose a novel approach to calibrate the yield stress to features of the ball punch test curve that decreases the uncertainty related to the post-yield behavior and that, as a consequence, makes the technique more

  11. Using stamping punch force variation for the identification of changes in lubrication and wear mechanism

    Science.gov (United States)

    Voss, B. M.; Pereira, M. P.; Rolfe, B. F.; Doolan, M. C.

    2017-09-01

    The growth in use of Advanced High Strength Steels in the automotive industry for light-weighting and safety has increased the rates of tool wear in sheet metal stamping. This is an issue that adds significant costs to production in terms of manual inspection and part refinishing. To reduce these costs, a tool condition monitoring system is required and a firm understanding of process signal variation must form the foundation for any such monitoring system. Punch force is a stamping process signal that is widely collected by industrial presses and has been linked closely to part quality and tool condition, making it an ideal candidate as a tool condition monitoring signal. In this preliminary investigation, the variation of punch force due to different lubrication conditions and progressive wear are examined. Linking specific punch force signature changes to developing lubrication and wear events is valuable for die wear and stamping condition monitoring. A series of semi-industrial channel forming trials were conducted under different lubrication regimes and progressive die wear. Punch force signatures were captured for each part and Principal Component Analysis (PCA) was applied to determine the key Principal Components of the signature data sets. These Principal Components were linked to the evolution of friction conditions over the course of the stroke for the different lubrication regimes and mechanism of galling wear. As a result, variation in punch force signatures were correlated to the current mechanism of wear dominant on the formed part; either abrasion or adhesion, and to changes in lubrication mechanism. The outcomes of this study provide important insights into punch force signature variation, that will provide a foundation for future work into the development of die wear and lubrication monitoring systems for sheet metal stamping.

  12. Prediction of punching shear capacities of two-way concrete slabs reinforced with FRP bars

    Directory of Open Access Journals (Sweden)

    Ibrahim M. Metwally

    2013-08-01

    Full Text Available Where corrosion of steel reinforcement is a concern, fiber-reinforced polymer (FRP reinforcing bar or grid reinforcement provides an alternative reinforcement for concrete flat slabs. The existing provisions for punching of slabs in most international design standards for reinforced concrete are based on tests of steel reinforced slabs. The elastic stiffness and bonding characteristics of FRP reinforcement are sufficiently different from those of steel to affect punching strength [1]. This paper evaluates the punching shear strength of concrete flat slabs reinforced with different types of fiber-reinforced polymer (FRP. A total of 59 full-size slabs were constructed and tested collected from the literature of FRP bars reinforced concrete slabs. The test parameters were the amount of FRP reinforcing bars, Young’s modulus of FRP bars, slab thickness, loaded areas and concrete compressive strength. The experimental punching shear strengths were compared with the available theoretical predictions, including the ACI 318 Code, BS 8110 Code, ACI 440 design guidelines, and a number of models proposed by some researchers in the literature. Two approaches for predicting the punching strength of FRP-reinforced slabs are examined. The first is an empirical new model which is considered as a modification of El-Gamal et al. [2] model. The second is a Neural Networks Technique; which has been developed to predict the punching shear capacity of FRP reinforced concrete slabs. The accuracies of both methods were evaluated against the experimental test data. They attained excellent agreement with available test results compared to the existing design formulas.

  13. Global actions of nicotine on the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Victor E Plata

    2013-11-01

    Full Text Available The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA, the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  14. Global actions of nicotine on the striatal microcircuit.

    Science.gov (United States)

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

    2013-01-01

    what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  15. A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

    Energy Technology Data Exchange (ETDEWEB)

    Vanzi, Eleonora; De Cristofaro, Maria T.; Sotgia, Barbara; Mascalchi, Mario; Formiconi, Andreas R. [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2007-09-15

    The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-{beta}-carboxymethoxy-3-{beta}-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs. (orig.)

  16. Non-linear finite element analysis of reinforced concrete members and punching shear strength of HSC slabs

    Directory of Open Access Journals (Sweden)

    Nassim Kernou

    2018-01-01

    Full Text Available A rational three-dimensional nonlinear finite element model (NLFEAS is used for evaluating the behavior of high strength concrete slabs under monotonic transverse load. The non-linear equations of equilibrium have been solved using the incremental-iterative technique based on the modified Newton-Raphson method. The convergence of the solution was controlled by a load convergence criterion. The validity of the theoretical formulations and the program used was verified, through comparison with results obtained using ANSYS program and with available experimental test results. A parametric study was conducted to investigate the effect of different parameters on the behavior of slabs which was evaluated in terms of loaddeflection characteristics, concrete and steel stresses and strains, and failure mechanisms. Also, punching shear resistance of slabs was numerically evaluated and compared with the prediction specified by some design codes.

  17. Usage of prestressed vertical bolts for retrofitting flat slabs damaged due to punching shear

    Directory of Open Access Journals (Sweden)

    Hamed S. Askar

    2015-09-01

    An experimental investigation with the objective of retrofitting flat slabs damaged due to punching shear using prestressed vertical bolts is presented in this paper. The parameters examined in this study are vertical prestressed bolts with different ratios within the slab thickness, slab thickness and central column size. Through the experimental tests the load carrying capacity, deformation characteristics and the cracking behavior have been investigated. A comparison between the behavior of retrofitted slabs and their references showed that the proposed system of repair is effective and could be used in practice. A comparison between the experimental results and calculated punching failure load based on the formulas adopted by different codes, showed a reasonable agreement.

  18. Experimental and Computational Study of Ductile Fracture in Small Punch Tests

    Directory of Open Access Journals (Sweden)

    Betül Gülçimen Çakan

    2017-10-01

    Full Text Available A unified experimental-computational study on ductile fracture initiation and propagation during small punch testing is presented. Tests are carried out at room temperature with unnotched disks of different thicknesses where large-scale yielding prevails. In thinner specimens, the fracture occurs with severe necking under membrane tension, whereas for thicker ones a through thickness shearing mode prevails changing the crack orientation relative to the loading direction. Computational studies involve finite element simulations using a shear modified Gurson-Tvergaard-Needleman porous plasticity model with an integral-type nonlocal formulation. The predicted punch load-displacement curves and deformed profiles are in good agreement with the experimental results.

  19. Experimental and Computational Study of Ductile Fracture in Small Punch Tests.

    Science.gov (United States)

    Gülçimen Çakan, Betül; Soyarslan, Celal; Bargmann, Swantje; Hähner, Peter

    2017-10-17

    A unified experimental-computational study on ductile fracture initiation and propagation during small punch testing is presented. Tests are carried out at room temperature with unnotched disks of different thicknesses where large-scale yielding prevails. In thinner specimens, the fracture occurs with severe necking under membrane tension, whereas for thicker ones a through thickness shearing mode prevails changing the crack orientation relative to the loading direction. Computational studies involve finite element simulations using a shear modified Gurson-Tvergaard-Needleman porous plasticity model with an integral-type nonlocal formulation. The predicted punch load-displacement curves and deformed profiles are in good agreement with the experimental results.

  20. Fabrication and loading of oral drug delivery microcontainers using hot punching

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Borre, Mads T.; Keller, Stephan Sylvest

    2015-01-01

    In this paper, poly-l-lactic acid (PLLA) solution is spin coated to achieve a PLLA layer of 55 μm thickness. Hot punching with a Ni stamp is optimized to fabricate microcontainers in PLLA. Process optimization of thermal bonding of the microcontainers to a poly acrylic acid (PAA) layer is perform...... by modifying sample preparation and varying temperature. The fabricated microcontainers are loaded by hot punching in a spin coated drug polymer film of furosemide and poly-e-caprolactone (PCL)....

  1. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  2. Enhancements to the Image Analysis Tool for Core Punch Experiments and Simulations (vs. 2014)

    Energy Technology Data Exchange (ETDEWEB)

    Hogden, John Edward [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Unal, Cetin [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-06

    A previous paper (Hogden & Unal, 2012, Image Analysis Tool for Core Punch Experiments and Simulations) described an image processing computer program developed at Los Alamos National Laboratory. This program has proven useful so developement has been continued. In this paper we describe enhacements to the program as of 2014.

  3. Newborn screening blood spot analysis in the UK: influence of spot size, punch location and haematocrit.

    Science.gov (United States)

    Lawson, A J; Bernstone, L; Hall, S K

    2016-03-01

    In dried blood spot analysis, punch location and variations in applied sample volume and haematocrit can produce different measured concentrations of analytes. We investigated the magnitude of these effects in newborn screening in the UK. Heparinized blood spiked with thyroid stimulating hormone (TSH), phenylalanine, tyrosine, leucine, methionine, octanoyl carnitine (C8), and immunoreactive trypsinogen (IRT) was spotted onto filter paper: (i) at a constant haematocrit of 50% at various volumes, and (ii) at a range of haematocrits using a constant volume. Subpunches (3.2 mm) of the dried blood spots were then analysed. Compared with a central punch from a 50 µL blood spot with 50% haematocrit, 10 µL spots can have significantly lower measured concentrations of all analytes, with decreases of 15% or more observed for leucine, methionine, phenylalanine, and tyrosine. Punching at the edge of a spot can increase measured concentrations up to 35%. Higher haematocrit decreased measured TSH and C8 yet increased amino acids and IRT by 15% compared with 50% haematocrit. Lower haematocrits had the opposite effect, but only with higher concentrations of some analytes. Differences in blood spot size, haematocrit and punch location substantially affect measured concentrations for analytes used in the UK newborn screening programme, and this could affect false positive and negative rates. To minimize analytical bias, these variables should be controlled or adjusted for where possible. © The Author(s) 2015.

  4. Effect of Friction Coefficient on the Small Punch Creep Behavior of AISI 316L Stainless Steel

    International Nuclear Information System (INIS)

    Kim, Bum-Joon; Cho, Nam-Hyuck; Kim, Moon-K; Lim, Byeong-Soo

    2011-01-01

    Small punch creep testing has received attention due to the convenience of using smaller specimens than those of conventional uniaxial creep tests, which enables creep testing on developing or currently operational components. However, precedent studies have shown that it is necessary to consider friction between the punch and specimen when computing uniaxial equivalent stress from a finite element model. In this study, small punch creep behaviors of AISI 316L stainless steel, which is widely used in high temperature-high pressure machineries, have been compared for the two different ceramic balls such as Si 3 N 4 and Al 2 O 3 . The optimal range of the friction coefficient is 0.4⁓0.5 at 650°C for the best fit between experimental and simulation data of AISI 316 L stainless steel. The higher the friction coefficient, the longer the creep rupture time is. Therefore, the type of ceramic ball used must be specified for standardization of small punch creep testing.

  5. Short term creep small punch testing of P91 and P92 steels,

    Czech Academy of Sciences Publication Activity Database

    Dymáček, Petr

    2011-01-01

    Roč. 465, - (2011), s. 179-182 ISSN 1013-9826. [Materials Structure & Micromechanics of Fracture 6. Brno, 28.6.2010-30.6,2010] R&D Projects: GA AV ČR(CZ) IAA200410801 Institutional research plan: CEZ:AV0Z20410507 Keywords : creep * small punch test * chromium steel Subject RIV: JG - Metallurgy

  6. Splitting behaviour of timber loaded perpendicular to the grain by punched metal plates

    NARCIS (Netherlands)

    Schoenmakers, J.C.M.; Jorissen, A.J.M.; Leijten, A.J.M.; Aratake, S. xx

    2008-01-01

    Nowadays, prefabricated timber trusses are widely used as load-bearing roof structures. The majority of these trusses are produced with punched metal plates (PMP) to connect two or more timber elements of the same thickness, see Figure 2. In these structures sufficient overlap is required to prevent

  7. Analysis of ancient Indian silver punch-marked coins by external PIXE

    International Nuclear Information System (INIS)

    Rautray, Tapash R.; Nayak, Suman S.; Tripathy, Bipin B.; Das, Saubhagyalaxmi; Das, Manas R.; Das, Satya R.; Chattopadhyay, Pranab K.

    2011-01-01

    Seven silver punch-marked coins were analysed using external particle induced X-ray emission technique. The main group of elements like Ag, Cu, Au, Pb and Fe were estimated along with a number of trace/minor elements such as K, Ca, Ti, V, Cr, Mn, Co, Ni and Rb in the analysed silver coins. Gold was found in all the coins and varied between 0.7% and 6.2% indicating the better economic condition of that civilisation. - Highlights: → The silver punch-marked coins, in the current study, were in use in India between 6th century BC to 6th century AD and have been analysed by in-air PIXE. → These sets of coins have immense archaeological importance because of their very rare availability. → These coins are distinguished from other coins because of the presence of gold as major element. → While the British period coins were fabricated using modern technologies, the punch-marked coins were shaped manually with developed metal technology. → The analysis of punch-marked coins using external PIXE beam has been done for the first time, which is unique of its kind.

  8. Book review: Introduction to Social Research: Quantitative and Qualitative Approaches, Third Edition, by Keith F Punch

    NARCIS (Netherlands)

    Lecheler, S.

    2014-01-01

    In Introduction to Social Research, Keith F. Punch wants to ‘demystify’ and ‘simplify’ the research process, in an attempt to show that quality research can always be achieved. With its straightforward language, an intuitive structure, and well-defined learning objectives, this book does just that,

  9. Evaluation of Replacement Grafts and Punch Grafts in the Treatment of Vitiligo

    Directory of Open Access Journals (Sweden)

    Singh Ajit Kumar

    1980-01-01

    Full Text Available Thirtycasesof vitiligo eachwithminimum of two lesions undent replacement graft and multiple punch grafts in one lesion each. Complications observed at the recipient site like infection and raised nigosed surface were significantly more in replacement grafts. Hypopigmentation of the graft was significantly more when the disease was progressive.

  10. Small Punch Tests at Oxide Scales Surface of Structural Steel and Low Silicon Steel

    Czech Academy of Sciences Publication Activity Database

    Hrabovský, J.; Dobeš, Ferdinand; Horský, J.

    2014-01-01

    Roč. 82, 3-4 (2014), s. 297-310 ISSN 0030-770X Institutional support: RVO:68081723 Keywords : Small punch * Oxide scales * X-ray diffraction * Mechanical properties Subject RIV: JK - Corrosion ; Surface Treatment of Materials Impact factor: 1.140, year: 2014

  11. Review of Punching Shear Behaviour of Flat Slabs Reinforced with FRP Bars

    Science.gov (United States)

    Mohamed, Osama A.; Khattab, Rania

    2017-10-01

    Using Fibre Reinforced Polymer (FRP) bars to reinforce two-way concrete slabs can extend the service life, reduce maintenance cost and improve-life cycle cost efficiency. FRP reinforcing bars are more environmentally friendly alternatives to traditional reinforcing steel. Shear behaviour of reinforced concrete structural members is a complex phenomenon that relies on the development of internal load-carrying mechanisms, the magnitude and combination of which is still a subject of research. Many building codes and design standards provide design formulas for estimation of punching shear capacity of FRP reinforced flat slabs. Building code formulas take into account the effects of the axial stiffness of main reinforcement bars, the ratio of the perimeter of the critical section to the slab effective depth, and the slab thickness on the punching shear capacity of two-way slabs reinforced with FRP bars or grids. The goal of this paper is to compare experimental data published in the literature to the equations offered by building codes for the estimation of punching shear capacity of concrete flat slabs reinforced with FRP bars. Emphasis in this paper is on two North American codes, namely, ACI 440.1R-15 and CSA S806-12. The experimental data covered in this paper include flat slabs reinforced with GFRP, BFRP, and CFRP bars. Both ACI 440.1R-15 and CSA S806-12 are shown to be in good agreement with test results in terms of predicting the punching shear capacity.

  12. Effect of CFRP and TRM Strengthening of RC Slabs on Punching Shear Strength

    Directory of Open Access Journals (Sweden)

    Husain Abbas

    Full Text Available Abstract The paper presents experiments involving punching of RC slabs strengthened using externally bonded carbon fiber reinforced polymer (CFRP sheet and textile reinforced mortar (TRM. Twelve RC slab specimens of two concrete grades (39.9 and 63.2 MPa and employing two strengthening schemes (CFRP and TRM were tested. Specimens were supported on two opposite edges. Experimental load-displacement variations show two peak loads in strengthened slabs and one peak followed by a plateau in control. Second peak or the plateau corresponds to the combined action of aggregate interlock and the dowel action of back face rebars and strengthening layers. The dowel action of back face rebars and strengthening layers had no role in ultimate punching load (i.e. first peak. Strengthened slabs showed 9-18% increase in ultimate punching load (i.e. first peak whereas there was significant increase in the second peak load (190-276% for CFRP; 55-136% for TRM and energy absorption (~66% for CFRP and 22-56% for TRM. An analytical model was also developed for predicting the punching shear strength (first and second peaks of strengthened slabs showing good comparison with experiments.

  13. Fracture-based correlation of uniaxial and small punch creep data

    Czech Academy of Sciences Publication Activity Database

    Dobeš, Ferdinand; Dymáček, Petr

    2016-01-01

    Roč. 86, DEC (2016), s. 34-38 ISSN 0167-8442 R&D Projects: GA MŠk LM2015069; GA MŠk(CZ) LQ1601 Institutional support: RVO:68081723 Keywords : Creep * Small punch test * Chromium steel Subject RIV: JG - Metallurgy Impact factor: 2.659, year: 2016

  14. HOW BOXERS DECIDE TO PUNCH A TARGET: EMERGENT BEHAVIOUR IN NONLINEAR DYNAMICAL MOVEMENT SYSTEMS

    Directory of Open Access Journals (Sweden)

    Robert Hristovski

    2006-07-01

    Full Text Available Previous research has shown how dynamical systems theory provides a relevant framework for investigating decision-making behavior in sport. The aim of this study was to adopt concepts and tools from nonlinear dynamics in examining effects of boxer-target distance and perceived punching efficiency on emergent decision-making during a typical practice task in boxing. Results revealed the existence of critical values of scaled distances between boxers and targets for first time appearance and disappearance of a diverse range of boxing actions including jabs, hooks and uppercuts. Reasons for the diversity of actions were twofold: i abrupt (qualitative changes in the number of the possible punches, i.e. motor solutions to the hitting task; and ii, fine modification of the probabilities of selecting specific striking patterns. Boxers were able to exploit the emerging perception of strikeability, leading to a changing diversity of selected actions and a cascade of abrupt changes in the perceptual-motor work space of the task. Perceived efficiency of a punching action by the participants also changed as a function of the scaled distance to a target and was correlated with the probability of occurrence of specific boxing actions. Accordingly, scaled distance-dependent perceived efficiency seems an important perceptual constraint in the training task of punching a heavy bag in boxers

  15. Very heavy iron-punching concretes; Betons tres lourds a base de riblons

    Energy Technology Data Exchange (ETDEWEB)

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

    1966-07-01

    The present report deals with all the heavy iron-punching concretes, metallic wastes produced by the transformation industry. After a detailed description of the physical properties of metallic aggregates, a classification of heavy mortars is given, into three main categories: steel-shot grouts d = 5,3 - 6; steel-shot grouts mixed with a mineral d = 3,7 - 4,2; injection heavy grouts d = 3,5 - 4. The following chapter describes iron-punching concretes the most used in the atomic industry: iron-punching concretes mixed with cast-iron - iron-punching concretes mixed with magnetite; iron-punching concretes mixed with barite; iron-punching concretes mixed with limonite; iron-punching concretes mixed with boron. The compositions of these concretes are given together with their physical and mechanical characteristics. Numerous diagrams make it possible to find rapidly the proportions of the constituents of these concretes as a function of the required density. Technical advice and specifications are given in an appendix together with a bibliography of these heavy concretes. (author) [French] Le present rapport traite de l'ensemble des betons lourds realises a l'aide de riblons, dechets metalliques fournis par l'industrie de transformation. Apres une description detaillee des proprietes physiques des agregats metalliques, les mortiers lourds sont d'abord presentes en les classant en trois grandes categories: les mortiers a base de grenailles d 5,3 a 6; les mortiers a base de grenailles avec addition d'un mineral d 3,7 a 4,2; les mortiers lourds injectables d = 3,5 a 4. Le chapitre suivant decrit les betons a base de riblons les plus utilises, dans l'industrie atomique: les betons de riblons avec addition de fonte; les betons de riblons avec addition de magnetite; les betons de riblons avec addition de barytine; les betons de riblons avec addition de limonite; les betons de riblons avec addition de bore. Les compositions de ces betons ainsi que leurs caracteristiques

  16. Very heavy iron-punching concretes; Betons tres lourds a base de riblons

    Energy Technology Data Exchange (ETDEWEB)

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

    1966-07-01

    The present report deals with all the heavy iron-punching concretes, metallic wastes produced by the transformation industry. After a detailed description of the physical properties of metallic aggregates, a classification of heavy mortars is given, into three main categories: steel-shot grouts d = 5,3 - 6; steel-shot grouts mixed with a mineral d = 3,7 - 4,2; injection heavy grouts d = 3,5 - 4. The following chapter describes iron-punching concretes the most used in the atomic industry: iron-punching concretes mixed with cast-iron - iron-punching concretes mixed with magnetite; iron-punching concretes mixed with barite; iron-punching concretes mixed with limonite; iron-punching concretes mixed with boron. The compositions of these concretes are given together with their physical and mechanical characteristics. Numerous diagrams make it possible to find rapidly the proportions of the constituents of these concretes as a function of the required density. Technical advice and specifications are given in an appendix together with a bibliography of these heavy concretes. (author) [French] Le present rapport traite de l'ensemble des betons lourds realises a l'aide de riblons, dechets metalliques fournis par l'industrie de transformation. Apres une description detaillee des proprietes physiques des agregats metalliques, les mortiers lourds sont d'abord presentes en les classant en trois grandes categories: les mortiers a base de grenailles d 5,3 a 6; les mortiers a base de grenailles avec addition d'un mineral d 3,7 a 4,2; les mortiers lourds injectables d = 3,5 a 4. Le chapitre suivant decrit les betons a base de riblons les plus utilises, dans l'industrie atomique: les betons de riblons avec addition de fonte; les betons de riblons avec addition de magnetite; les betons de riblons avec addition de barytine; les betons de riblons avec addition de limonite; les betons de riblons avec addition de bore. Les compositions de ces betons ainsi que

  17. Does human presynaptic striatal dopamine function predict social conformity?

    Science.gov (United States)

    Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

    2014-03-01

    Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

  18. Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's disease patients

    International Nuclear Information System (INIS)

    Chang Icheng; Lue Kunhan; Hsieh Hungjen; Liu Shuhsin; Kao, Chinhao K.

    2011-01-01

    6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. (author)

  19. Effect of cutter tip angle on cutting characteristics of acrylic worksheet subjected to punch/die shearing

    Directory of Open Access Journals (Sweden)

    Masami Kojima

    2016-12-01

    Full Text Available This paper aims to describe the effect of tool geometry on cutting characteristics of a 1.0 mm thickness acrylic worksheet subjected to a punch/die shearing. A set of side-wedge punch and side-wedge die which had the edge angle of 30°, 60° and/or 90° was prepared and used for cutting off the worksheet. A load cell and a CCD camera were installed in the cutting system to investigate the cutting load resistance and the side-view deformation of the worksheet. From experimental results, it was revealed that a cracking pattern at a sheared zone was remarkably affected by the edge angle of cutting tool. A cracking direction was almost coincident to the edge angle when considering the punch/die edge angle of 30°, while any matching of them was not observed in case of the punch/die edge angle of 60°, 90°. By using the 30° side-wedge tool, a flat-smooth sheared surface was generated. When combing the punch edge angle of 90° and the die edge angle of 60°, the cracking profile was characterized by the both edge angles for each part (die and punch. Carrying out an elasto-plastic finite element method analysis of cutter indentation with a few of symmetric and asymmetric punch/die edges, the stress distribution and deformation flow at the sheared zone were discussed with the initiation of surface cracks

  20. Reduced striatal D2 receptor binding in myoclonus-dystonia

    International Nuclear Information System (INIS)

    Beukers, R.J.; Weisscher, N.; Tijssen, M.A.J.; Booij, J.; Zijlstra, F.; Amelsvoort, T.A.M.J. van

    2009-01-01

    To study striatal dopamine D 2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using 123 I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D 2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. (orig.)

  1. No association between striatal dopamine transporter binding and body mass index

    DEFF Research Database (Denmark)

    van de Giessen, Elsmarieke; Hesse, Swen; Caan, Matthan W A

    2013-01-01

    Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine...... transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated....

  2. The development of a tensile-shear punch correlation for yield properties of model austenitic alloys

    Energy Technology Data Exchange (ETDEWEB)

    Hankin, G.L.; Faulkner, R.G. [Loughborough Univ. (United Kingdom); Hamilton, M.L.; Garner, F.A. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-08-01

    The effective shear yield and maximum strengths of a set of neutron-irradiated, isotopically tailored austentic alloys were evaluated using the shear punch test. The dependence on composition and neutron dose showed the same trends as were observed in the corresponding miniature tensile specimen study conducted earlier. A single tensile-shear punch correlation was developed for the three alloys in which the maximum shear stress or Tresca criterion was successfully applied to predict the slope. The correlation will predict the tensile yield strength of the three different austenitic alloys tested to within {+-}53 MPa. The accuracy of the correlation improves with increasing material strength, to within {+-} MPa for predicting tensile yield strengths in the range of 400-800 MPa.

  3. A possible mechanism for electron-bombardment-induced loop punching in helium-implanted materials

    International Nuclear Information System (INIS)

    Donnelly, S.E.

    1983-01-01

    The recently proposed mechanism for the punching of dislocation loops by overpressurized helium bubbles in molybdenum is studied quantitatively. According to this mechanism, under the electron beam of the transmission microscope, He atoms are excited or ionized and the resulting excited species (excited He atoms and free electrons) are responsible for the pressure rise in the gas beyond the threshold for loop punching. In the model, the pressure increase is attributed to a reduction of the effective volume accessible to the gas due to the formation of a cavity around each excited species. The radius of this cavity is evaluated and, also, the excited fraction required to reach the threshold is discussed in terms of excitation life times. (author)

  4. The development of a tensile-shear punch correlation for yield properties of model austenitic alloys

    International Nuclear Information System (INIS)

    Hankin, G.L.; Faulkner, R.G.; Hamilton, M.L.; Garner, F.A.

    1997-01-01

    The effective shear yield and maximum strengths of a set of neutron-irradiated, isotopically tailored austentic alloys were evaluated using the shear punch test. The dependence on composition and neutron dose showed the same trends as were observed in the corresponding miniature tensile specimen study conducted earlier. A single tensile-shear punch correlation was developed for the three alloys in which the maximum shear stress or Tresca criterion was successfully applied to predict the slope. The correlation will predict the tensile yield strength of the three different austenitic alloys tested to within ±53 MPa. The accuracy of the correlation improves with increasing material strength, to within ± MPa for predicting tensile yield strengths in the range of 400-800 MPa

  5. Influence of friction on stress and strain distributions in small punch creep test models

    Czech Academy of Sciences Publication Activity Database

    Dymáček, Petr; Seitl, Stanislav; Milička, Karel; Dobeš, Ferdinand

    417-418, - (2010), s. 561-564 ISSN 1013-9826. [International Conference on Fracture and Damage Mechanics /8./. Malta, 08.09.2009-10.09.2009] R&D Projects: GA AV ČR(CZ) IAA200410801; GA AV ČR(CZ) 1QS200410502 Institutional research plan: CEZ:AV0Z20410507 Keywords : small punch test * creep * chromium steel * finite element method Subject RIV: JG - Metallurgy www.scientific.net/KEM.417-418.561

  6. Hot embossing and mechanical punching of biodegradable microcontainers for oral drug delivery

    DEFF Research Database (Denmark)

    Petersen, Ritika Singh; Mahshid, Rasoul; Andersen, Nis Korsgaard

    2015-01-01

    A process has been developed to fabricate discrete three-dimensional microcontainers for oral drug delivery application in Poly-L-Lactic Acid (PLLA) polymer. The method combines hot embossing for the definition of holes in a PLLA film and mechanical punching to penetrate the polymer layer around...... and shapes of microcontainers. Finally, the process is compatible with roll-to-roll processing that could lead to low cost high volume production. © 2014 Elsevier B.V. All rights reserved....

