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Sample records for routine modified d2

  1. Eating routines. Embedded, value based, modifiable, and reflective.

    PubMed

    Jastran, Margaret M; Bisogni, Carole A; Sobal, Jeffery; Blake, Christine; Devine, Carol M

    2009-02-01

    Eating routines are a compelling issue because recurring eating behaviors influence nutrition and health. As non-traditional and individualized eating patterns have become more common, new ways of thinking about routine eating practices are needed. This study sought to gain conceptual understanding of working adults' eating routines. Forty-two purposively sampled US adults reported food intake and contextual details about eating episodes in qualitative 24-h dietary recalls conducted over 7 consecutive days. Using the constant comparative method, researchers analyzed interview transcripts for recurrent ways of eating that were either explicitly reported by study participants as "routines" or emergent in the data. Participants' eating routines included repetition in food consumption as well as eating context, and also involved sequences of eating episodes. Eating routines were embedded in daily schedules for work, family, and recreation. Participants maintained purposeful routines that helped balance tension between demands and values, but they modified routines as circumstances changed. Participants monitored and reflected upon their eating practices and tended to assess their practices in light of their personal identities. These findings provide conceptual insights for food choice researchers and present a perspective from which practitioners who work with individuals seeking to adopt healthful eating practices might usefully approach their tasks. PMID:18835305

  2. Eating routines: Embedded, value based, modifiable, and reflective

    PubMed Central

    Jastran, Margaret; Bisogni, Carole A.; Sobal, Jeffery; Blake, Christine; Devine, Carol M.

    2009-01-01

    Eating routines are a compelling issue because recurring eating behaviors influence nutrition and health. As non-traditional and individualized eating patterns have become more common, new ways of thinking about routine eating practices are needed. This study sought to gain conceptual understanding of working adults' eating routines. Forty-two purposively sampled US adults reported food intake and contextual details about eating episodes in qualitative 24-hour dietary recalls conducted over 7 consecutive days. Using the constant comparative method, researchers analyzed interview transcripts for recurrent ways of eating that were either explicitly reported by study participants as “routines” or emergent in the data. Participants' eating routines included repetition in food consumption as well as eating context, and also involved sequences of eating episodes. Eating routines were embedded in daily schedules for work, family, and recreation. Participants maintained purposeful routines that helped balance tension between demands and values, but they modified routines as circumstances changed. Participants monitored and reflected upon their eating practices and tended to assess their practices in light of their personal identities. These findings provide conceptual insights for food choice researchers and present a perspective from which practitioners who work with individuals seeking to adopt healthful eating practices might usefully approach their tasks. PMID:18835305

  3. Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents

    PubMed Central

    Corcoran, Aoife; Nadkarni, Sharmin; Yasuda, Kaori; Sakaki, Toshiyuki; Brown, Geoffrey; Kutner, Andrzej; Marcinkowska, Ewa

    2016-01-01

    Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist. PMID:26840307

  4. Modified cIg-FISH protocol for multiple myeloma in routine cytogenetic laboratory practice.

    PubMed

    Gole, Leena; Lin, Adeline; Chua, Constance; Chng, Wee Joo

    2014-01-01

    The International Myeloma Working Group recommends that fluorescence in situ hybridization (FISH) be performed on specifically identified plasma cells (PC). This is because chromosomal abnormalities are not frequently detected by traditional karyotyping due to the low proliferative rate of PC in multiple myeloma (MM). Conventional FISH enhances the sensitivity but lacks the specificity, as it does not distinguish PC from other hematopoetic cells. To fulfill this recommendation, PC need to be selected either by flow cytometry or immunomagnetic bead-based PC sorting or by concomitant labeling of the cytoplasmic immunoglobulin light chain, which allows for unambiguous identification. These techniques require expertise, time, and funding and are not easily incorporated into the routine workflow of the cytogenetic laboratory. We have modified and refined the technique using fixed cell pellets to achieve nicely separated and easily identifiable PC. With immunostaining and subsequent FISH (i.e., cytoplasmic immunoglobulin FISH, cIg-FISH), this technique can be easily incorporated into every cytogenetic laboratory. Twenty samples from patients with MM were subjected to routine FISH, cIg-FISH, and chromosomal karyotyping and the results were compared. Three FISH probes, which enabled detection of the t(4;14), t(14;16) and deletion of TP53, were used to validate this modified technique successfully. PMID:24485403

  5. Loss of PEG chain in routine SDS-PAGE analysis of PEG-maleimide modified protein.

    PubMed

    Zhang, Chun; Liu, Yongdong; Feng, Cui; Wang, Qi; Shi, Hong; Zhao, Dawei; Yu, Rong; Su, Zhiguo

    2015-01-01

    SDS-PAGE represents a quick and simple method for qualitative and quantitative analysis of protein and protein-containing conjugates, mostly pegylated proteins. PEG-maleimide (MAL) is frequently used to site-specifically pegylate therapeutic proteins via free cysteine residue by forming a thiosuccinimide structure for pursuing homogeneous products. The C-S linkage between protein and PEG-MAL is generally thought to be relatively stable. However, loss of intact PEG chain in routine SDS-PAGE analysis of PEG-maleimide modified protein was observed. It is a thiol-independent thioether cleavage and the shedding of PEG chain exclusively happens to PEG-MAL modified conjugates although PEG-vinylsulfone conjugates to thiol-containing proteins also through a C-S linkage. Cleavage kinetics of PEG40k-MAL modified ciliary neurotrophic factor showed this kind of degradation could immediately happen even in 1 min incubation at high temperature and could be detected at physiological temperature and pH, although the rate was relatively slow. This may provide another degradation route for maleimide-thiol conjugate irrespective of reactive thiol, although the specific mechanism is still not very clear for us. It would also offer a basis for accurate characterization of PEG-MAL modified protein/peptide by SDS-PAGE analysis. PMID:25265901

  6. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

    PubMed Central

    Piotrowska, Anna; Wierzbicka, Justyna; Nadkarni, Sharmin; Brown, Geoffrey; Kutner, Andrzej; Żmijewski, Michał A.

    2016-01-01

    Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs. PMID:26760999

  7. A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function

    PubMed Central

    Shabrish, Snehal; Gupta, Maya; Madkaikar, Manisha

    2016-01-01

    Natural killer (NK) cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a) is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC) or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA) and calcium ionophore (Ca2+-ionophore) instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p < 0.0001). It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL) with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells. PMID:27413758

  8. A modified simplified reference tissue model for the quantification of dopamine D2/3 receptors with [18F]fallypride images.

    PubMed

    Tsartsalis, Stergios; Moulin-Sallanon, Marcelle; Dumas, Noé; Tournier, Benjamin B; Ginovart, Nathalie; Millet, Philippe

    2014-01-01

    Defluorination of [18F]fallypride and accumulation of 18F in skull and glands leads to the contamination of brain structures with spillover activity due to partial volume effects, leading to considerable errors in binding potential estimations. Here we propose a modification of the simplified reference tissue model (SRTM) to take into account the contribution of skull activity to the radioactivity kinetic pattern in cerebellum and target regions. It consists of the introduction of an additional parameter for each volume of interest (sT) and one for the cerebellum (sR), corresponding to the fraction of skull activity contaminating these structures. Using five rat positron emission tomography experiments, we applied the modified SRTM (SRTMc), which resulted in excellent fits. As a relative means of comparison of results, we applied factor analysis (FA) to decompose dynamic data into images corresponding to brain and skull activity. With the skull factor images, we estimated the "true" sT and sR values, ultimately permitting us to fix the sR value. Parameters obtained with the SRTMc were closely correlated with values obtained from FA-corrected data. In conclusion, we propose an efficient method for reliable quantification of dopamine D2/3 receptors with single-injection [18F]fallypride scans that is potentially applicable to human studies where 18F skull accumulation compromises binding parameter estimation. PMID:25248453

  9. Modifying the Clinical Outcomes in Routine Evaluation Measure for Use with People Who Have a Learning Disability

    ERIC Educational Resources Information Center

    Marshall, Keith; Willoughby-Booth, Simon

    2007-01-01

    There are few reliable self-report measures suitable for people with a learning disability in reporting psychological distress. This study examines the modification of the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), exploring its reliability, using two different presentation styles. One style included a sequencing task then…

  10. Interference-free determination of thallium in aqua regia leaches from rocks, soils and sediments by D(2)-ETAAS method using mixed palladium-citric acid-lithium chemical modifier.

    PubMed

    Husáková, Lenka; Cernohorský, Tomás; Srámková, Jitka; Hubácková, Katerina; Dolezalová, Iva

    2008-04-28

    The mixture of palladium (chloride) with citric acid and lithium is proposed as a new chemical modifier for the elimination of interference occurred during the determination of Tl in aqua regia extracts from rocks, soils and sediments by electrothermal atomic absorption spectrometry using instrumentation with deuterium-lamp background correction (D(2)-ETAAS). Palladium was preferred to rhodium and platinum as to analyte stabilization, citric acid served as an effective reducing agent facilitating formation of Pd-Tl stable covalent bonds playing an important role in the analyte stabilization. Citric acid in addition helps to remove most of interfering chloride at low temperature. The further addition of Li increased significantly the robustness of chemical modifier against strongly interfering ZnCl2 matrix by binding free chlorine into a more stable LiCl molecule. In the presence of the proposed chemical modifier the temperature for the final step of pyrolysis was adjustable up to 1000 degrees C, without any noticeable loss of volatile Tl species and the interference of the rest chloride matrix was significantly reduced. The application of the modifier to direct determination of Tl in aqua regia extracts from rocks, soils and sediments has ensured the characteristic mass and LOD value for the original sample 13 pg and 0.043 microg g(-1), respectively (10-microL aliquots of sample) and has enabled the use of matrix-free standard solutions for attaining accurate analysis. The accuracy was verified by the analysis of certified reference samples and by the comparison of results with those found by an inductively coupled plasma orthogonal acceleration time-of-flight mass spectrometer (ICP-oa-TOFMS) method. PMID:18405679

  11. Development and validation of a liquid medium (M7H9C) for routine culture of Mycobacterium avium subsp. paratuberculosis to replace modified Bactec 12B medium.

    PubMed

    Whittington, Richard J; Whittington, Ann-Michele; Waldron, Anna; Begg, Douglas J; de Silva, Kumi; Purdie, Auriol C; Plain, Karren M

    2013-12-01

    Liquid culture of Mycobacterium avium subsp. paratuberculosis from clinical samples, such as feces, is the most sensitive antemortem test for the diagnosis of Johne's disease in ruminants. In Australia, New Zealand, the United States, and some other countries, the Bactec 460 system with modified Bactec 12B medium (Becton, Dickinson) has been the most commonly used liquid culture system, but it was discontinued in 2012. In this study, a new liquid culture medium, M7H9C, was developed. It consists of a Middlebrook 7H9 medium base with added Casitone, albumin, dextrose, catalase, egg yolk, mycobactin J, and a cocktail of antibiotics. We found that polyoxyethylene stearate (POES) was not essential for the cultivation of M. avium subsp. paratuberculosis in either the Bactec 12B or the M7H9C medium. The limit of detection determined using pure cultures of the C and S strains of M. avium subsp. paratuberculosis was 7 bacilli per 50 μl inoculum in the two media. The new medium was validated using 784 fecal and tissue samples from sheep and cattle, >25% of which contained viable M. avium subsp. paratuberculosis. Discrepant results for the clinical samples between the two media were mostly associated with samples that contained <10 viable bacilli per gram, but these results were relatively uncommon, and the performances of the two media were not significantly different. M7H9C medium was less than half the cost of the Bactec 12B medium and did not require regular examination during incubation, but a confirmatory IS900 PCR test had to be performed on every culture after the predetermined incubation period. PMID:24048541

  12. Development and Validation of a Liquid Medium (M7H9C) for Routine Culture of Mycobacterium avium subsp. paratuberculosis To Replace Modified Bactec 12B Medium

    PubMed Central

    Whittington, Ann-Michele; Waldron, Anna; Begg, Douglas J.; de Silva, Kumi; Purdie, Auriol C.; Plain, Karren M.