  7. Treatment of Die-Punch Fractures with 3D Printing Technology.

    Science.gov (United States)

    Chen, Chunhui; Cai, Leyi; Zhang, Chuanxu; Wang, Jianshun; Guo, Xiaoshan; Zhou, Yifei

    2017-07-19

    We evaluated the feasibility, accuracy and effectiveness of applying three-dimensional (3D) printing technology for preoperative planning for die-punch fractures. A total of 107 patients who underwent die-punch fracture surgery were enrolled in the study. They were randomly divided into two groups: 52 cases in the 3D model group and 55 cases in the routine group. A 3D digital model of each die-punch fracture was reconstructed in the 3D group. The 3D digital model was imported to a 3D printer to build the full solid model. The operation time, blood loss volume, and the number of intraoperative fluoroscopy were recorded. Follow-up was performed to evaluate the patients' surgical outcomes. Treatment of die-punch fractures using the 3D printing approach reduced the number of intraoperative fluoroscopy, blood loss volume, and operation time, but did not improve wrist function compared to those in the routine group. The patients wanted the doctor to use the 3D model to introduce the condition and operative plan because it was easier for them to understand. The orthopedic surgeons thought that the 3D model was useful for communicating with their patients, but their satisfaction with the preoperative plan was much lower than the benefit of using the 3D model to communicate with their patients. 3D printing technology produced more accurate morphometric information for orthopedists to provide personalized surgical planning and communicate better with their patients. However, it is difficult to use widely in the department of orthopedics.

  8. Estimation of ductility of Fe-Al alloys by means of small punch test

    Czech Academy of Sciences Publication Activity Database

    Dobeš, Ferdinand; Milička, Karel

    Roč.18, č.7 (2010), s. 1357-1359 ISSN 0966-9795. [Discussion Meeting on the Development of Innovative Iron Aluminium Alloys /5./. Praha, 21.09.2009-24.09.2009] R&D Projects: GA ČR GA106/08/1238 Institutional research plan: CEZ:AV0Z20410507 Keywords : iron aluminides * brittleness * small punch test Subject RIV: JG - Metallurgy Impact factor: 2.327, year: 2010

  9. Study of the upper die clamping conditions in the small punch test

    Czech Academy of Sciences Publication Activity Database

    Andrés, D.; Dymáček, Petr

    86A, DEC (2016), s. 117-123 ISSN 0167-8442 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068 Institutional support: RVO:68081723 Keywords : Small punch test * Finite element method * Parametric study * High temperature * Creep Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.659, year: 2016 http://www.sciencedirect.com/science/article/pii/S0167844216301835

  10. The Effects of Biomechanical Factors to Teach Different Hook Punch Techniques in Boxing and Education Strategies

    Science.gov (United States)

    Bingul, Bergun Meric; Bulgun, Cigdem; Tore, Ozlem; Bal, Erdal; Aydin, Mensure

    2018-01-01

    The aim of this study was to investigate the effects of biomechanic factors to teach different hook punches in boxing. Eight light middleweight boxing athletes (mean age ± SD 19.00 ± 2.00 yrs, mean height ± SD 173.88 ± 3.89 cm, mean weight ± SD 64.25 ± 4.66 kg) participated in this study. Athletes performed a trial using three different hook punch…

  11. Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

    Science.gov (United States)

    Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

    2017-06-30

    Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

  12. Striatal volume predicts level of video game skill acquisition.

    Science.gov (United States)

    Erickson, Kirk I; Boot, Walter R; Basak, Chandramallika; Neider, Mark B; Prakash, Ruchika S; Voss, Michelle W; Graybiel, Ann M; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

    2010-11-01

    Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.

  13. Experimental and numerical analysis of micromechanical damage in the punching process for High-Strength Low-Alloy steels

    OpenAIRE

    ACHOURI, Mohamed; GERMAIN, Guénaël; DAL SANTO, Philippe; SAIDANE, Delphine

    2014-01-01

    Sequential sheet metal forming processes can result in the accumulation of work hardening and damage effects in the workpiece material. The mechanical strength of the final component depends on the “evolution” of these two characteristics in the different production steps. The punching process, which is usually in the beginning of the production chain, has an important impact on the stress, strain and damage states in the punched zones. It is essential that the influence of these mechanical f...

  14. Examining the microtexture evolution in a hole-edge punched into 780 MPa grade hot-rolled steel

    Energy Technology Data Exchange (ETDEWEB)

    Shin, J.H.; Kim, M.S. [Department of Printed Electronics Engineering, Sunchon National University, 315 Maegok, Sunchon, Jeonnam 540-950 (Korea, Republic of); Kim, S.I.; Seo, S.J. [POSCO Technical Research Laboratories, Gwangyang 545-090 (Korea, Republic of); Choi, S.-H., E-mail: shihoon@sunchon.ac.kr [Department of Printed Electronics Engineering, Sunchon National University, 315 Maegok, Sunchon, Jeonnam 540-950 (Korea, Republic of)

    2016-08-15

    The deformation behavior in the hole-edge of 780 MPa grade hot-rolled steel during the punching process was investigated via microstructure characterization and computational simulation. Microstructure characterization was conducted to observe the edges of punched holes through the thickness direction, and electron back-scattered diffraction (EBSD) was used to analyze the heterogeneity of the deformation. Finite element analysis (FEA) that could account for a ductile fracture criterion was conducted to simulate the deformation and fracture behaviors of 780 MPa grade hot-rolled steel during the punching process. Calculation of rotation rate fields at the edges of the punched holes during the punching process revealed that metastable orientations in Euler space were confined to specific orientation groups. Rotation-rate fields effectively explained the stability of the initial texture components in the hole-edge region during the punching process. A visco-plastic self-consistent (VPSC) polycrystal model was used to calculate the microtexture evolution in the hole-edge region during the punching process. FEA revealed that the heterogeneous effective strain was closely related to the heterogeneity of the Kernel average misorientation (KAM) distribution in the hole-edge region. A simulation of the deformation microtexture evolution in the hole-edge region using a VPSC model was in good agreement with the experimental results. - Highlights: •We analyzed the microstructure in a hole-edge punched in HR 780HB steel. •Rotation rate fields revealed the stability of the initial texture components. •Heterogeneous effective stain was closely related to the KAM distribution. •VPSC model successfully simulated the deformation microtexture evolution.

  15. Cost Optimization on Energy Consumption of Punching Machine Based on Green Manufacturing Method at PT Buana Intan Gemilang

    OpenAIRE

    Prillia Ayudia; Rachmat Haris; Mulyana Tatang

    2017-01-01

    PT Buana Intan Gemilang is a company engaged in textile industry. The curtain textile production need punching machine to control the fabric process. The operator still works manually so it takes high cost of electrical energy consumption. So to solve the problem can implement green manufacturing on punching machine. The method include firstly to identify the color by classifying the company into the black, brown, gray or green color categories using questionnaire. Secondly is improvement are...

  16. Circumferential scouting punch biopsies to delineate surgical margin for dermatofibrosarcoma protuberans

    Directory of Open Access Journals (Sweden)

    Tsung-Mao Huang

    2012-03-01

    Full Text Available Dermatofibrosarcoma protuberans (DFSP is an uncommon soft-tissue tumor involving the dermis and subcutaneous tissue with a high local recurrence rate after standard excision. Mohs micrographic surgery offers a lower recurrence rate. However, the procedure requires multiple stages of excision with intraoperative histopathological mapping, which is time consuming and expensive. We report our experience of using circumferential scouting punch biopsy technique in five patients to determine in advance the resection margins for DFSP prior to wide excision. Multiple 4 mm punches, usually eight in number, were performed 1–2.5 cm around the palpable borders of DFSP to delineate the resection margins in five consecutive patients. Tumors were excised at a later date along the margin defined by these biopsies and the wounds were repaired with skin graft. The operation was completed in 2 hours in all cases excluding one that required frozen sections for deep margin. No recurrence was noted 2–10 years after the operations. The results suggest that circumferential scouting punch biopsies before wide excision may be an alternative method to define the resection margins for DFSP when Mohs surgery is not available.

  17. Highly sensitive photodetector based on ge double-barrier punch-through structure

    Directory of Open Access Journals (Sweden)

    Abdulkhaev O. A.

    2015-08-01

    Full Text Available In recent years, transmission and reception systems of optical signals are widely used. Receiving the optical signal in such systems is carried by photoreceiving modules based on a photodetector, which defines the quality of the received signal, the range and speed of the entire system. However, hitherto used p–i–n- and avalanche photodiodes do not fully meet the growing demands. The present work is devoted to investigate the photovoltaic characteristics of semiconductor thin base transistor structure based on germanium, which is superior the silicon counterparts by speed and gain. Investigated p+–n–p-structures were obtained by diffusion of antimony onto the substrate of p-type germanium to a depth of 1 micron and alloying of indium to the part of its surface which creates diffusion layer of ?+-type and with thickness of 0,5 microns. Experiments have shown that the reverse biasing of a single p+-n-emitter-base junction leads to a smooth increase in reverse current, at the same time when it is connected in series to forward biased collector p-n-junction there is a sharp increase in the current by voltage, giving properties of voltage surge suppressor. This behavior of the current-voltage characteristics can be explained by the punch-through effect when the space charge regions of the emitter junction and the space charge region of collector junction touch each other and the conditions are realized for double carrier injection into a fully depleted region of the transistor. At the same time giving small fixed voltages 0,1—0,15 V to the collector-base junction the output static characteristics can be received with an operating voltage of 3—3,5 V. A characteristic feature of the investigated transistor is that when the base region under illumination by integrated light intensity (50 and 3000 lux light current appears, whose magnitude with the increase of operating voltage (up to 1.7 V increases nonlinearly, resulting in increased

  18. High temperature strength analysis of welded joint of RAF's by small punch test

    Energy Technology Data Exchange (ETDEWEB)

    Kato, T. [Muroran Institute of Technology, Dept. of Materials Science and Engineeering, Hokkaido (Japan); Komazaki, S.; Kohno, Y. [Muroran Institute of Technology, Muroran (Japan); Tanigawa, H. [Japan Atomic Energy Agency, Naga-gun, Ibaraki-ken (Japan); Kohyama, A. [Kyoto Univ., Institute of Advanced Energy (Japan)

    2007-07-01

    Full text of publication follows: Nucleation and growth of microvoids and/or small cracks in fine-grained heat affected zone (HAZ) after long-term service operation, which is recognized as Type IV creep damage, has recently been a worldwide issue for high Cr ferritic steels. In our group, a small punch (SP) creep test has been successfully applied to evaluate this damage of low alloy ferritic steel. However, the HAZ of fusion reactor material welded by electron-beam (EB) welding is so narrow that it is not easy to evaluate its mechanical properties by conventional tests including the SP creep test with a plate-type specimen (10 x 10 x 0.5 mm{sup 3}). In this study, the SP creep test using a further miniaturized specimen was developed and applied to the welded joint of reduced activation ferritic steels (RAFs), F82H-IEA (Fe-8Cr-2W-0.2V-0.02Ta), for measuring creep properties of the HAZ. For the SP creep test, TEM disk-type samples (diam. 3.0 x 0.30 mm) were removed from the base metal (BM), weld metal (WM) and HAZ, respectively. The specimen surfaces were polished up to a 0.05 {mu}m alumina powder finish and the specimen's thickness was finally adjusted to 0.25 mm. The SP creep tests were performed at temperatures of 823{approx}973 K and under loads ranging from 20 to 200 N. A constant load was applied to the center of the specimen through the Si{sub 3}N{sub 4} bail (diam. 1.0 mm) using the electric servo motor. The central deflection of the specimen was monitored by measuring the displacement of the compression rod. The tests were carried out in an argon gas atmosphere and the gas was continuously passed through during the test to prevent severe oxidation of the specimen. The differences in SP creep properties such as rupture time and minimum creep rate between the BM, WM and HAZ were discussed in terms of microstructural changes during welding thermal cycles. In addition, the result obtained from the BM was correlated with those of uniaxial creep test

  19. Oxidative metabolism and Ca2+ handling in isolated brain mitochondria and striatal neurons from R6/2 mice, a model of Huntington's disease.

    Science.gov (United States)

    Hamilton, James; Pellman, Jessica J; Brustovetsky, Tatiana; Harris, Robert A; Brustovetsky, Nickolay

    2016-07-01

    Alterations in oxidative metabolism and defects in mitochondrial Ca 2+ handling have been implicated in the pathology of Huntington's disease (HD), but existing data are contradictory. We investigated the effect of human mHtt fragments on oxidative metabolism and Ca 2+ handling in isolated brain mitochondria and cultured striatal neurons from the R6/2 mouse model of HD. Non-synaptic and synaptic mitochondria isolated from the brains of R6/2 mice had similar respiratory rates and Ca 2+ uptake capacity compared with mitochondria from wild-type (WT) mice. Respiratory activity of cultured striatal neurons measured with Seahorse XF24 flux analyzer revealed unaltered cellular respiration in neurons derived from R6/2 mice compared with neurons from WT animals. Consistent with the lack of respiratory dysfunction, ATP content of cultured striatal neurons from R6/2 and WT mice was similar. Mitochondrial Ca 2+ accumulation was also evaluated in cultured striatal neurons from R6/2 and WT animals. Our data obtained with striatal neurons derived from R6/2 and WT mice show that both glutamate-induced increases in cytosolic Ca 2+ and subsequent carbonilcyanide p-triflouromethoxyphenylhydrazone-induced increases in cytosolic Ca 2+ were similar between WT and R6/2, suggesting that mitochondria in neurons derived from both types of animals accumulated comparable amounts of Ca 2+ Overall, our data argue against respiratory deficiency and impaired Ca 2+ handling induced by human mHtt fragments in both isolated brain mitochondria and cultured striatal neurons from transgenic R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Study of the mechanical properties of the electric power station components: the punch test; Etude des proprietes mecaniques des composants de centrales thermiques: l'essai punch test

    Energy Technology Data Exchange (ETDEWEB)

    Isselin, J

    2003-03-15

    The aging of the electric production park implies an increasing need of knowledge concerning the evolution of the mechanical properties of its components. With regard to this problem, the availability in material is more and more small. This work proposes to characterize these properties through a mechanical test called Punch test. The main characteristic of this test is to use very small volume samples. The development of this test has been carried out by the study of a 15 MDV 4-05 steel coming from a steam drum of a thermal power plant after 145000 hours of service. At first, we have measured the influence of the parameters of this test. Then, the study has dealt more particularly on the transition temperature of the material. With the finite element simulation method, the strain hardening coefficient of the material has been determined. (O.M.)

  1. Feasibility of attaining uniform grain structure and enhanced ductility in aluminum alloy by employing a beveled punch in equal-channel angular pressing

    Energy Technology Data Exchange (ETDEWEB)

    Nejadseyfi, Omid, E-mail: o.nejadseyfi@gmail.com [Advanced Materials and Nanotechnology Research Lab, Department of Mechanical Engineering, K.N. Toosi University of Technology, Tehran (Iran, Islamic Republic of); Shokuhfar, Ali [Advanced Materials and Nanotechnology Research Lab, Department of Mechanical Engineering, K.N. Toosi University of Technology, Tehran (Iran, Islamic Republic of); Sadeghi, Seyedali [Department of Mechanical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

    2016-01-10

    The advantage of using a beveled-edge punch in equal-channel angular pressing is investigated. Lambda angle (λ), the clockwise angle between the theoretical shear plane and punch/billet interface, is used to demonstrate how the punch tip is inclined. Transmission electron microscope is used to assess the microstructure of the samples processed using a beveled-edge punch. In addition, tensile tests at elevated temperature are performed. The results show that using a beveled-edge punch (λ=90°) in the process leads to formation of uniform subgrain structure and increases the tensile ductility for the samples at elevated temperature. Additionally, finite element simulations are performed to study the correlation between measured properties and mechanism of material deformation by employing a beveled-edge punch. Numerical simulations confirm the irregular deformation in case of λ=0° and uniform strain distribution for λ=90°, which were the main reasons of variation in mechanical properties.

  2. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux

    2015-07-01

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  3. Pleuroscopic punch biopsy using insulated-tip diathermic knife-2 for the diagnosis of desmoplastic malignant mesothelioma.

    Science.gov (United States)

    Masai, Kyohei; Sasada, Shinji; Izumo, Takehiro; Taniyama, Tomoko; Nakamura, Yukiko; Chavez, Christine; Sakurai, Hiroyuki; Tsuta, Koji; Tsuchida, Takaaki

    2013-10-01

    Desmoplastic malignant mesothelioma (DMM) is a rare subtype of malignant pleural mesothelioma (MPM) and is often difficult to distinguish from pleural fibrosis and reactive mesothelial hyperplasia, especially if the biopsy samples are small. We performed full-thickness pleural biopsy on a lesion suspected to be DMM using an insulated-tip diathermic knife-2 (IT knife-2) during flex-rigid pleuroscopy. IT knife-2 is a novel electrosurgical device for endoscopic submucosal dissection in the early gastrointestinal cancer. It consists of a needle knife with 3 short blades at the distal end attached to an insulated ceramic tip. A 54-year-old man presenting with chest wall mass and thickened pleura, in whom a computed tomography-guided percutaneous needle aspiration had remained negative, underwent flex-rigid pleuroscopy for definitive diagnosis. While applying electric current, we used the IT knife-2 to incise the pleura in a circular shape just above the endothoracic fascia. The incised pleura was removed by forceps and examined pathologically. The microscopic examination was compatible with DMM. We discovered that pleuroscopic punch biopsy using IT knife-2 can diagnose DMM. Use of IT knife-2 during flex-rigid pleuroscopy can obtain sufficient samples from densely thickened pleura, which is difficult to diagnose with small biopsies.

  4. A study on stress analysis of small punch-creep test and its experimental correlations with uniaxial-creep test

    International Nuclear Information System (INIS)

    Lee, Song In; Baek, Seoung Se; Kwon, Il Hyun; Yu, Hyo Sun

    2002-01-01

    A basic research was performed to ensure the usefulness of Small Punch-creep(SP-creep) test for residual life evaluation of heat resistant components effectively. This paper presents analytical results of initial stress and strain distributions in SP specimen caused by constant loading for SP-creep test and its experimental correlations with uniaxial creep(Ten-creep) test on 9CrlMoVNb steel. It was shown that the initial maximum equivalent stress, σ eq · max from FE analysis was correlated with steady-state equivalent creep strain rate, ε qf-ss , rupture time, t r , activation energy, Q and Larson-Miller parameter, LMP during SP-creep deformation. The simple correlation laws, σ SP - σ TEN , P SP -σ TEN and Q SP -Q TEN adopted to established a quantitative correlation between SP-creep and Ten-creep test data. Especially, the activation energy obtained from SP-creep test is linearly related to that from Ten-creep test at 650 deg. C as follows : Q SP-P =1.37 Q TEN , Q SP-σ =1.53 Q TEN

  5. Development of evaluation technique of high temperature creep characteristics by small punch-creep test method (I)

    International Nuclear Information System (INIS)

    Baek, Seung Se; Na, Sung Hun; Yu, Hyo Sun; Na, Eui Gyun

    2001-01-01

    In this study, a Small Punch Creep(SP-Creep) test using miniaturized specimen(10 x 10 x 0.5mm) is described to develop the new creep test method for high temperature structural materials. The SP-Creep test is applied to 2.25Cr-1Mo(STBA24) steel which is widely used as boiler tube material. The test temperatures applied for the creep deformation of miniaturized specimens are between 550∼600 .deg. C. The SP-Creep curves depend definitely on applied load and creep temperature, and show the three stages of creep behavior like in conventional uniaxial tensile creep curves. The load exponent of miniaturized specimen decrease with increasing test temperature, and its behavior is similar to stress exponent behavior of uniaxial creep test. The creep activation energy obtained from the relationship between SP-Creep rate and test temperature decreases as the applied load increases. A predicting equation of SP-Creep rate for 2.25Cr-1Mo steel is suggested, and a good agreement between experimental and calculated data has been found

  6. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    Science.gov (United States)

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

  7. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  8. Centrality of striatal cholinergic transmission in basal ganglia function

    Directory of Open Access Journals (Sweden)

    Paola eBonsi

    2011-02-01

    Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

  9. Distinctive striatal dopamine signaling after dieting and gastric bypass.

    Science.gov (United States)

    Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

    2015-05-01

    Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  11. Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

    Science.gov (United States)

    Galván, Adriana; McGlennen, Kristine M

    2013-02-01

    Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

  12. Motor tics evoked by striatal disinhibition in the rat

    Science.gov (United States)

    Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

    2013-01-01

    Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

  13. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  14. Molecular substrates of action control in cortico-striatal circuits.

    Science.gov (United States)

    Shiflett, Michael W; Balleine, Bernard W

    2011-09-15

    The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Adrenergic receptor-mediated modulation of striatal firing patterns.

    Science.gov (United States)

    Ohta, Hiroyuki; Kohno, Yu; Arake, Masashi; Tamura, Risa; Yukawa, Suguru; Sato, Yoshiaki; Morimoto, Yuji; Nishida, Yasuhiro; Yawo, Hiromu

    2016-11-01

    Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α 1 -AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α 1 -ARs work in opposition controlling the striatal firing initiation and the firing increment. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  16. The role of striatal NMDA receptors in drug addiction.

    Science.gov (United States)

    Ma, Yao-Ying; Cepeda, Carlos; Cui, Cai-Lian

    2009-01-01

    The past decade has witnessed an impressive accumulation of evidence indicating that the excitatory amino acid glutamate and its receptors, in particular the N-methyl-D-aspartate (NMDA) receptor subtype, play an important role in drug addiction. Various lines of research using animal models of drug addiction have demonstrated that drug-induced craving is accompanied by significant upregulation of NR2B subunit expression. Furthermore, selective blockade of NR2B-containing NMDA receptors in the striatum, especially in the nucleus accumbens (NAc) can inhibit drug craving and reinstatement. The purpose of this review is to examine the role of striatal NMDA receptors in drug addiction. After a brief description of glutamatergic innervation and NMDA receptor subunit distribution in the striatum, we discuss potential mechanisms to explain the role of striatal NMDA receptors in drug addiction by elucidating signaling cascades involved in the regulation of subunit expression and redistribution, phosphorylation of receptor subunits, as well as activation of intracellular signals triggered by drug experience. Understanding the mechanisms regulating striatal NMDA receptor changes in drug addiction will provide more specific and rational targets to counteract the deleterious effects of drug addiction.

  17. In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

    Science.gov (United States)

    Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

    2012-12-16

    Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

  18. Fractal analysis of striatal dopamine re-uptake sites

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

    1997-01-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab

  19. Fractal analysis of striatal dopamine re-uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T.; Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Tiihonen, J.; Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Karhu, J. [Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio (Finland)

    1997-09-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT). The mean fractal dimension was 1.15{+-}0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19{+-}0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab.

  20. Transient and steady-state selection in the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Adam eTomkins

    2014-01-01

    Full Text Available Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role the striatal microcircuit plays in action selection in the basal ganglia-thalamo-cortical loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-thalamo-cortical loop, to asses the computational role the striatum plays in action selection. We identify a robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's Disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. Thus our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients.

  1. Contact stresses by rounded punch subject to axial and transverse shear

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-05-01

    Contact shear stresses by rounded punch were evaluated numerically. Numerical program was successfully implemented by using an influence function method. To simulate the physical fretting problem, a closed load path of shear was considered. The influence functions on surface displacements fo both axial and transverse direction were calculated using a triangular shear traction element. Behaviour of the contact surface, such as stick and slip region during the load path was investigated together with compliance change. Irreversibility of the shear stress was shown. The importance and the utilization of the present research were discussed for analyzing the material failure induced by contact such as fretting wear and fatigue.

  2. Contact stresses by rounded punch subject to axial and transverse shear

    International Nuclear Information System (INIS)

    Kim, Hyung Kyu

    1999-01-01

    Contact shear stresses by rounded punch were evaluated numerically. Numerical program was successfully implemented by using an influence function method. To simulate the physical fretting problem, a closed load path of shear was considered. The influence functions on surface displacements fo both axial and transverse direction were calculated using a triangular shear traction element. Behaviour of the contact surface, such as stick and slip region during the load path was investigated together with compliance change. Irreversibility of the shear stress was shown. The importance and the utilization of the present research were discussed for analyzing the material failure induced by contact such as fretting wear and fatigue

  3. Backward can extrusion with conical,rotating punch as a cold forging tribology test

    DEFF Research Database (Denmark)

    Ceron, Ermanno; Bay, Niels; Tetsuo, A.

    2011-01-01

    with an analysis of the sliding velocity distribution along the punch nose. The latter is determined by FE analysis of the test. Results show friction stress for unalloyed low C-steel provided with different types of lubricants, e.g. phosphate coating plus soap, phosphate coating plus MoS2 and single bathe...... lubrication with PULS. The new test is so severe, that it is possible to break down the best lubrication systems for cold forging, such as phosphate coating plus soap and MoS2....

  4. Tooling solutions for sheet metal forming and punching of lean duplex stainless steel

    DEFF Research Database (Denmark)

    Wadman, Boel; Madsen, Erik; Bay, Niels

    2012-01-01

    .4509 and lean duplex EN1.4162 in a production designed for austenitic stainless steels, such as EN1.4301 and 1.4401. The result is a guideline that summarizes how stainless material properties may affect tool degradation, and suggests tool solutions for reduced production disturbances and tool maintenance cost.......For producers of advanced stainless components the choice of stainless material influences not only the product properties, but also the tooling solution for sheet metal stamping. This work describes how forming and punching tools will be affected when introducing the stainless alloys ferritic EN1...

  5. Strain gradient effects in periodic flat punch indenting at small scales

    DEFF Research Database (Denmark)

    Nielsen, Kim Lau; Niordson, Christian Frithiof; Hutchinson, J. W.

    2014-01-01

    Experiments on soft polycrystalline aluminum have yielded evidence that, besides the required punch load, both the size and shape of imprinted features are affected by the scale of the set-up, e.g. substantial details are lost when the characteristic length is on the order of 10μm. The objective...... are employed. During a largely non-homogeneous deformation, the material is forced up in between the indenters so that an array of identical imprinted features is formed once the tool is retreated. It is confirmed that the additional hardening owing to plastic strain gradients severely affects both the size...

  6. Contact Problem for an Elastic Layer on an Elastic Half Plane Loaded by Means of Three Rigid Flat Punches

    Directory of Open Access Journals (Sweden)

    T. S. Ozsahin

    2013-01-01

    Full Text Available The frictionless contact problem for an elastic layer resting on an elastic half plane is considered. The problem is solved by using the theory of elasticity and integral transformation technique. The compressive loads P and Q (per unit thickness in direction are applied to the layer through three rigid flat punches. The elastic layer is also subjected to uniform vertical body force due to effect of gravity. The contact along the interface between elastic layer and half plane is continuous, if the value of the load factor, λ, is less than a critical value, . In this case, initial separation loads, and initial separation points, are determined. Also the required distance between the punches to avoid any separation between the punches and the elastic layer is studied and the limit distance between punches that ends interaction of punches is investigated for various dimensionless quantities. However, if tensile tractions are not allowed on the interface, for the layer separates from the interface along a certain finite region. Numerical results for distance determining the separation area, vertical displacement in the separation zone, contact stress distribution along the interface between elastic layer and half plane are given for this discontinuous contact case.

  7. Cracking the code: a decode strategy for the international business machines punch cards of Korean war soldiers.

    Science.gov (United States)

    Mitsunaga, Erin M

    2006-05-01

    During the Korean War, International Business Machines (IBM) punch cards were created for every individual involved in military combat. Each card contained all pertinent personal information about the individual and was utilized to keep track of all soldiers involved. However, at present, all of the information known about these punch cards reveals only their format and their significance; there is little to no information on how these cards were created or how to interpret the information contained without the aid of the computer system used during the war. Today, it is believed there is no one available to explain this computerized system, nor do the original computers exist. This decode strategy is the result of an attempt to decipher the information on these cards through the use of all available medical and dental records for each individual examined. By cross-referencing the relevant personal information with the known format of the cards, a basic guess-and-check method was utilized. After examining hundreds of IBM punch cards, however, it has become clear that the punch card method of recording information was not infallible. In some cases, there are gaps of information on cards where there are data recorded on personal records; in others, information is punched incorrectly onto the cards, perhaps as the result of a transcription error. Taken all together, it is clear that the information contained on each individual's card should be taken solely as another form of personal documentation.

  8. Joint punching and frequency effects on practical magnetic characteristics of electrical steels for high-speed machines

    Science.gov (United States)

    Kedous-Lebouc, A.; Messal, O.; Youmssi, A.

    2017-03-01

    Mechanical punching of electrical steels causes a degradation of their magnetic characteristics which can extend several millimeters from the cut edge. So, in the field of industrial applications, particularly that of small electrical machines, the stator core made of rigid and thin teeth would be subject to more losses. Thus, this topic of the effect of punching has to be submitted to further deep characterization and development in order to give some insight into the different mechanisms. In this framework, this paper evaluates the combined effect of punching and frequency on the magnetization curve and iron losses in thin SiFe and CoFe soft magnetic sheets. These alloys are typically suitable for the manufacture of high-speed electrical machines used in on board applications (aircraft power generators, automotive, etc). Two SiFe alloys and a CoFe alloy have been investigated. First, different rectangular samples of variable width (15, 10, 5, 3 mm) have been industrially punched. Then, a dedicated magnetic characterization has been made, using basically a mini-Epstein frame. Measurements have been performed from 50 Hz to 1 kHz and from 0.3 T to near saturation. Both rolling and transverse directions have been considered. Finally, a first attempt to predict the degradation due to the punching is presented. A useful description of the magnetic permeability as a function of B and f is given and the degradation parameters are estimated based on the knowledge of the reference permeability.

  9. Joint punching and frequency effects on practical magnetic characteristics of electrical steels for high-speed machines

    Energy Technology Data Exchange (ETDEWEB)

    Kedous-Lebouc, A. [Univ. Grenoble Alpes, G2Elab, F-38000 Grenoble, France — CNRS, G2Elab, F-38000 Grenoble (France); Messal, O., E-mail: oualid.messal@g2elab.grenoble-inp.fr [Univ. Grenoble Alpes, G2Elab, F-38000 Grenoble, France — CNRS, G2Elab, F-38000 Grenoble (France); Youmssi, A. [Université de N’gaoundéré, BP. 455 N’Gaoundéré (Cameroon)

    2017-03-15

    Mechanical punching of electrical steels causes a degradation of their magnetic characteristics which can extend several millimeters from the cut edge. So, in the field of industrial applications, particularly that of small electrical machines, the stator core made of rigid and thin teeth would be subject to more losses. Thus, this topic of the effect of punching has to be submitted to further deep characterization and development in order to give some insight into the different mechanisms. In this framework, this paper evaluates the combined effect of punching and frequency on the magnetization curve and iron losses in thin SiFe and CoFe soft magnetic sheets. These alloys are typically suitable for the manufacture of high-speed electrical machines used in on board applications (aircraft power generators, automotive, etc). Two SiFe alloys and a CoFe alloy have been investigated. First, different rectangular samples of variable width (15, 10, 5, 3 mm) have been industrially punched. Then, a dedicated magnetic characterization has been made, using basically a mini-Epstein frame. Measurements have been performed from 50 Hz to 1 kHz and from 0.3 T to near saturation. Both rolling and transverse directions have been considered. Finally, a first attempt to predict the degradation due to the punching is presented. A useful description of the magnetic permeability as a function of B and f is given and the degradation parameters are estimated based on the knowledge of the reference permeability.

  10. [3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

    International Nuclear Information System (INIS)

    Thompson, J.M.

    1981-01-01

    Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

  11. Adversity in childhood linked to elevated striatal dopamine function in adulthood

    OpenAIRE

    Egerton, A.; Valmaggia, L. R.; Howes, O. D.; Day, F.; Chaddock, C. A.; Allen, P.; Winton-Brown, T. T.; Bloomfield, M. A. P.; Bhattacharyya, S.; Chilcott, J.; Lappin, J. M.; Murray, R. M.; McGuire, P.

    2016-01-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and he...

  12. "One can't shake off the women": images of sport and gender in Punch, 1901-10.

    Science.gov (United States)

    Constanzo, Marilyn

    2002-01-01

    Examining the manner in which the popular press portrayed middle-class Edwardian women's activity in sport provides insight into the social liberation of English women. The popular middle-class British journal Punch included thousands of images of sportswomen. Despite the misogynistic satirizing of inept women, Punch's cartoons and articles depict distinct changes in women's behavior and social expectations that are linked to their increasing involvement in sport. By engaging in sport, women unconsciously challenged and permanently altered the pervasive middle-class Victorian ideology. The contents of Punch suggests that middle-class women's participation in sport, though perhaps begun in a conservative manner, completely altered and expanded their social role and changed the traditional image of womanhood.

  13. Treatment of a Refractory Skin Ulcer Using Punch Graft and Autologous Platelet-Rich Plasma

    Directory of Open Access Journals (Sweden)

    Mauro Carducci

    2016-01-01

    Full Text Available Background. Chronic ulceration of the lower legs is a relatively common condition amongst adults: one that causes pain and social distress and results in considerable healthcare and personal costs. The technique of punch grafting offers an alternative approach to the treatment of ulcers of the lower limbs. Objective. Combining platelet-rich plasma and skin graft enhances the efficacy of treating chronic diabetic wounds by enhancing healing rate and decreasing recurrence rate. Platelet-rich plasma could, by stimulating dermal regeneration, increase the take rate after skin grafting or speed up reepithelialization. Methods and Materials. The ulcer was prepared by removing fibrin with a curette and the edges of the ulcer were freshened. The platelet-rich plasma has been infiltrated on the bottom and edges of the ulcer. The punch grafts were placed in 5 mm holes arranged. The ulcer was medicated with hydrogel and a pressure dressing was removed after 8 days. Results. After a few days the patient did not report more pain. Granulation tissue appeared quickly between implants. Most of the grafts were viable in 2-3 weeks. The grafts gradually came together to close the ulcer and were completed in four months.

  14. Studying the sensor response in the punch-through-protection region

    CERN Document Server

    Poley, Anne-luise; The ATLAS collaboration

    2017-01-01

    For the Phase-II Upgrade of the ATLAS detector, a new, all-silicon tracker will be constructed in order to cope with the increased track density and radiation level of the High Luminosity Large Hadron Collider. While silicon strip sensors are designed to minimise the fraction of dead material and maximise the active area of a sensor, concessions must be made to the requirements of operating a sensor in a particle physics detector. Sensor geometry features like the punch-through protection deviate from the standard sensor architecture and thereby affect the charge collection in that area. In order to study the signal collection of silicon strip sensors over their punch-through-protection area, ATLAS silicon strip sensors were scanned with a micro-focused X-ray beam at the Diamond Light Source. Due to the highly focused X-ray beam (2 × 3 µm) and the short average path length of an electron after interaction with an X-ray photon (≤ 2 μm), local signal collection in different sensor areas can be studied with...

  15. Effects of laser power density and initial grain size in laser shock punching of pure copper foil

    Science.gov (United States)

    Zheng, Chao; Zhang, Xiu; Zhang, Yiliang; Ji, Zhong; Luan, Yiguo; Song, Libin

    2018-06-01

    The effects of laser power density and initial grain size on forming quality of holes in laser shock punching process were investigated in the present study. Three different initial grain sizes as well as three levels of laser power densities were provided, and then laser shock punching experiments of T2 copper foil were conducted. Based upon the experimental results, the characteristics of shape accuracy, fracture surface morphology and microstructures of punched holes were examined. It is revealed that the initial grain size has a noticeable effect on forming quality of holes punched by laser shock. The shape accuracy of punched holes degrades with the increase of grain size. As the laser power density is enhanced, the shape accuracy can be improved except for the case in which the ratio of foil thickness to initial grain size is approximately equal to 1. Compared with the fracture surface morphology in the quasistatic loading conditions, the fracture surface after laser shock can be divided into three zones including rollover, shearing and burr. The distribution of the above three zones strongly relates with the initial grain size. When the laser power density is enhanced, the shearing depth is not increased, but even diminishes in some cases. There is no obvious change of microstructures with the enhancement of laser power density. However, while the initial grain size is close to the foil thickness, single-crystal shear deformation may occur, suggesting that the ratio of foil thickness to initial grain size has an important impact on deformation behavior of metal foil in laser shock punching process.

  16. A DLC-Punch Array to Fabricate the Micro-Textured Aluminum Sheet for Boiling Heat Transfer Control

    Directory of Open Access Journals (Sweden)

    Tatsuhio Aizawa

    2018-03-01

    Full Text Available A diamond-like carbon (DLC film, coated on an SKD11 (alloy tool steel substrate, was shaped by plasma oxidation to form an assembly of DLC macro-pillars and to be used as a DLC-punch array that is micro-embossed into aluminum sheets. First, the SKD11 steel die substrate was prepared and DLC-coated to have a film thickness of 10 μm. This DLC coating worked as a punch material. The two-dimensional micro-patterns were printed onto this DLC film by maskless lithography. The unprinted DLC films were selectively removed by plasma oxidation to leave the three-dimensional DLC-punch array on the SKD11 substrate. Each DLC punch had a head of 3.5 μm × 3.5 μm and a height of 8 μm. This DLC-punch array was fixed into the cassette die set for a micro-embossing process using a table-top servo-stamper. Furthermore, through numerically controlled micro-embossing, an alignment of rectangular punches was transcribed into a micro-cavity array in the aluminum sheet. The single micro-cavity had a bottom surface of 3.2 μm × 3.2 μm and an average depth of 7.5 μm. A heat-transfer experiment in boiling water was also performed to investigate the effect of micro-cavity texture on bubbling behavior and the boiling curve.

  17. Development of a Small Punch Test Technique for an Evaluation of the Mechanical Properties of Irradiated Materials in a Hot Cell

    International Nuclear Information System (INIS)

    Kim, Do-Sik; Ahn, Sang-Bok; Yoo, Byung-Ok; Choo, Yong-Sun; Hong, Kwon-Pyo

    2006-01-01

    Miniaturized specimens have been widely used to evaluate the mechanical properties of steels and plastics. Especially for a study on the irradiation effects in nuclear materials, the small specimen test techniques have attracted considerable attention. Therefore, it is essential that the test techniques be developed and verified to extract the mechanical properties information from small specimens. Among the test techniques using small specimens, the small punch (SP) test technique using small disc-sized specimen has been successfully used to estimate the tensile properties (yield strength and ultimate tensile strength), DBTT (ductile-brittle transition temperature), fracture toughness and creep properties of metals irradiated in a reactor or a proton accelerator. In this paper, the existing SP test techniques are reviewed and summarized. In addition, the information on the development of the SP test procedure is obtained to evaluate the radiation effects on the mechanical properties of nuclear materials in a hot cell

  18. Effects of Sparring Load on Reaction Speed and Punch Force During the Precompetition and Competition Periods in Boxing.

    Science.gov (United States)

    Hukkanen, Esa; Häkkinen, Keijo

    2017-06-01

    Seven, male, national-level boxers (age, 20.3 ± 2.7 years; height, 1.80 ± 0.06 m; mass, 73.8 ± 11.1 kg) participated in this study to investigate the effects of sparring on reaction time and punch force of straight punches measured during the precompetition and competition periods. Heart rate and blood lactate concentrations were also monitored. Sparring load was chosen in accordance with the current rules: 3 × 3-minute bouts with 1-minute break in between. Reaction time of rear straight lengthened (p boxing-specific and explosive strength training.

  19. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity

    NARCIS (Netherlands)

    Fongers, A.; Wolkerstorfer, A.; Nieuweboer-Krobotova, L.; Krawczyk, P.; Tóth, G. G.; van der Veen, J. P. W.

    2009-01-01

    Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long-term results are exceptional. Objectives To evaluate the long-term results of 2-mm punch grafting in patients with vitiligo vulgaris

  20. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo : effect of disease activity

    NARCIS (Netherlands)

    Fongers, A.; Wolkerstorfer, A.; Nieuweboer-Krobotova, L.; Krawczyk, P.; Toth, G. G.; van der Veen, J. P. W.

    Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long-term results are exceptional. Objectives To evaluate the long-term results of 2-mm punch grafting in patients with vitiligo vulgaris

  1. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo : effect of disease activity

    NARCIS (Netherlands)

    Fongers, A.; Wolkerstorfer, A.; Nieuweboer-Krobotova, L.; Krawczyk, P.; Toth, G. G.; van der Veen, J. P. W.

    2009-01-01

    Background Punch grafting is a simple and frequently used technique for the treatment of stable vitiligo, resistant to medical therapy. However, studies reporting long-term results are exceptional. Objectives To evaluate the long-term results of 2-mm punch grafting in patients with vitiligo vulgaris

  2. Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding.

    Directory of Open Access Journals (Sweden)

    Nicole Speed

    Full Text Available The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt involved in insulin signaling induced by exposure to a high-fat (HF diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT. Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food

  3. Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

    Science.gov (United States)

    Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

    2012-08-01

    Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict

  4. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

    2012-07-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

  5. Striatal pre- and postsynaptic profile of adenosine A(2A receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Marco Orru

    2011-01-01

    Full Text Available Striatal adenosine A(2A receptors (A(2ARs are highly expressed in medium spiny neurons (MSNs of the indirect efferent pathway, where they heteromerize with dopamine D(2 receptors (D(2Rs. A(2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1 receptors (A(1Rs. It has been hypothesized that postsynaptic A(2AR antagonists should be useful in Parkinson's disease, while presynaptic A(2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261 showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2AR-D(2R and A(1R-A(2AR heteromers to determine possible differences in the affinity of these compounds for different A(2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2AR when co-expressed with D(2R than with A(1R. KW-6002 showed the best relative affinity for A(2AR co-expressed with D(2R than co-expressed with A(1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile

  6. Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

    Science.gov (United States)

    London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

    2018-04-04

    population calcium activity from the dorsal striatum during ad libitum feeding and an operant task that resulted in mice obtaining food pellets. Dorsal striatal neurons exhibited long ramps in activity that preceded actions by several seconds, and may reflect upcoming actions. Understanding how the striatum controls the preparation and generation of actions may lead to improved therapies for disorders, such as drug addiction or obesity. Copyright © 2018 the authors 0270-6474/18/383547-12$15.00/0.

  7. HIV infection results in ventral-striatal reward system hypo-activation during cue processing

    NARCIS (Netherlands)

    Plessis, Stéfan du; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to

  8. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  9. The influence of punching process on residual stress and magnetic domain structure of non-oriented silicon steel

    International Nuclear Information System (INIS)

    Cao, Hongzhi; Hao, Linpo; Yi, Jingwen; Zhang, Xianglin; Luo, Zhonghan; Chen, Shenglin; Li, Rongfeng

    2016-01-01

    The main purpose of this paper is to investigate the influence of punching process on residual stress and magnetic domain structure. The residual stress in non-oriented silicon steel after punching process was measured by nanoindentation. The maximum depth was kept constant as 300 nm during nanoindentation. The material around indentation region exhibited no significant pile-up deformation. The calculation of residual stress was based on the Suresh theoretical model. Our experimental results show that residual compressive stress was generated around the sheared edge after punching. The width of residual stress affected zone by punching was around 0.4–0.5 mm. After annealing treatment, the residual stress was significantly decreased. Magnetic domain structure was observed according to the Bitter method. The un-annealed sample exhibited complicated domain patterns, and the widths of the magnetic domains varied between 3 µm and 8 µm. Most of the domain patterns of the annealed sample were 180°-domains and 90°-domains, and the widths of the domains decreased to 1–3 µm. - Highlights: • The residual stress distribution on sheared edge was measured. • The residual compressive stress was generated around the sheared edge. • The width of residual stress affected zone was about 0.4–0.5 mm. • The shape and width of the domain structure would be changed by annealing.

  10. Study of neuropeptide distribution in the central nervous system by the combined use of radioimmunoassay with the neuroatomic punch technique

    International Nuclear Information System (INIS)

    Valenca, M.M.; Negro Vilar, A.

    1991-01-01

    In order to demonstrate an experimental method to study neuropeptide distribution in the central nervous system, the content of beta-endorphin present in several brain regions was determined by the combined use of radioimmunoassay with the neuroanatomic punch technique described by Palkovits. (author)

  11. Automated intelligent rotor tine cultivation and punch planting to improve the selectivity of mechanical intra-row weed control

    DEFF Research Database (Denmark)

    Rasmussen, Jesper; Griepentrog, Hans W.; Nielsen, Jon

    2012-01-01

    in sugar beet and carrot crops showed no synergistic effects between plant establishment procedures and selectivity of post-emergence weed harrowing. Even if punch planting and automated intelligent rotor tine cultivation were not combined, the results indicated that there was no reason to believe...... that mainly work through soil burial....

  12. Assessment of strength characteristics of Al2024 ECAP metal using small punch testing

    International Nuclear Information System (INIS)

    Ma, Young Wha; Choi, Jeong Woo; Yoon, Kee Bong; Kim, Seon Hwa

    2006-01-01

    When subjected to severe shear deformation by ECAP, microstructure of Al2024 becomes extremely refined. To measure the strength of that, Small Punch(SP) testing method was adopted as a substitute for the conventional uniaxial tensile testing because the size of material processed by ECAP were limited to ψ12 mm in transverse direction. SP tests were performed with specimens in longitudinal and transverse directions of Al2024 ECAP metal. For comparing the strength values with those assessed by SP tests, uniaxial tensile tests were also conducted with specimens in longitudinal direction. Failure surfaces of the tested SP specimens showed that failure mode was shear deformation and Al2024 ECAP metal has an anisotropy in strength. Thus, conventional equations proposed for assessing the strength characteristics were improper to assess those of Al2024 ECAP metal. In this paper a way of assessing the strength of Al2024 ECAP metal was proposed and was proven to be effective

  13. Study of the mechanical properties of the electric power station components: the punch test

    International Nuclear Information System (INIS)

    Isselin, J.

    2003-03-01

    The aging of the electric production park implies an increasing need of knowledge concerning the evolution of the mechanical properties of its components. With regard to this problem, the availability in material is more and more small. This work proposes to characterize these properties through a mechanical test called Punch test. The main characteristic of this test is to use very small volume samples. The development of this test has been carried out by the study of a 15 MDV 4-05 steel coming from a steam drum of a thermal power plant after 145000 hours of service. At first, we have measured the influence of the parameters of this test. Then, the study has dealt more particularly on the transition temperature of the material. With the finite element simulation method, the strain hardening coefficient of the material has been determined. (O.M.)

  14. From Punched Cards to "Big Data": A Social History of Database Populism

    Directory of Open Access Journals (Sweden)

    Kevin Driscoll

    2012-08-01

    Full Text Available Since the diffusion of the punched card tabulator following the 1890 U.S. Census, mass-scale information processing has been alternately a site of opportunity, ambivalence and fear in the American imagination. While large bureaucracies have tended to deploy database technology toward purposes of surveillance and control, the rise of personal computing made databases accessible to individuals and small businesses for the first time. Today, the massive collection of trace communication data by public and private institutions has renewed popular anxiety about the role of the database in society. This essay traces the social history of database technology across three periods that represent significant changes in the accessibility and infrastructure of information processing systems. Although many proposed uses of "big data" seem to threaten individual privacy, a largely-forgotten database populism from the 1970s and 1980s suggests that a reclamation of small-scale data processing might lead to sharper popular critique in the future.

  15. Finite-Element Modeling of Timber Joints with Punched Metal Plate Fasteners

    DEFF Research Database (Denmark)

    Ellegaard, Peter

    2006-01-01

    The focus of this paper is to describe the idea and the theory behind a finite-element model developed for analysis of timber trusses with punched metal plate fasteners (nail plates). The finite-element model includes the semirigid and nonlinear behavior of the joints (nonlinear nail and plate...... elements) and contact between timber beams, if any (bilinear contact elements). The timber beams have linear-elastic properties. The section forces needed for design of the joints are given directly by the finite-element model, since special elements are used to model the nail groups and the nail plate...... the behavior of the joints very well at lower load levels. At higher load levels the stiffness is overestimated due to development of cracks in the timber and the linear-elastic timber properties in the finite-element model....

  16. Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

    Directory of Open Access Journals (Sweden)

    Sergi Ferré

    2007-01-01

    Full Text Available By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS. Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit, where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.

  17. Reward inference by primate prefrontal and striatal neurons.

    Science.gov (United States)

    Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

    2014-01-22

    The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

  18. Classification of H2O2 as a Neuromodulator that Regulates Striatal Dopamine Release on a Subsecond Time Scale

    Science.gov (United States)

    2012-01-01

    Here we review evidence that the reactive oxygen species, hydrogen peroxide (H2O2), meets the criteria for classification as a neuromodulator through its effects on striatal dopamine (DA) release. This evidence was obtained using fast-scan cyclic voltammetry to detect evoked DA release in striatal slices, along with whole-cell and fluorescence imaging to monitor cellular activity and H2O2 generation in striatal medium spiny neurons (MSNs). The data show that (1) exogenous H2O2 suppresses DA release in dorsal striatum and nucleus accumbens shell and the same effect is seen with elevation of endogenous H2O2 levels; (2) H2O2 is generated downstream from glutamatergic AMPA receptor activation in MSNs, but not DA axons; (3) generation of modulatory H2O2 is activity dependent; (4) H2O2 generated in MSNs diffuses to DA axons to cause transient DA release suppression by activating ATP-sensitive K+ (KATP) channels on DA axons; and (5) the amplitude of H2O2-dependent inhibition of DA release is attenuated by enzymatic degradation of H2O2, but the subsecond time course is determined by H2O2 diffusion rate and/or KATP-channel kinetics. In the dorsal striatum, neuromodulatory H2O2 is an intermediate in the regulation of DA release by the classical neurotransmitters glutamate and GABA, as well as other neuromodulators, including cannabinoids. However, modulatory actions of H2O2 occur in other regions and cell types, as well, consistent with the widespread expression of KATP and other H2O2-sensitive channels throughout the CNS. PMID:23259034

  19. Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

    International Nuclear Information System (INIS)

    Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

    1992-01-01

    Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

  20. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    International Nuclear Information System (INIS)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging

  1. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

  2. Ventral striatal activity links adversity and reward processing in children.

    Science.gov (United States)

    Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

    2017-08-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Striatal activation reflects urgency in perceptual decision making.

    Science.gov (United States)

    van Maanen, Leendert; Fontanesi, Laura; Hawkins, Guy E; Forstmann, Birte U

    2016-10-01

    Deciding between multiple courses of action often entails an increasing need to do something as time passes - a sense of urgency. This notion of urgency is not incorporated in standard theories of speeded decision making that assume information is accumulated until a critical fixed threshold is reached. Yet, it is hypothesized in novel theoretical models of decision making. In two experiments, we investigated the behavioral and neural evidence for an "urgency signal" in human perceptual decision making. Experiment 1 found that as the duration of the decision making process increased, participants made a choice based on less evidence for the selected option. Experiment 2 replicated this finding, and additionally found that variability in this effect across participants covaried with activation in the striatum. We conclude that individual differences in susceptibility to urgency are reflected by striatal activation. By dynamically updating a response threshold, the striatum is involved in signaling urgency in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Ladinsky, H.

    1986-01-01

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  5. Ventral striatal activity links adversity and reward processing in children

    Directory of Open Access Journals (Sweden)

    Niki H. Kamkar

    2017-08-01

    Full Text Available Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain’s sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

  6. AFM Colloidal Probe Measurements Implicate Capillary Condensation in Punch-Particle Surface Interactions during Tableting.

    Science.gov (United States)

    Badal Tejedor, Maria; Nordgren, Niklas; Schuleit, Michael; Millqvist-Fureby, Anna; Rutland, Mark W

    2017-11-21

    Adhesion of the powders to the punches is a common issue during tableting. This phenomenon is known as sticking and affects the quality of the manufactured tablets. Defective tablets increase the cost of the manufacturing process. Thus, the ability to predict the tableting performance of the formulation blend before the process is scaled-up is important. The adhesive propensity of the powder to the tableting tools is mostly governed by the surface-surface adhesive interactions. Atomic force microscopy (AFM) colloidal probe is a surface characterization technique that allows the measurement of the adhesive interactions between two materials of interest. In this study, AFM steel colloidal probe measurements were performed on ibuprofen, MCC (microcrystalline cellulose), α-lactose monohydrate, and spray-dried lactose particles as an approach to modeling the punch-particle surface interactions during tableting. The excipients (lactose and MCC) showed constant, small, attractive, and adhesive forces toward the steel surface after a repeated number of contacts. In comparison, ibuprofen displayed a much larger attractive and adhesive interaction increasing over time both in magnitude and in jump-in/jump-out separation distance. The type of interaction acting on the excipient-steel interface can be related to a van der Waals force, which is relatively weak and short-ranged. By contrast, the ibuprofen-steel interaction is described by a capillary force profile. Even though ibuprofen is not highly hydrophilic, the relatively smooth surfaces of the crystals allow "contact flooding" upon contact with the steel probe. Capillary forces increase because of the "harvesting" of moisture-due to the fast condensation kinetics-leaving a residual condensate that contributes to increase the interaction force after each consecutive contact. Local asperity contacts on the more hydrophilic surface of the excipients prevent the flooding of the contact zone, and there is no such adhesive

  7. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    Science.gov (United States)

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  8. Delamination measurement of a laminates composite panel due to hole punching based on the focus variation technique

    Science.gov (United States)

    Abdullah, A. B.; Zain, M. S. M.; Abdullah, M. S.; Samad, Z.

    2017-07-01

    Structural materials, such as composite panels, must be assembled, and such panels are typically constructed via the insertion of a fastener through a drilled hole. The main problem encountered in drilling is delamination, which affects assembly strength. The cost of drilling is also high because of the severe wear on drill bits. The main goal of this research is to develop a new punching method as an alternative to drilling during hole preparation. In this study, the main objective is to investigate the effect of different puncher profiles on the quality of holes punched into carbon fiber reinforcement polymer (CFRP) composite panels. Six types of puncher profiles were fabricated with minimum die clearance (1%), and two quality aspects, namely, incomplete shearing and delamination factor, were measured. The conical puncher incurred the least defects in terms of delamination and yielded an acceptable amount of incomplete shearing in comparison with the other punchers.

  9. Influence of the column rectangularity index and of the boundary conditions in the punching resistance of slab-column connections

    Directory of Open Access Journals (Sweden)

    O. S. PAIVA

    Full Text Available Experimental evidence indicates that both the column rectangularity index and the boundary conditions of the connection may affect the ultimate punching resistance. This paper presents general aspects of these topics and, through the analysis of experimental results of tests on 131 slabs, evaluates the accuracy and suitability of recommendations presented by ABNT NBR 6118, Eurocode 2, ACI 318 and fib Model Code 2010. Experimental results showed that the security level of normative estimates trend to reduce as the column rectangularity increases, and in some cases, the punching resistance was overestimated. Finally, adjustments are suggested in equations presented by NBR 6118 and MC2010 in order to eliminate this trend of unsafe results.

  10. Striatal and extra-striatal dopamine transporter in cannabis and tobacco addiction: a high resolution PET study

    International Nuclear Information System (INIS)

    Leroy, C.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Ribeiro, M.J.; Trichard, Ch.; Karila, L.; Lukasiewicz, M.; Benyamina, A.; Reynaud, M.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Comtat, C.; Artiges, E.; Trichard, Ch.

    2011-01-01

    The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extra-striatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [ 11 C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects. (authors)

  11. "Center punch" and "whole spot" bioanalysis of apixaban in human dried blood spot samples by UHPLC-MS/MS.

    Science.gov (United States)

    Zheng, Naiyu; Yuan, Long; Ji, Qin C; Mangus, Heidi; Song, Yan; Frost, Charles; Zeng, Jianing; Aubry, Anne-Françoise; Arnold, Mark E

    2015-04-15

    Apixaban (Eliquis™) was developed by Bristol-Myers Squibb (BMS) and Pfizer to use as an antithrombotic/anticoagulant agent and has been recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. A clinical study of apixaban, sponsored by BMS and Pfizer, included a pilot exploratory portion to evaluate the potential for future drug concentration monitoring using dried blood spot (DBS) sample collection. For DBS sample collection, a fixed blood volume was dispensed onto a DBS card by either regular volumetric pipette (venous blood collection) or capillary dispenser (finger prick blood collection). A 96-well semi-automated liquid-liquid extraction sample preparation procedure was developed to provide clean extracts for UHPLC-MS/MS quantitation. Assays using both partial-spot center punch and whole spot punch were developed and validated. The linear dynamic ranges for all the analyses were from 0.5 to 500 ng/mL. The coefficient of determination (r(2)) values was >0.9944 for all the validation runs. For the center punch approach, the intra-assay precision (%CV) was within 4.4% and inter-assay precision was within 2.6%. The assay accuracy, expressed as %Dev., was within ± 5.4% of the nominal concentrations. One accuracy and precision run was performed using the whole spot approach, the intra-assay precision (%CV) was within 7.1% and the accuracy was within ± 8.0% of the nominal concentrations. In contrast to the center punch approach, the whole spot approach eliminated the effect of hematocrit and high lipids on the analysis of apixaban in human DBS when an accurate sample blood volume was collected on DBS cards. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Analytical and experimental investigation of the elastic and plastic behavior of plates on foundations subjected to dynamic punch loading

    International Nuclear Information System (INIS)

    Duffey, T.A.; Sutherland, S.H.; Cheresh, M.