    2013-01-01

    Liquid culture of Mycobacterium avium subsp. paratuberculosis from clinical samples, such as feces, is the most sensitive antemortem test for the diagnosis of Johne's disease in ruminants. In Australia, New Zealand, the United States, and some other countries, the Bactec 460 system with modified Bactec 12B medium (Becton, Dickinson) has been the most commonly used liquid culture system, but it was discontinued in 2012. In this study, a new liquid culture medium, M7H9C, was developed. It consists of a Middlebrook 7H9 medium base with added Casitone, albumin, dextrose, catalase, egg yolk, mycobactin J, and a cocktail of antibiotics. We found that polyoxyethylene stearate (POES) was not essential for the cultivation of M. avium subsp. paratuberculosis in either the Bactec 12B or the M7H9C medium. The limit of detection determined using pure cultures of the C and S strains of M. avium subsp. paratuberculosis was 7 bacilli per 50 μl inoculum in the two media. The new medium was validated using 784 fecal and tissue samples from sheep and cattle, >25% of which contained viable M. avium subsp. paratuberculosis. Discrepant results for the clinical samples between the two media were mostly associated with samples that contained <10 viable bacilli per gram, but these results were relatively uncommon, and the performances of the two media were not significantly different. M7H9C medium was less than half the cost of the Bactec 12B medium and did not require regular examination during incubation, but a confirmatory IS900 PCR test had to be performed on every culture after the predetermined incubation period. PMID:24048541

  13. Data format translation routines

    SciTech Connect

    Burris, R.D.

    1981-02-01

    To enable the effective connection of several dissimilar computers into a network, modification of the data being passed from one computer to another may become necessary. This document describes a package of routines which permit the translation of data in PDP-8 formats to PDP-11 or DECsystem-10 formats or from PDP-11 format to DECsystem-10 format. Additional routines are described which permit the effective use of the translation routines in the environment of the Fusion Energy Division (FED) network and the Elmo Bumpy Torus (EBT) data base.

  14. Daily exercise routines

    NASA Technical Reports Server (NTRS)

    Anderson, Patrick L.; Amoroso, Michael T.

    1990-01-01

    Viewgraphs on daily exercise routines are presented. Topics covered include: daily exercise and periodic stress testings; exercise equipment; physiological monitors; exercise protocols; physiological levels; equipment control; control systems; and fuzzy logic control.

  15. Routine sputum culture

    MedlinePlus

    Sputum culture ... There, it is placed in a special dish (culture). It is then watched to see if bacteria ... Chernecky CC, Berger BJ. Culture, routine. In: Chernecky CC, Berger BJ, ... . 6th ed. Philadelphia, PA: Elsevier Saunders; 2013:409- ...

  16. Importance of Family Routines

    MedlinePlus

    ... Listen Español Text Size Email Print Share The Importance of Family Routines Page Content ​Every family needs ... child to sleep. These rituals can include storytelling, reading aloud, conversation, and songs. Try to avoid exciting ...

  17. D2 Inertial Measurement Unit

    NASA Astrophysics Data System (ADS)

    Dewar, Patrick; Gido, Joseph; Carroll, Joseph

    1993-06-01

    The D2 Hypervelocity Projectile is a Strategic Defense Initiative sponsored technology program that is designed to provide low endo-atmospheric, kinetic kill defense against strategic reentry vehicles. The D2 program is funded through the U.S. Army Space and Strategic Defense Command (SSDC) in Huntsville, AL and contracted through the U.S. Army Armament Research and Development Engineering Center (ARDEC) at Picatinny Arsenal, NJ. In GFY 93 the program began an integration and flight demonstration phase with the Hypervelocity Fire Control System (HVFC) and the Solid Propellant Electro Thermal Chemical (SPETC) launcher. The Inertial Measurement Unit (IMU) necessary to perform the autopilot and guidance data gathering must be extremely small, lightweight and shock hardened. The IMU is comprised of three Honeywell GG1308 miniature Ring Laser Gyros (RLG), and three Endevco 7290-M19 miniature silicon accelerometers. The IMU has self-contained high voltage Power Supply (HVPS) processor and memory electronics providing a complete stand alone, three axis measurement package. This Inertial Cluster Assembly (ICA) is then packaged into a cylindrical housing, approximately 1.9 inches in diameter and 1.3 inches in length.

  18. Routine DNA testing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Routine DNA testing. It’s done once you’ve Marker-Assisted Breeding Pipelined promising Qantitative Trait Loci within your own breeding program and thereby established the performance-predictive power of each DNA test for your germplasm under your conditions. By then you are ready to screen your par...

  19. Graph-Plotting Routine

    NASA Technical Reports Server (NTRS)

    Kantak, Anil V.

    1987-01-01

    Plotter routine for IBM PC (AKPLOT) designed for engineers and scientists who use graphs as integral parts of their documentation. Allows user to generate graph and edit its appearance on cathode-ray tube. Graph may undergo many interactive alterations before finally dumped from screen to be plotted by printer. Written in BASIC.

  20. PROPER: Optical propagation routines

    NASA Astrophysics Data System (ADS)

    Krist, John E.

    2014-05-01

    PROPER simulates the propagation of light through an optical system using Fourier transform algorithms (Fresnel, angular spectrum methods). Distributed as IDL source code, it includes routines to create complex apertures, aberrated wavefronts, and deformable mirrors. It is especially useful for the simulation of high contrast imaging telescopes (extrasolar planet imagers like TPF).

  1. Routine neonatal circumcision?

    PubMed Central

    Tran, P. T.; Giacomantonio, M.

    1996-01-01

    Routine neonatal circumcision is still a controversial procedure. This article attempts to clarify some of the advantages and disadvantages of neonatal circumcision. The increased rate of penile cancer among uncircumcised men appears to justify the procedure, but that alone is not sufficient justification. The final decision on neonatal circumcision should be made by parents with balanced counsel from attending physicians. PMID:8939321

  2. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  3. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  4. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  5. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  6. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  7. Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium.

    PubMed

    Gantz, Stephanie C; Robinson, Brooks G; Buck, David C; Bunzow, James R; Neve, Rachael L; Williams, John T; Neve, Kim A

    2015-01-01

    D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors. PMID:26308580

  8. CALIPSO User-Provided Routines

    Atmospheric Science Data Center

    2013-04-01

    ... data files. These routines are written in Interactive Data Language (IDL). A README file demonstrating use of the routines is also available. Interactive Data Language (IDL) is available from  Exelis Visual Information Solutions . ...

  9. Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-21

    PubMed Central

    Pettit, George R.; Quistorf, Peter D.; Fry, Jeremy A.; Herald, Delbert L.; Hamel, Ernest; Chapuis, Jean-Charles

    2009-01-01

    A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25–28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39–41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties. PMID:20161135

  10. Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2014-03-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437

  11. Systemic factors of errors in the case identification process of the national routine health information system: A case study of Modified Field Health Services Information System in the Philippines

    PubMed Central

    2011-01-01

    Background The quality of data in national health information systems has been questionable in most developing countries. However, the mechanisms of errors in the case identification process are not fully understood. This study aimed to investigate the mechanisms of errors in the case identification process in the existing routine health information system (RHIS) in the Philippines by measuring the risk of committing errors for health program indicators used in the Field Health Services Information System (FHSIS 1996), and characterizing those indicators accordingly. Methods A structured questionnaire on the definitions of 12 selected indicators in the FHSIS was administered to 132 health workers in 14 selected municipalities in the province of Palawan. A proportion of correct answers (difficulty index) and a disparity of two proportions of correct answers between higher and lower scored groups (discrimination index) were calculated, and the patterns of wrong answers for each of the 12 items were abstracted from 113 valid responses. Results None of 12 items reached a difficulty index of 1.00. The average difficulty index of 12 items was 0.266 and the discrimination index that showed a significant difference was 0.216 and above. Compared with these two cut-offs, six items showed non-discrimination against lower difficulty indices of 0.035 (4/113) to 0.195 (22/113), two items showed a positive discrimination against lower difficulty indices of 0.142 (16/113) and 0.248 (28/113), and four items showed a positive discrimination against higher difficulty indices of 0.469 (53/113) to 0.673 (76/113). Conclusions The results suggest three characteristics of definitions of indicators such as those that are (1) unsupported by the current conditions in the health system, i.e., (a) data are required from a facility that cannot directly generate the data and, (b) definitions of indicators are not consistent with its corresponding program; (2) incomplete or ambiguous, which allow

  12. Lidar Altitude Data Read Routine

    Atmospheric Science Data Center

    2013-03-19

    ... Profile products. It is written in Interactive Data Language (IDL) and uses HDF routine calls to read the altitude data which are ... Data Read routine  (1.5 KB) Interactive Data Language (IDL) is available from  Exelis Visual Information Solutions . ...

  13. Improvements of AIMS D2DB matching for product patterns

    NASA Astrophysics Data System (ADS)

    Nishiguchi, Masaharu; Kanno, Koichi; Miyashita, Hiroyuki; Ohara, Kana; Son, Donghwan; Tolani, Vikram; Satake, Masaki

    2015-07-01

    AIMSTM is mainly used in photomask industry for verifying the print impact of mask defects on wafer CD in DUV lithography process. AIMS verification is typically used in D2D configuration, wherein two AIMS images, reference and defect, are captured and compared. Criticality of defects is then analyzed off these images using a number of criteria. As photomasks with aggressive OPC, sub-resolution assist features (SRAFs), and single-die are being routinely manufactured in production environment, it is required to improve cycle time through the AIMS step by saving time in searching for and capturing an adequate reference AIMS image. One solution is to use AIMS D2DB methodology which compares AIMS defect image with a reference image simulated from the corresponding mask design data. In general, such simulation needs calibration with the native images captured on the AIMS tool. In our previous paper we evaluated a calibration procedure directly using the defect AIMS image and compared the analysis results with a D2D capture using AIA (Aerial Image Analyzer) software product from Luminescent Technologies (now part of KLA-Tencor Corporation). The results showed that calibration using defect AIMS image does not influence AIMS judgment as long as the defect size is less than 100nm in case of typical basic patterns. When applying this methodology to product patterns, it was found that there were differences between reference AIMS image and simulation image. These differences influenced AIMS verification. Then new method to compensate would be needed. Our approach to compensate the difference between AIMS image and simulated image is examination with some factors likely to cause the difference.

  14. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  15. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  16. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  17. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  18. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  19. D2N: Distance to the native.

    PubMed

    Mishra, Avinash; Rana, Prashant Singh; Mittal, Aditya; Jayaram, B

    2014-10-01

    Root-mean-square-deviation (RMSD), of computationally-derived protein structures from experimentally determined structures, is a critical index to assessing protein-structure-prediction-algorithms (PSPAs). The development of PSPAs to obtain 0Å RMSD from native structures is considered central to computational biology. However, till date it has been quite challenging to measure how far a predicted protein structure is from its native - in the absence of a known experimental/native structure. In this work, we report the development of a metric "D2N" (distance to the native) - that predicts the "RMSD" of any structure without actually knowing the native structure. By combining physico-chemical properties and known universalities in spatial organization of soluble proteins to develop D2N, we demonstrate the ability to predict the distance of a proposed structure to within ±1.5Ǻ error with a remarkable average accuracy of 93.6% for structures below 5Ǻ from the native. We believe that this work opens up a completely new avenue towards assigning reliable structures to whole proteomes even in the absence of experimentally determined native structures. The D2N tool is freely available at http://www.scfbio-iitd.res.in/software/d2n.jsp. PMID:25062912

  20. Freezing D2O clay gels.

    PubMed

    Letellier, M

    1998-01-01

    To obtain the T1 surface value in smectites/D2O diluted suspensions or gels, as was obtained on a monolayer deuterated clay, we freeze them. The broad Pake's doublets similar to ice doublets and with the same T1 show that we can separate frozen from unfrozen D2O. The latter exhibits a narrower line and a single T1 and is attributed to the liquid surface water layer in rapid exchange with the nearby supercooled water, the quantity of which diminishes with the lowering of the temperature depending on the gel porosity. It is possible to measure the supercooled water quantity and to correct the T1 measured values to extract the T1 surface. The value extrapolated at room temperature allows the complete clay surface area measurement. The example of a montmorillonite is given and a comparison with laponite is made. PMID:9803898

  1. Neptune's small dark spot (D2)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This bulls-eye view of Neptune's small dark spot (D2) was obtained by Voyager 2's narrow-angle camera. Banding surrounding the feature indicates unseen strong winds, while structures within the bright spot suggest both active upwelling of clouds and rotation about the center. A rotation rate has not yet been measured, but the V-shaped structure near the right edge of the bright area indicates that the spot rotates clockwise. Unlike the Great Red Spot on Jupiter, which rotates counterclockwise, if the D2 spot on Neptune rotates clockwise, the material will be descending in the dark oval region. The fact that infrared data will yield temperature information about the region above the clouds makes this observation especially valuable. The Voyager Mission is conducted by JPL for NASA's Office of Space Science and Applications.

  2. Polarization Rotation and Circular Dichroism Near the Potassium D2 Lines

    NASA Astrophysics Data System (ADS)

    Conover, Charles; Thiha, Htet; Dahnke, Jennifer

    2010-03-01

    We have experimentally measured the Faraday rotation and the differential absorption of the two circular polarizations for light tuned near the D2 line in potassium (766.7 nm). In particular we have explored the vapor temperature and magnetic field dependence of the frequency of the zero crossings of the lineshapes from the circular analyzer and the balanced polarimeter used in the measurements. These signals are routinely used as frequency references for laser locking and we discuss the sensitivity to experimental parameters.