    1980-01-01

    Analytical solutions and experimental results are presented for the response of foundation-backed plates to static and dynamic punch loading. Tests were performed on polyurethane foam-backed and unbacked plates; plates were centrally loaded over a range-in plastic deformations up to complete failure. This is part of an attempt to understand the puncture resistance of the sidewalls of containers used to ship hazardous wastes

  13. Numerical And Experimental Analysis Of The Process Of Aviation Drawpiece Forming Using Rigid And Rubber Punch With Various Properties

    Directory of Open Access Journals (Sweden)

    Kut S.

    2015-09-01

    Full Text Available This paper presents the results of the numerical analysis and experimental research of the forming process of aviation drawpiece made from 0.6 mm thick Inconel 625 sheet metal. First phase of testing was conducted using rigid steel tools for drawpiece forming. Results of conducted simulations show that during rigid tool forming, the middle of the drawpiece losses stability. In consequence, rigid tool forming leads to the formation of unacceptable wrinkles on the drawpiece. Subsequent experimental research confirmed wrinkles of the metal drawpiece in this area. It was assumed that in order to eliminate this negative phenomenon, minor changes in technology and tool construction would have to be made. The drawpiece will be shaped by means of a flexible tool, than re-shaped using rigid tools. In the second phase of the research, tooling design changes have been made. They consisted of replacing the steel punch with a specially designed stamp susceptible for deformation. FEM numerical simulations were performed for flexible punch forming made of polyurethane elastomer with different hardness (50, 70, 85 and 90 Sh A. On their basis, the effect on the mechanical characteristics of the elastomeric drawing process and the formation of wrinkles was shown. They can be effectively eliminated by the use of a punch with hardness of 90 Sh A, which has also been confirmed by experimental research. In addition, the paper presents a comparative analysis of the deformations in selected actual drawpiece areas and in the elastomeric punch with hardness 90 Sh A computer model. The actual drawpiece deformation schedule and the values were determined using photogrammetric system Argus v.6.3., while the computer modeled drawpiece was based on FEM calculations performed in the MARC / Mentat system. In conclusion the difficulties as well as the advantages and disadvantages in determining the deformation of sheet metal parts were indicated using photogrammetric system

  14. Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

    DEFF Research Database (Denmark)

    Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N

    2004-01-01

    (DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported...

  15. Punching shear in reinforced concrete flat slabs with hole adjacent to the column and moment transfer

    Directory of Open Access Journals (Sweden)

    D. C. Oliveira

    Full Text Available The structural behavior and the ultimate punching shear resistance of internal reinforced concrete flat slab-column connections, with one hole adjacent to the column, with or without flexural moment transfer of the slab to the column was investigated. Main variables were: the existence whether or not hole, flexural reinforcement layout and ratio, the direction and sense of the moment transferred and the eccentricity of the load (M (moment transferred to column / V (shear ratio at the connection - 0,50 m or 0,25 m. Seven internal slab-column joining were tested and ultimate loads, cracking, deflections, concrete and reinforcement strains were analyzed. The existence of hole adjacent to the smaller column dimension, the hole dimension, flexural reinforcement rate and placing, the variation of relation Mu/Vu in function of the load, and, than, of eccentricity of the load, influenced the slabs behavior and rupture load. Test results were compared with the estimations from CEB-FIP/MC1990 [7], EC2/2004 [12], ACI-318:2011 [1] and NBR 6118:2007 [5]. ACI [1] and EC2 [12] presented most conservative estimates, although have presented some non conservative estimates. Brazilian NBR [5], even though being partly based in EC2 [12], presented smaller conservative estimates and more non conservative estimates. A modification on all codes is proposed for taking in account the moment caused by the eccentricity at the critical perimeter for slabs with holes.

  16. A creep life assessment method for boiler pipes using small punch creep test

    International Nuclear Information System (INIS)

    Izaki, Toru; Kobayashi, Toshimi; Kusumoto, Junichi; Kanaya, Akihiro

    2009-01-01

    The small punch creep (SPC) test is considered as a highly useful method for creep life assessment for high temperature plant components. SPC uses miniature-sized specimens and does not cause any serious sampling damages, and its assessment accuracy is at a high level. However, in applying the SPC test to the residual creep life assessment of the boiler in service, there are some issues to be studied. In order to apply SPC test to the residual creep life assessment of the 2.25Cr-1Mo steel boiler pipe, the relationship between uniaxial creep stress and the SPC test load has been studied. The virgin material, pre-crept, weldment and service aged samples of 2.25Cr-1Mo steel were tested. It was confirmed that the relationship between uniaxial creep stress and the SPC test load at the same rupture time can be described as a single straight line independent of test conditions and materials. Therefore a life assessment is possible by using SPC test in place of uniaxial creep tests. The creep life assessment using SPC was applied to actual thermal power plant components which are in service.

  17. Failure criterion of concrete type material and punching failure analysis of thick mortar plate

    International Nuclear Information System (INIS)

    Ohno, T.; Kuroiwa, M.; Irobe, M.

    1979-01-01

    In this paper falure surface of concrete type material is proposed and its validity to structural analysis is examined. The study is an introductory part of evaluation for ultimate strength of reinforced and prestressed concrete structures in reactor technology. The failure surface is expressed in a linear form in terms of octahedral normal and shear stresses. Coefficient of the latter stress is given by a trigonometric series in threefold angle of similarity. Hence, its meridians are multilinear and traces of its deviatoric sections are smooth curves having periodicity of 2π/3 around space diagonal in principal stress space. The mathematical expression of the surface has an arbitraty number of parameters so that material test results are well reflected. To confirm the effectiveness of proposed failure criterion, experiment and numerical analysis by the finite element method on punching failure of thick mortar plate in axial symmetry are compared. In the numerical procedure yield surface of the material is assumed to exist mainly in compression region, since a brittle cleavage or elastic fracture occurs in the concrete type material under stress state with tension, while a ductile or plastic fracture occurs under compressive stress state. (orig.)

  18. Application of the small punch test to determine the fatigue properties of additive manufactured aerospace alloys

    Directory of Open Access Journals (Sweden)

    Lancaster Robert

    2018-01-01

    Full Text Available Additive layer manufacturing (ALM processes are becoming increasingly prevalent in the aerospace industry as design engineers look to profit from the numerous advantages that these advanced techniques can offer. However, given the safety critical nature and arduous operating conditions to which these components will be exposed to whilst in service, it is essential that the mechanical properties of such structures are fully understood. Transient microstructures are a typical characteristic of ALM components and resulting from the thermal cycles that occur during the build operation. Those microstructures make any mechanical assessment an involved procedure when assessing the process variables for any given parameter set. A useful mechanical test technique is small-scale testing, in particular, the small punch (SP test. SP testing is capable of localised sampling of a larger scale component and presents an attractive option to mechanically assess complex parts with representative geometries, that would not be possible using more conventional uniaxial test approaches. This paper will present the recent development of a small-scale testing methodology capable of inducing fatigue damage and a series of novel tests performed on different variants of Ti-6Al-4V.

  19. WHAT IS THE BEST RADIOGRAPHIC VIEW FOR "DIE PUNCH" DISTAL RADIUS FRACTURES? A CADAVER MODEL STUDY.

    Science.gov (United States)

    Falcochio, Diego Figueira; Crepaldi, Bruno Eiras; Trindade, Christiano Augusto; da Costa, Antonio Carlos; Chakkour, Ivan

    2012-01-01

    the aim of this study is try to show the best view for distal radius fractures so called die-punch fractures. There has been used a human cadaver radius bone from the Salvador Arena Tissue Bank. This bone was cleaned up after removing the soft tissues and osteotomies created displaced lunate fossa fractures of 0, 1, 2, 3 and 5 mm. We have fixed this fragment with adhesive tape. Then the joint deviation were significantly increased with step-offs of 1 mm. Radiographs were then taken into 5 different positions: postero-anterior view, lateral view, oblique views and tangencial view for each of the deviations. The resulting lunate fossa depression in each X-ray film was analyzed by the AutoCAD 2010® software. The tangencial view was the best one to see the 1mm and 3mm bone degrees and the second one view to see the 2mm and 5 mm degrees. The pronated oblique view was the best to see the 2mm degrees and the oblique supinated view wasn't able to see the degrees between 1 and 2mm. The tangencial view was the best one to see the 1mm and 3mm bone degrees and the second one view to see the 2mm and 5 mm degrees.

  20. User-Authentication on Wearable Devices Based on Punch Gesture Biometrics

    Directory of Open Access Journals (Sweden)

    Liang Guan-Cheng

    2017-01-01

    Full Text Available Due to commoditization and convenience, wearable technology are interwoven with our daily life. However, privacy sensitive data stored on those devices such as personal email, message can be easily stolen. Most devices require a PIN input to unlock. However, this mechanism is vulnerable to shoulder surfing attack. Thus many novel authentication approaches have been proposed to solve this problem. And biometric-based methods have been adopted by many researchers because of the efficiency and excellent performance. In this paper, we propose a new biometric-based authentication system. We focus on how the user performs a straight punch gesture subconsciously. By analysis the acceleration data from the smartwatch when user performing the gesture, we are able to profile the user. And we authenticate the user according to the biometrics of this action. This mechanism is light-weighted and do not require user to remember any secret code. We develop an authentication system on Samsung Gear Fit 2 and conducted a real-world experiment on 20 volunteers. And we collected 13000 gesture samples to evaluate our system. Results show that our system can achieve a classification accuracy of at least 95.45%. In attacking scenario, our system can achieve an equal error rate lower than 4%. The maximum number of samples required by a well-trained classifier is 25.

  1. Analyses of Small Punch Creep Deformation Behavior of 316LN Stainless Steel Having Different Nitrogen Contents

    Science.gov (United States)

    Ganesh Kumar, J.; Laha, K.; Ganesan, V.; Prasad Reddy, G. V.

    2018-04-01

    The small punch creep (SPC) behavior of 316LN stainless steel (SS) containing 0.07, 0.11 and 0.14 wt.% nitrogen has been investigated at 923 K. The transient and tertiary SPC deformation of 316LN SS with various nitrogen contents have been analyzed according to the equation proposed for SPC deflection, δ = δ0 + δT (1 - e^{ - κ t} ) + \\dot{δ }s t + δ3 e^[ φ( t - tr ) ]. The relationships among the rate of exhaustion of transient creep (κ), steady-state deflection rate (\\dot{δ }s ) and the rate of acceleration of tertiary creep (φ) revealed the interrelationships among the three stages of SPC curve. The first-order reaction rate theory was found to be applicable to SPC deformation throughout the transient as well as tertiary region, in all the investigated steels. The initial and final creep deflection rates were decreased, whereas time to attain steady-state deflection rate increased with the increase in nitrogen content. By increasing the nitrogen content in 316LN SS from 0.07 to 0.14 wt.%, each stage of SPC was prolonged, and consequently, the values of κ, \\dot{δ }s and φ were lowered. Using the above parameters, the master curves for both transient and tertiary SPC deflections were constructed for 316LN SS containing different nitrogen contents.

  2. Accelerated aging, natural aging, and small punch testing of gamma-air sterilized polycarbonate urethane acetabular components.

    Science.gov (United States)

    Kurtz, S M; Siskey, R; Reitman, M

    2010-05-01

    The objectives of this study were three-fold: (1) to determine the applicability of the small punch test to characterize Bionate 80A polycarbonate urethane (PCU) acetabular implants; (2) to evaluate the susceptibility of PCU acetabular implants to exhibit degradation of mechanical behavior following gamma irradiation in air and accelerated aging; and (3) to compare the oxidation of gamma-air sterilized PCU following accelerated aging and 5 years of natural shelf aging. In addition to attenuated total reflectance-Fourier transform infrared spectroscopy, we also adapted a miniature specimen mechanical test, the small punch test, for the deformable PCU cups. Accelerated aging was performed using ASTM F2003, a standard test that represents a severe oxidative challenge. The results of this study suggest that the small punch test is sufficiently sensitive and reproducible to discriminate slight differences in the large-deformation mechanical behavior of Bionate 80A following accelerated aging. The gamma-air sterilized PCU had a reduction of 9% in ultimate load after aging. Five years of shelf aging had little effect on the mechanical properties of the PCU. Overall, our findings suggest that the Bionate 80A material has greater oxidative stability than ultra-high molecular weight polyethylene following gamma irradiation in air and exposure to a severe oxidative challenge. (c) 2010 Wiley Periodicals, Inc.

  3. APPLICATION OF PBL IN THE COURSE FLUID AND ELECTRICAL DRIVE SYSTEMS, CASE STUDY: MANUFACTURING AN AUTOMATED PUNCH MACHINE

    Directory of Open Access Journals (Sweden)

    Ahmad Sedaghat

    2017-01-01

    Full Text Available The PBL unit of fluid and electrical drive systems is taught in final semester of undergraduates in mechanical engineering department of the Australian College of Kuwait (ACK. The recent project on an automated punching machine is discovered more appealing to both students and instructors in triggering new ideas and satisfaction end results. In this case study, the way this PBL unit is coordinated and facilitated is explained. Two examples of student works are presented. The aim is to expose the students to real world engineering problems but in a satisfying manner. Similar to real life problems for engineers, restrictions are applied for the students on costs, availability of ACK facilities, and application of automation tools. Students are directly engaged by using technical standards on punching heads and dies, standard tensile testing of plates, and so on. Arduino microprocessor programming, an open-source hardware and software electronic platform, and electro-pneumatic devices are adopted for developing the automated punching machine. The goal of the PBL course is to acquaint students learning based on the concepts of team working, engineering design, professional manufacturing, and sequential testing of the end product. It is found that students achieved their best and developed new skills in this PBL unit as reflected in their portfolios.

  4. Effect of in vitro gamma exposure on rat mesencephalic and striatal cellular types and processes length

    International Nuclear Information System (INIS)

    Coffigny, H.; Court, L.

    1994-01-01

    The isolated mesencephalic and striatal cells were irradiated in a dose-range of 0.25 to 3 Gy followed by 3 day of culture. The proportion of monopolar, bipolar, tripolar and multipolar cell population was not obviously modified by irradiation. The processes length was similar to controls, except after 3 Gy exposure, for monopolar and bipolar mesencephalic cells and the tripolar striatal cells where it was increased. In these populations, only cells with long processes seemed to survive. (author)

  5. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

    OpenAIRE

    Herbort, Maike C.; Soch, Joram; W?stenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, J?rgen; Walter, Henrik; Roepke, Stefan; Schott, Bj?rn H.

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BP...

  6. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Science.gov (United States)

    Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

    2010-02-22

    Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  7. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Directory of Open Access Journals (Sweden)

    Alessandro Bertolino

    2010-02-01

    Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  8. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

    OpenAIRE

    Egerton, A.; Howes, O. D.; Houle, S.; McKenzie, K.; Valmaggia, L. R.; Bagby, M. R.; Tseng, H-H; Bloomfield, M. A. P.; Kenk, M.; Bhattacharyya, S.; Suridjan, I.; Chaddock, C. A.; Winton-Brown, T. T.; Allen, P.; Rusjan, P.

    2017-01-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capaci...

  9. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  10. The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

    2017-01-01

    Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener ...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

  11. Striatal [[sup 11]C]-N-methyl-spiperone binding in patients with focal dystonia (torticollis) using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Leenders, K [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Hartvig, P [Hospital Pharmacy, Univ. Hospital, Uppsala (Sweden); Forsgren, L; Holmgren, G; Almay, B [Dept. of Neurology, Umeaa Univ., Umeaa (Sweden); Eckernaes, S A [Dept. of Neurology, Univ. Hospital, Uppsala (Sweden); Lundqvist, H; Laangstroem, B [Uppsala Univ. PET-Center, Uppsala (Sweden)

    1993-01-01

    Specific binding of [[sup 11]C]-N-methyl-spiperone to striatal dopamine D2 receptors was assessed using positron emission tomography (PET) in 6 patients with adult-onset focal dystonia (predominantly spasmodic torticollis) and in 5 healthy subjects. No significant difference in average specific striatal tracer uptake between patients and healthy subjects was found. However, in the 5 patients showing lateralisation of clinical signs a trend to higher striatal tracer uptake in the contralateral hemisphere was observed. (authors).

  12. Free radical production induced by methamphetamine in rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Pubill, David; Chipana, Carlos; Camins, Antonio; Pallas, Merce; Camarasa, Jordi; Escubedo, Elena

    2005-01-01

    The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 μM) prevented METH-induced ROS production, thus implicating calcium and α7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 μM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 μM) for 30 min reduced [ 3 H]DA uptake by 60%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of α 7 nicotinic receptors and Ca 2+ entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates α 7 nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca 2+ . This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA

  13. Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder

    Directory of Open Access Journals (Sweden)

    Haifeng Hou

    2012-01-01

    Full Text Available In recent years, internet addiction disorder (IAD has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT levels measured by T99mc-TRODAT-1 single photon emission computed tomography (SPECT brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V and weight (W of bilateral corpus striatum as well as the T99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

  14. The neostriatal mosaic: striatal patch-matrix organization is related to cortical lamination.

    Science.gov (United States)

    Gerfen, C R

    1989-10-20

    The basal ganglia, of which the striatum is the major component, process inputs from virtually all cerebral cortical areas to affect motor, emotional, and cognitive behaviors. Insights into how these seemingly disparate functions may be integrated have emerged from studies that have demonstrated that the mammalian striatum is composed of two compartments arranged as a mosaic, the patches and the matrix, which differ in their neurochemical and neuroanatomical properties. In this study, projections from prefrontal, cingulate, and motor cortical areas to the striatal compartments were examined with the Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde axonal tracer in rats. Each cortical area projects to both the patches and the matrix of the striatum; however, deep layer V and layer VI corticostriatal neurons project principally to the patches, whereas superficial layer V and layer III and II corticostriatal neurons project principally to the matrix. The relative contribution of patch and matrix corticostriatal projections varies among the cortical areas examined such that allocortical areas provide a greater number of inputs to the patches than to the matrix, whereas the reverse obtains for neocortical areas. These results demonstrate that the compartmental organization of corticostriatal inputs is related to their laminar origin and secondarily to the cytoarchitectonic area of origin.

  15. Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

    Directory of Open Access Journals (Sweden)

    Jovana eBelic

    2016-03-01

    Full Text Available We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the healthy state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

  16. β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

    Science.gov (United States)

    Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

    2010-01-01

    Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

  17. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

    Science.gov (United States)

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-07-01

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

  18. D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

    Science.gov (United States)

    Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

    2011-02-14

    Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  20. Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

    Science.gov (United States)

    Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

    2018-01-01

    Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

  1. Ability of 18F-DOPA PET/CT and fused 18F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

    International Nuclear Information System (INIS)

    Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Puntoni, Matteo; Garre, Maria Luisa; Massollo, Michela; Naseri, Merhdad; Piccardo, Arnoldo; Lopci, Egesta

    2016-01-01

    To assess the diagnostic performance of 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with 18 F-DOPA PET/CT and brain MRI. Fused 18 F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for 18 F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for 18 F-DOPA PET/CT, respectively. 18 F-DOPA PET/MRI showed a trend towards higher accuracy compared with 18 F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with 18 F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and 18 F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of 18 F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the 18 F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by 18 F-DOPA PET/MRI. Physiological striatal 18 F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement. 18 F-DOPA PET/CT correctly detected

  2. The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain; II. Correlation between positron emission tomography and reaching behaviour

    International Nuclear Information System (INIS)

    Dunnett, S.B.; Brooks, D.J.; Ashworth, S.; Opacka-Juffrey, J.; Myers, R.; Hume, S.P.; Torres, E.M.; Fricker, R.A.

    1997-01-01

    Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the 'staircase task' of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter postiron emission tomography scanner, using ligands to the dopamine D 1 and D 2 receptors, [ 11 C]SCH 23390 and [ 11 C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the 'staircase test'. No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D 1 and D 2 receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts.These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts prepared from older embryos. This recovery is due to both the

  3. Demonstration of the self-magnetic-pinch diode as an X-ray source for flash core-punch radiography

    International Nuclear Information System (INIS)

    Cordova, Steve Ray; Rovang, Dean Curtis; Portillo, Salvador; Oliver, Bryan Velten; Bruner, Nichelle Lee; Ziska, Derek Raymond

    2007-01-01

    Minimization of the radiographic spot size and maximization of the radiation dose is a continuing long-range goal for development of electron beam driven X-ray radiography sources. In collaboration with members of the Atomic Weapons Establishment(AWE), Aldermaston UK, the Advanced Radiographic Technologies Dept. 1645 is conducting research on the development of X-ray sources for flash core-punch radiography. The Hydrodynamics Dept. at AWE has defined a near term radiographic source requirement for scaled core-punch experiments to be 250 rads(at)m with a 2.75 mm source spot-size. As part of this collaborative effort, Dept. 1645 is investigating the potential of the Self-Magnetic-Pinched (SMP) diode as a source for core-punch radiography. Recent experiments conducted on the RITS-6 accelerator [1,2] demonstrated the potential of the SMP diode by meeting and exceeding the near term radiographic requirements established by AWE. During the demonstration experiments, RITS-6 was configured with a low-impedance (40 (Omega)) Magnetically Insulated Transmission Line (MITL), which provided a 75-ns, 180-kA, 7.5-MeV forward going electrical pulse to the diode. The use of a low-impedance MITL enabled greater power coupling to the SMP diode and thus allowed for increased radiation output. In addition to reconfiguring the driver (accelerator), geometric changes to the diode were also performed which allowed for an increase in dose production without sacrificing the time integrated spot characteristics. The combination of changes to both the pulsed power driver and the diode significantly increased the source x-ray intensity

  4. Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jae Jung Lee

    2015-09-01

    Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

  5. Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

    Science.gov (United States)

    Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

    1998-08-01

    The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

  6. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Youngbin Kwak

    2010-09-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

  7. Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

    International Nuclear Information System (INIS)

    Wolf, M.E.

    1986-01-01

    Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K + , however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with [ 3 H]-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K + -evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis

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

    Science.gov (United States)

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

    1992-06-01

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

  9. Effects of Polarization on Mechanical Properties of Lead Zirconate Titanate Ceramics Evaluated by Modified Small Punch Tests

    Science.gov (United States)

    Deng, Qihuang; Fan, Yuchi; Wang, Lianjun; Xiong, Zhi; Wang, Hongzhi; Li, Yaogang; Zhang, Qinghong; Kawasaki, Akira; Jiang, Wan

    2012-01-01

    Pb(Zr,Ti)O3 (PZT) ceramics were prepared by the conventional mixed oxide method, and the strength of the resultant PZT ceramics was evaluated using modified small punch (MSP) tests. Load-displacement curve test results showed that the crack-initiation and fracture strengths of PZT ceramics decreased after polarization. The effect of the polarization accelerated the fatigue properties of PZT ceramics. Scanning electron microscopy (SEM) results showed that microcracks were formed before the maximum load in the MSP test, and the first load drop corresponded to crack initiation.

  10. Criteria for initiation of delamination in quasi-static punch-shear tests of a carbon-fiber composite material.

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Eric Brian [Sandia National Lab. (SNL-CA), Livermore, CA (United States); English, Shawn Allen [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Briggs, Timothy [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2015-09-01

    V arious phenomenological delamination initiation criteria are analyzed in quasi - static punch - shear tests conducted on six different geometries. These six geometries are modeled and analyzed using elastic, large - deformation finite element analysis. Analysis output is post - processed to assess different delamination initiation criteria, and their applicability to each of the geometries. These criteria are compared to test results to assess whether or not they are appropriate based on what occurred in testing. Further, examinations of CT scans and ultrasonic images o f test specimens are conducted in the appendix to determine the sequence of failure in each test geometry.

  11. Performance testing of a semi-automatic card punch system, using direct STR profiling of DNA from blood samples on FTA™ cards.

    Science.gov (United States)

    Ogden, Samantha J; Horton, Jeffrey K; Stubbs, Simon L; Tatnell, Peter J

    2015-01-01

    The 1.2 mm Electric Coring Tool (e-Core™) was developed to increase the throughput of FTA(™) sample collection cards used during forensic workflows and is similar to a 1.2 mm Harris manual micro-punch for sampling dried blood spots. Direct short tandem repeat (STR) DNA profiling was used to compare samples taken by the e-Core tool with those taken by the manual micro-punch. The performance of the e-Core device was evaluated using a commercially available PowerPlex™ 18D STR System. In addition, an analysis was performed that investigated the potential carryover of DNA via the e-Core punch from one FTA disc to another. This contamination study was carried out using Applied Biosystems AmpflSTR™ Identifiler™ Direct PCR Amplification kits. The e-Core instrument does not contaminate FTA discs when a cleaning punch is used following excision of discs containing samples and generates STR profiles that are comparable to those generated by the manual micro-punch. © 2014 American Academy of Forensic Sciences.

  12. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. MODERN METHODS OF DESIGN AND ARRANGEMENT OF RAMMING PILES IN PUNCHED HOLES

    Directory of Open Access Journals (Sweden)

    ZOTSENKO N. L.

    2015-10-01

    Full Text Available Problem statement. Ramming piles in punched holes (RPPH differ of high degree of use of supporting capacity of base because of forming in it a compacted zone at the expense of displacement of soil in the volume rammer and compacted material of expansion. The method of their construction almost exclude excavation and formwork, reducing the consumption of concrete, metal, accelerates zero cycle compared to the foundations raised and excavation and immersion into the soil of precast elements. The expansion of the normative base, their design and construction should be for further implementation of of natural objects. The correctness of the geomechanical model of plane and spatial version of finite element method (FEM should be proved for the calculation of cooperative work of RPPH as part of grillages with base. The most effective kinds of equipment and technological schemes of construction of RPPH should be noticed. Conclusions. The paper presents the main regulations on the design and the arrangement RPPH, corresponding of construction norms of Ukraine. The results of experimental and theoretical studies conducted by the authors for over thirty years, and the experience of the use of these piles on the objects of civil engineering, industrial and agricultural construction made their base. The use of the elastoplastic model with the criterion of Mohr-Coulomb strength for designing of the system "grillage -RPPH- soil" was substantiated. The designing in plane and spatial problems of FEM is proved that in the distance between the axes of adjacent piles up to five diameters is a correct choice of a flat version and simplifying of calculating scheme to the conventional strip foundation. An improved. The method of calculating of RPPH as part of grillages ribbon, where as the width of the foundation was taken a diameter of the broadening of the pile, and the depth of its inception corresponds to the bottom of it. The supporting layer of base under the

  14. Development of a New Punch Head Shape to Replicate Scale-Up Issues on a Laboratory Tablet Press III: Replicating sticking phenomenon using the SAS punch and evaluation by checking the tablet surface using 3D laser scanning microscope.

    Science.gov (United States)

    Ito, Manabu; Aoki, Shigeru; Uchiyama, Jumpei; Yamato, Keisuke

    2018-04-20

    Sticking is a common observation in the scale-up stage on the punch tip using a commercial tableting machine. The difference in the total compression time between a laboratory and a commercial tableting machine is considered one of the main root causes of scale up issues in the tableting processes. The proposed Size Adjusted for Scale-up (SAS) punch can be used to adjust the consolidation and dwell times for commercial tableting machine. As a result, the sticking phenomenon is able to be replicated at the pilot scale stage. As reported in this paper, the quantification of sticking was measured using a 3D laser scanning microscope to check the tablet surface. It was shown that the sticking area decreased with the addition of magnesium stearate in the formulation, but the sticking depth was not affected by the additional amount of magnesium stearate. It is proposed that use of a 3D laser scanning microscope can be applied to evaluate sticking as a process analytical technology (PAT) tool and so sticking can be monitored continuously without stopping the machine. Copyright © 2018. Published by Elsevier Inc.

  15. Elevated Striatal Reactivity Across Monetary and Social Rewards in Bipolar I Disorder

    Science.gov (United States)

    Dutra, Sunny J.; Cunningham, William A.; Kober, Hedy; Gruber, June

    2016-01-01

    Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation employed both a monetary and social incentive delay task among adults with remitted BD type I (N=24) and a healthy non-psychiatric control group (HC; N=25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated ventral and dorsal striatal reactivity across monetary and social reward receipt, but not anticipation, in the BD group. Post-hoc analyses further suggested that greater striatal reactivity to reward receipt across monetary and social reward tasks predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC, but not BD, group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of reward reactivity. PMID:26390194

  16. Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

    International Nuclear Information System (INIS)

    Cherubini, Marta; Ginés, Silvia

    2017-01-01

    Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

  17. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  18. Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Zwiers, Marcel P.; Forde, Natalie J.; Williams, Steven C. R.; Durston, Sarah; Brandeis, Daniel; Glennon, Jeffrey C.; Franke, Barbara; Lythgoe, David J.; Buitelaar, Jan K.

    Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We

  19. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

  20. [Women boxing athletes' EMG of upper limbs and lumbar muscles in the training of air striking of straight punch].

    Science.gov (United States)

    Zhang, Ri-Hui; Kang, Zhi-Xin

    2011-05-01

    To study training effect of upper limbs and lumbar muscles in the proceed of air striking of straight punch by analyzing boxing athletes' changes of electromyogram (EMG). We measured EMG of ten women boxing athletes' upper arm biceps (contractor muscle), upper arm triceps (antagonistic muscle), forearm flexor muscle (contractor muscle), forearm extensor muscle (antagonistic muscle), and lumbar muscles by ME6000 (Mega Electronics Ltd.). The stipulated exercise was to do air striking of straight punch with loads of 2.5 kg of dumbbell in the hand until exhausted. In the proceed of exercise-induce exhausted, the descend magnitude and speed of median frequency (MF) in upper limb antagonistic muscle exceeded to contracting muscle, moreover, the work percentage showed that contractor have done a larger percentage of work than antagonistic muscle. Compared with world champion's EMG, the majority of ordinary athletes' lumbar muscles MF revealed non-drop tendency, and the work percentage showed that lumbar muscles had a very little percentage of work. After comparing the EMG test index in upper limb and lumbar muscle of average boxing athletes with that of the world champion, we find the testees lack of the training of upper limb antagonistic muscle and lumbar muscle, and more trainings aimed at these muscles need to be taken.

  1. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.

    Science.gov (United States)

    Kaasinen, Valtteri; Vahlberg, Tero

    2017-12-01

    A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882. © 2017 American Neurological Association.

  2. Differential distribution of striatal [123I]β-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography

    International Nuclear Information System (INIS)

    Messa, C.; Volonte, M.A.; Fazio, F.; Zito, F.; Carpinelli, A.; D'Amico, A.; Rizzo, G.; Moresco, R.M.; Paulesu, E.; Franceschi, M.; Lucignani, G.

    1998-01-01

    Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-β-carboxymethoxy-3-β-(4-iodophenyl)tropane ([ 123 I]β-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [ 123 I]β-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24±2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3''). ANOVA revealed a global reduction of V3'' in all ROIs of PD and PSP patients compared with normal controls (P 123 I]β-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP. (orig.)

  3. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  4. Learning new sequential stepping patterns requires striatal plasticity during the earliest phase of acquisition.

    Science.gov (United States)

    Nakamura, Toru; Nagata, Masatoshi; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo; Kitsukawa, Takashi

    2017-04-01

    Animals including humans execute motor behavior to reach their goals. For this purpose, they must choose correct strategies according to environmental conditions and shape many parameters of their movements, including their serial order and timing. To investigate the neurobiology underlying such skills, we used a multi-sensor equipped, motor-driven running wheel with adjustable sequences of foothold pegs on which mice ran to obtain water reward. When the peg patterns changed from a familiar pattern to a new pattern, the mice had to learn and implement new locomotor strategies in order to receive reward. We found that the accuracy of stepping and the achievement of water reward improved with the new learning after changes in the peg-pattern, and c-Fos expression levels assayed after the first post-switch session were high in both dorsolateral striatum and motor cortex, relative to post-switch plateau levels. Combined in situ hybridization and immunohistochemistry of striatal sections demonstrated that both enkephalin-positive (indirect pathway) neurons and substance P-positive (direct pathway) neurons were recruited specifically after the pattern switches, as were interneurons expressing neuronal nitric oxide synthase. When we blocked N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum by injecting the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), we found delays in early post-switch improvement in performance. These findings suggest that the dorsolateral striatum is activated on detecting shifts in environment to adapt motor behavior to the new context via NMDA-dependent plasticity, and that this plasticity may underlie forming and breaking skills and habits as well as to behavioral difficulties in clinical disorders. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  5. Study of the mechanical properties of the electric power station components: the punch test; Etude des proprietes mecaniques des composants de centrales thermiques: l'essai punch test

    Energy Technology Data Exchange (ETDEWEB)

    Isselin, J

    2003-03-15

    The aging of the electric production park implies an increasing need of knowledge concerning the evolution of the mechanical properties of its components. With regard to this problem, the availability in material is more and more small. This work proposes to characterize these properties through a mechanical test called Punch test. The main characteristic of this test is to use very small volume samples. The development of this test has been carried out by the study of a 15 MDV 4-05 steel coming from a steam drum of a thermal power plant after 145000 hours of service. At first, we have measured the influence of the parameters of this test. Then, the study has dealt more particularly on the transition temperature of the material. With the finite element simulation method, the strain hardening coefficient of the material has been determined. (O.M.)

  6. Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

    International Nuclear Information System (INIS)

    Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

    1988-01-01

    Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

  7. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

    NARCIS (Netherlands)

    Mencacci, N.E.; Kamsteeg, E.J.; Nakashima, K.; R'Bibo, L.; Lynch, D.S.; Balint, B.; Willemsen, M.A.A.P.; Adams, M.E.; Wiethoff, S.; Suzuki, K.; Davies, C.H.; Ng, J.; Meyer, E.; Veneziano, L.; Giunti, P.; Hughes, D.; Raymond, F.L.; Carecchio, M.; Zorzi, G.; Nardocci, N.; Barzaghi, C.; Garavaglia, B.; Salpietro, V.; Hardy, J.; Pittman, A.M.; Houlden, H.; Kurian, M.A.; Kimura, H.; Vissers, L.E.L.M.; Wood, N.W.; Bhatia, K.P.

    2016-01-01

    Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very

  8. Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

    2005-01-01

    Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

  9. Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

    Science.gov (United States)

    Cyr, Marilyn; Yang, Xiao; Horga, Guillermo; Marsh, Rachel

    2018-04-01

    This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions. © 2018 Wiley Periodicals, Inc.

  10. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    International Nuclear Information System (INIS)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W.

    1992-01-01

    An 123 I labeled cocaine analog, 4'-[ 123 I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author)

  11. Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

    Science.gov (United States)

    Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

    2016-08-23

    Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

  12. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  13. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jilly Naaijen

    2017-01-01

    Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

  14. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Forde, Natalie J.; Lythgoe, David J.; Akkermans, Sophie E. A.; Openneer, Thaira J. C.; Dietrich, Andrea; Zwiers, Marcel P.; Hoekstra, Pieter J.; Buitelaar, Jan K.

    2017-01-01

    Objective: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently

  15. Adversity in childhood linked to elevated striatal dopamine function in adulthood.

    Science.gov (United States)

    Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

    2016-10-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

    DEFF Research Database (Denmark)

    Ziebell, Morten; Andersen, Birgitte B; Pinborg, Lars H

    2013-01-01

    cognitively evaluated with the Mini Mental State Examination. RESULTS: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. CONCLUSION: In patients with newly diagnosed DLB...

  17. Role of contingency in striatal response to incentive in adolescents with anxiety.

    Science.gov (United States)

    Benson, Brenda E; Guyer, Amanda E; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

    2015-03-01

    This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

  18. Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

    Directory of Open Access Journals (Sweden)

    Nicola J Platt

    Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

  19. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

    Science.gov (United States)

    Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

    2016-12-01

    Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos + D2 MSNs and decreased c-Fos + non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Automated washing of FTA Card punches and PCR setup for reference samples using a LIMS-controlled Sias Xantus automated liquid handler

    DEFF Research Database (Denmark)

    Stangegaard, Michael; Olsen, Addie Nina; Frøslev, Tobias G.

    2009-01-01

    We have implemented and validated automated methods for washing FTA Card punches containing buccal samples and subsequent PCR setup using a Sias Xantus automated liquid handler. The automated methods were controlled by worklists generated by our LabWare Laboratory Information Management System...

  1. A small punch test technique for characterizing the elastic modulus and fracture behavior of PMMA bone cement used in total joint replacement.

    Science.gov (United States)

    Giddings, V L; Kurtz, S M; Jewett, C W; Foulds, J R; Edidin, A A

    2001-07-01

    Polymethylmethacrylate (PMMA) bone cement is used in total joint replacements to anchor implants to the underlying bone. Establishing and maintaining the integrity of bone cement is thus of critical importance to the long-term outcome of joint replacement surgery. The goal of the present study was to evaluate the suitability of a novel testing technique, the small punch or miniaturized disk bend test, to characterize the elastic modulus and fracture behavior of PMMA. We investigated the hypothesis that the crack initiation behavior of PMMA during the small punch test was sensitive to the test temperature. Miniature disk-shaped specimens, 0.5 mm thick and 6.4 mm in diameter, were prepared from PMMA and Simplex-P bone cement according to manufacturers' instructions. Testing was conducted at ambient and body temperatures, and the effect of test temperature on the elastic modulus and fracture behavior was statistically evaluated using analysis of variance. For both PMMA materials, the test temperature had a significant effect on elastic modulus and crack initiation behavior. At body temperature, the specimens exhibited "ductile" crack initiation, whereas at room temperature "brittle" crack initiation was observed. The small punch test was found to be a sensitive and repeatable test method for evaluating the mechanical behavior of PMMA. In light of the results of this study, future small punch testing should be conducted at body temperature.

  2. Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

    Science.gov (United States)

    Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

    2013-01-01

    Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

  3. Foulant analysis of hollow fine fiber (HFF) membranes in Red Sea SWRO plants using membrane punch autopsy (MPA)

    KAUST Repository

    Green, Troy N.

    2017-06-12

    Membrane punch autopsy (MPA) is a procedure for quantitative foulant analysis of hollow fine fiber (HFF) permeators. In the past, quantitative autopsies of membranes were restricted to spiral wound. This procedure was developed at SWCC laboratories and tested on permeators of two commercial Red Sea reverse osmosis plants. For membrane autopsies, stainless steel hollow bore picks were penetrated to membrane cores and fibers extracted for foulant analysis. Quantitative analysis of extracted materials contained inorganic and organic foulants including bacteria. Fourier transform infrared spectroscopy analysis confirmed the presence of organic fouling functional groups and scanning electron microscopy with energy dispersive X-ray spectroscopy in the presence of diatoms and silica most likely not from particulate sand. API analysis revealed the presence of Shewanella and two Vibrio microbial species confirmed by 16S rDNA sequence library. It was observed that fouling content of HFF cellulose triacetate (CTA) membranes were more than 800 times than polyamide spiral wound membranes.

  4. Machine for casting and punching grids for lead batteries. Maschine zum Giessen und Stanzen von Gittern fuer Bleiakkumulatoren

    Energy Technology Data Exchange (ETDEWEB)

    Sperling, F; Hennecke, A

    1981-10-29

    The invention describes a machine, which places the cast parts from a two-part, vertical casting mould onto a transport unit using a lifting device, without any danger of deformation of the not yet hardened grid plates by mechanical loads. The lifting device and rider of the transport unit have guides, in which the plate rests with its grid wings. The transport unit consists of endless chains of variable distance and is also used for cooling, by taking air, for example, as cooling medium through a suitably shaped metal jacket. At the end of the cooling area, the castings are gripped at the bottom by axially controlled pegs pointing towards the inside, and are brought into the horizontal level by a movement of the chains. They are laid on a plate fitted between the chain wheels and are taken by side cams to the punch, from which they are discharged via a further pair of cams on to a belt.

  5. Effect of Chord Splice Joints on Force Distribution and Deformations in Trusses with Punched Metal Plate Fasteners

    DEFF Research Database (Denmark)

    Ellegaard, Peter

    2007-01-01

    The span of roof trusses with punched metal plate fasteners (nail plates) makes it often necessary to use splice joints in the top and bottom chords. In the finite element models used for design of the trusses these splice joints are normally assumed to be either rotationally stiff or pinned....... Timber-to-timber contact and non-linear elastic behaviour are included in the model. Results from tests with joints under fourpoint bending are compared with predictions given by TrussLab, and a good agreement is found. Splice joints in trusses with nail plates may be assumed to be rotationally stiff...... if their deformation has no significant effect upon the distribution of member forces according to Eurocode 5. Two simple guidelines for the design and location of splice joints are given in Eurocode 5 for treating the splice joints as rotationally stiff. The reasonability of these guidelines and the influence...

  6. Obtaining of inulin acetate

    OpenAIRE

    Khusenov, Arslonnazar; Rakhmanberdiev, Gappar; Rakhimov, Dilshod; Khalikov, Muzaffar

    2014-01-01

    In the article first obtained inulin ester inulin acetate, by etherification of inulin with acetic anhydride has been exposed. Obtained product has been studied using elementary analysis and IR spectroscopy.

  7. Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

    Science.gov (United States)

    Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

    2014-05-01

    Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by

  8. Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Win, Maartje M.L. de; Lavini, Cristina Mphil; Heeten, Gerard J. den; Habraken, Jan

    2003-01-01

    A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand 123 I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [ 123 I]FP-CIT binding ratios of the test/retest studies were 1.7 ± 0.2 and 1.6 ± 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [ 123 I]FP-CIT binding ratios in rats is highly reproducible

  9. Pre-pulse inhibition and striatal dopamine in subjects at an ultra-high risk for psychosis

    NARCIS (Netherlands)

    de Koning, Mariken B.; Bloemen, Oswald J. N.; van Duin, Esther D. A.; Booij, Jan; Abel, Kathryn M.; de Haan, Lieuwe; Linszen, Don H.; van Amelsvoort, Thérèse A. M. J.

    2014-01-01

    Reduced prepulse inhibition (PPI) of the acoustic startle response is thought to represent a robust biomarker in schizophrenia. Reduced PPI has been demonstrated in subjects at ultra high risk (UHR) for developing psychosis. Imaging studies report disruption of striatal dopaminergic

  10. Right anterior cingulate cortical thickness and bilateral striatal volume correlate with child behavior checklist aggressive behavior scores in healthy children.

    Science.gov (United States)

    Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D; Evans, Alan C; Karama, Sherif

    2011-08-01

    The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. A new framework for cortico-striatal plasticity: behavioural theory meets in vitro data at the reinforcement-action interface.

    Directory of Open Access Journals (Sweden)

    Kevin N Gurney

    2015-01-01

    Full Text Available Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface. Much evidence suggests that this occurs when phasic dopamine, acting as a reinforcement prediction error, gates plasticity at cortico-striatal synapses, and thereby changes the future likelihood of selecting the action(s coded by striatal neurons. But this hypothesis faces serious challenges. First, cortico-striatal plasticity is inexplicably complex, depending on spike timing, dopamine level, and dopamine receptor type. Second, there is a credit assignment problem-action selection signals occur long before the consequent dopamine reinforcement signal. Third, the two types of striatal output neuron have apparently opposite effects on action selection. Whether these factors rule out the interface hypothesis and how they interact to produce reinforcement learning is unknown. We present a computational framework that addresses these challenges. We first predict the expected activity changes over an operant task for both types of action-coding striatal neuron, and show they co-operate to promote action selection in learning and compete to promote action suppression in extinction. Separately, we derive a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then show this model produces the predicted activity changes necessary for learning and extinction in an operant task, a remarkable convergence of a bottom-up data-driven plasticity model with the top-down behavioural requirements of learning theory. Moreover, we show the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. Validating the model, we show it can account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. By bridging the levels between the single synapse and

  12. Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

    OpenAIRE

    Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

    1999-01-01

    Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

  13. Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt.

    Science.gov (United States)

    Sweitzer, Maggie M; Geier, Charles F; Denlinger, Rachel; Forbes, Erika E; Raiff, Bethany R; Dallery, Jesse; McClernon, F J; Donny, Eric C

    2016-03-01

    Tobacco smoking is associated with dysregulated reward processing within the striatum, characterized by hypersensitivity to smoking rewards and hyposensitivity to non-smoking rewards. This bias toward smoking reward at the expense of alternative rewards is further exacerbated by deprivation from smoking, which may contribute to difficulty maintaining abstinence during a quit attempt. We examined whether abstinence-induced changes in striatal processing of rewards predicted lapse likelihood during a quit attempt supported by contingency management (CM), in which abstinence from smoking was reinforced with money. Thirty-six non-treatment-seeking smokers participated in two functional MRI (fMRI) sessions, one following 24-h abstinence and one following smoking as usual. During each scan, participants completed a rewarded guessing task designed to elicit striatal activation in which they could earn smoking and monetary rewards delivered after the scan. Participants then engaged in a 3-week CM-supported quit attempt. As previously reported, 24-h abstinence was associated with increased striatal activation in anticipation of smoking reward and decreased activation in anticipation of monetary reward. Individuals exhibiting greater decrements in right striatal activation to monetary reward during abstinence (controlling for activation during non-abstinence) were more likely to lapse during CM (p reward. These results are consistent with a growing number of studies indicating the specific importance of disrupted striatal processing of non-drug reward in nicotine dependence and highlight the importance of individual differences in abstinence-induced deficits in striatal function for smoking cessation.

  14. Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds.

    Science.gov (United States)

    Tokarev, Kirill; Hyland Bruno, Julia; Ljubičić, Iva; Kothari, Paresh J; Helekar, Santosh A; Tchernichovski, Ofer; Voss, Henning U

    2017-08-11

    In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate's song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

  15. Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L--Tyrosine PET

    Directory of Open Access Journals (Sweden)

    Claire E. Wilcox

    2010-01-01

    Full Text Available Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[18F]-fluoro-L--tyrosine (FMT positron emission tomography (PET uptake in striatal subregions was correlated with BMI (kg/m2 and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (=.05. These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

  16. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

    2012-01-01

    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  17. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  18. Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior.

    Science.gov (United States)

    Burke, Mary V; Small, Dana M

    2016-06-01

    Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

  19. Running wheel exercise before a binge regimen of methamphetamine does not protect against striatal dopaminergic damage.

    Science.gov (United States)

    O'dell, Steven J; Marshall, John F

    2014-09-01

    Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic nerve terminals as measured by decreases in tissue dopamine (DA) content and levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell bodies from which the DA terminals arise survive, and previous reports show that striatal DA markers return to control levels by 12 months post-mAMPH, suggesting long-term repair or regrowth of damaged DA terminals. We previously showed that when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced decreases in striatal DAT. However, these data left unresolved the question of whether exercise protected against the initial neurotoxicity from the mAMPH binge or accelerated the repair of the damaged DA terminals. The present experiments were designed to test whether exercise protects against the mAMPH-induced injury. Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an additional week before autoradiographic determination of striatal DAT binding. The autoradiographic findings showed that prior exercise provided no protection against mAMPH-induced damage to striatal DA terminals. These results, together with analyses from our previous experiments, suggest that voluntary exercise may accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise may be useful as therapeutic adjunct in the treatment mAMPH addicts. © 2014 Wiley Periodicals, Inc.

  20. Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

    Science.gov (United States)

    Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

    2017-07-01

    Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

  1. Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability

    OpenAIRE

    Miller, Michael L.; Ren, Yanhua; Szutorisz, Henrietta; Warren, Noël A.; Tessereau, Chloé; Egervári, Gábor; Mlodnicka, Agnieszka; Kapoor, Manav; Chaarani, Bader; Morris, Claudia V.; Schumann, Gunter; Garavan, Hugh; Goate, Alison M.; Bannon, Michael J.; Halperin, Jeffrey M.

    2017-01-01

    Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood. Here we report the critical role of ventral striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vulnerability. Using an ADHD rat mode...

  2. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

    Directory of Open Access Journals (Sweden)

    Marios Politis

    2017-01-01

    Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

  3. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments

    Directory of Open Access Journals (Sweden)

    Jill R. Crittenden

    2011-09-01

    Full Text Available The striatum is composed principally of GABAergic, medium spiny projection neurons (MSNs that can be categorized based on their gene expression, electrophysiological profiles and input-output circuits. Major subdivisions of MSN populations include 1 those in ventromedial and dorsolateral striatal regions, 2 those giving rise to the direct and indirect pathways, and 3 those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input-output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in

  4. Concomitant Appearance of Pisa Syndrome and Striatal Hand in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2011-10-01

    Full Text Available Pisa syndrome is (PS usually seen in patients receiving antipsychotic drugs and characterised by lateral flexion of trunk and axial dystonia. It is believed that antipsychotic drugs lead to dopamine blockage causing PS. We describe a Parkinson’s disease patient who was doing well with levodopa/carbidopa for 3 years and developed lateral flexion of trunk. His abnormal posture used to completely improve upon lying down position. He also had striatal hand deformity suggestive of focal dystonia.

  5. Prolonged striatal disinhibition as a chronic animal model of tic disorders.

    Science.gov (United States)

    Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

    2017-12-01

    Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

  7. Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

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    McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

    1990-01-01

    Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

  8. DISC1 and striatal volume: a potential risk phenotype for mental illness

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    M. Mallar eChakravarty

    2012-06-01

    Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

  9. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

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    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho; Seppaenen, Marko; Noponen, Tommi

    2014-01-01

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [ 123 I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  10. Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats.

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    Qiqi Feng

    Full Text Available Huntington's disease (HD is a neurological degenerative disease and quinolinic acid (QA has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv+ and neuropeptide Y (NPY+ interneurons were both significantly reduced while those of calretinin (Cr+ and choline acetyltransferase (ChAT+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD.

  11. Anatomical and electrophysiological changes in striatal TH interneurons after loss of the nigrostriatal dopaminergic pathway.

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    Ünal, Bengi; Shah, Fulva; Kothari, Janish; Tepper, James M

    2015-01-01

    Using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the tyrosine hydroxylase (TH) promoter, we have previously shown that there are approximately 3,000 striatal EGFP-TH interneurons per hemisphere in mice. Here, we report that striatal TH-EGFP interneurons exhibit a small, transient but significant increase in number after unilateral destruction of the nigrostriatal dopaminergic pathway. The increase in cell number is accompanied by electrophysiological and morphological changes. The intrinsic electrophysiological properties of EGFP-TH interneurons ipsilateral to 6-OHDA lesion were similar to those originally reported in intact mice except for a significant reduction in the duration of a characteristic depolarization induced plateau potential. There was a significant change in the distribution of the four previously described electrophysiologically distinct subtypes of striatal TH interneurons. There was a concomitant increase in the frequency of both spontaneous excitatory and inhibitory post-synaptic currents, while their amplitudes did not change. Nigrostriatal lesions did not affect somatic size or dendritic length or branching, but resulted in an increase in the density of proximal dendritic spines and spine-like appendages in EGFP-TH interneurons. The changes indicate that electrophysiology properties and morphology of striatal EGFP-TH interneurons depend on endogenous levels of dopamine arising from the nigrostriatal pathway. Furthermore, these changes may serve to help compensate for the changes in activity of spiny projection neurons that occur following loss of the nigrostriatal innervation in experimental or in early idiopathic Parkinson's disease by increasing feedforward GABAergic inhibition exerted by these interneurons.

  12. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

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    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  13. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

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    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-02-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  14. Electrical and chemical transmission between striatal GABAergic output neurones in rat brain slices

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    Venance, Laurent; Glowinski, Jacques; Giaume, Christian

    2004-01-01

    Basal ganglia are interconnected subcortical nuclei, connected to the thalamus and all cortical areas involved in sensory motor control, limbic functions and cognition. The striatal output neurones (SONs), the major striatal population, are believed to act as detectors and integrators of distributed patterns of cerebral cortex inputs. Despite the key role of SONs in cortico-striatal information processing, little is known about their local interactions. Here, we report the existence and characterization of electrical and GABAergic transmission between SONs in rat brain slices. Tracer coupling (biocytin) incidence was high during the first two postnatal weeks and then decreased (postnatal days (P) 5–25, 60%; P25–30, 29%; n = 61). Electrical coupling was observed between 27% of SON pairs (coupling coefficient: 3.1 ± 0.3%, n = 89 at P15) and as shown by single-cell RT-PCR, several connexin (Cx) mRNAs were found to be expressed (Cx31.1, Cx32, Cx36 and Cx47). GABAergic synaptic transmission (abolished by bicuculline, a GABAA receptor antagonist) observed in 19% of SON pairs (n = 62) was reliable (mean failure rate of 6 ± 3%), precise (variation coefficient of latency, 0.06), strong (IPSC amplitudes of 38 ± 12 pA) and unidirectional. Interestingly, electrical and chemical transmission were mutually exclusive. These results suggest that preferential networks of electrically and chemically connected SONs, might be involved in the channelling of cortico-basal ganglia information processing. PMID:15235091

  15. Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

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    Alex G. Lee

    2016-06-01

    Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  16. Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

    Science.gov (United States)

    Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

    2017-07-01

    Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

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    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  18. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

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    Bart P de Kwaasteniet

    Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

  19. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

    Science.gov (United States)

    Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

    2017-03-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  20. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder.

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    Herbort, Maike C; Soch, Joram; Wüstenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, Jürgen; Walter, Henrik; Roepke, Stefan; Schott, Björn H

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

  1. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

    Science.gov (United States)

    Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

    2015-12-07

    Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

  2. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  3. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

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    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  4. Rapid eye movement sleep behaviour disorder and striatal dopamine depletion in patients with Parkinson's disease.

    Science.gov (United States)

    Chung, S J; Lee, Y; Lee, J J; Lee, P H; Sohn, Y H

    2017-10-01

    Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion. A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan. Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less-affected side and axial symptoms, and were prescribed higher levodopa-equivalent doses at follow-up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less-affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables. These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism. © 2017 EAN.

  5. Age related changes in striatal resting state functional connectivity in autism

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    Aarthi ePadmanabhan

    2013-11-01

    Full Text Available Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity with resting state fMRI from late childhood to early adulthood (8-36 years, using a seed based functional connectivity method with the striatum. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to TD participants. In addition, ASD participants showed aberrant age-related changes in connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g. fusiform gyrus, inferior and superior temporal gyri. In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which also may help clarify discrepant findings in the literature.

  6. Postural & striatal deformities in Parkinson`s disease: Are these rare?

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    Sanjay Pandey

    2016-01-01

    Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

  7. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

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    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  8. Increased coherence among striatal regions in the theta range during attentive wakefulness

    Directory of Open Access Journals (Sweden)

    G. Lepski

    2012-08-01

    Full Text Available The striatum, the largest component of the basal ganglia, is usually subdivided into associative, motor and limbic components. However, the electrophysiological interactions between these three subsystems during behavior remain largely unknown. We hypothesized that the striatum might be particularly active during exploratory behavior, which is presumably associated with increased attention. We investigated the modulation of local field potentials (LFPs in the striatum during attentive wakefulness in freely moving rats. To this end, we implanted microelectrodes into different parts of the striatum of Wistar rats, as well as into the motor, associative and limbic cortices. We then used electromyograms to identify motor activity and analyzed the instantaneous frequency, power spectra and partial directed coherence during exploratory behavior. We observed fine modulation in the theta frequency range of striatal LFPs in 92.5 ± 2.5% of all epochs of exploratory behavior. Concomitantly, the theta power spectrum increased in all striatal channels (P 0.7 between the primary motor cortex and the rostral part of the caudatoputamen nucleus, as well as among all striatal channels (P < 0.001. Conclusively, we observed a pattern of strong theta band activation in the entire striatum during attentive wakefulness, as well as a strong coherence between the motor cortex and the entire striatum. We suggest that this activation reflects the integration of motor, cognitive and limbic systems during attentive wakefulness.

  9. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    Science.gov (United States)

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  10. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  11. Small punch tensile/fracture test data and 3D specimen surface data on Grade 91 ferritic/martensitic steel from cryogenic to room temperature.

    Science.gov (United States)

    Bruchhausen, Matthias; Lapetite, Jean-Marc; Ripplinger, Stefan; Austin, Tim

    2016-12-01

    Raw data from small punch tensile/fracture tests at two displacement rates in the temperature range from -196 °C to room temperature on Grade 91 ferritic/martensitic steel are presented. A number of specimens were analyzed after testing by means of X-ray computed tomography (CT). Based on the CT volume data detailed 3D surface maps of the specimens were established. All data are open access and available from Online Data Information Network (ODIN)https://odin.jrc.ec.europa.eu. The data presented in the current work has been analyzed in the research article "On the determination of the ductile to brittle transition temperature from small punch tests on Grade 91 ferritic-martensitic steel" (M. Bruchhausen, S. Holmström, J.-M. Lapetite, S. Ripplinger, 2015) [1].