  3. MISR Conversion to ASCII Routines

    Atmospheric Science Data Center

    2013-04-01

    ... These routines are written in Exelis Visual Information Solutions IDL programming language. They can be run either with a licensed ... with IDL and is available from  Exelis Visual Information Solutions . The IDL VM software can be downloaded from this site or ordered ...

  4. Learning Routines in Innovation Processes

    ERIC Educational Resources Information Center

    Hoeve, Aimee; Nieuwenhuis, Loek F. M.

    2006-01-01

    Purpose: This paper aims to generate both a theoretical and an empirical basis for a research model that serves in further research as an analytical tool for understanding the complex phenomenon of learning at different levels in a work organisation. The key concept in this model is the routine concept of Nelson and Winter.…

  5. Multiple electron scattering routines for PEREGRINE

    SciTech Connect

    White, J A

    1999-08-23

    The Monte Carlo electron scattering routines solve multiple elastic scatters in a condensed history approach. The Goudsmit-Saunderson scattering model is used and its implementation is taken from Kawrakow and Bielajew[l]. The subroutines produce an exit angle representing a likely scattering angle of a single incident electron after scattering elastically over a given step size. Two input parameters, {lambda} and {eta}, that depend on the atomic species and incident energy must first be specified. The mapping from species and energy to 77 and {lambda} already existed in the PEREGRINE code and was not redone or modified in any way. The software has been validated by comparisons to Moliere and Goudsmit-Saunderson models of D.W.O. Rogers[2]. As required by licensing considerations, no public domain or copyrighted software has been used in any phase of the preparation of any of these sub-routines or data files. Apart from needing to have {eta} and {lambda} specified through PEREGRINE, the code provided is completely self-contained. Everything is written in the FORTRAN 77 language to simplify inclusion in the existing PEREGRINE package.

  6. MATHEMATICAL ROUTINES FOR ENGINEERS AND SCIENTISTS

    NASA Technical Reports Server (NTRS)

    Kantak, A. V.

    1994-01-01

    The purpose of this package is to provide the scientific and engineering community with a library of programs useful for performing routine mathematical manipulations. This collection of programs will enable scientists to concentrate on their work without having to write their own routines for solving common problems, thus saving considerable amounts of time. This package contains sixteen subroutines. Each is separately documented with descriptions of the invoking subroutine call, its required parameters, and a sample test program. The functions available include: maxima, minima, and sort of vectors; factorials; random number generator (uniform or Gaussian distribution); complimentary error function; fast Fourier Transformation; Simpson's Rule integration; matrix determinate and inversion; Bessel function (J Bessel function for any order, and modified Bessel function for zero order); roots of a polynomial; roots of non-linear equation; and the solution of first order ordinary differential equations using Hamming's predictor-corrector method. There is also a subroutine for using a dot matrix printer to plot a given set of y values for a uniformly increasing x value. This package is written in FORTRAN 77 (Super Soft Small System FORTRAN compiler) for batch execution and has been implemented on the IBM PC computer series under MS-DOS with a central memory requirement of approximately 28K of 8 bit bytes for all subroutines. This program was developed in 1986.

  7. [Pharmacogenomics in routine medical care].

    PubMed

    Rosskopf, D; Meyer zu Schwabedissen, H E; Kroemer, H K; Siegmund, W

    2010-01-01

    Pharmacogenomics investigates inherited differences in drug responses including beneficial and adverse reactions. While a considerable amount of evidence for genetic influences on drug responses has been accumulated within the last decade, predominantly in small studies, its value in routine therapy is still a matter of debate. The aim of this review is to discuss well established examples where pharmacogenomic techniques can improve routine treatment. Examples include genotyping of CYP2D6 in the context of antidepressant therapy, analysis of TPMT variants for the prediction of mercaptopurine-induced bone marrow depression, VKORC1 and CYP2C9 analyses for a better control of anticoagulant administration and the SLCO1B1 variant in the context of statin-induced myopathies. PMID:20101557

  8. Memos trace routine radiation overexposures

    SciTech Connect

    Lobsenz, G.

    1994-03-09

    Workers at the Energy Department's Fernald plant routinely received [open quotes]gross,[close quotes] [open quotes]unacceptable[close quotes] and [open quotes]undue[close quotes] radiation exposures during uranium processing operations from the 1950s through the early 1970s, according to internal Fernald memos. The documents come to light as DOE continues to pay hundreds of thousands of dollars every month to defend its former Fernald contractor, NLO Inc., from a workers' lawsuit seeking compensation for alleged injuries from poor safety practices at the Ohio facility. DOE officials have contended the NLO defense effort is justified because there is no evidence that any former Fernald workers have suffered injury as a result of radiation exposures at the plant. However, the internal Fernald memos document major concerns expressed by Fernald health officials about unsafe working conditions at the plant and what appear in some cases to be routine overexposures of workers.

  9. Routine outcome measurement in Australia.

    PubMed

    Burgess, Philip; Pirkis, Jane; Coombs, Tim

    2015-08-01

    Australia has been implementing routine outcome measurement in its specialized public sector mental health services for over a decade. It uses a range of clinician-rated and consumer-rated measures that are administered at set times during episodes of inpatient, ambulatory and community residential episodes of care. Routine outcome measurement is now embedded in service delivery, and data are made available in a variety of ways to different audiences. These data are used by policy-makers and planners to inform decisions about system-wide reforms, by service managers to monitor quality and effectiveness, and by clinicians to guide clinical decision-making and to promote dialogue with consumers. Consumers, carers and the general community can use these data to ensure that services are accountable for the care they deliver. This paper describes the status quo in Australia with respect to routine outcome measurement, discusses the factors that led to its successful implementation, and considers the steps that are necessary for its continued development. PMID:25768326

  10. Binding Interactions of Dopamine and Apomorphine in D2High and D2Low States of Human Dopamine D2 Receptor Using Computational and Experimental Techniques.

    PubMed

    Durdagi, Serdar; Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip

    2016-02-17

    We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model. PMID:26645629

  11. Global routine vaccination coverage, 2009.

    PubMed

    2010-10-29

    The widespread use of vaccines has greatly improved global public health, preventing millions of childhood hospitalizations and deaths each year. Vaccination of children also is projected to avert adult deaths through the prevention of hepatitis B (HepB) virus--related chronic liver disease and liver cancer and human papilloma virus--related cervical cancer. When the World Health Organization (WHO) began the Expanded Programme on Immunization in 1974, <5% of the world's children had been fully vaccinated with bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) vaccine, oral poliovirus vaccine, and measles-containing vaccine (MCV) during the first year of life. Since then, increased vaccination coverage has resulted in substantial reductions in morbidity and mortality, including a >99% decline in polio incidence since 1988, with eradication on the horizon, and a 78% decline in measles-associated mortality from 2000 to 2008 With the introduction of Haemophilus influenzae type b (Hib) vaccine, HepB vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine into many countries' routine vaccination schedules, further reductions in morbidity and mortality are expected. However, based on an annual global birth cohort of approximately 130 million, an estimated 23 million infants worldwide still do not receive the benefits of routine vaccination (i.e., 3 doses of DTP during the first year of life). The Global Immunization Vision and Strategy (GIVS), developed in 2005 by WHO and UNICEF, assists countries in strengthening immunization programs and vaccinating more persons. GIVS aims to achieve 90% national 3-dose DTP (DTP3) coverage by age 12 months in all countries, and 80% coverage in every district or equivalent administrative unit by 2010 (and to sustain these levels through 2015). This report summarizes global routine vaccination coverage during 2000--2009 and progress toward achieving GIVS goals. PMID:21030941

  12. Higher Spins in D = 2 + 1

    NASA Astrophysics Data System (ADS)

    Campoleoni, Andrea

    2013-07-01

    We give a brief overview of some three-dimensional toy models for higher-spin interactions. We first review the construction of pure higher-spin gauge theories in terms of Chern-Simons theories. We then discuss how this setup could be modified along the lines of the known topologically massive theories. Based on the talk presented at the 49th Course of the International School of Subnuclear Physics, Erice, Italy, 24 June - 3 July 2011

  13. Global routine vaccination coverage, 2013.

    PubMed

    Harris, Jennifer B; Gacic-Dobo, Marta; Eggers, Rudolf; Brown, David W; Sodha, Samir V

    2014-11-21

    In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization to ensure that all children have access to routinely recommended vaccines. Since then, global coverage with the four core vaccines (Bacille Calmette-Guérin vaccine [for protection against tuberculosis], diphtheria-tetanus-pertussis vaccine [DTP], polio vaccine, and measles vaccine) has increased from <5% to ≥84%, and additional vaccines have been added to the recommended schedule. Coverage with the third dose of DTP vaccine (DTP3) by age 12 months is a key indicator of immunization program performance. Estimated global DTP3 coverage has remained at 83%-84% since 2009, with estimated 2013 coverage at 84%. Global coverage estimates for the second routine dose of measles-containing vaccine (MCV2) are reported for the first time in 2013; global coverage was 35% by the end of the second year of life and 53% when including older age groups. Improvements in equity of access and use of immunization services will help ensure that all children are protected from vaccine-preventable diseases. PMID:25412062

  14. Increased Detection of Lymphatic Vessel Invasion by D2-40 (Podoplanin) in Early Breast Cancer: Possible Influence on Patient Selection for Accelerated Partial Breast Irradiation

    SciTech Connect

    Debald, Manuel; Poelcher, Martin; Flucke, Uta; Walgenbach-Bruenagel, Gisela

    2010-07-15

    Purpose: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. Patients and Methods: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine the eligibility for APBI: invasive ductal adenocarcinoma of {<=}3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. Results: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). Conclusion: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.

  15. Role of the type 2 iodothyronine deiodinase (D2) in the control of thyroid hormone signaling☆

    PubMed Central

    Drigo, Rafael Arrojo; Fonseca, Tatiana L.; Werneck-de-Castro, Joao Pedro Saar; Bianco, Antonio C.

    2016-01-01

    Scope of the review This review covers the recent advances in D2 biology, a member of the iodothyronine deiodinase family, thioredoxin fold-containing selenoenzymes that modify thyroid hormone signaling in a time- and cell-specific manner. The type II (D2) deiodinase catalyzes T4-to-T3 conversion as opposed to the type III (D3) deiodinase that terminates thyroid hormone action. Major conclusions D2-catalyzed T3 production increases thyroid hormone signaling whereas blocking D2 activity or disruption of the Dio2 gene leads to a state of localized hypothyroidism. D2 expression is regulated by different developmental, metabolic or environmental cues such as the hedgehog pathway, the adrenergic-and the TGR5-activated cAMP pathway, by xenobiotic molecules such as flavonols and by stress in the endoplasmic reticulum, which specifically reduces de novo synthesis of D2 via an eIF2a-mediated mechanism. Thus, D2 plays a central role in important physiological processes such as determining T3 content in developing tissues and in the adult brain, and promoting adaptive thermogenesis in brown adipose tissue. Notably, D2 is critical in the T4-mediated negative feed-back at the pituitary and hypothalamic levels, whereby T4 inhibits TSH and TRH expression, respectively. Notably, ubiquitination is a major step in the control of D2 activity, whereby T4 binding to and/or T4 catalysis triggers D2 inactivation by ubiquitination that is mediated by the E3 ubiquitin ligases WSB-1 and/or TEB4. Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis. General significance Here we review the recent advances in the understanding of D2 biology focusing on the mechanisms that regulate its expression and their biological significance in metabolically relevant tissues. This article is part of a Special Issue entitled Thyroid hormone signalling. PMID

  16. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  17. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland.

    PubMed

    Slominski, Andrzej T; Kim, Tae-Kang; Shehabi, Haleem Z; Tang, Edith K Y; Benson, Heather A E; Semak, Igor; Lin, Zongtao; Yates, Charles R; Wang, Jin; Li, Wei; Tuckey, Robert C

    2014-03-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)₂D2, 1,20(OH)₂D2, 25(OH)D2 and 1,25(OH)₂D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)₂D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)₂D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  18. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... CONSUMPTION Special Dietary and Nutritional Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance...

  19. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source...) Vitamin D2 bakers yeast is the substance produced by exposing bakers yeast (Saccharomyces cerevisiae)...

  20. 26 CFR 1.1092(d)-2 - Personal property.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Personal property. 1.1092(d)-2 Section 1.1092(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Wash Sales of Stock Or Securities § 1.1092(d)-2 Personal property. (a) Special...

  1. 26 CFR 31.3406(d)-2 - Payee certification failure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Payee certification failure. 31.3406(d)-2 Section 31.3406(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Collection of Income Tax at Source § 31.3406(d)-2 Payee certification failure. (a) Requirement...