  12. A distinct species, Dodona formosana, detected in the Dodona eugenes species complex: clarification of the taxonomic status of the Punch butterfly in Taiwan

    Science.gov (United States)

    Wu, Li-Wei; Lin, Wen-Jie; Hsu, Yu-Feng

    2018-01-01

    Abstract The Tailed Punch, Dodona eugenes, is widely distributed in East Asia with seven subspecies currently recognized. However, two of them, namely ssp. formosana and ssp. esakii found in Taiwan, are hard to distinguish from each other due to ambiguous diagnostic characters. In this study, their taxonomic status is clarified by comparing genitalia characters and phylogenetic relationships based on mitochondrial sequences, COI and COII (total 2211 bps). Our results show that there is no reliable feature to separate these two subspecies. Surprisingly we found that Dodona in Taiwan is more closely related to the Orange Punch, D. egeon, than to other subspecies of D. eugenes. Therefore, the following nomenclatural changes are proposed: Dodona eugenes formosana is revised to specific status as Dodona formosana Matsumura, 1919, stat. rev, and ssp. esakii is sunk to a junior synonym of Dodona formosana syn. n. PMID:29674868

  13. A distinct species, Dodona formosana, detected in the Dodona eugenes species complex: clarification of the taxonomic status of the Punch butterfly in Taiwan

    Directory of Open Access Journals (Sweden)

    Li-Wei Wu

    2018-02-01

    Full Text Available The Tailed Punch, Dodona eugenes, is widely distributed in East Asia with seven subspecies currently recognized. However, two of them, namely ssp. formosana and ssp. esakii found in Taiwan, are hard to distinguish from each other due to ambiguous diagnostic characters. In this study, their taxonomic status is clarified by comparing genitalia characters and phylogenetic relationships based on mitochondrial sequences, COI and COII (total 2211 bps. Our results show that there is no reliable feature to separate these two subspecies. Surprisingly we found that Dodona in Taiwan is more closely related to the Orange Punch, D. egeon, than to other subspecies of D. eugenes. Therefore, the following nomenclatural changes are proposed: Dodona eugenes formosana is revised to specific status as Dodona formosana Matsumura, 1919, stat. rev, and ssp. esakii is sunk to a junior synonym of Dodona formosana syn. n.

  14. A simple algorithm for subregional striatal uptake analysis with partial volume correction in dopaminergic PET imaging

    International Nuclear Information System (INIS)

    Lue Kunhan; Lin Hsinhon; Chuang Kehshih; Kao Chihhao, K.; Hsieh Hungjen; Liu Shuhsin

    2014-01-01

    In positron emission tomography (PET) of the dopaminergic system, quantitative measurements of nigrostriatal dopamine function are useful for differential diagnosis. A subregional analysis of striatal uptake enables the diagnostic performance to be more powerful. However, the partial volume effect (PVE) induces an underestimation of the true radioactivity concentration in small structures. This work proposes a simple algorithm for subregional analysis of striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging. The PVC algorithm analyzes the separate striatal subregions and takes into account the PVE based on the recovery coefficient (RC). The RC is defined as the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration, and is derived from a combination of the traditional volume of interest (VOI) analysis and the large VOI technique. The clinical studies, comprising 11 patients with Parkinson's disease (PD) and 6 healthy subjects, were used to assess the impact of PVC on the quantitative measurements. Simulations on a numerical phantom that mimicked realistic healthy and neurodegenerative situations were used to evaluate the performance of the proposed PVC algorithm. In both the clinical and the simulation studies, the striatal-to-occipital ratio (SOR) values for the entire striatum and its subregions were calculated with and without PVC. In the clinical studies, the SOR values in each structure (caudate, anterior putamen, posterior putamen, putamen, and striatum) were significantly higher by using PVC in contrast to those without. Among the PD patients, the SOR values in each structure and quantitative disease severity ratings were shown to be significantly related only when PVC was used. For the simulation studies, the average absolute percentage error of the SOR estimates before and after PVC were 22.74% and 1.54% in the healthy situation, respectively; those in the neurodegenerative situation were 20.69% and 2

  15. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  16. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

    Science.gov (United States)

    Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

    2017-10-11

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

  17. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  18. Efficacy of Punch Elevation Combined with Fractional Carbon Dioxide Laser Resurfacing in Facial Atrophic Acne Scarring: A Randomized Split-face Clinical Study

    Science.gov (United States)

    Faghihi, Gita; Nouraei, Saeid; Asilian, Ali; Keyvan, Shima; Abtahi-Naeini, Bahareh; Rakhshanpour, Mehrdad; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayed Mohsen

    2015-01-01

    Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18–55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID:26538695

  19. Efficacy of punch elevation combined with fractional carbon dioxide laser resurfacing in facial atrophic acne scarring: A randomized split-face clinical study

    Directory of Open Access Journals (Sweden)

    Gita Faghihi

    2015-01-01

    Full Text Available Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO 2 laser resurfacing combined with punch elevation with fractional CO 2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18-55 with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO 2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO 2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56. Their evaluation found that fractional CO 2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO 2 laser treatment alone, assessed 4 months after treatment (P = 0.02. Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO 2 laser treatment was significant on both treatment sides (P < 0.05. Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring.

  20. Observation of Anisotropy of Creep Fracture Using Small Punch Test for Al-Al4C3 System Produced by Equal Channel Angular Pressing

    Czech Academy of Sciences Publication Activity Database

    Besterci, M.; Dobeš, Ferdinand; Ballóková, B.; Sülleiová, K.; Kvačkaj, T.

    2011-01-01

    Roč. 30, č. 3 (2011), s. 205-210 ISSN 0334-6455 R&D Projects: GA AV ČR 1QS200410502; GA AV ČR IAA200410801 Grant - others:Vega(SK) 2/0025/11 Institutional research plan: CEZ:AV0Z20410507 Keywords : Equal channel angular pressing * small-punch creep * fracture * metal-matrix composites Subject RIV: JI - Composite Materials Impact factor: 0.242, year: 2011

  1. A Study on the Small Punch Test for Fracture Strength Evaluation of CANDU Pressure Tube Embrittled by Hydrogen

    International Nuclear Information System (INIS)

    Nho, Seung Hwan; Ong, Jang Woo; Yu, Hyo Sun; Chung, Se Hi

    1996-01-01

    The purpose of this study is to investigate the usefulness of small punch(SP) test using miniaturized specimens as a method for fracture strength evaluation of CANDU pressure tube embrittled by hydrogen. According to the test results, the fracture strength evaluation as a function of hydrogen concentration at -196 .deg. C was much better than that at room temperature, as the difference of SP fracture energy(Esp) with hydrogen concentration was more significant at -196 .deg. C than at room temperature for the hydrogen concentration up to 300ppm-H. It was also observed that the peak of average AE energy, the cumulative average AE energy and the cumulative average AE energy per equivalent fracture, strain increased with the increase of hydrogen concentration. From the results of load-displacement behaviors, Esp behaviors, macro- and micro-SEM fractographs and AE test it has been concluded that the SP test method using miniaturized specimen(10mmx10mmx0.5mm) will be a useful test method to evaluate the fracture strength for CANDU pressure tube embrittled by hydrogen

  2. Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study

    Directory of Open Access Journals (Sweden)

    Beltrame Francesco

    2010-11-01

    Full Text Available Abstract Background Tissue MicroArray technology aims to perform immunohistochemical staining on hundreds of different tissue samples simultaneously. It allows faster analysis, considerably reducing costs incurred in staining. A time consuming phase of the methodology is the selection of tissue areas within paraffin blocks: no utilities have been developed for the identification of areas to be punched from the donor block and assembled in the recipient block. Results The presented work supports, in the specific case of a primary subtype of breast cancer (tubular breast cancer, the semi-automatic discrimination and localization between normal and pathological regions within the tissues. The diagnosis is performed by analysing specific morphological features of the sample such as the absence of a double layer of cells around the lumen and the decay of a regular glands-and-lobules structure. These features are analysed using an algorithm which performs the extraction of morphological parameters from images and compares them to experimentally validated threshold values. Results are satisfactory since in most of the cases the automatic diagnosis matches the response of the pathologists. In particular, on a total of 1296 sub-images showing normal and pathological areas of breast specimens, algorithm accuracy, sensitivity and specificity are respectively 89%, 84% and 94%. Conclusions The proposed work is a first attempt to demonstrate that automation in the Tissue MicroArray field is feasible and it can represent an important tool for scientists to cope with this high-throughput technique.

  3. Evaluation of slim-edge, multi-guard, and punch-through-protection structures before and after proton irradiation

    Science.gov (United States)

    Mitsui, S.; Unno, Y.; Ikegami, Y.; Takubo, Y.; Terada, S.; Hara, K.; Takahashi, Y.; Jinnouchi, O.; Nagai, R.; Kishida, T.; Yorita, K.; Hanagaki, K.; Takashima, R.; Kamada, S.; Yamamura, K.

    2013-01-01

    Planar geometry silicon pixel and strip sensors for the high luminosity upgrade of the LHC (HL-LHC) require a high bias voltage of 1000 V in order to withstand a radiation damage caused by particle fluences of 1×1016 1 MeV neq/cm2 and 1×1015 1 MeV neq/cm2 for pixel and strip detectors, respectively. In order to minimize the inactive edge space that can withstand a bias voltage of 1000 V, edge regions susceptible to microdischarge (MD) should be carefully optimized. We fabricated diodes with various edge distances (slim-edge diodes) and with 1-3 multiple guard rings (multi-guard diodes). AC coupling insulators of strip sensors are vulnerable to sudden heavy charge deposition, such as an accidental beam splash, which may destroy the readout AC capacitors. Thus various types of punch-through-protection (PTP) structures were implemented in order to find the most effective structure to protect against heavy charge deposition. These samples were irradiated with 70 MeV protons at fluences of 5×1012 1 MeV neq/cm2-1×1016 1 MeV neq/cm2. Their performances were evaluated before and after irradiation in terms of an onset voltage of the MD, a turn-on voltage of the PTP, and PTP saturation resistance.

  4. Evaluation of ductile-brittle transition behavior with neutron irradiation in nuclear reactor pressure vessel steels using small punch test

    International Nuclear Information System (INIS)

    Kim, M. C.; Lee, B. S.; Oh, Y. J.

    2003-01-01

    A Small Punch (SP) test was performed to evaluate the ductile-brittle transition temperature before and after neutron irradiation in Reactor Pressure Vessel (RPV) steels produced by different manufacturing (refining) processes. The results were compared to the standard transition temperature shifts from the Charpy test and Master Curve fracture toughness test in accordance with the ASTM standard E1921. The samples were taken from 1/4t location of the vessel thickness and machined into a 10x10x0.5mm dimension. Irradiation of the samples was carried out in the research reactor at KAERI (HANARO) at about 290 .deg. C of the different fluence levels respectively. SP tests were performed in the temperature range of RT to -196 .deg. C using a 2.4mm diameter ball. For the materials before and after irradiation, SP transition temperatures (T sp ), which are determined at the middle of the upper and lower SP energies, showed a linear correlation with the Charpy index temperature, T 41J . T sp from the irradiated samples was increased as the fluence level increased and was well within the deviation range of the unirradiated data. The TSP had a correlation with the reference temperature (T 0 ) from the master curve method using a pre-cracked Charpy V-notched (PCVN) specimen

  5. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

    Science.gov (United States)

    Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

    2015-08-01

    Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

  6. Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

    2016-05-01

    Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

  7. DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

    Science.gov (United States)

    Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

    2013-01-01

    The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

  8. Design and applications of a pneumatic accelerator for high speed punching

    International Nuclear Information System (INIS)

    Yaldiz, Sueleyman; Saglam, Haci; Unsacar, Faruk; Isik, Hakan

    2007-01-01

    High speed forming is an important production method that requires specially designed HERF (high energy rate forming) machines. Most of the HERF machines are devices that consist of a system in which energy is stored and a differential piston mechanism is used to release the energy at high rate. In order to eliminate the usage of specially designed HERF machines and to obtain the high speed forming benefits, the accelerator which can be adapted easily onto conventional presses has been designed and manufactured in this study. The designed energy accelerator can be incorporated into mechanical press to convert the low speed operation into high-speed operation of a hammer. Expectations from this work are reduced distortion rates, increased surface quality and precise dimensions in metal forming operations. From the performance test, the accelerator is able to achieve high speed and energy which require for high speed blanking of thick sheet metals

  9. Mechanical modeling and characterization of meniscus tissue using flat punch indentation and inverse finite element method.

    Science.gov (United States)

    Seyfi, Behzad; Fatouraee, Nasser; Imeni, Milad

    2018-01-01

    In this paper, to characterize the mechanical properties of meniscus by considering its local microstructure, a novel nonlinear poroviscoelastic Finite Element (FE) model has been developed. To obtain the mechanical response of meniscus, indentation experiments were performed on bovine meniscus samples. The ramp-relaxation test scenario with different depths and preloads was designed to capture the mechanical characteristics of the tissue in different regions of the medial and lateral menisci. Thereafter, a FE simulation was performed considering experimental conditions. Constitutive parameters were optimized by solving a FE-based inverse problem using the heuristic Simulated Annealing (SA) optimization algorithm. These parameters were ranged according to previously reported data to improve the optimization procedure. Based on the results, the mechanical properties of meniscus were highly influenced by both superficial and main layers. At low indentation depths, a high percentage relaxation (p < 0.01) with a high relaxation rate (p < 0.05) was obtained, due to the poroelastic and viscoelastic nature of the superficial layer. Increasing both penetration depth and preload level involved the main layer response and caused alterations in hyperelastic and viscoelastic parameters of the tissue, such that for both layers, the shear modulus was increased (p < 0.01) while the rate and percentage of relaxation were decreased (p < 0.01). Results reflect that, shear modulus of the main layer in anterior region is higher than central and posterior sites in medial meniscus. In contrast, in lateral meniscus, posterior side is stiffer than central and anterior sides. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, G L; Szabo, G; Telegdy, G [Institute of Pathophysiology, University Medical School, Szeged, Hungary; Penke, B [Institute of Medical Chemistry, University Medical School, Szeged, Hungary

    1981-01-29

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of ..cap alpha..-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of (/sup 3/H)DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10/sup -5/ M). Potassium-induced in vitro release of (/sup 3/H)DA from striatal slices was significantly increased by 10/sup -5/ M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

  11. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    International Nuclear Information System (INIS)

    Kovacs, G.L.; Szabo, G.; Telegdy, G.; Penke, B.

    1981-01-01

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of α-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [ 3 H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10 -5 M). Potassium-induced in vitro release of [ 3 H]DA from striatal slices was significantly increased by 10 -5 M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions. (Auth.)

  12. Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

    Science.gov (United States)

    Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

    2016-06-01

    Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0

  13. Diagnosis of aggressive subtypes of eyelid basal cell carcinoma by 2-mm punch biopsy: prospective and comparative study.

    Science.gov (United States)

    Rossato, Luiz Angelo; Carneiro, Rachel Camargo; Macedo, Erick Marcet Santiago de; Lima, Patrícia Picciarelli de; Miyazaki, Ahlys Ayumi; Matayoshi, Suzana

    2016-01-01

    : to compare the accuracy of preoperative 2-mm punch biopsy at one site and at two sites in the diagnosis of aggressive subtypes of eyelid basal cell carcinoma (BCC). : we randomly assigned patients to Group 1 (biopsy at one site) and Group 2 (biopsy at two sites). We compared the biopsy results to the gold standard (pathology of the surgical specimen). We calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Kappa coefficient to determine the level of agreement in both groups. : we analyzed 105 lesions (Group 1: n = 44; Group 2: n = 61). The agreement was 54.5% in Group 1 and 73.8% in Group 2 (p = 0.041). There was no significant difference between the groups regarding the distribution of quantitative and qualitative variables (gender, age, disease duration, tumor larger diameter, area and commitment of margins). Biopsy at two sites was two times more likely to agree with the gold standard than the biopsy of a single site. : the accuracy and the performance indicators were better for 2-mm punch biopsy in two sites than in one site for the diagnosis of aggressive subtypes of eyelid BCC. comparar a acurácia da biópsia pré-operatória por trépano de 2mm em um sítio e em dois sítios no diagnóstico dos subtipos agressivos de carcinoma basocelular (CBC) palpebral. os pacientes foram distribuídos aleatoriamente em Grupo 1 (biópsia em um sítio) e Grupo 2 (biópsia em dois sítios). Os resultados das biópsias foram comparados com o padrão-ouro (exame anatomopatológico da peça cirúrgica). A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo, precisão e coeficiente Kappa foram calculados para determinar o nível de concordância nos dois grupos. foram analisadas 105 lesões (Grupo 1: n = 44; Grupo 2: n = 61). A concordância foi de 54,5% no Grupo 1 e 73,8% no Grupo 2 (p-valor = 0,041). Não houve diferença significativa entre os grupos quanto à distribuição das vari

  14. Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

    Science.gov (United States)

    Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

    2014-02-01

    Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

  15. Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

    Science.gov (United States)

    Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

    2014-09-01

    Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  16. Striatal Dopamine Depletion Patterns and Early Non-Motor Burden in Parkinsons Disease.

    Directory of Open Access Journals (Sweden)

    Su Jin Chung

    Full Text Available The mechanism underlying non-motor symptoms in Parkinson's disease has not yet been elucidated. In this study, we hypothesized that Parkinson patients with more non-motor symptoms have a different pattern of striatal dopamine depletion, particularly in areas other than the sensorimotor striatum, compared to those with fewer non-motor symptoms.We conducted a prospective survey of the degree of non-motor symptoms (using the Korean version of the Non-Motor Symptoms Scale; K-NMSS in 151 patients with early-stage Parkinson's disease who had undergone a dopamine transporter PET scan as an initial diagnostic procedure. We classified the patients into two groups; high non-motor patients (HNM-PD; K-NMSS score ≥ 41 and low non-motor patients (LNM-PD.Patients in the HNM-PD group (n = 71 were older, had longer symptom duration, exhibited more severe motor deficits, and had been prescribed higher levodopa-equivalent doses at follow-up than those in the LNM-PD group. However, dopamine transporter binding to the striatal sub-regions and inter-sub-regional binding ratios were comparable between the two groups. A general linear model showed that the HNM-PD group had significantly more severe motor deficits than the LNM-PD group after controlling for age, gender, symptom duration, and dopamine transporter binding to the sensorimotor striatum.This study demonstrated that the pattern of striatal dopamine depletion does not contribute to early non-motor burden in Parkinson's disease. Our results suggest that LNM-PD patients may have a more benign course of motor symptom progression than HNM-PD patients.

  17. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

  18. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

    Directory of Open Access Journals (Sweden)

    Ismael Huertas

    Full Text Available Parkinson's disease (PD patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA, a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36, intermediate (I, n = 22, and tremor-dominant (TD, n = 17 subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001 and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25% and I (45% patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  19. Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

    Directory of Open Access Journals (Sweden)

    Mathieu Baudonnat

    2017-05-01

    Full Text Available Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R learning critically depends on the dorsal striatum (DS, spatial memory relies on the hippocampus (HPC. Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments.

  20. Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Johnson, B J; Bruno, J P

    1995-02-01

    A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

  1. Arc mRNA induction in striatal efferent neurons associated with response learning.

    Science.gov (United States)

    Daberkow, D P; Riedy, M D; Kesner, R P; Keefe, K A

    2007-07-01

    The dorsal striatum is involved in motor-response learning, but the extent to which distinct populations of striatal efferent neurons are differentially involved in such learning is unknown. Activity-regulated, cytoskeleton-associated (Arc) protein is an effector immediate-early gene implicated in synaptic plasticity. We examined arc mRNA expression in striatopallidal vs. striatonigral efferent neurons in dorsomedial and dorsolateral striatum of rats engaged in reversal learning on a T-maze motor-response task. Male Sprague-Dawley rats learned to turn right or left for 3 days. Half of the rats then underwent reversal training. The remaining rats were yoked to rats undergoing reversal training, such that they ran the same number of trials but ran them as continued-acquisition trials. Brains were removed and processed using double-label fluorescent in situ hybridization for arc and preproenkephalin (PPE) mRNA. In the reversal, but not the continued-acquisition, group there was a significant relation between the overall arc mRNA signal in dorsomedial striatum and the number of trials run, with rats reaching criterion in fewer trials having higher levels of arc mRNA expression. A similar relation was seen between the numbers of PPE(+) and PPE(-) neurons in dorsomedial striatum with cytoplasmic arc mRNA expression. Interestingly, in behaviourally activated animals significantly more PPE(-) neurons had cytoplasmic arc mRNA expression. These data suggest that Arc in both striatonigral and striatopallidal efferent neurons is involved in striatal synaptic plasticity mediating motor-response learning in the T-maze and that there is differential processing of arc mRNA in distinct subpopulations of striatal efferent neurons.

  2. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

    Science.gov (United States)

    Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

    2013-09-11

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

  3. Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

    Directory of Open Access Journals (Sweden)

    Andreas eKlaus

    2011-07-01

    Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

  4. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  5. Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal Excitation Leads to Tremor.

    Science.gov (United States)

    Oran, Yael; Bar-Gad, Izhar

    2018-02-14

    Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum. The tremor was accompanied by coherent oscillations in the local field potential (LFP). Individual neuron activity patterns became oscillatory and coherent in the tremor frequency. Striatal neurons, but not GP neurons, displayed additional temporal, nonoscillatory correlations. The subsequent reduction in the corticostriatal input following muscimol injection to the corresponding somatotopic location in the primary motor cortex led to disruption of the tremor and a reduction of the LFP oscillations and individual neuron's phase-locked activity. The breakdown of the normal balance of excitation and inhibition in the striatum has been shown previously to be related to different motor abnormalities. Our results further indicate that the balance between excitatory corticostriatal input and feedforward FSI inhibition is sufficient to break down the striatal decorrelation process and generate oscillations resulting in rest tremor typical of multiple basal ganglia disorders. SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs) play a key role in normal striatal processing by exerting powerful inhibitory control over the network. FSI malfunctions have been associated with abnormal processing of information within the striatum that leads to multiple movement disorders. Here, we study the changes in neuronal activity and movement kinematics following selective inhibition of these

  6. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

    Science.gov (United States)

    Sameiro-Barbosa, Catia M; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system.

  7. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  8. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation

    Science.gov (United States)

    Sameiro-Barbosa, Catia M.; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  9. Ventral striatal activity correlates with memory confidence for old- and new-responses in a difficult recognition test.

    Directory of Open Access Journals (Sweden)

    Ulrike Schwarze

    Full Text Available Activity in the ventral striatum has frequently been associated with retrieval success, i.e., it is higher for hits than correct rejections. Based on the prominent role of the ventral striatum in the reward circuit, its activity has been interpreted to reflect the higher subjective value of hits compared to correct rejections in standard recognition tests. This hypothesis was supported by a recent study showing that ventral striatal activity is higher for correct rejections than hits when the value of rejections is increased by external incentives. These findings imply that the striatal response during recognition is context-sensitive and modulated by the adaptive significance of "oldness" or "newness" to the current goals. The present study is based on the idea that not only external incentives, but also other deviations from standard recognition tests which affect the subjective value of specific response types should modulate striatal activity. Therefore, we explored ventral striatal activity in an unusually difficult recognition test that was characterized by low levels of confidence and accuracy. Based on the human uncertainty aversion, in such a recognition context, the subjective value of all high confident decisions is expected to be higher than usual, i.e., also rejecting items with high certainty is deemed rewarding. In an accompanying behavioural experiment, participants rated the pleasantness of each recognition response. As hypothesized, ventral striatal activity correlated in the current unusually difficult recognition test not only with retrieval success, but also with confidence. Moreover, participants indicated that they were more satisfied by higher confidence in addition to perceived oldness of an item. Taken together, the results are in line with the hypothesis that ventral striatal activity during recognition codes the subjective value of different response types that is modulated by the context of the recognition test.

  10. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  11. Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

    Science.gov (United States)

    Snyder-Keller, A; Costantini, L C; Graber, D J

    2001-01-01

    Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

  12. Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

    Science.gov (United States)

    Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

    2016-03-01

    Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

  13. Fast oscillations in cortical-striatal networks switch frequency following rewarding events and stimulant drugs.

    Science.gov (United States)

    Berke, J D

    2009-09-01

    Oscillations may organize communication between components of large-scale brain networks. Although gamma-band oscillations have been repeatedly observed in cortical-basal ganglia circuits, their functional roles are not yet clear. Here I show that, in behaving rats, distinct frequencies of ventral striatal local field potential oscillations show coherence with different cortical inputs. The approximately 50 Hz gamma oscillations that normally predominate in awake ventral striatum are coherent with piriform cortex, whereas approximately 80-100 Hz high-gamma oscillations are coherent with frontal cortex. Within striatum, entrainment to gamma rhythms is selective to fast-spiking interneurons, with distinct fast-spiking interneuron populations entrained to different gamma frequencies. Administration of the psychomotor stimulant amphetamine or the dopamine agonist apomorphine causes a prolonged decrease in approximately 50 Hz power and increase in approximately 80-100 Hz power. The same frequency switch is observed for shorter epochs spontaneously in awake, undrugged animals and is consistently provoked for reward receipt. Individual striatal neurons can participate in these brief high-gamma bursts with, or without, substantial changes in firing rate. Switching between discrete oscillatory states may allow different modes of information processing during decision-making and reinforcement-based learning, and may also be an important systems-level process by which stimulant drugs affect cognition and behavior.

  14. Interaction of structural analogs of dopamine, chlorpromazine and sulpiride with striatal dopamine receptors

    International Nuclear Information System (INIS)

    Wallace, R.A.

    1987-01-01

    The objectives of these studies were to determine if the nitrogen atom of dopaminergic agonists and antagonists drugs is required for interaction with the D-1 and D-2 dopamine receptors and whether the positively charged or uncharged molecular species interacts with these receptors. To address these issues, permanently charged analogs of dopamine, chlorpromazine and sulpiride were synthesized in which a dimethylsulfonium, dimethylselenonium or quaternary ammonium group replaced the amine group. Permanently uncharged analogs which contained a methylsulfide, methylselenide and sulfoxide group instead of an amine group were also synthesized. The interactions of these compounds with striatal dopamine receptors were studied. We found that the permanently charged dopamine analogs bound to the D-2 receptor of striatal membranes like conventional dopaminergic agonists and displayed agonist activity at the D-2 receptor regulating potassium-evoked [ 3 H] acetylcholine release. In contrast, the permanently uncharged analogs bound only to the high affinity state of the D-2 receptor and had neither agonist or antagonist activity

  15. Selective updating of working memory content modulates meso-cortico-striatal activity.

    Science.gov (United States)

    Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

    2011-08-01

    Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

  16. Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

    Science.gov (United States)

    Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

    2014-01-01

    Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

  17. Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability.

    Science.gov (United States)

    Damasceno, Alfredo; Damasceno, Benito Pereira; Cendes, Fernando

    2016-05-01

    MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Forty-nine relapsing-remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue. © The Author(s), 2015.

  18. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  19. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease

    International Nuclear Information System (INIS)

    Tanaka, Yasuhiro; Meguro, Kenichi; Yamaguchi, Satoshi

    2003-01-01

    Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D 2 receptor density in Alzheimer's disease (AD). Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [ 11 C]raclopride (D 2 antagonist). The uptake of [ 11 C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD. (author)

  20. KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

    Directory of Open Access Journals (Sweden)

    M. Belén Pérez-Ramírez

    2015-01-01

    Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

  1. Impulsivity in Parkinson’s Disease Is Associated With Alterations in Affective and Sensorimotor Striatal Networks

    Directory of Open Access Journals (Sweden)

    Marit F. L. Ruitenberg

    2018-04-01

    Full Text Available A subset of patients with Parkinson’s disease (PD experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD.

  2. Levodopa administration modulates striatal processing of punishment-associated items in healthy participants.

    Science.gov (United States)

    Wittmann, Bianca C; D'Esposito, Mark

    2015-01-01

    Appetitive and aversive processes share a number of features such as their relevance for action and learning. On a neural level, reward and its predictors are associated with increased firing of dopaminergic neurons, whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission. Recent data indicate, however, that the dopaminergic system also responds to aversive stimuli and associated actions. In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans. Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks. Levodopa administration increased striatal activations for cues presented in punishment blocks. In an interaction with individual personality scores, levodopa also enhanced striatal activation for punishment-predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension. These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation. These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum, suggesting an optimal level of dopamine release for motivational processing.