  2. 26 CFR 31.3406(d)-2 - Payee certification failure.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Payee certification failure. 31.3406(d)-2 Section 31.3406(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Collection of Income Tax at Source § 31.3406(d)-2 Payee certification failure. (a) Requirement...

  3. 26 CFR 31.3406(d)-2 - Payee certification failure.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Payee certification failure. 31.3406(d)-2 Section 31.3406(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Collection of Income Tax at Source § 31.3406(d)-2 Payee certification failure. (a) Requirement...

  4. 26 CFR 31.3406(d)-2 - Payee certification failure.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Payee certification failure. 31.3406(d)-2 Section 31.3406(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Collection of Income Tax at Source § 31.3406(d)-2 Payee certification failure. (a) Requirement...

  5. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a) Loss disallowance—(1) General rule. No deduction is allowed...

  6. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... § 1.337(d)-2T as contained in the 26 CFR part 1 in effect on March 2, 2005. ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME...

  7. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  8. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  9. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  10. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  11. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  12. 26 CFR 31.3406(d)-2 - Payee certification failure.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Payee certification failure. 31.3406(d)-2 Section 31.3406(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... SOURCE Collection of Income Tax at Source § 31.3406(d)-2 Payee certification failure. (a) Requirement...

  13. VII: VME/IORFI-II interface routines

    SciTech Connect

    Alleva, D.

    1988-07-07

    This document describes the VME/IORFI-II Interface routines (VII). These routines where designed to meet two needs. First, the routines enable programs written in PILS running on a MVME 101 under Valet-Plus to control an IORFI-II interface from VME. Secondly, the routines provide a high level language version of the FASTBUS standard routines for the IORFI-II which can easily be translated into other high level languages (like C). The routines fall into two general types, control and transaction. The control routines work directly with the interface registers. These routines set up and monitor operations between VME and the IORFI-II. The control routines are usually used indirectly by the programmer through the transaction routines. The transaction routines, such as VIIreverse arrowWRITEreverse arrowDAT, use the control routines to carry out complete functions on FASTBUS. Most FASTBUS operations have been implemented except for the compound routines and some low level routines. To facilitate access to the IORFI-II registers from VME, a Super-VIOR DMA board was used as a set of I/O registers tied to the IORFI-II's front panel connectors. The DMA controller on the Super-VIOR was not used and a much simpler board (only containing a set of four registers accessible from VME) could replace the Super-VIOR. The routines are written in PILS, a high-level language similar to BASIC and Pascal which is powerful and fast enough for most applications. However, PILS has proven to be too slow for efficient control of the IORFI-II. This is discussed further in this paper along with a discussion of possible future implementations of the routines.

  14. Evolutionary Dynamics of Digitized Organizational Routines

    ERIC Educational Resources Information Center

    Liu, Peng

    2013-01-01

    This dissertation explores the effects of increased digitization on the evolutionary dynamics of organizational routines. Do routines become more flexible, or more rigid, as the mix of digital technologies and human actors changes? What are the mechanisms that govern the evolution of routines? The dissertation theorizes about the effects of…

  15. 42 CFR 493.931 - Routine chemistry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a...

  16. 42 CFR 493.931 - Routine chemistry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a...

  17. 42 CFR 493.931 - Routine chemistry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a...

  18. 42 CFR 493.931 - Routine chemistry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a...

  19. 42 CFR 493.931 - Routine chemistry.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a...

  20. Routine outcome measures in Canada.

    PubMed

    Kisely, Steve; Adair, Carol E; Lin, Elizabeth; Marriott, Brian

    2015-01-01

    Canada is a federal country of 10 provinces and three territories. High level information on mental health conditions and service use has mostly been generated from administrative data collected by provinces and territories. These include four major types - hospital admissions and discharges, physician billings, ambulatory care services, and drug databases. At the national level, the Canadian Institute for Health Information brings together this information to produce indicators of outcome. Although these data provide information on patient and health system characteristics, they do not capture the full spectrum of formal and informal mental healthcare. These include changes in health status, functioning, community integration and quality of life. As a result, some jurisdictions have begun to implement more standardized measures of outcome such as the clinician-rated Health of the Nation Outcome Scales or the inpatient Resident Assessment Instrument - Mental Health. In this paper we provide an overview of mental-health-related data sources in Canada, highlight some of the more progressive practices beginning to emerge, and conclude with some thoughts about how the routine measurement and reporting of mental health outcomes in Canada might be advanced including efforts at engaging both clinicians and decision-makers. PMID:25738745

  1. Routine fetal genitourinary tract screening.

    PubMed

    Arger, P H; Coleman, B G; Mintz, M C; Snyder, H P; Camardese, T; Arenson, R L; Gabbe, S G; Aquino, L

    1985-08-01

    To evaluate routine fetal genitourinary tract obstetrical ultrasound screening, and to determine what size renal pelvis is indicative of significant renal disease, we reviewed 4,832 examinations, which had been performed over 2 years, of 3,530 consecutive obstetrical patients. Any fetus that had a renal pelvis greater than 5 mm or a definable cystic area was identified for follow-up. The fetuses of 39 patients (1.1%) who underwent 112 examinations fulfilled these criteria and constitute the basis of this report. A variety of examination criteria were recorded and analyzed in relationship to the follow-up, which ranged from 2-3 days to 21 months. The fetuses of the 39 patients were grouped into three categories: those with renal pelves between 5 and 9 mm in size; those with renal pelves larger than 10 mm; and those with cystic abnormalities. Those with renal pelves larger than 10 mm had either an obstructing lesion or exceptional extrarenal pelves. The clinical and pathologic aspects of these three groups are detailed, discussed, and analyzed. Criteria for significant fetal renal hydronephrosis and aspects of a loculated appearance are given. PMID:3892578

  2. The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat.

    PubMed

    Ferrari, F; Giuliani, D

    1994-01-01

    The selective D2 antagonist eticlopride, at a dose (0.01 mg/kg, s.c.) that fails to modify the normal behavior of rats, significantly reversed all the behavioral effects exerted by the selective D2 agonist SND 919 (0.1 mg/kg, i.p.), namely, the stimulation of stretching-yawning, penile erection and sedation and the inhibition of grooming. In the copulatory test, eticlopride at the same dose did not affect animal sexual behavior but potently counteracted the reduction in mount and intromission frequency and latency to ejaculation induced by SND 919 at 0.1 mg/kg, a behavioral pattern which might possibly be proposed as an animal model for human ejaculatio praecox. PMID:7916439

  3. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria.

    PubMed

    Kranendijk, Martijn; Struys, Eduard A; van Schaftingen, Emile; Gibson, K Michael; Kanhai, Warsha A; van der Knaap, Marjo S; Amiel, Jeanne; Buist, Neil R; Das, Anibh M; de Klerk, Johannis B; Feigenbaum, Annette S; Grange, Dorothy K; Hofstede, Floris C; Holme, Elisabeth; Kirk, Edwin P; Korman, Stanley H; Morava, Eva; Morris, Andrew; Smeitink, Jan; Sukhai, Rám N; Vallance, Hilary; Jakobs, Cornelis; Salomons, Gajja S

    2010-10-15

    Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer. PMID:20847235

  4. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as...

  5. Investigation of Solid D2 for UCN Sources

    PubMed Central

    Atchison, F.; Bodek, K.; van den Brandt, B.; Bryś, T.; Daum, M.; Fierlinger, P.; Geltenbort, P.; Giersch, M.; Hautle, P.; Hino, M.; Henneck, R.; Kasprzak, M.; Kirch, K.; Kohlbrecher, J.; Konter, J. A.; Kühne, G.; Kuźniak, M.; Mishima, K.; Pichlmaier, A.; Rätz, D.; Serebrov, A.; Utsuro, M.; Wokaun, A.; Zmeskal, J.

    2005-01-01

    Solid deuterium (sD2) will be used for the production of ultra-cold neutrons (UCN) in a new generation of UCN sources. Scattering cross sections of UCN in sD2 determine the source yield but until now have not been investigated. We report first results from transmission and scattering experiments with cold, very cold and ultra-cold neutrons on sD2 along with light transmission and Raman scattering studies showing the influence of the sD2 crystal properties. PMID:27308173

  6. Parental employment, family routines and childhood obesity.

    PubMed

    Anderson, Patricia M

    2012-12-01

    Using the Early Childhood Longitudinal Survey-Kindergarten Class of 1998-1999 (ECLS-K) data from kindergarten through eighth grade, this paper investigate the relationships among maternal employment, family routines and obesity. More hours worked by the mother tend to be negatively related to positive routines like eating meals as a family or at regular times, or having family rules about hours of television watched. Many of these same routines are significantly related to the probability of being obese, implying that family routines may be a mechanism by which maternal employment intensity affects children's obesity. However, inclusion of family routines in the obesity regression does not appreciably change the estimated effect of maternal employment hours. Thus, the commonly estimated deleterious effect of maternal employment on children's obesity cannot be explained by family routines, leaving the exact mechanisms an open question for further exploration. PMID:22622096

  7. Assessment of routine malaria diagnosis in the Venezuelan Amazon.

    PubMed

    Metzger, W G; Vivas-Martínez, S; Giron, A; Vaccari, E; Campos, E; Rodríguez, I; Miranda, E; Terán, E; Olivo, L; Magris, M

    2011-05-01

    The quality of routine malaria diagnosis is a crucial topic of malaria control. The aim of this assessment was to monitor and evaluate the quality of routine malaria diagnosis in Amazonas (Venezuela) and to improve the quality control system. The traditional non-blinded quality control system was found to be overburdened with diagnostic samples. A modified sampling system with fewer samples to be tested was proposed. Expert microscopists blindly double-checked 1000 slides and 550 rapid diagnostic tests (RDT) (OptiMAL-IT) from health posts (HP). For Plasmodium vivax, HP microscopy and OptiMAL-IT showed sensitivies of 86% and 63%, respectively. For P. falciparum, HP microscopy and OptiMAL-IT showed sensitivities of 68% and 89%, respectively. Both methods lost accuracy when fewer parasites occurred in the sample. HP microscopists from different municipalities displayed significant differences in diagnostic quality. Overall, quality of routine malaria diagnosis in the Venezuelan Amazon is good but not optimal. The change from the traditional non-blinded quality control system to blinded cross-checking of a minimal selection of samples is - comparatively - a low cost intervention with possibly high impact on the quality of routine malaria diagnosis. The introduction of RDTs should be discussed carefully in order not to displace an existing network of HP microscopists. PMID:21376357

  8. Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status.

    PubMed

    Eisenstein, Sarah A; Bogdan, Ryan; Love-Gregory, Latisha; Corral-Frías, Nadia S; Koller, Jonathan M; Black, Kevin J; Moerlein, Stephen M; Perlmutter, Joel S; Barch, Deanna M; Hershey, Tamara

    2016-10-01

    In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are nonselective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N-[(11) C]methyl)benperidol ([(11) C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in two independent samples. Sample 1 (n = 39) was composed of obese and nonobese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5 to 12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1-), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1- was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [(11) C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states. PMID:27241797

  9. 26 CFR 1.1092(d)-2 - Personal property.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 11 2012-04-01 2012-04-01 false Personal property. 1.1092(d)-2 Section 1.1092(d... (CONTINUED) INCOME TAXES (CONTINUED) Wash Sales of Stock Or Securities § 1.1092(d)-2 Personal property. (a) Special rules for stock. Under section 1092(d)(3)(B), personal property includes any stock that is part...

  10. Effect of age on extrastriatal dopamine D2 receptor availability

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Fowler, J.S. |

    1996-05-01

    It is known that dopamine (DA) D2 receptor availability in basal ganglia decreases with age. This study was done to assess the effects of age on extrastriatal DA D2 receptors. DA D2 receptor availability was evaluated in 42 healthy male subjects (age mean 41 {plus_minus} 16, range 21 -86 year old) using positron emission tomography (PET) and [C-11]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen, thalamus, frontal, occipital cortices, temporal insula, cingulate and orbitofrontal gyri) to that in the cerebellum which is a function of B{sub max.}/K{sub d}. Pearson product-moment correlation was used to evaluate the correlation between age and D2 receptor availability. DA D2 receptor availability in putamen (r {le} 0.0001), caudate (r {le} 0.0002), thalamus (r {le} 0.03), and temporal insula (r {le} 0.01) were significantly correlated with age. The decrements in D2 receptors with age were lower in extrastriatal than in striatal regions and corresponded to a decrease of 4.7% per decade in caudate, 6.2% in putamen, 2.1% in thalamus and 2.5% in temporal insula. This study documents age related decrement of DA D2 receptor availability in striatal and extrastriatal regions.

  11. ISCCP-D2like-GEO Ed3A

    Atmospheric Science Data Center

    2016-06-08

    ... and Order:  Reverb   Reverb Tutorial Subset/Visualization Tool:  CERES Order Tool Order Data:  ... Detailed CERES ISCCP-D2like Product Information Data Products Catalog:  DPC_ISCCP-D2like-GEO_R5V3 ...

  12. 10 CFR 1017.20 - Routine access.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INFORMATION Access to Unclassified Controlled Nuclear Information § 1017.20 Routine access. (a) Authorized... 10 Energy 4 2011-01-01 2011-01-01 false Routine access. 1017.20 Section 1017.20 Energy DEPARTMENT... access to the UCNI, subject to limitations in paragraph (b) of this section, and who may...

  13. 10 CFR 1017.20 - Routine access.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INFORMATION Access to Unclassified Controlled Nuclear Information § 1017.20 Routine access. (a) Authorized... 10 Energy 4 2010-01-01 2010-01-01 false Routine access. 1017.20 Section 1017.20 Energy DEPARTMENT... access to the UCNI, subject to limitations in paragraph (b) of this section, and who may...

  14. Achieving Communicative Competence Through Gambits and Routines.

    ERIC Educational Resources Information Center

    Siskin, H. Jay; Spinelli, Emily

    1987-01-01

    Analyzes the importance of conversational gambits and routines in achieving second language communicative competence and then presents a model which uses telephone conversations as a means of achieving this goal. Exercises for drilling and testing gambits and routines are also presented. (Author/CB)

  15. Making Routine Letters Have Positive Effects.

    ERIC Educational Resources Information Center

    Walsh, S. M.

    While few business people dispute the importance of carefully crafting persuasive, demanding, conciliatory, and bad-news letters, the regular flow of routine communications receives very little meaningful consideration or scrutiny. These routine communications (letters, inquiries, requests, collection letters, complaints, confirmations,…

  16. 40 CFR 141.621 - Routine monitoring.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Routine monitoring. 141.621 Section 141.621 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Stage 2 Disinfection Byproducts Requirements § 141.621 Routine monitoring. (a) Monitoring. (1) If...

  17. Active Movement Warm-Up Routines

    ERIC Educational Resources Information Center

    Walter, Teri; Quint, Ashleigh; Fischer, Kim; Kiger, Joy

    2011-01-01

    This article presents warm-ups that are designed to physiologically and psychologically prepare students for vigorous physical activity. An active movement warm-up routine is made up of three parts: (1) active warm-up movement exercises, (2) general preparation, and (3) the energy system. These warm-up routines can be used with all grade levels…

  18. Metadata Extraction Routines for Improving Infobutton Performance

    PubMed Central

    Hulse, Nathan C.; Haug, Peter J.

    2010-01-01

    Infobuttons have been proven as an effective means for providing quick, context-specific links to pertinent information resources at the point of care. Current infobutton manager implementations, however, lack the ability to exchange metadata, are limited to a relatively small set of information providers, and are targeted primarily for a clinician audience. As part of a local effort to implement infobuttons for patient use via a tethered personal health record, we present a series of metadata extraction routines. These routines were constructed to extract key pieces of information from health information providers on the Internet, including content coverage, language availability, and readability scores. The extraction routines were tested using thirty different disease conditions against eight different providers. The routines yielded 183 potential infobutton targets and associated metadata for each. The capabilities of the extraction routines will be expanded to cover new types of metadata in the future. PMID:21346994

  19. Marfan Database (third edition): new mutations and new routines for the software.

    PubMed Central

    Collod-Béroud, G; Béroud, C; Ades, L; Black, C; Boxer, M; Brock, D J; Holman, K J; de Paepe, A; Francke, U; Grau, U; Hayward, C; Klein, H G; Liu, W; Nuytinck, L; Peltonen, L; Alvarez Perez, A B; Rantamäki, T; Junien, C; Boileau, C

    1998-01-01

    The Marfan database is a software that contains routines for the analysis of mutations identified in the FBN1 gene that encodes fibrillin-1. Mutations in this gene are associated not only with Marfan syndrome but also with a spectrum of overlapping disorders. The third version of the Marfan database contains 137 entries. The software has been modified to accommodate four new routines and is now accessible on the World Wide Web at http://www.umd.necker.fr PMID:9399842

  20. Increased Exposure to Rigid Routines Can Lead to Increased Challenging Behavior Following Changes to Those Routines

    ERIC Educational Resources Information Center

    Bull, Leah E.; Oliver, Chris; Callaghan, Eleanor; Woodcock, Kate A.

    2015-01-01

    Several neurodevelopmental disorders are associated with preference for routine and challenging behavior following changes to routines. We examine individuals with Prader-Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to…

  1. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  2. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  3. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  4. Increased Exposure to Rigid Routines can Lead to Increased Challenging Behavior Following Changes to Those Routines.

    PubMed

    Bull, Leah E; Oliver, Chris; Callaghan, Eleanor; Woodcock, Kate A

    2015-06-01

    Several neurodevelopmental disorders are associated with preference for routine and challenging behavior following changes to routines. We examine individuals with Prader-Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to that routine. Play based challenges exposed 16 participants to routines, which were either adhered to or changed. Temper outburst behaviors, heart rate and movement were measured. As participants were exposed to routines for longer before a change (between 10 and 80 min; within participants), more temper outburst behaviors were elicited by changes. Increased emotional arousal was also elicited, which was indexed by heart rate increases not driven by movement. Further study will be important to understand whether current intervention approaches that limit exposure to changes, may benefit from the structured integration of flexibility to ensure that the opportunity for routine establishment is also limited. PMID:25422033

  5. Habitual routines in task-performing groups

    NASA Technical Reports Server (NTRS)

    Gersick, C. J.; Hackman, J. R.

    1990-01-01

    Groups, like individuals, often develop habitual routines for dealing with frequently encountered stimuli. Although such routines are consequential for group life and work, little is known about them. This paper reconnoiters the territory of habitual behavior in groups that perform work within organizations. We offer a definition of group habits, identify their functions and dysfunctions, suggest how they develop and are maintained, and identify the circumstances when they are likely to be altered or abandoned. Throughout, we give special attention to the social nature of habitual routines in groups, to the interaction between habitual behavior and group life cycle phenomena, and to the role of the organizational context in prompting, shaping, and terminating habitual routines.

  6. Taking medicine at home - create a routine

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000613.htm Taking medicine at home - create a routine To use the ... teeth. Find Ways to Help You Remember Your Medicines You can: Set the alarm on your clock, ...

  7. Pituitary and Brain Dopamine D2 Receptors Regulate Liver Gene Sexual Dimorphism

    PubMed Central

    Ramirez, Maria Cecilia; Ornstein, Ana Maria; Luque, Guillermina Maria; Perez Millan, Maria Ines; Garcia-Tornadu, Isabel; Rubinstein, Marcelo

    2015-01-01

    Liver sexual gene dimorphism, which depends mainly on specific patterns of GH secretion, may underlie differential susceptibility to some liver diseases. Because GH and prolactin secretion are regulated by dopaminergic pathways, we studied the participation of brain and lactotrope dopamine 2 receptors (D2Rs) on liver gene sexual dimorphism, to explore a link between the brain and liver gene expression. We used global D2R knockout mice (Drd2−/−) and conducted a functional dissection strategy based on cell-specific Drd2 inactivation in neurons (neuroDrd2KO) or pituitary lactotropes. Disruption of neuronal D2Rs (which impaired the GH axis) decreased most of male or female-predominant class I liver genes and increased female–predominant class II genes in males, consistent with the positive (class I) or negative (class II) regulation of these genes by GH. Notably, sexual dimorphism was lost for class I and II genes in neuroDrd2KO mice. Disruption of lactotrope D2Rs did not modify class I or II genes in either sex, because GH axis was preserved. But surprisingly, 1 class II gene (Prlr) and female-predominant class I genes were markedly up-regulated in lacDrd2KO females, pointing to direct or indirect effects of prolactin in the regulation of selected female-predominant liver genes. This suggestion was strengthened in the hyperprolactinemic Drd2−/− female mouse, in which increased expression of the same 4 liver genes was observed, despite a decreased GH axis. We hereby demonstrate endocrine-mediated D2R actions on sexual dimorphic liver gene expression, which may be relevant during chronic dopaminergic medications in psychiatric disease. PMID:25545383

  8. A ROLE FOR DOPAMINE D2 RECEPTORS IN REVERSAL LEARNING

    PubMed Central

    DeSTENO, D. A.; SCHMAUSS, C.

    2010-01-01

    Reversal learning has been shown to require intact serotonergic innervation of the forebrain neocortex. Whether dopamine acting through D2 receptors plays a complementary role in this anatomic area is still unclear. Here we show that mice lacking dopamine D2 receptors exhibited significantly impaired performance in the reversal learning phase of an attention-set-shifting task (ASST) and that wild type mice treated chronically with the D2-like receptor antagonist haloperidol exhibited the same cognitive deficit. The test-phase-specific deficits of D2 mutants and haloperidol-treated mice were also accompanied by deficits in the induction of expression of early growth response gene 2 (egr-2), a regulatory transcription factor previously shown to be selectively induced in the ventrolateral orbital frontal cortex and the pre-and infralimbic medial prefrontal cortex of ASST-tested mice. D2-receptor knockout mice and haloperidol-treated wild type, however, exhibited lower egr-2 expression in these anatomic regions after completion of an ASST-test phase that required reversal learning but not after completion of set-shifting phases without rule reversals. In contrast, mice treated chronically with clozapine, an atypical neuroleptic drug with lower D2-receptor affinity and broader pharmacological effects, had deficits in compound discrimination phases of the ASST, but also these deficits were accompanied by lower egr-2 expression in the same anatomic subregions. Thus, the findings indicate that egr-2 expression is a sensitive indicator of test-phase-specific performance in the ASST and that normal function of D2 receptors in subregions of the orbital frontal and the medial prefrontal cortex is required for cognitive flexibility in tests involving rule reversals. PMID:19401217

  9. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.

    PubMed

    Pani, Luca; Pira, Luigi; Marchese, Giorgio

    2007-07-01

    Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008

  10. Role of Dopamine D2 Receptors in Human Reinforcement Learning

    PubMed Central

    Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

    2014-01-01

    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. PMID:24713613

  11. [Effect of flunarizine hydrochloride on striatal D-2 dopamine receptors].

    PubMed

    Ogawa, N; Asanuma, M; Takayama, H; Sato, H; Nukina, I

    1990-11-01

    Flunarizine hydrochloride (FZ) is used to improve cerebral circulation and possesses Ca antagonistic effects. In recent years, this drug has been reported to induce parkinsonism and depressive symptoms as side effects, particularly in the elderly. Effects of FZ on dopamine receptors of the rat striatum were studied by radiolabeled receptor assay to clarify the mechanism of onset of parkinsonism in response to FZ. FZ was found to directly and competitively affect D-2 receptors without affecting D-1 receptors. Furthermore, the effect of FZ on D-2 receptors was found to be antagonistic based on the finding that the displacement curve for FZ in the binding of [3H]spiperone to D-2 receptors remained unchanged even after the addition of GppNHp. The effect of FZ on the D-2 receptors in aged rats was more marked than that in young-adult rats. In addition, the tertiary structures of FZ and the anti-schizophrenic agents, pimozide and haloperidol, were examined using computer graphics. FZ was found to have a tertiary structure highly analogous to pimozide and haloperidol, and FZ also had an alkyl structure linking a fluorophenyl group and a nitrogen atom, believed to be particularly necessary for the binding of anti-schizophrenic agents to D-2 receptors. These results may contribute to clarifying the mechanism of onset of parkinsonism in response to FZ, especially in the elderly. PMID:2150791

  12. Routines for Computing Pressure Drops in Venturis

    NASA Technical Reports Server (NTRS)

    de Quay, Laurence

    2004-01-01

    A set of computer-program routines has been developed for calculating pressure drops and recoveries of flows through standard venturis, nozzle venturis, and orifices. Relative to prior methods used for such calculations, the method implemented by these routines offers greater accuracy because it involves fewer simplifying assumptions and is more generally applicable to wide ranges of flow conditions. These routines are based on conservation of momentum and energy equations for real nonideal fluids, the properties of which are calculated by curve-fitting subroutines based on empirical properties data. These routines are capable of representing cavitating, choked, non-cavitating, and unchoked flow conditions for liquids, gases, and supercritical fluids. For a computation of flow through a given venturi, nozzle venturi, or orifice, the routines determine which flow condition occurs: First, they calculate a throat pressure under the assumption that the flow is unchoked or non-cavitating, then they calculate the throat pressure under the assumption that the flow is choked or cavitating. The assumption that yields the higher throat pressure is selected as the correct one.