  3. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    Science.gov (United States)

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  4. Phasic dopamine release drives rapid activation of striatal D2-receptors

    Science.gov (United States)

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  5. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  6. Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

    Science.gov (United States)

    Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

    2015-02-01

    Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Interaction between striatal volume and DAT1 polymorphism predicts working memory development during adolescence

    Directory of Open Access Journals (Sweden)

    F. Nemmi

    2018-04-01

    Full Text Available There is considerable inter-individual variability in the rate at which working memory (WM develops during childhood and adolescence, but the neural and genetic basis for these differences are poorly understood. Dopamine-related genes, striatal activation and morphology have been associated with increased WM capacity after training. Here we tested the hypothesis that these factors would also explain some of the inter-individual differences in the rate of WM development.We measured WM performance in 487 healthy subjects twice: at age 14 and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of five single nucleotide polymorphisms (SNPs in or close to the dopamine genes DRD2, DAT-1 and COMT, which have previously been associated with gains in WM after WM training. We then analyzed which biological factors predicted the rate of increase in WM between ages 14 and 19.We found a significant interaction between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC heterozygotes with a larger putamen at age 14 showed greater WM improvement at age 19.The effect of the DAT1 polymorphism on WM development was exerted in interaction with striatal morphology. These results suggest that development of WM partially share neuro-physiological mechanism with training-induced plasticity. Keywords: Working memory, Development, Dopamine, Striatum, DAT-1, rs40184

  8. Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

    Science.gov (United States)

    Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

    2016-04-01

    Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

  9. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  10. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  11. Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study

    Directory of Open Access Journals (Sweden)

    Pitcher Toni L

    2012-08-01

    Full Text Available Abstract Background The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease (PD is still poorly understood. Methods High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Results Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001 and putamen volumes by 8.1% (p = 0.025. PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Conclusion Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.

  12. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    Science.gov (United States)

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

  13. Perineuronal nets play a role in regulating striatal function in the mouse.

    Directory of Open Access Journals (Sweden)

    Hyunchul Lee

    Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  14. Perineuronal nets play a role in regulating striatal function in the mouse.

    Science.gov (United States)

    Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu

    2012-01-01

    The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  15. Narrar la historia: la internacionalización de las ideas en las portadas de Punch-Puk-Caras y Caretas

    OpenAIRE

    Díaz Juárez, María Virginia

    2017-01-01

    Esta investigación tiene por objeto el estudio de la caricatura como género de opinión en la revista inglesa Punch, la estadounidense Puck y la uruguaya Caras y Caretas. Si bien pertenecen a distintos países, las tres fueron fundadas durante el siglo XIX. El trabajo presenta una aproximación a cómo las distintas publicaciones plasman los acontecimientos y personajes de la época por medio de la caricatura. Existe un gran valor testimonial en ellas que permite conocer la Historia desde otro lug...

  16. Contact problem on indentation of an elastic half-plane with an inhomogeneous coating by a flat punch in the presence of tangential stresses on a surface

    Science.gov (United States)

    Volkov, Sergei S.; Vasiliev, Andrey S.; Aizikovich, Sergei M.; Sadyrin, Evgeniy V.

    2018-05-01

    Indentation of an elastic half-space with functionally graded coating by a rigid flat punch is studied. The half-plane is additionally subjected to distributed tangential stresses. Tangential stresses are represented in a form of Fourier series. The problem is reduced to the solution of two dual integral equations over even and odd functions describing distribution of unknown normal contact stresses. The solutions of these dual integral equations are constructed by the bilateral asymptotic method. Approximated analytical expressions for contact normal stresses are provided.

  17. Numerical development of a new correlation between biaxial fracture strain and material fracture toughness for small punch test

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pradeep [Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India); Dutta, B.K., E-mail: bijon.dutta@gmail.com [Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India); Chattopadhyay, J. [Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India); Reactor Safety Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2017-04-01

    The miniaturized specimens are used to determine mechanical properties of the materials, such as yield stress, ultimate stress, fracture toughness etc. Use of such specimens is essential whenever limited quantity of material is available for testing, such as aged/irradiated materials. The miniaturized small punch test (SPT) is a technique which is widely used to determine change in mechanical properties of the materials. Various empirical correlations are proposed in the literature to determine the value of fracture toughness (J{sub IC}) using this technique. bi-axial fracture strain is determined using SPT tests. This parameter is then used to determine J{sub IC} using available empirical correlations. The correlations between J{sub IC} and biaxial fracture strain quoted in the literature are based on experimental data acquired for large number of materials. There are number of such correlations available in the literature, which are generally not in agreement with each other. In the present work, an attempt has been made to determine the correlation between biaxial fracture strain (ε{sub qf}) and crack initiation toughness (J{sub i}) numerically. About one hundred materials are digitally generated by varying yield stress, ultimate stress, hardening coefficient and Gurson parameters. Such set of each material is then used to analyze a SPT specimen and a standard TPB specimen. Analysis of SPT specimen generated biaxial fracture strain (ε{sub qf}) and analysis of TPB specimen generated value of J{sub i}. A graph is then plotted between these two parameters for all the digitally generated materials. The best fit straight line determines the correlation. It has been also observed that it is possible to have variation in J{sub i} for the same value of biaxial fracture strain (ε{sub qf}) within a limit. Such variation in the value of J{sub i} has been also ascertained using the graph. Experimental SPT data acquired earlier for three materials were then used to get J

  18. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

    NARCIS (Netherlands)

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with

  19. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease

    NARCIS (Netherlands)

    Antonini, A; Leenders, KL; Vontobel, P; Maguire, RP; Missimer, J; Psylla, M; Gunther, [No Value

    1997-01-01

    We used PET with the tracers [F-18]fluorodeoxyglucose (FDG), [F-18]fluorodopa (FDOPA) and [C-11]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D-2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's

  20. A case of Cotard syndrome: (123)I-IBZM SPECT imaging of striatal D(2) receptor binding.

    Science.gov (United States)

    De Risio, Sergio; De Rossi, Giuseppe; Sarchiapone, Marco; Camardese, Giovanni; Carli, Vladimir; Cuomo, Chiara; Satta, Maria Antonietta; Di Giuda, Daniela

    2004-01-15

    A case of 'dèlire de nègation' that suddenly appeared in a 43-year-old male is presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO-SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2) receptor binding that further decreased after treatment.

  1. Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease.

    Science.gov (United States)

    Ciucci, Michelle R; Schaser, Allison J; Russell, John A

    2013-09-01

    Unilateral lesions to the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) lead to force and timing deficits during a complex licking task. We hypothesized that training targeting tongue force generation during licking would improve timing and force measures and also lead to striatal dopamine sparing. Nine month-old male Fisher344/Brown Norway rats were used in this experiment. Sixteen rats were in the control condition and received tongue exercise (n=8) or no exercise (n=8). Fourteen rats were in the 6-OHDA lesion condition and underwent tongue exercise (n=7) and or no exercise (n=7). Following 4 weeks of training and post-training measures, all animals underwent bilateral stimulation of the hypoglossal nerves to measure muscle contractile properties and were then transcardially perfused and brain tissues collected for immunohistochemistry to examine striatal dopamine content. Results demonstrated that exercise animals performed better for maximal force, average force, and press rate than their no-exercise counterparts, and the 6-OHDA animals that underwent exercise performed as well as the Control No Exercise group. Interestingly, there were no group differences for tetanic muscle force, despite behavioral recovery of forces. Additionally, behavioral and neurochemical analyses indicate that there were no differences in striatal dopamine. Thus, targeted exercise can improve tongue force and timing deficits related to 6-OHDA lesions and this exercise likely has a central, versus peripheral (muscle strength) mechanism. However, this mechanism is not related to sparing of striatal dopamine content. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W. (Brookhaven National Lab., Upton, NY (United States))

    1992-03-01

    An {sup 123}I labeled cocaine analog, 4'-({sup 123}I)iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author).

  3. Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

    Science.gov (United States)

    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

    Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include

  4. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-01-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  5. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  6. Characterization of a 14Cr ODS steel by means of small punch and uniaxial testing with regard to creep and fatigue at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Bruchhausen, M., E-mail: matthias.bruchhausen@ec.europa.eu [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, 1755 ZG Petten (Netherlands); Turba, K. [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, 1755 ZG Petten (Netherlands); Lund University, Division of Materials Engineering, P.O. Box 118, SE-221 00 Lund (Sweden); Haan, F. de; Hähner, P.; Austin, T. [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, 1755 ZG Petten (Netherlands); Carlan, Y. de [CEA, DEN, Service de Recherches Métallurgiques Appliquées, 91191 Gif-sur-Yvette (France)

    2014-01-15

    A 14Cr ODS steel was characterized at elevated temperatures with regard to its behavior in small punch and uniaxial creep tests and in low cycle fatigue tests. A comparison of small punch and uniaxial creep tests at 650 °C revealed a strong anisotropy of the material when strained parallel and perpendicular to the extrusion direction with rupture times being several orders of magnitude lower for the perpendicular direction. The stress-rupture and Larson–Miller plots show a very large scatter of the creep data. This scatter is strongly reduced when rupture time is plotted against minimum deflection rate or minimum creep rate (Monkman–Grant plot). Fatigue tests have been carried out at 650 °C and 750 °C. The alloy is cyclically very stable with practically no hardening/softening. Results from the tests at both temperatures can be described by a common power law. An increase in the test temperature has little influence on the fatigue ductility exponent. For a given total strain level, the fatigue life of the alloy is reduced with increasing temperature.

  7. Studying signal collection in the punch-through protection area of a silicon micro-strip sensor using a micro-focused X-ray beam

    CERN Document Server

    Poley, Anne-luise; The ATLAS collaboration

    2018-01-01

    For the Phase-II Upgrade of the ATLAS detector, a new, all-silicon tracker will be constructed in order to cope with the increased track density and radiation level of the High-Luminosity Large Hadron Collider. While silicon strip sensors are designed to minimise the fraction of dead material and maximise the active area of a sensor, concessions must be made to the requirements of operating a sensor in a particle physics detector. Sensor geometry features like the punch-through protection deviate from the standard sensor architecture and thereby affect the charge collection in that area. In order to study the signal collection of silicon strip sensors over their punch-through-protection area, ATLAS silicon strip sensors were scanned with a micro-focused X-ray beam at the Diamond Light Source. Due to the highly focused X-ray beam ($\\unit[2\\times3]{\\upmu\\text{m}}^2$) and the short average path length of an electron after interaction with an X-ray photon ($\\unit[\\leq2]{\\upmu\\text{m}}$), local signal collection i...

  8. Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons.

    Science.gov (United States)

    Winland, Carissa D; Welsh, Nora; Sepulveda-Rodriguez, Alberto; Vicini, Stefano; Maguire-Zeiss, Kathleen A

    2017-11-01

    Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca 2+ ] i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca 2+ ] i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca 2+ ] i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca 2+ ] i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus and a non-vocal learner bird (Colinus virginianus

    Directory of Open Access Journals (Sweden)

    Elena eGarcia-Calero

    2013-12-01

    Full Text Available Striatal projecting neurons, known as medium spiny neurons (MSNs, segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+ MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird: the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order and the non-vocal learner bird quail (representative of galliformes order. We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail, but also between close vocal learner bird families.

  10. Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease

    International Nuclear Information System (INIS)

    Spiegel, J.; Fassbender, K.; Dillmann, U.; Hellwig, D.; Samnick, S.; Moellers, M.-O.; Kirsch, C.-M.; Jost, W.

    2007-01-01

    In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I- 123 ]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p 0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor. (author)

  11. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior.

    Science.gov (United States)

    O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry; Calakos, Nicole

    2017-09-05

    Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

  12. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    DEFF Research Database (Denmark)

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  13. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

    Science.gov (United States)

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-10-11

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

  14. Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

    Science.gov (United States)

    Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

    2017-12-13

    A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

  15. Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington's disease.

    Science.gov (United States)

    Buren, Caodu; Parsons, Matthew P; Smith-Dijak, Amy; Raymond, Lynn A

    2016-03-01

    Huntington's disease (HD) is a genetically inherited neurodegenerative disease caused by a mutation in the gene encoding the huntingtin protein. This mutation results in progressive cell death that is particularly striking in the striatum. Recent evidence indicates that early HD is initially a disease of the synapse, in which subtle alterations in synaptic neurotransmission, particularly at the cortico-striatal (C-S) synapse, can be detected well in advance of cell death. Here, we used a cell culture model in which striatal neurons are co-cultured with cortical neurons, and monitored the development of C-S connectivity up to 21days in vitro (DIV) in cells cultured from either the YAC128 mouse model of HD or the background strain, FVB/N (wild-type; WT) mice. Our data demonstrate that while C-S connectivity in WT co-cultures develops rapidly and continuously from DIV 7 to 21, YAC128 C-S connectivity shows no significant growth from DIV 14 onward. Morphological and electrophysiological data suggest that a combination of pre- and postsynaptic mechanisms contribute to this effect, including a reduction in both the postsynaptic dendritic arborization and the size and replenishment rate of the presynaptic readily releasable pool of excitatory vesicles. Moreover, a chimeric culture strategy confirmed that the most robust impairment in C-S connectivity was only observed when mutant huntingtin was expressed both pre- and postsynaptically. In all, our data demonstrate a progressive HD synaptic phenotype in this co-culture system that may be exploited as a platform for identifying promising therapeutic strategies to prevent early HD-associated synaptopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

    Science.gov (United States)

    Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

    2014-09-01

    Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  17. Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

    Science.gov (United States)

    Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

    2016-02-01

    Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

  18. Behavioral control by striatal adenosine A2A -dopamine D2 receptor heteromers.

    Science.gov (United States)

    Taura, J; Valle-León, M; Sahlholm, K; Watanabe, M; Van Craenenbroeck, K; Fernández-Dueñas, V; Ferré, S; Ciruela, F

    2018-04-01

    G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes that include molecularly different GPCR (ie, GPCR heteromers), which endow them with singular functional and pharmacological characteristics. The relative expression of GPCR heteromers remains a matter of intense debate. Recent studies support that adenosine A 2A receptors (A 2A R) and dopamine D 2 receptors (D 2 R) predominantly form A 2A R-D 2 R heteromers in the striatum. The aim of the present study was evaluating the behavioral effects of pharmacological manipulation and genetic blockade of A 2A R and D 2 R within the frame of such a predominant striatal heteromeric population. First, in order to avoid possible strain-related differences, a new D 2 R-deficient mouse with the same genetic background (CD-1) than the A 2A R knock-out mouse was generated. Locomotor activity, pre-pulse inhibition (PPI) and drug-induced catalepsy were then evaluated in wild-type, A 2A R and D 2 R knock-out mice, with and without the concomitant administration of either the D 2 R agonist sumanirole or the A 2A R antagonist SCH442416. SCH442416-mediated locomotor effects were demonstrated to be dependent on D 2 R signaling. Similarly, a significant dependence on A 2A R signaling was observed for PPI and for haloperidol-induced catalepsy. The results could be explained by the existence of one main population of striatal postsynaptic A 2A R-D 2 R heteromers, which may constitute a relevant target for the treatment of Parkinson's disease and other neuropsychiatric disorders. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  19. Altered effect of dopamine transporter 3'UTR VNTR genotype on prefrontal and striatal function in schizophrenia.

    Science.gov (United States)

    Prata, Diana P; Mechelli, Andrea; Picchioni, Marco M; Fu, Cynthia H Y; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Murray, Robin M; Collier, David A; McGuire, Philip

    2009-11-01

    The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Case-control study. Psychiatric research center. Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia

  20. Cue-induced striatal dopamine release in Parkinson's disease-associated impulsive-compulsive behaviours.

    Science.gov (United States)

    O'Sullivan, Sean S; Wu, Kit; Politis, Marios; Lawrence, Andrew D; Evans, Andrew H; Bose, Subrata K; Djamshidian, Atbin; Lees, Andrew J; Piccini, Paola

    2011-04-01

    Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive

  1. Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.

    Science.gov (United States)

    Balsters, Joshua H; Mantini, Dante; Wenderoth, Nicole

    2018-04-15

    Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss.

    Science.gov (United States)

    Baldo, Brian A; Hanlon, Erin C; Obermeyer, William; Bremer, Quentin; Paletz, Elliott; Benca, Ruth M

    2013-12-01

    Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

  3. 2D CFD description of the kinematic effects of movable inlet and outlet die wall transport motion and punch shape geometry on the dynamics of viscous flow during ECAE through Segal 2θ-dies for a range of channel angles

    Directory of Open Access Journals (Sweden)

    Alexander V. Perig

    2017-11-01

    Full Text Available Minimization of the dead zone (DZA in the process of material forming is a materials science problem. Geometric and kinematic approaches to the minimization of the DZA during Equal Channel Angular Extrusion (ECAE have been proposed, developed, analyzed, and documented. The present article is focused on a 2D Computational Fluid Dynamics (CFD description of the kinematic effects of punch shape geometry and inlet (IDW and outlet (ODW die wall motion on the DZA during ECAE of Viscous Incompressible Continuum (VIC through a Segal 2θ-die for a range of channel angles 60° ≤ 2θ ≤ 135°. Due attention has been given to the independent alternating transport motions of the IDW and ODW. Punch shape geometry and the kinematic modes of IDW and ODW motions for DZA minimization have been determined with a numerical solution of the boundary value problem for the Navier-Stokes equations in curl transfer form for VIC. Experimental verification was accomplished with an introduction of initial circular gridlines-based physical simulation techniques. For the first time, experimental verification of CFD-derived results was made through an additional superposition of empirically-derived digital photos with deformed elliptical gridlines in the channel intersection deformation zones and correspondent 2D numerical plots with CFD-derived flow lines and full flow velocities. An empirical DZA localization was experimentally determined as the location of minimally-deformed near circular markers. The computational DZA localization was numerically determined as a flow-lines-free zone (the first hypothesis or as a zone with near-zero values of full flow velocities (the second hypothesis. The relative DZA was estimated as a ratio of the measured DZA with respect to the area of the deformation zone in the channel intersection region. A good agreement was obtained between DZA values obtained with the first hypothesis and experimental results.

  4. Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC mouse

    Directory of Open Access Journals (Sweden)

    Belknap John

    2010-10-01

    Full Text Available Abstract Background The current study focused on the extent genetic diversity within a species (Mus musculus affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS formed from the same eight inbred strains that have been used to create the collaborative cross (CC. The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6 × DBA/2J (D2 F2 intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA. Results Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F2 modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes. Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. Conclusions Despite the marked

  5. Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-10-15

    Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

  6. No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [I-123]FP-CIT (DaTSCAN) and SPECT

    NARCIS (Netherlands)

    Thomsen, Gerda; Knudsen, Gitte Moos; Jensen, Peter S.; Ziebell, Morten; Holst, Klaus K.; Asenbaum, Susanne; Booij, Jan; Darcourt, Jacques; Dickson, John C.; Kapucu, Ozlem L.; Nobili, Flavio; Sabri, Osama; Sera, Terez; Tatsch, Klaus; Tossici-Bolt, Livia; van Laere, Koen; Borght, Thierry Vander; Varrone, Andrea; Pagani, Marco; Pinborg, Lars Hageman

    2013-01-01

    Background: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D-2-like

  7. Cortical Regulation of Striatal Medium Spiny Neuron Dendritic Remodeling in Parkinsonism: Modulation of Glutamate Release Reverses Dopamine Depletion–Induced Dendritic Spine Loss

    OpenAIRE

    Garcia, Bonnie G.; Neely, M. Diana; Deutch, Ariel Y.

    2010-01-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if dec...

  8. Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake

    Science.gov (United States)

    Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Weng, Yi-Hsin

    2015-01-01

    Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [99mTc]-TRODAT with SPECT imaging. Procedures. A normal [99mTc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R 2 = 0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients. PMID:26366413

  9. Fully Automated Quantification of the Striatal Uptake Ratio of [(99m)Tc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake.

    Science.gov (United States)

    Fang, Yu-Hua Dean; Chiu, Shao-Chieh; Lu, Chin-Song; Yen, Tzu-Chen; Weng, Yi-Hsin

    2015-01-01

    We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [(99m)Tc]-TRODAT with SPECT imaging. A normal [(99m)Tc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R (2) = 0.84. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

  10. Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson’s Disease and the Temporal Regression of Striatal Tracer Uptake

    Directory of Open Access Journals (Sweden)

    Yu-Hua Dean Fang

    2015-01-01

    Full Text Available Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging. Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365 and nPD subjects (28 healthy controls and 33 essential tremor patients were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR. The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R2=0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

  11. A Comparative study for striatal-direct and -indirect pathway neurons to DA depletion-induced lesion in a PD rat model.

    Science.gov (United States)

    Zheng, Xuefeng; Wu, Jiajia; Zhu, Yaofeng; Chen, Si; Chen, Zhi; Chen, Tao; Huang, Ziyun; Wei, Jiayou; Li, Yanmei; Lei, Wanlong

    2018-04-16

    Striatal-direct and -indirect Pathway Neurons showed different vulnerability in basal ganglia disorders. Therefore, present study aimed to examine and compare characteristic changes of densities, protein and mRNA levels of soma, dendrites, and spines between striatal-direct and -indirect pathway neurons after DA depletion by using immunohistochemistry, Western blotting, real-time PCR and immunoelectron microscopy techniques. Experimental results showed that: 1) 6OHDA-induced DA depletion decreased the soma density of striatal-direct pathway neurons (SP+), but no significant changes for striatal-indirect pathway neurons (ENK+). 2) DA depletion resulted in a decline of dendrite density for both striatal-direct (D1+) and -indirect (D2+) pathway neurons, and D2+ dendritic density declined more obviously. At the ultrastructure level, the densities of D1+ and D2+ dendritic spines reduced in the 6OHDA groups compared with their control groups, but the density of D2+ dendritic spines reduced more significant than that of D1. 3) Striatal DA depletion down-regulated protein and mRNA expression levels of SP and D1, on the contrary, ENK and D2 protein and mRNA levels of indirect pathway neurons were up-regulated significantly. Present results suggested that indirect pathway neurons be more sensitive to 6OHDA-induced DA depletion. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Experimental Investigation on Mechanical and Thermal Properties of Marble Dust Particulate-Filled Needle-Punched Nonwoven Jute Fiber/Epoxy Composite

    Science.gov (United States)

    Sharma, Ankush; Patnaik, Amar

    2018-03-01

    The present investigation evaluates the effects of waste marble dust, collected from the marble industries of Rajasthan, India, on the mechanical properties of needle-punched nonwoven jute fiber/epoxy composites. The composites with varying filler contents from 0 wt.% to 30 wt.% marble dust were prepared using vacuum-assisted resin-transfer molding. The influences of the filler material on the void content, tensile strength, flexural strength, interlaminar shear strength (ILSS), and thermal conductivity of the hybrid composites have been analyzed experimentally under the desired optimal conditions. The addition of marble dust up to 30 wt.% increases the flexural strength, ILSS, and thermal conductivity, but decreases the tensile strength. Subsequently, the fractured surfaces of the particulate-filled jute/epoxy composites were analyzed microstructurally by field-emission scanning electron microscopy.

  13. Raman chemical mapping of magnesium stearate delivered by a punch-face lubrication system on the surface of placebo and active tablets.

    Science.gov (United States)

    Šašiċ, Slobodan; Ojakovo, Peter; Warman, Martin; Sanghvi, Tapan

    2013-09-01

    Raman chemical mapping was used to determine the distribution of magnesium stearate, a lubricant, on the surface of tablets. The lubrication was carried out via a punch-face lubrication system with different spraying rates applied on placebo and active-containing tablets. Principal component analysis was used for decomposing the matrix of Raman mapping spectra. Some of the loadings associated with minuscule variation in the data significantly overlap with the Raman spectrum of magnesium stearate in placebo tablets and allow for imaging the domains of magnesium stearate via corresponding scores. Despite the negligible variation accounted for by respective principal components, the score images seem reliable as demonstrated through thresholding the one-dimensional representation and the spectra of the hot pixels that show a weak but perceivable magnesium stearate band at 1295 cm(-1). The same approach was applied on the active formulation, but no magnesium stearate was identified, presumably due to overwhelming concentration and spectral contribution of the active pharmaceutical ingredient.

  14. Selective increase of auditory cortico-striatal coherence during auditory-cued Go/NoGo discrimination learning.

    Directory of Open Access Journals (Sweden)

    Andreas L. Schulz

    2016-01-01

    Full Text Available Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcementmodels, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functionalcoupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed.

  15. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

    DEFF Research Database (Denmark)

    Storgaard, J; Kornblit, B T; Zimmer, J

    2000-01-01

    of lactate dehydrogenase in the medium and glutamic acid decarboxylase in tissue homogenates. 3-NPA toxicity (25-100 microM in 5 mM glucose, 24-48 h) appeared to be highly dependent on culture medium glucose levels. 3-NPA treatment caused also a dose-dependent lactate increase, reaching a maximum......Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay...... of threefold increase above control at 100 microM. Both a high dose of glutamate (5 mM) and glutamate uptake blockade by dl-threo-beta-hydroxyaspartate potentiated 3-NPA neurotoxicity in corticostriatal slice cultures. Furthermore, striatum from corticostriatal cocultures was more sensitive to 3-NPA than...

  16. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Hansen, Freja Herborg; Sørensen, Gunnar

    2013-01-01

    believed to bind synaptic scaffolding proteins, but its functional significance is uncertain. Here we demonstrate that two different dopamine transporter knock-in mice with disrupted PDZ-binding motifs (dopamine transporter-AAA and dopamine transporter+Ala) are characterized by dramatic loss of dopamine......The dopamine transporter mediates reuptake of dopamine from the synaptic cleft. The cellular mechanisms controlling dopamine transporter levels in striatal nerve terminals remain poorly understood. The dopamine transporters contain a C-terminal PDZ (PSD-95/Discs-large/ZO-1) domain-binding sequence...... transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization...

  17. Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

    Science.gov (United States)

    Nazari, Qand Agha; Kume, Toshiaki; Izuo, Naotaka; Takada-Takatori, Yuki; Imaizumi, Atsushi; Hashimoto, Tadashi; Izumi, Yasuhiko; Akaike, Akinori

    2013-01-01

    Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

  18. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

    1999-07-01

    Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

  19. In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography

    International Nuclear Information System (INIS)

    Aquilonius, S.-M.; Bergstroem, K.; Eckernaes, S.-Aa.; Leenders, K.L.; Hartvig, P.; Lundquist, H.; Antoni, G.; Gee, A.; Rimland, A.; Uhlin, J.; Langstroem, B.

    1987-01-01

    In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11 C-nomifensine was administered i.v. in trace amounts (10-50 μg) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the timecourse of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11 C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11 C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11 C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11 C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11 C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11 C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo. (author)

  20. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho [University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Seppaenen, Marko [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland); Noponen, Tommi [University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland)

    2014-10-15

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [{sup 123}I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  1. Individual differences in the motivation to communicate relate to levels of midbrain and striatal catecholamine markers in male European starlings

    OpenAIRE

    Heimovics, Sarah A; Salvante, Katrina G; Sockman, Keith W; Riters, Lauren V

    2011-01-01

    Individuals display dramatic differences in social communication even within similar social contexts. Across vertebrates dopaminergic projections from the ventral tegmental area (VTA) and midbrain central gray (GCt) strongly influence motivated, reward-directed behaviors. Norepinephrine is also rich in these areas and may alter dopamine neuronal activity. The present study was designed to provide insight into the roles of dopamine and norepinephrine in VTA and GCt and their efferent striatal ...

  2. Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.

    Science.gov (United States)

    Taurisano, Paolo; Romano, Raffaella; Mancini, Marina; Giorgio, Annabella Di; Antonucci, Linda A; Fazio, Leonardo; Rampino, Antonio; Quarto, Tiziana; Gelao, Barbara; Porcelli, Annamaria; Papazacharias, Apostolos; Ursini, Gianluca; Caforio, Grazia; Masellis, Rita; Niccoli-Asabella, Artor; Todarello, Orlando; Popolizio, Teresa; Rubini, Giuseppe; Blasi, Giuseppe; Bertolino, Alessandro

    2014-01-01

    "Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.

  3. [18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease.

    Science.gov (United States)

    Stark, Adam J; Smith, Christopher T; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Donahue, Manus J; Kessler, Robert M; Deutch, Ariel Y; Zald, David H; Claassen, Daniel O

    2018-01-01

    Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18 F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

  4. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    Science.gov (United States)

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  5. Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence.Methamphetamine users and non-user controls (n = 18 per group completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride.The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008, but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622. The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010, but not methamphetamine users (r = 0.281, p = 0.258, and the group-wise interaction was significant (p = 0.030.These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.

  6. Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion.