  13. Jet spectroscopy of benzyl and benzyl-α-d2

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaru; Obi, Kinichi

    1992-03-01

    Benzyl and benzyl-α-d2 radicals are produced by the ArF laser (193 nm) photolysis of benzylchloride and benzylchloride-α-d2, respectively, in a supersonic free jet. The spectroscopy of the D1 1 2A2-D0 1 2B1 transition of these radicals is studied by means of the laser induced fluorescence (LIF) method. LIF excitation spectra show well resolved but unusual vibrational structure. The assignments of vibronic bands have been carried out on the basis of dispersed spectra from the single vibronic level (SVL) and transition band types derived from rotational analysis of high resolution LIF excitation spectra. The intensity anomaly of the vibronic bands in the excitation spectra is interpreted as the breakdown of the accidental forbidden character of the D1-D0 and D2-D0 electronic transitions, whose mechanism will be discussed in terms of vibronic coupling.

  14. Active stereo vision routines using PRISM-3

    NASA Astrophysics Data System (ADS)

    Antonisse, Hendrick J.

    1992-11-01

    This paper describes work in progress on a set of visual routines and supporting capabilities implemented on the PRISM-3 real-time vision system. The routines are used in an outdoor robot retrieval task. The task requires the robot to locate a donor agent -- a Hero2000 -- which holds the object to be retrieved, to navigate to the donor, to accept the object from the donor, and return to its original location. The routines described here will form an integral part of the navigation and wide-area search tasks. Active perception is exploited to locate the donor using real-time stereo ranging directed by a pan/tilt/verge mechanism. A framework for orchestrating visual search has been implemented and is briefly described.

  15. Routine Radiological Environmental Monitoring Plan. Volume 1

    SciTech Connect

    Bechtel Nevada

    1999-12-31

    The U.S. Department of Energy manages the Nevada Test Site in a manner that meets evolving DOE Missions and responds to the concerns of affected and interested individuals and agencies. This Routine Radiological Monitoring Plan addressess complicance with DOE Orders 5400.1 and 5400.5 and other drivers requiring routine effluent monitoring and environmental surveillance on the Nevada Test Site. This monitoring plan, prepared in 1998, addresses the activities conducted onsite NTS under the Final Environmental Impact Statement and Record of Decision. This radiological monitoring plan, prepared on behalf of the Nevada Test Site Landlord, brings together sitewide environmental surveillance; site-specific effluent monitoring; and operational monitoring conducted by various missions, programs, and projects on the NTS. The plan provides an approach to identifying and conducting routine radiological monitoring at the NTS, based on integrated technical, scientific, and regulatory complicance data needs.

  16. Evidence against dopamine D1/D2 receptor heteromers

    PubMed Central

    Frederick, Aliya L.; Yano, Hideaki; Trifilieff, Pierre; Vishwasrao, Harshad D.; Biezonski, Dominik; Mészáros, József; Sibley, David R.; Kellendonk, Christoph; Sonntag, Kai C.; Graham, Devon L.; Colbran, Roger J.; Stanwood, Gregg D.; Javitch, Jonathan A.

    2014-01-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

  17. Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice.

    PubMed

    França, Arthur S C; Muratori, Larissa; Nascimento, George Carlos; Pereira, Catia Mendes; Ribeiro, Sidarta; Lobão-Soares, Bruno

    2016-07-15

    Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/-), with synaptic dopaminergic levels situated between those shown by DAT -/- homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/- mice showed a deficit in object recognition upon subsequent testing 24h later. This deficit was compensated by a single 0.05mg/kg haloperidol injection 30min before training. In all mice, a 0.3mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity. PMID:27059337

  18. [D2-type dopaminergic receptors and anxiety-depression-like behavior in female rats].

    PubMed

    Fedotova, Iu O

    2012-01-01

    Results of a comparative study of the effects of chronic administration of the D2-receptor agonist quinperole (0.1 mg/kg, i.p.) and the D2-receptor antagonist sulpiride (10.0 mg/kg, i.p.) for 14 days on anxiety- and depressive-like behavior in key phases of the ovarian cycle in adult female rats are presented. The model of depression in rats was implemented in Porsolt test, while the anxiety level was assessed in the elevated plus maze test. It is established that the chronic administration of quinperole produced an anxiolytic action in female rats during diesrous, estrous and proestrous phases, but failed to modify depression-like behavior during the entire ovarian cycle. Sulpiride administration resulted in anxiogenic effect in all phases of the ovarian cycle. It was also found that sulpiride produced some modulation of depression-like behavior in connection to ovarian cycle phases, which was a prodepressive action at a moderate level of estrogens and an antidepressant effect at a reduced/enhanced level of estrogen. It is suggested that the extent of involvement of D2-receptors in the mechanisms of anxiety-depressive-like behavior can vary depending on alterations of the hormonal balance during the ovarian cycle. The data obtained are indicative of a close interaction between ovarian hormonal and dopaminergic systems of the brain involved in the mechanisms of anxiety and depression. PMID:22550850

  19. Celestial: Common astronomical conversion routines and functions

    NASA Astrophysics Data System (ADS)

    Robotham, Aaron S. G.

    2016-02-01

    The R package Celestial contains common astronomy conversion routines, particularly the HMS and degrees schemes, and a large range of functions for calculating properties of different cosmologies (as used by the cosmocalc website). This includes distances, ages, growth rate/factor and densities (e.g., Omega evolution and critical energy density). It also includes functions for calculating thermal properties of the CMB and Planck's equations and virial properties of halos in different cosmologies, and standard NFW and weak-lensing formulas and low level orbital routines for calculating Roche properties, Vis-Viva and free-fall times.

  20. ANSYS duplicate finite-element checker routine

    NASA Technical Reports Server (NTRS)

    Ortega, R.

    1995-01-01

    An ANSYS finite-element code routine to check for duplicated elements within the volume of a three-dimensional (3D) finite-element mesh was developed. The routine developed is used for checking floating elements within a mesh, identically duplicated elements, and intersecting elements with a common face. A space shuttle main engine alternate turbopump development high pressure oxidizer turbopump finite-element model check using the developed subroutine is discussed. Finally, recommendations are provided for duplicate element checking of 3D finite-element models.

  1. Eigenvalue routines in NASTRAN: A comparison with the Block Lanczos method

    NASA Technical Reports Server (NTRS)

    Tischler, V. A.; Venkayya, Vipperla B.

    1993-01-01

    The NASA STRuctural ANalysis (NASTRAN) program is one of the most extensively used engineering applications software in the world. It contains a wealth of matrix operations and numerical solution techniques, and they were used to construct efficient eigenvalue routines. The purpose of this paper is to examine the current eigenvalue routines in NASTRAN and to make efficiency comparisons with a more recent implementation of the Block Lanczos algorithm by Boeing Computer Services (BCS). This eigenvalue routine is now available in the BCS mathematics library as well as in several commercial versions of NASTRAN. In addition, CRAY maintains a modified version of this routine on their network. Several example problems, with a varying number of degrees of freedom, were selected primarily for efficiency bench-marking. Accuracy is not an issue, because they all gave comparable results. The Block Lanczos algorithm was found to be extremely efficient, in particular, for very large size problems.

  2. Eigenvalue routines in NASTRAN: A comparison with the Block Lanczos method

    NASA Astrophysics Data System (ADS)

    Tischler, V. A.; Venkayya, Vipperla B.

    1993-09-01

    The NASA STRuctural ANalysis (NASTRAN) program is one of the most extensively used engineering applications software in the world. It contains a wealth of matrix operations and numerical solution techniques, and they were used to construct efficient eigenvalue routines. The purpose of this paper is to examine the current eigenvalue routines in NASTRAN and to make efficiency comparisons with a more recent implementation of the Block Lanczos algorithm by Boeing Computer Services (BCS). This eigenvalue routine is now available in the BCS mathematics library as well as in several commercial versions of NASTRAN. In addition, CRAY maintains a modified version of this routine on their network. Several example problems, with a varying number of degrees of freedom, were selected primarily for efficiency bench-marking. Accuracy is not an issue, because they all gave comparable results. The Block Lanczos algorithm was found to be extremely efficient, in particular, for very large size problems.

  3. Depletion studies of two contrasting D-2 reefs

    SciTech Connect

    Gillund, G.N.; Patel, C.

    1980-01-01

    The Nisku B and G pools are 2 W. Pembina D-2 pools with contrasting reservoir properties. Average porosity, permeability, and maximum thickness are 5%, 130 md, and 95 m; and 16.4%, 7100 md and 19 m, respectively. The results of the depletion model studies of waterflooding and miscible flooding and some of the problems that occurred during these studies are reviewed.

  4. Stripping lead from D2EHPA by direct displacement reactions

    SciTech Connect

    Chia, L.M.; O`Keefe, T.J.

    1995-07-01

    The direct removal of lead ions from D2EHPA-kerosene using metallic zinc as the reducing agent was evaluated. The electrochemical process, called galvanic stripping, is a potential alternative stripping technique when standard chemical methods are not adequate. Four parameters found to be important in the rate of lead removal were studied in a factorially designed experiment. The variable evaluated included D2EHPA concentration, temperature, zinc surface area and solution agitation. Temperature and surface area were found to be the most significant, while agitation and D2EHPA concentration had less influence on the reaction. An activation energy of 22.5 Kcal/mole was calculated indicating a chemically-controlled process. The reaction was also sensitive to the concentration of oxygen in the system. The zinc required was considerably in excess of stoichiometry, possibly due to the dissolution and redeposition of lead. In general, the results were encouraging and demonstrated that lead impurities could be removed from D2EHPA using cementation type reactions.

  5. Midbrain dopamine D2/3 receptor binding in schizophrenia.

    PubMed

    Tuppurainen, Heli; Kuikka, Jyrki T; Laakso, Mikko P; Viinamäki, Heimo; Husso, Minna; Tiihonen, Jari

    2006-09-01

    Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D(2/3 )receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [(123)I]epidepride for imaging D(2/3 )receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D(2/3 )values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D(2/3 )receptor binding and general psychopathological schizophrenic symptoms (r from -0.78 to -0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients. PMID:16783502

  6. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain... at NARA, call 202-741-6030 or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html... D2 is produced by ultraviolet irradiation of ergosterol isolated from yeast and is purified...

  7. Dopamine D2-like receptor signaling suppresses human osteoclastogenesis.

    PubMed

    Hanami, Kentaro; Nakano, Kazuhisa; Saito, Kazuyoshi; Okada, Yosuke; Yamaoka, Kunihiro; Kubo, Satoshi; Kondo, Masahiro; Tanaka, Yoshiya

    2013-09-01

    Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole reduced the formation of TRAP-positive multi-nucleated cells, cathepsin K mRNA expression, and pit formation area in vitro. These inhibitory effects were reversed by pre-treatment with a D2-like receptor antagonist haloperidol or a Gαi inhibitor pertussis toxin, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, suppressed intracellular cAMP concentration as well as RANKL-meditated induction of c-Fos and NFATc1 mRNA expression in human osteoclast precursor cells. Finally, the dopamine D2-like receptor agonist suppressed LPS-induced osteoclast formation in murine bone marrow culture ex vivo. These findings indicate that dopaminergic signaling plays an important role in bone homeostasis via direct effects upon osteoclast differentiation and further suggest that the clinical use of neuroleptics is likely to affect bone mass. PMID:23631878

  8. Antiretroviral drug resistance and routine therapy, Cameroon.

    PubMed

    Laurent, Christian; Kouanfack, Charles; Vergne, Laurence; Tardy, Michèle; Zekeng, Léopold; Noumsi, Nathalie; Butel, Christelle; Bourgeois, Anke; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Peeters, Martine; Delaporte, Eric

    2006-06-01

    Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.5% had resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 10.2% to non-NRTIs, and 2.3% to protease inhibitors. PMID:16707062

  9. 7 CFR 4287.107 - Routine servicing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE SERVICING Servicing Business and Industry Guaranteed... the December 31 semiannual status report in accordance with 7 CFR part 4279, subpart B, § 4279.107. (b... 7 Agriculture 15 2012-01-01 2012-01-01 false Routine servicing. 4287.107 Section...

  10. 7 CFR 4287.107 - Routine servicing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE SERVICING Servicing Business and Industry Guaranteed... the December 31 semiannual status report in accordance with 7 CFR part 4279, subpart B, § 4279.107. (b... 7 Agriculture 15 2013-01-01 2013-01-01 false Routine servicing. 4287.107 Section...

  11. 7 CFR 4287.107 - Routine servicing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE SERVICING Servicing Business and Industry Guaranteed... the December 31 semiannual status report in accordance with 7 CFR part 4279, subpart B, § 4279.107. (b... 7 Agriculture 15 2014-01-01 2014-01-01 false Routine servicing. 4287.107 Section...

  12. 7 CFR 4287.107 - Routine servicing.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE SERVICING Servicing Business and Industry Guaranteed... the December 31 semiannual status report in accordance with 7 CFR part 4279, subpart B, § 4279.107. (b... 7 Agriculture 15 2011-01-01 2011-01-01 false Routine servicing. 4287.107 Section...