    Science.gov (United States)

    Gomide, Vânia C; Chadi, Gerson

    2004-01-01

    Pregnant Wistar rats received a hyperproteic liquid diet containing 37.5% ethanol-derived calories during gestation. Isocaloric amount of liquid diet, with maltose-dextrin substituted for ethanol, was given to control pair-fed dams. Offsprings were allowed to survive until 24 months of age. A set of aged female offsprings of both control diet and ethanol diet groups was registered for spontaneous motor activity, by means of an infrared motion sensor activity monitor, or for apomorphine-induced rotational behavior, while another lot of male offsprings was submitted to an unilateral striatal small mechanical lesion by a needle, 6 days before rotational recordings. Prenatal ethanol did not alter spontaneous motor parameters like resting time as well as the events of small and large movements in the aged offsprings. Bilateral circling behavior was already increased 5 min after apomorphine in the unlesioned offsprings of both the control and ethanol diet groups. However, it lasted more elevated for 45- to 75-min time intervals in the gestational ethanol-exposed offsprings, while decreasing faster in the control offsprings. Apomorphine triggered a strong and sustained elevation of contraversive turns in the striatal-lesioned 24-month-old offsprings of the ethanol group, but only a small and transient elevation was seen in the offsprings of the control diet group. Astroglial and microglial reactions were seen surrounding the striatal needle track lesion. Microdensitometric image analysis demonstrated no differences in the levels of tyrosine hydroxylase immunoreactivity in the striatum of 24-month-old unlesioned and lesioned offsprings of control and alcohol diet groups. The results suggest that ethanol exposure during gestation may alter the sensitivity of dopamine receptor in aged offsprings, which is augmented by even a small striatal lesion.

  7. Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.

    Science.gov (United States)

    Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre

    2017-12-15

    Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D 1 or D 2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D 2 than on D 1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine

  8. Brain Pharmacokinetics and the Pharmacological Effects on Striatal Neurotransmitter Levels of Pueraria lobata Isoflavonoids in Rat

    Directory of Open Access Journals (Sweden)

    Bingxin Xiao

    2017-09-01

    Full Text Available Isoflavonoids are putatively active components of Pueraria lobata and has been demonstrated prominent neuro-protection effect against cerebrovascular disorders, hypertension or Parkinson's disease (PD. However, the molecular basis for the beneficial effect of Pueraria lobata on nervous systems has not been well revealed. The present study aims to assess striatum exposure to main active isoflavonoids and changes of striatal extracellular neurotransmitters levels in rat brain after intravenous administration of Pueraria lobata isoflavonoids extracts (PLF, to further elucidate its' substantial bases for neuro activities. Fifteen rats were divided into 3 groups (five rats in each group to receive a dose of PLF at 80 or 160 mg/kg or normal saline (vehicle, respectively. An LC-MS/MS method was employed to determine the concentrations of five main isoflavonoids and multiple neurotransmitters in microdialysate from striatal extracellular fluid (ECF of the rats. The exposed quantities of puerarin (PU, 3′-methoxypuerarin (MPU, daidzein-8-C-apiosyl-(1-6-glucoside (DAC, and 3′-hydroxypuerarin (HPU in striatum were dose-dependent. The content of daidzein (DAZ was too low to be detected in all dialysate samples through the experiment. Optimal dose PLF (80 mg/kg promoted DA metabolism and inhibited 5-HT metabolism. No obvious change in the level of GLu was determined. The concentration of GABA presented a temporary decline firstly and then a gradual uptrend followed by a further downtrend. Higher dose (160 mg/kg PLF could enhance the metabolism of both DA and 5-HT, and lower the extracellular level of GLu, without changing GABA concentrations, which might result in alleviation on excitatory toxicity under conditions, such as ischemia. The results infer that different dose of PLF should be chosen to achieve appropriate neurochemical modulation effects under conditions, such as hypertension or ischemia/stroke. These findings may significantly contribute to a

  9. Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

    Science.gov (United States)

    Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

    2013-06-01

    Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Exploring personality traits related to dopamine D2/3 receptor availability in striatal subregions of humans.

    Science.gov (United States)

    Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

    2016-04-01

    While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  11. Revisiting the 'self-medication' hypothesis in light of the new data linking low striatal dopamine to comorbid addictive behavior.

    Science.gov (United States)

    Awad, A George; Voruganti, Lakshmi L N P

    2015-06-01

    Persons with schizophrenia are at a high risk, almost 4.6 times more likely, of having drug abuse problems than persons without psychiatric illness. Among the influential proposals to explain such a high comorbidity rate, the 'self-medication hypothesis' proposed that persons with schizophrenia take to drugs in an effort to cope with the illness and medication side effects. In support of the self-medication hypothesis, data from our earlier clinical study confirmed the strong association between neuroleptic dysphoria and negative subjective responses and comorbid drug abuse. Though dopamine has been consistently suspected as one of the major culprits for the development of neuroleptic dysphoria, it is only recently our neuroimaging studies correlated the emergence of neuroleptic dysphoria to the low level of striatal dopamine functioning. Similarly, more evidence has recently emerged linking low striatal dopamine with the development of vulnerability for drug addictive states in schizophrenia. The convergence of evidence from both the dysphoria and comorbidity research, implicating the role of low striatal dopamine in both conditions, has led us to propose that the person with schizophrenia who develops dysphoria and comorbid addictive disorder is likely to be one and the same.

  12. Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration

    Science.gov (United States)

    Bhalla, Upinder S.; Hellgren Kotaleski, Jeanette

    2016-01-01

    In reward learning, the integration of NMDA-dependent calcium and dopamine by striatal projection neurons leads to potentiation of corticostriatal synapses through CaMKII/PP1 signaling. In order to elicit the CaMKII/PP1-dependent response, the calcium and dopamine inputs should arrive in temporal proximity and must follow a specific (dopamine after calcium) order. However, little is known about the cellular mechanism which enforces these temporal constraints on the signal integration. In this computational study, we propose that these temporal requirements emerge as a result of the coordinated signaling via two striatal phosphoproteins, DARPP-32 and ARPP-21. Specifically, DARPP-32-mediated signaling could implement an input-interval dependent gating function, via transient PP1 inhibition, thus enforcing the requirement for temporal proximity. Furthermore, ARPP-21 signaling could impose the additional input-order requirement of calcium and dopamine, due to its Ca2+/calmodulin sequestering property when dopamine arrives first. This highlights the possible role of phosphoproteins in the temporal aspects of striatal signal transduction. PMID:27584878

  13. Increased ventral-striatal activity during monetary decision making is a marker of problem poker gambling severity.

    Science.gov (United States)

    Brevers, Damien; Noël, Xavier; He, Qinghua; Melrose, James A; Bechara, Antoine

    2016-05-01

    The aim of this study was to examine the impact of different neural systems on monetary decision making in frequent poker gamblers, who vary in their degree of problem gambling. Fifteen frequent poker players, ranging from non-problem to high-problem gambling, and 15 non-gambler controls were scanned using functional magnetic resonance imaging (fMRI) while performing the Iowa Gambling Task (IGT). During IGT deck selection, between-group fMRI analyses showed that frequent poker gamblers exhibited higher ventral-striatal but lower dorsolateral prefrontal and orbitofrontal activations as compared with controls. Moreover, using functional connectivity analyses, we observed higher ventral-striatal connectivity in poker players, and in regions involved in attentional/motor control (posterior cingulate), visual (occipital gyrus) and auditory (temporal gyrus) processing. In poker gamblers, scores of problem gambling severity were positively associated with ventral-striatal activations and with the connectivity between the ventral-striatum seed and the occipital fusiform gyrus and the middle temporal gyrus. Present results are consistent with findings from recent brain imaging studies showing that gambling disorder is associated with heightened motivational-reward processes during monetary decision making, which may hamper one's ability to moderate his level of monetary risk taking. © 2015 Society for the Study of Addiction.

  14. 6-hydroxydopamine-induced degeneration of nigral dopamine neurons: differential effect on nigral and striatal D-1 dopamine receptors

    International Nuclear Information System (INIS)

    Porceddu, M.L.; Giorgi, O.; De Montis, G.; Mele, S.; Cocco, L.; Ongini, E.; Biggio, G.

    1987-01-01

    Dopamine-sensitive adenylate cyclase and 3 H-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of 3 H-SCH 23390 to rat nigral D-1 dopamine receptors were markedly decreased after the lesion. On the contrary, 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine pathway enhanced both adenylate cyclase activity and the density of 3 H-SCH 23390 binding sites in striatal membrane preparations. The changes in 3 H-SCH 23390 binding found in both nigral and striatal membrane preparations were associated with changes in the total number of binding sites with no modifications in their apparent affinity. The results indicate that: a) within the substantia nigra a fraction (30%) of D-1 dopamine receptors coupled to the adenylate cyclase is located on cell bodies and and/or dendrites of dopaminergic neurons; b) striatal D-1 dopamine receptors are tonically innervated by nigrostriatal afferent fibers. 24 references, 1 figure, 1 table

  15. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism

    International Nuclear Information System (INIS)

    Booij, J.; Speelman, J.DE.; Horstink, M. W.I.M.; Wolters, E.C.

    2001-01-01

    [ 123 I]FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several ''presynaptic parkinsonian'' syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [ 123 I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with ''presynaptic parkinsonism'' from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [ 123 I]FP-CIT SPET. Using [ 123 I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [ 123 I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases

  16. Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence.

    Science.gov (United States)

    Becker, Alena; Kirsch, Martina; Gerchen, Martin Fungisai; Kiefer, Falk; Kirsch, Peter

    2017-05-01

    According to prevailing neurobiological theories of addiction, altered function in neural reward circuitry is a central mechanism of alcohol dependence. Growing evidence postulates that the ventral striatum (VS), as well as areas of the prefrontal cortex, contribute to the increased incentive salience of alcohol-associated cues, diminished motivation to pursue non-drug rewards and weakened strength of inhibitory cognitive control, which are central to addiction. The present study aims to investigate the neural response and functional connectivity underlying monetary, non-drug reward processing in alcohol dependence. We utilized a reward paradigm to investigate the anticipation of monetary reward in 32 alcohol-dependent inpatients and 35 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation and connectivity. Alcohol-dependent patients showed increased activation of the VS during anticipation of monetary gain compared with healthy controls. Generalized psychophysiological interaction analyses revealed decreased functional connectivity between the VS and the dorsolateral prefrontal cortex in alcohol dependent patients relative to controls. Increased activation of the VS and reduced frontostriatal connectivity were associated with increased craving. These findings provide evidence that alcohol dependence is rather associated with disrupted integration of striatal and prefrontal processes than with a global reward anticipation deficit. © 2016 Society for the Study of Addiction.

  17. Maternal obesity caused by overnutrition exposure leads to reversal learning deficits and striatal disturbance in rats.

    Directory of Open Access Journals (Sweden)

    Ting Wu

    Full Text Available Maternal obesity caused by overnutrition during pregnancy increases susceptibility to metabolic risks in adulthood, such as obesity, insulin resistance, and type 2 diabetes; however, whether and how it affects the cognitive system associated with the brain remains elusive. Here, we report that pregnant obesity induced by exposure to excessive high fatty or highly palatable food specifically impaired reversal learning, a kind of adaptive behavior, while leaving serum metabolic metrics intact in the offspring of rats, suggesting a much earlier functional and structural defects possibly occurred in the central nervous system than in the metabolic system in the offspring born in unfavorable intrauterine nutritional environment. Mechanically, we found that above mentioned cognitive inflexibility might be associated with significant striatal disturbance including impaired dopamine homeostasis and disrupted leptin signaling in the adult offspring. These collective data add a novel perspective of understanding the adverse postnatal sequelae in central nervous system induced by developmental programming and the related molecular mechanism through which priming of risk for developmental disorders may occur during early life.

  18. Striatal-enriched Tyrosine Protein Phosphatase (STEP) in the Mechanisms of Depressive Disorders.

    Science.gov (United States)

    Kulikova, Elizabeth; Kulikov, Alexander

    2017-08-30

    Striatal-enriched tyrosine protein phosphatase (STEP) is expressed mainly in the brain. Its dysregulation is associated with Alzheimer's and Huntington's diseases, schizophrenia, fragile X syndrome, drug abuse and stroke/ischemia. However, an association between STEP and depressive disorders is still obscure. The review discusses the theoretical foundations and experimental facts concerning possible relationship between STEP dysregulation and depression risk. STEP dephosphorylates and inactivates several key neuronal signaling proteins such as extracellular signal-regulating kinase 1 and 2 (ERK1/2), stress activated protein kinases p38, the Src family tyrosine kinases Fyn, Pyk2, NMDA and AMPA glutamate receptors. The inactivation of these proteins decreases the expression of brain derived neurotrophic factor (BDNF) necessary for neurogenesis and neuronal survival. The deficit of BDNF results in progressive degeneration of neurons in the hippocampus and cortex and increases depression risk. At the same time, a STEP inhibitor, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), increases BDNF expression in the hippocampus and attenuated the depressivelike behavior in mice. Thus, STEP is involved in the mechanism of depressive disorders and it is a promising molecular target for atypical antidepressant drugs of new generation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. The 5-HT2A receptor antagonist M100907 produces antiparkinsonian effects and decreases striatal glutamate

    Directory of Open Access Journals (Sweden)

    Twum eAnsah

    2011-06-01

    Full Text Available 5-HT plays a regulatory role in voluntary movements of the basal ganglia and have a major impact on disorders of the basal ganglia such as Parkinson’s disease (PD. Clinical studies have suggested that 5-HT2 receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT2A receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT2A receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT2A receptors may represent a novel therapeutic target for the motor symptoms of Parkinson’s disease.

  20. Dissociable contribution of prefrontal and striatal dopaminergic genes to learning in economic games.

    Science.gov (United States)

    Set, Eric; Saez, Ignacio; Zhu, Lusha; Houser, Daniel E; Myung, Noah; Zhong, Songfa; Ebstein, Richard P; Chew, Soo Hong; Hsu, Ming

    2014-07-01

    Game theory describes strategic interactions where success of players' actions depends on those of coplayers. In humans, substantial progress has been made at the neural level in characterizing the dopaminergic and frontostriatal mechanisms mediating such behavior. Here we combined computational modeling of strategic learning with a pathway approach to characterize association of strategic behavior with variations in the dopamine pathway. Specifically, using gene-set analysis, we systematically examined contribution of different dopamine genes to variation in a multistrategy competitive game captured by (i) the degree players anticipate and respond to actions of others (belief learning) and (ii) the speed with which such adaptations take place (learning rate). We found that variation in genes that primarily regulate prefrontal dopamine clearance--catechol-O-methyl transferase (COMT) and two isoforms of monoamine oxidase--modulated degree of belief learning across individuals. In contrast, we did not find significant association for other genes in the dopamine pathway. Furthermore, variation in genes that primarily regulate striatal dopamine function--dopamine transporter and D2 receptors--was significantly associated with the learning rate. We found that this was also the case with COMT, but not for other dopaminergic genes. Together, these findings highlight dissociable roles of frontostriatal systems in strategic learning and support the notion that genetic variation, organized along specific pathways, forms an important source of variation in complex phenotypes such as strategic behavior.

  1. Differential coding of reward and movement information in the dorsomedial striatal direct and indirect pathways.

    Science.gov (United States)

    Shin, Jung Hwan; Kim, Dohoung; Jung, Min Whan

    2018-01-26

    The direct and indirect pathways of the basal ganglia have long been thought to mediate behavioral promotion and inhibition, respectively. However, this classic dichotomous model has been recently challenged. To better understand neural processes underlying reward-based learning and movement control, we recorded from direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in the dorsomedial striatum of D1-Cre and D2-Cre mice performing a probabilistic Pavlovian conditioning task. dSPNs tend to increase activity while iSPNs decrease activity as a function of reward value, suggesting the striatum represents value in the relative activity levels of dSPNs versus iSPNs. Lick offset-related activity increase is largely dSPN selective, suggesting dSPN involvement in suppressing ongoing licking behavior. Rapid responses to negative outcome and previous reward-related responses are more frequent among iSPNs than dSPNs, suggesting stronger contributions of iSPNs to outcome-dependent behavioral adjustment. These findings provide new insights into striatal neural circuit operations.

  2. Release of [3H]-monoamines from superfused rat striatal slices by methylenedioxymethamphetamine (MDMA)

    International Nuclear Information System (INIS)

    Levin, J.A.; Schmidt, C.J.; Lovenberg, W.

    1986-01-01

    MDMA is a phenylisopropylamine which is reported to have unique behavioral effects in man. Because of its structural similarities to the amphetamines the authors have compared the effects of MDMA and two related amphetamines on the spontaneous release of tritiated dopamine (DA) and serotonin (5HT) from superfused rat striatal slices. At concentrations of 10 -7 - 10 -5 M MDMA and the serotonergic neurotoxin, p-chloroamphetamine, were equipotent releasers of [ 3 H]5HT being approximately 10x more potent than methamphetamine. However, methamphetamine was the more potent releaser of [ 3 H]DA by a factor of approximately 10x. MDMA-induced release of both [ 5 H]5HT and [ 3 H]DA was Ca 2+ -independent and inhibited by selective monoamine uptake blockers suggesting a carrier-dependent release mechanism. Synaptosomal uptake experiments with (+)[ 3 H]MDMA indicated no specific uptake of the drug further suggesting the effect of uptake blockers may be to inhibit the carrier-mediated export of amines displaced by MDMA

  3. Dopamine signaling negatively regulates striatal phosphorylation of Cdk5 at tyrosine 15 in mice.

    Directory of Open Access Journals (Sweden)

    Yukio eYamamura

    2013-02-01

    Full Text Available Striatal functions depend on the activity balance between the dopamine and glutamate neurotransmissions. Glutamate inputs activate cyclin-dependent kinase 5 (Cdk5, which inhibits postsynaptic dopamine signaling by phosphorylating DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa at Thr75 in the striatum. c-Abelson tyrosine kinase (c-Abl is known to phosphorylate Cdk5 at Tyr15 (Tyr15-Cdk5 and thereby facilitates the Cdk5 activity. We here report that Cdk5 with Tyr15 phosphorylation (Cdk5-pTyr15 is enriched in the mouse striatum, where dopaminergic stimulation inhibited phosphorylation of Tyr15-Cdk5 by acting through the D2 class dopamine receptors. Moreover, in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine mouse model, dopamine deficiency caused increased phosphorylation of both Tyr15-Cdk5 and Thr75-DARPP-32 in the striatum, which could be attenuated by administration of L-3,4-dihydroxyphenylalanine and imatinib (STI-571, a selective c-Abl inhibitor. Our results suggest a functional link of Cdk5-pTyr15 with postsynaptic dopamine and glutamate signals through the c-Abl kinase activity in the striatum.

  4. Magnetic resonance imaging (MRI to study striatal iron accumulation in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Ana Virel

    Full Text Available Abnormal accumulation of iron is observed in neurodegenerative disorders. In Parkinson's disease, an excess of iron has been demonstrated in different structures of the basal ganglia and is suggested to be involved in the pathogenesis of the disease. Using the 6-hydroxydopamine (6-OHDA rat model of Parkinson's disease, the edematous effect of 6-OHDA and its relation with striatal iron accumulation was examined utilizing in vivo magnetic resonance imaging (MRI. The results revealed that in comparison with control animals, injection of 6-OHDA into the rat striatum provoked an edematous process, visible in T2-weighted images that was accompanied by an accumulation of iron clearly detectable in T2*-weighted images. Furthermore, Prussian blue staining to detect iron in sectioned brains confirmed the existence of accumulated iron in the areas of T2* hypointensities. The presence of ED1-positive microglia in the lesioned striatum overlapped with this accumulation of iron, indicating areas of toxicity and loss of dopamine nerve fibers. Correlation analyses demonstrated a direct relation between the hyperintensities caused by the edema and the hypointensities caused by the accumulation of iron.

  5. History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine.

    Science.gov (United States)

    Oswald, Lynn M; Wand, Gary S; Kuwabara, Hiroto; Wong, Dean F; Zhu, Shijun; Brasic, James R

    2014-06-01

    Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, aged 18-29 years, underwent two consecutive 90-min positron emission tomography studies with high specific activity [(11)C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

  6. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.

    Science.gov (United States)

    Rothwell, Patrick E; Fuccillo, Marc V; Maxeiner, Stephan; Hayton, Scott J; Gokce, Ozgun; Lim, Byung Kook; Fowler, Stephen C; Malenka, Robert C; Südhof, Thomas C

    2014-07-03

    In humans, neuroligin-3 mutations are associated with autism, whereas in mice, the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse and thereby provide a plausible circuit substrate for autism pathophysiology. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Age differences in striatal delay sensitivity during intertemporal choice in healthy adults

    Directory of Open Access Journals (Sweden)

    Gregory R Samanez-Larkin

    2011-11-01

    Full Text Available Intertemporal choices are a ubiquitous class of decisions that involve selecting between outcomes available at different times in the future. We investigated the neural systems supporting intertemporal decisions in healthy younger and older adults. Using functional neuroimaging, we find that aging is associated with a shift in the brain areas that respond to delayed rewards. Although we replicate findings that brain regions associated with the mesolimbic dopamine system respond preferentially to immediate rewards, we find a separate region in the ventral striatum with very modest time dependence in older adults. Activation in this striatal region was relatively insensitive to delay in older but not younger adults. Since the dopamine system is believed to support associative learning about future rewards over time, our observed transfer of function may be due to greater experience with delayed rewards as people age. Identifying differences in the neural systems underlying these decisions may contribute to a more comprehensive model of age-related change in intertemporal choice.

  8. Familial Risk for Major Depression is Associated with Lower Striatal 5-HT4 Receptor Binding

    DEFF Research Database (Denmark)

    Madsen, Karine; Torstensen, Eva; Holst, Klaus K

    2014-01-01

    was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [(11)C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. METHODS: We studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first......-degree relatives treated for MDD. RESULTS: We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first......-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). CONCLUSIONS: Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression...

  9. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Science.gov (United States)

    Warren, Emily Booth; Aicher, Aidan Edward; Fessel, Joshua Patrick; Konradi, Christine

    2017-01-01

    Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  10. Effect of in vitro inorganic lead on dopamine release from superfused rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Minnema, D.J.; Greenland, R.D.; Michaelson, I.A.

    1986-01-01

    The effect of inorganic lead in vitro in several aspects of [ 3 H]dopamine release from superfused rat striatal synaptosomes was examined. Under conditions of spontaneous release, lead (1-30 microM) induced dopamine release in a concentration-dependent manner. The onset of the lead-induced release was delayed by approximately 15-30 sec. The magnitude of dopamine release induced by lead was increased when calcium was removed from the superfusing buffer. Lead-induced release was unaffected in the presence of putative calcium, sodium, and/or potassium channel blockers (nickel, tetrodotoxin, tetraethylammonium, respectively). Depolarization-evoked dopamine release, produced by a 1-sec exposure to 61 mM potassium, was diminished at calcium concentrations below 0.254 mM. The onset of depolarization-evoked release was essentially immediate following exposure of the synaptosomes to high potassium. The combination of lead (3 or 10 microM) with high potassium reduced the magnitude of depolarization-evoked dopamine release. This depression of depolarization-evoked release by lead was greater in the presence of 0.25 mM than 2.54 mM calcium in the superfusing buffer. These findings demonstrate multiple actions of lead on synaptosomal dopamine release. Lead can induce dopamine release by yet unidentified neuronal mechanisms independent of external calcium. Lead can also reduce depolarization-evoked dopamine release by apparent competition with calcium influx at the neuronal membrane calcium channel

  11. Study of the neural basis of striatal modulation of the jaw-opening reflex.

    Science.gov (United States)

    Barceló, Ana C; Fillipini, B; Pazo, Jorge Horacio

    2010-02-01

    Previous experimental data from this laboratory demonstrated the participation of the striatum and dopaminergic pathways in central nociceptive processing. The objective of this study was to examine the possible pathways and neural structures associated with the analgesic action of the striatum. The experiments were carried out in rats anesthetized with urethane. The jaw-opening reflex (JOR) was evoked by electrical stimulation of the tooth pulp of lower incisors and recorded in the anterior belly of the digastric muscles. Intrastriatal microinjection of apomorphine, a nonspecific dopamine agonist, reduced or abolished the JOR amplitude. Electrolytic or kainic acid lesions, unilateral to the apomorphine-injected striatum, of the globus pallidus, substantia nigra pars reticulata, subthalamic nucleus and bilateral lesion the rostroventromedial medulla (RVM), blocked the inhibition of the JOR by striatal stimulation. These findings suggest that the main output nuclei of the striatum and the RVM may be critical elements in the neural pathways mediating the inhibition of the reflex response, evoked in jaw muscles by noxious stimulation of dental pulp.

  12. Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

    Science.gov (United States)

    Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

    2016-08-01

    The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

  13. Functional role for suppression of the insular-striatal circuit in modulating interoceptive effects of alcohol.

    Science.gov (United States)

    Jaramillo, Anel A; Agan, Verda E; Makhijani, Viren H; Pedroza, Stephen; McElligott, Zoe A; Besheer, Joyce

    2017-09-27

    The insular cortex (IC) is a region proposed to modulate, in part, interoceptive states and motivated behavior. Interestingly, IC dysfunction and deficits in interoceptive processing are often found among individuals with substance-use disorders. Furthermore, the IC projects to the nucleus accumbens core (AcbC), a region known to modulate the discriminative stimulus/interoceptive effects of alcohol and other drug-related behaviors. Therefore, the goal of the present work was to investigate the possible role of the IC ➔ AcbC circuit in modulating the interoceptive effects of alcohol. Thus, we utilized a chemogenetic technique (hM4D i designer receptor activation by designer drugs) to silence neuronal activity in the IC of rats trained to discriminate alcohol (1 g/kg, IG) versus water using an operant or Pavlovian alcohol discrimination procedure. Chemogenetic silencing of the IC or IC ➔ AcbC neuronal projections resulted in potentiated sensitivity to the interoceptive effects of alcohol in both the operant and Pavlovian tasks. Together, these data provide critical evidence for the nature of the complex IC circuitry and, specifically, suppression of the insular-striatal circuit in modulating behavior under a drug stimulus control. © 2017 Society for the Study of Addiction.

  14. Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

    Directory of Open Access Journals (Sweden)

    Emily Booth Warren

    Full Text Available Mitochondrial DNA (mtDNA, the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD patients who had developed L-DOPA Induced Dyskinesia (LID, compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

  15. Q-switched YAG laser vs. punch biopsy excision for iatrogenic radiation tattoo markers--a randomized controlled trial

    DEFF Research Database (Denmark)

    Bregnhøj, A; Haedersdal, M

    2010-01-01

    Ink markers are tattooed as landmarks before radiotherapy of breast cancer with the purpose of obtaining a precise radiation field. The black tattoo spots may cause potential psychological distress for the affected women.......Ink markers are tattooed as landmarks before radiotherapy of breast cancer with the purpose of obtaining a precise radiation field. The black tattoo spots may cause potential psychological distress for the affected women....

  16. 煤层底板穿层钻孔水力冲孔技术的应用及效果考察%Coal Floor Layer of Drilling Hydraulic Punching Technology Application and Effect of Investigation

    Institute of Scientific and Technical Information of China (English)

    殷庆超; 廉有轩; 王恩营; 刘度

    2015-01-01

    End of the alley pumping wear layer drilling hydraulic punching pressure, the anti-reflection measures can effectively en-hance the permeability of coal seam, expanding radius of extraction and improve the effect of the gas extraction., on the basis of the principle of antireflection unloading hydraulic punching in for zhengzhou mining revitalization of two coal mine hydraulic punching plate wear layer, gas drainage concentration before and after the hydraulic punching, the change of coal seam permeability and the gas flow attenuation coefficient and so on.The test results show that the average single-hole gas drainage concentration is 11.02%, after hy-draulic punching is 2.14%, the anti-reflection measures of improve 4 times; Coefficient of permeability of coal seam after taking steps to improve the 39 times;The gas flow attenuation coefficient is reduced nearly 3 times.Using the method of pressure measured at the same time the mine hydraulic punching effective drainage radius to 10 m.%采用底抽巷穿层钻孔水力冲孔卸压增透措施,可以有效增强煤层的透气性、扩大抽采半径和提高瓦斯抽采效果。基于水力冲孔卸压增透原理,对郑州矿区振兴二矿突出煤层实施底板穿层水力冲孔,考察水力冲孔前后瓦斯抽放浓度、煤层透气性和瓦斯流量衰减系数等的变化。试验结果表明:单孔平均瓦斯抽放浓度在水力冲孔后为11.02%,较未采取增透措施时的2.14%,提高了4倍;煤层透气性系数在采取措施后提高了39倍;瓦斯流量衰减系数则减小了近3倍。同时运用压力法测得该