  13. An Examination of Latino Students' Homework Routines

    ERIC Educational Resources Information Center

    Martinez, Sylvia

    2011-01-01

    Homework appears to be positively associated with better student outcomes. Although some researchers have explored the connection between time spent on homework and minority student achievement, few have examined the homework routines of Latino youth. Interviews with Latino high school students show that they have some difficulty completing daily…

  14. Routine Markerless Gene Replacement in Bacillus anthracis

    PubMed Central

    Janes, Brian K.; Stibitz, Scott

    2006-01-01

    An improved genetic tool suitable for routine markerless allelic exchange in Bacillus anthracis has been constructed. Its utility was demonstrated by the introduction of insertions, deletions, and missense mutations on the chromosome and plasmid pXO1 of the Sterne strain of B. anthracis. PMID:16495572

  15. Modular thermal analyzer routine, volume 1

    NASA Technical Reports Server (NTRS)

    Oren, J. A.; Phillips, M. A.; Williams, D. R.

    1972-01-01

    The Modular Thermal Analyzer Routine (MOTAR) is a general thermal analysis routine with strong capabilities for performing thermal analysis of systems containing flowing fluids, fluid system controls (valves, heat exchangers, etc.), life support systems, and thermal radiation situations. Its modular organization permits the analysis of a very wide range of thermal problems for simple problems containing a few conduction nodes to those containing complicated flow and radiation analysis with each problem type being analyzed with peak computational efficiency and maximum ease of use. The organization and programming methods applied to MOTAR achieved a high degree of computer utilization efficiency in terms of computer execution time and storage space required for a given problem. The computer time required to perform a given problem on MOTAR is approximately 40 to 50 percent that required for the currently existing widely used routines. The computer storage requirement for MOTAR is approximately 25 percent more than the most commonly used routines for the most simple problems but the data storage techniques for the more complicated options should save a considerable amount of space.

  16. Routines. Infant/Toddler Caregiving: A Guide.

    ERIC Educational Resources Information Center

    Gonzalez-Mena, Janet

    Intended for use in conjunction with videos illustrating key concepts and caregiving techniques, this guide focuses on how the daily routines of caring for infants and toddlers can become opportunities for promoting the child's learning and development and for deepening the relationship between child and caregiver. Special attention is given to…

  17. Workout to Go: A Sample Exercise Routine

    MedlinePlus

    Workout to Go A Sample Exercise Routine from the National Institute on Aging at NIH i Workout to Go Are you just starting to exercise? Getting back ... into your purse or travel bag, Workout to Go can help you stay in shape for the ...

  18. Individual Values, Learning Routines and Academic Procrastination

    ERIC Educational Resources Information Center

    Dietz, Franziska; Hofer, Manfred; Fries, Stefan

    2007-01-01

    Background: Academic procrastination, the tendency to postpone learning activities, is regarded as a consequence of postmodern values that are prominent in post-industrialized societies. When students strive for leisure goals and have no structured routines for academic tasks, delaying strenuous learning activities becomes probable. Aims: The…

  19. Is routine drainage necessary after pancreaticoduodenectomy?

    PubMed

    Wang, Qiang; Jiang, Yong-Jian; Li, Ji; Yang, Feng; Di, Yang; Yao, Lie; Jin, Chen; Fu, De-Liang

    2014-07-01

    With the development of imaging technology and surgical techniques, pancreatic resections to treat pancreatic tumors, ampulla tumors, and other pancreatic diseases have increased. Pancreaticoduodenectomy, one type of pancreatic resection, is a complex surgery with the loss of pancreatic integrity and various anastomoses. Complications after pancreaticoduodenectomy such as pancreatic fistulas and anastomosis leakage are common and significantly associated with patient outcomes. Pancreatic fistula is one of the most important postoperative complications; this condition can cause intraperitoneal hemorrhage, septic shock, or even death. An effective way has not yet been found to avoid the occurrence of pancreatic fistula. In most medical centers, the frequency of pancreatic fistula has remained between 9% and 13%. The early detection and routine drainage of anastomotic fistulas, pancreatic fistulas, bleeding, or other intra-abdominal fluid collections after pancreatic resections are considered as important and effective ways to reduce postoperative complications and the mortality rate. However, many recent studies have argued that routine drainage after abdominal operations, including pancreaticoduodenectomies, does not affect the incidence of postoperative complications. Although inserting drains after pancreatic resections continues to be a routine procedure, its necessity remains controversial. This article reviews studies of the advantages and disadvantages of routine drainage after pancreaticoduodenectomy and discusses the necessity of this procedure. PMID:25009383

  20. Is routine drainage necessary after pancreaticoduodenectomy?

    PubMed Central

    Wang, Qiang; Jiang, Yong-Jian; Li, Ji; Yang, Feng; Di, Yang; Yao, Lie; Jin, Chen; Fu, De-Liang

    2014-01-01

    With the development of imaging technology and surgical techniques, pancreatic resections to treat pancreatic tumors, ampulla tumors, and other pancreatic diseases have increased. Pancreaticoduodenectomy, one type of pancreatic resection, is a complex surgery with the loss of pancreatic integrity and various anastomoses. Complications after pancreaticoduodenectomy such as pancreatic fistulas and anastomosis leakage are common and significantly associated with patient outcomes. Pancreatic fistula is one of the most important postoperative complications; this condition can cause intraperitoneal hemorrhage, septic shock, or even death. An effective way has not yet been found to avoid the occurrence of pancreatic fistula. In most medical centers, the frequency of pancreatic fistula has remained between 9% and 13%. The early detection and routine drainage of anastomotic fistulas, pancreatic fistulas, bleeding, or other intra-abdominal fluid collections after pancreatic resections are considered as important and effective ways to reduce postoperative complications and the mortality rate. However, many recent studies have argued that routine drainage after abdominal operations, including pancreaticoduodenectomies, does not affect the incidence of postoperative complications. Although inserting drains after pancreatic resections continues to be a routine procedure, its necessity remains controversial. This article reviews studies of the advantages and disadvantages of routine drainage after pancreaticoduodenectomy and discusses the necessity of this procedure. PMID:25009383

  1. Differential Roles for Dopamine D1-Like and D2-Like Receptors in Mediating the Reinforcing Effects of Cocaine: Convergent Evidence from Pharmacological and Genetic Studies

    PubMed Central

    Hiranita, Takato; Collins, Gregory T

    2016-01-01

    A series of studies by Drs. Barak Caine, James Woods, Gregory Collins, Jonathan Katz and Takato Hiranita demonstrated a novel and unique reinforcing effect using dopamine (DA) D2-like receptor [D2-like R: D2, D3, and D4 receptor subtypes (respectively, D2R, D3R, and D4R)] agonists in rats and genetically modified mice. In order to understand how important their findings are, a comparison was made regarding the reinforcing effects of DA D2-like R full agonists with those of DA uptake inhibitors and of a DA D1-like receptor [D1-like R, D1 and D5 receptor subtypes (D1R and D5R)] full agonist (±)-SKF 82958. PMID:27390753

  2. Modified cyanobacteria

    DOEpatents

    Vermaas, Willem F J.

    2014-06-17

    Disclosed is a modified photoautotrophic bacterium comprising genes of interest that are modified in terms of their expression and/or coding region sequence, wherein modification of the genes of interest increases production of a desired product in the bacterium relative to the amount of the desired product production in a photoautotrophic bacterium that is not modified with respect to the genes of interest.

  3. COPD management: role of symptom assessment in routine clinical practice

    PubMed Central

    van der Molen, Thys; Miravitlles, Marc; Kocks, Janwillem WH

    2013-01-01

    Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life. Despite this, COPD treatment and its management are mainly based on lung function assessments. There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives. Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD. Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice. In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. PMID:24143085

  4. Surgical care quality and oncologic outcome after D2 gastrectomy for gastric cancer

    PubMed Central

    Mrena, Johanna; Mattila, Anne; Böhm, Jan; Jantunen, Ismo; Kellokumpu, Ilmo

    2015-01-01

    AIM: To examine the quality of surgical care and long-term oncologic outcome after D2 gastrectomy for gastric cancer. METHODS: From 1999 to 2008, a total of 109 consecutive patients underwent D2 gastrectomy without routine pancreaticosplenectomy in a multimodal setting at our institution. Oncologic outcomes together with clinical and histopathologic data were analyzed in relation to the type of surgery performed. Staging was carried out according to the Union for International Cancer Control criteria of 2002. Patients were followed-up for five years at the outpatient clinic. The primary measure of outcome was long-term survival with the quality of surgery as a secondary outcome measure. Clinical data were retrospectively collected from the patient records, and causes of death were obtained from national registries. RESULTS: A total of 109 patients (58 men) with a mean age of 67.4 ± 11.2 years underwent total gastrectomy or gastric resection with D2 lymph node dissection. The tumor stage distribution was as follows: stage I, (27/109) 24.8%; stage II, (31/109) 28.4%; stage III, (41/109) 37.6%; and stage IV, (10/109) 9.2%. Forty patients (36.7%) received chemotherapy or chemoradiotherapy. The five-year overall survival rate for all 109 patients was 45.0%, and was 47.1% for the 104 patients treated with curative R0 resection. The five-year disease-specific survival rates were 53.0% and 55.8%, respectively. In a multivariate analysis, body mass index and tumor stage were independent prognostic factors for overall survival (both P < 0.01), whereas body mass index, tumor stage, tumor site, Lauren classification, and lymph node invasion were prognostic factors for cancer-specific survival (all P < 0.05). Postoperative 30-d mortality was 1.8% and 30-d, surgical (including three anastomotic leaks, two of which were treated conservatively), and general morbidities were 26.6%, 12.8%, and 14.7%, respectively. CONCLUSION: D2 dissection is a safe surgical option for gastric

  5. The place of routine HIV testing.

    PubMed

    2011-08-01

    In 2009, around 86,500 people in the UK had HIV infection, of whom around a quarter were unaware of their condition. Of adults diagnosed in that year, around half were already at a late stage of disease (with a CD4 count below 350 cells/μL or presenting with an AIDS-defining event). Such late diagnosis represents a missed opportunity for treatment and prevention, and is associated with significant morbidity and mortality, reduced response to antiretroviral drugs and increased healthcare costs. In genitourinary medicine (GUM) clinics and during antenatal care, there is a high uptake rate of routine testing (i.e. HIV tests are offered as part of standard care and the individual has the option to decline). Increasing such testing across other healthcare settings could reduce late diagnosis. Here we examine issues around routine HIV testing. PMID:21813559

  6. PROFIT: Emission-line PROfile FITting routine

    NASA Astrophysics Data System (ADS)

    Riffel, Rogemar A.

    2012-04-01

    The PROFIT is an IDL routine to do automated fitting of emission-line profiles by Gaussian curves or Gauss-Hermite series otimized for use in Integral Field and Fabry-Perot data cubes. As output PROFIT gives two-dimensional FITS files for the emission-line flux distribution, centroid velocity, velocity dispersion and higher order Gauss-Hermite moments (h3 and h4).

  7. Is routine use of episiotomy justified?

    PubMed

    Lede, R L; Belizán, J M; Carroli, G

    1996-05-01

    Episiotomy, one of the most common surgical procedures, was introduced in clinical practice in the eighteenth century without having strong scientific evidence of its benefits. Its use was justified by the prevention of severe perineal tears, better future sexual function, and a reduction of urine and fecal incontinence. With regard to the first assumption, the evidence that is based on five randomized controlled trials shows a 9% reduction in severe perineal tears in the selective use of episiotomy, but this effect fluctuates between a 40% reduction and a 38% increase. In relation to long-term effects, women in whom management includes routine use of episiotomy have shown poorer future sexual function, similar pelvic floor muscle strength, and similar urinary incontinence in comparison with women in whom episiotomy is used in a selective manner. In summary, there is no reliable evidence that routine use of episiotomy has any beneficial effect; on the contrary, there is clear evidence that it may cause harm such as a greater need for surgical repair and a poorer future sexual capability. In view of the available evidence the routine use of episiotomy should be abandoned and episiotomy rates > 30% do not seem justified. PMID:9065102

  8. Update on Routine Childhood and Adolescent Immunizations.

    PubMed

    Ackerman, Lani K; Serrano, Jacquelyn L

    2015-09-15

    Recommendations for routine vaccinations in children and adolescents have changed multiple times in recent years, based on findings in clinical trials, licensure of new vaccines, and evidence of waning immunity. Despite the overwhelming success of vaccinations, vaccine delay and refusal are leading to pockets of vaccine-preventable diseases. Schedules for diphtheria and tetanus toxoids, and acellular pertussis (DTaP); hepatitis A and B; Haemophilus influenzae type b (Hib); inactivated poliovirus; varicella; and measles, mumps, and rubella are unchanged. However, since 2008, 13-valent pneumococcal conjugate vaccine has replaced the 7-valent vaccine; a new two-dose oral rotavirus vaccine has been approved; use of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been expanded to children seven to 10 years of age who received fewer than five doses of DTaP, as well as during each pregnancy; a booster dose of meningococcal vaccine is recommended in adolescents 16 to 18 years of age (unless the first dose was given after 16 years of age); new meningococcal vaccines have been approved for use in infants at high risk of meningococcal disease; influenza vaccine has been expanded to routine use in all children six months and older; and the human papillomavirus vaccine has been approved for routine immunization of adolescent boys and girls. For the 2015-2016 influenza season, either live attenuated or inactivated vaccine can be administered to healthy children two to eight years of age. PMID:26371731

  9. Freezing of heavy water (D2O) nanodroplets.

    PubMed

    Bhabhe, Ashutosh; Pathak, Harshad; Wyslouzil, Barbara E

    2013-07-01

    We follow the freezing of heavy water (D2O) nanodroplets formed in a supersonic nozzle apparatus using position resolved pressure trace measurements, Fourier transform infrared spectroscopy, and small-angle X-ray scattering. For these 3-9 nm radii droplets, freezing starts between 223 and 225 K, at volume based ice nucleation rates Jice,V on the order of 10(23) cm(-3) s(-1) or surface based ice nucleation rates Jice,S on the order of 10(16) cm(-2) s(-1). The temperatures corresponding to the onset of D2O ice nucleation are higher than those reported for H2O by Manka et al. [Manka, A.; Pathak, H.; Tanimura, S.; Wölk, J.; Strey, R.; Wyslouzil, B. E. Phys. Chem. Chem. Phys.2012, 14, 4505]. Although the values of Jice,S scale somewhat better with droplet size than values of Jice,V, the data are not accurate enough to state that nucleation is surface initiated. Finally, using current estimates of the thermophysical properties of D2O and the theoretical framework presented by Murray et al. [Murray, B. J.; Broadley, S. L.; Wilson, T. W.; Bull, S. J.; Wills, R. H.; Christenson, H. K.; Murray, E. J. Phys. Chem. Chem. Phys.2010, 12, 10380], we find that the theoretical ice nucleation rates are within 3 orders of magnitude of the measured rates over an ∼15 K temperature range. PMID:23763363

  10. Dopamine D2/D3 receptor availability and venturesomeness.

    PubMed

    Bernow, Nina; Yakushev, Igor; Landvogt, Christian; Buchholz, Hans-Georg; Smolka, Michael N; Bartenstein, Peter; Lieb, Klaus; Gründer, Gerhard; Vernaleken, Ingo; Schreckenberger, Mathias; Fehr, Christoph

    2011-08-30

    The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-Venturesomeness-Empathy questionnaire (I7). Image processing and statistical analysis was performed on a voxel-by-voxel basis using statistical parametric mapping (SPM) software. The I7 subscale venturesomeness correlated positively with the D2/D3 receptor availability within the left temporal cortex and the thalamus. Measures on the I7 subscale impulsiveness and empathy did not correlate with the D2/D3 receptor availability in any brain region investigated. Our results suggest the involvement of extrastriatal dopaminergic neurotransmission in venturesomeness, a component of impulsivity. PMID:21689908

  11. Parent routines for managing cystic fibrosis in children.

    PubMed

    Grossoehme, Daniel H; Filigno, Stephanie Spear; Bishop, Meredith

    2014-06-01

    Management of cystic fibrosis (CF) is burdensome and adherence is often suboptimal. Family routines are associated with adherence and health outcomes in other disease populations. Few studies have examined routines in CF. The study's aim was to describe parent experiences developing and utilizing CF care routines. Semi-structured interviews with a convenience sample of 25 parents of children under 13 years of age with CF were analyzed using phenomenological analysis. Three domains emerged: parent experiences developing a routine, support systems facilitating maintenance of routines, and challenges with maintaining care routines. Parents found routines difficult to establish, used trial and error, encountered barriers, and found support helpful to manage care demands. Some parents chose to deviate from their routine. Providing anticipatory guidance to promote the use of care routines and strategies to manage potential challenges may facilitate use of routines and improve CF management. PMID:24838648

  12. Dopamine D2 receptor status assessed by IBZM SPECT - A sensitive indicator for cerebral hypoxia

    SciTech Connect

    Tatsch, K.; Schwarz, J.; Welz, A.

    1995-05-01

    The striatum is highly sensitive to tissue hypoxia. Thus, it may be suggested that cerebral hypoxia could affect the integrity of the striatal receptor system. Purpose of the current SPECT investigations with IBZM was to evaluate whether hypoxic conditions cause detectable changes in the D2 receptor status. 25 controls and 30 pts with history of cerebral hypoxia (resuscitation after cardiac arrest: n=19, CABG surgery under cardiopulmonary bypass: n=11) were investigated with SPECT 2h p.i. of 185 MBq I-123 IBZM. For semiquant, evaluation transverse slices corrected for attenuation were used to calculate striatal to frontal cortex (S/FC) ratios. In 13/19 pts with cerebral hypoxia due to cardiac arrest IBZM binding was severely reduced after successful resuscitation. 7 died, 5 were in a vegetative state, 1 remained severely disabled. In 6/19 S/FC ratios were normal/mildly reduced, 2 of them had a good outcome, 4 were moderatley disabled. In pts with CABG IBZM binding was preoperatively normal. After hypoxia due to cardiac surgery striatal S/FC ratios decreased slightly, persisting on this level even 6 months after surgery. Neuropsychological/psychiatric testing showed only minor or transient changes in this group of patients. The striatal D2 receptor status seems to be a sensitive indicator for cerebral hypoxia. After hypoxia due to cardiac arrest IBZM results well correlate (in contrast to morphological or SEP findings) with the clinical outcome and thus may serve as early predictor of the individual prognosis. The moderate decline in IBZM binding following CABG surgery suggests mild cerebral hypoxia despite of protective hypothermia. Sensitively indicating cerebral hypoxia changes in the D2 receptor status assessed by IBZM SPECT may serve as a valuable diagnostic tool for testing neuroprotective drugs or modified surgical techniques.

  13. Functional dopamine D2 receptors on rat vagal afferent neurones.

    PubMed Central

    Lawrence, A J; Krstew, E; Jarrott, B

    1995-01-01

    1. In the present study in vitro electrophysiology and receptor autoradiography were used to determine whether rat vagal afferent neurones possess dopamine D2 receptors. 2. Dopamine (10-300 microM) elicited a temperature- and concentration-dependent depolarization of the rat isolated nodose ganglion preparation. When applied to the tissue 15 min prior to agonist, raclopride (10 microM), clozapine (10 microM) or a mixture of raclopride and clozapine (10 microM each) all produced a threefold parallel shift to the right of the dopamine concentration-response curve. In contrast, SCH 23390 (100 nM), phentolamine and propranolol (1 microM each) failed to antagonize the dopamine-mediated depolarization. 3. [125I]-NCQ 298 (0.5 nM), a D2 selective radioligand, bound topographically to sections of rat brainstem. Densitometric quantification of autoradiograms revealed 93.8 +/- 0.5% specific binding of this salicylamide radioligand, as determined by raclopride (10 microM, n = 10 animals). Binding was highest in the nucleus tractus solitarius (NTS), particularly the medial and gelatinous subnuclei. In addition, specific binding was also observed in the interpolar spinal trigeminal nucleus and the inferior olive. 4. Unilateral nodose ganglionectomy caused a 36.6 +/- 3.0% reduction in specific binding in the denervated NTS compared to the contralateral NTS. Furthermore, the loss of binding was confined to the dorsal aspect of the medial subnucleus of the NTS. Sham surgery had no effect on the binding of [125I]-NCQ 298 in rat brainstem. 5. The present data provide evidence for the presence of functionally relevant dopamine D2 receptors on both the soma and central terminals of rat vagal afferent neurones.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 3 PMID:7606337

  14. Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

    PubMed Central

    Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima; Nasello, Cara; Sarkar, Dipak K.

    2015-01-01

    Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells. PMID:26509893

  15. Anomeric and tautomeric equilibria in D-2-glucosamine Schiff bases

    NASA Astrophysics Data System (ADS)

    Kołodziej, B.; Grech, E.; Schilf, W.; Kamieński, B.; Makowski, M.; Rozwadowski, Z.; Dziembowska, T.

    2007-11-01

    The structure of some glucosamine Schiff bases has been studied by means of ab initio RHF and DFT calculation and CP/MAS 13C and 15N NMR measurements. The anomeric and tautomeric equilibria in a DMSO solution have been studied by 1H, 13C and 15N NMR spectroscopy. The anomeric composition of D-2-glucosamine Schiff bases in the solid state and in DMSO solution has been shown to depends on the tautomeric form of Schiff bases and electronic properties of substituents on the aromatic ring.

  16. Generating generalized G{sub D-2} solutions

    SciTech Connect

    Breton, N.; Lopez, L. A.; Feinstein, A.

    2008-06-15

    We show how one can systematically construct vacuum solutions to Einstein field equations with D-2 commuting Killing vectors in D>4 dimensions. The construction uses Einstein-scalar field seed solutions in four dimensions and is performed both for the case when all the Killing directions are spacelike, as well as when one of the Killing vectors is timelike. The later case corresponds to generalizations of stationary axially symmetric solutions to higher dimensions. Some examples representing generalizations of known higher dimensional stationary solutions are discussed in terms of their rod structure and horizon locations and deformations.

  17. Assessing 3D tunnel position in ACL reconstruction using a novel single image 3D-2D registration

    NASA Astrophysics Data System (ADS)

    Kang, X.; Yau, W. P.; Otake, Y.; Cheung, P. Y. S.; Hu, Y.; Taylor, R. H.

    2012-02-01

    The routinely used procedure for evaluating tunnel positions following anterior cruciate ligament (ACL) reconstructions based on standard X-ray images is known to pose difficulties in terms of obtaining accurate measures, especially in providing three-dimensional tunnel positions. This is largely due to the variability in individual knee joint pose relative to X-ray plates. Accurate results were reported using postoperative CT. However, its extensive usage in clinical routine is hampered by its major requirement of having CT scans of individual patients, which is not available for most ACL reconstructions. These difficulties are addressed through the proposed method, which aligns a knee model to X-ray images using our novel single-image 3D-2D registration method and then estimates the 3D tunnel position. In the proposed method, the alignment is achieved by using a novel contour-based 3D-2D registration method wherein image contours are treated as a set of oriented points. However, instead of using some form of orientation weighting function and multiplying it with a distance function, we formulate the 3D-2D registration as a probability density estimation using a mixture of von Mises-Fisher-Gaussian (vMFG) distributions and solve it through an expectation maximization (EM) algorithm. Compared with the ground-truth established from postoperative CT, our registration method in an experiment using a plastic phantom showed accurate results with errors of (-0.43°+/-1.19°, 0.45°+/-2.17°, 0.23°+/-1.05°) and (0.03+/-0.55, -0.03+/-0.54, -2.73+/-1.64) mm. As for the entry point of the ACL tunnel, one of the key measurements, it was obtained with high accuracy of 0.53+/-0.30 mm distance errors.

  18. CPU timing routines for a CONVEX C220 computer system

    NASA Technical Reports Server (NTRS)

    Bynum, Mary Ann

    1989-01-01

    The timing routines available on the CONVEX C220 computer system in the Structural Mechanics Division (SMD) at NASA Langley Research Center are examined. The function of the timing routines, the use of the timing routines in sequential, parallel, and vector code, and the interpretation of the results from the timing routines with respect to the CONVEX model of computing are described. The timing routines available on the SMD CONVEX fall into two groups. The first group includes standard timing routines generally available with UNIX 4.3 BSD operating systems, while the second group includes routines unique to the SMD CONVEX. The standard timing routines described in this report are /bin/csh time,/bin/time, etime, and ctime. The routines unique to the SMD CONVEX are getinfo, second, cputime, toc, and a parallel profiling package made up of palprof, palinit, and palsum.

  19. Just a routine operation: a critical discussion.

    PubMed

    McClelland, G; Smith, M B

    2016-05-01

    This article has summarised a critical discussion of the human factors that contributed to the death of a patient from a failure to respond appropriately to a 'can't intubate, can't ventilate' scenario. The contributory factors included the clinical team's inability to communicate, prioritise tasks and demonstrate effective leadership and assertive followership. The film Just a routine operation has now been in circulation for several years. When a system is designed and introduced with the intention of making a change to clinical practice, it can quickly become just another component of an organisation's architecture and complacency around its use can develop. This article has been written specifically for perioperative practitioners to renew the debate around the human factors that contribute to patient harm. By critically discussing Just a routine operation and attempting to review why the incident occurred, this article has attempted to emphasise that some of the conditions and behaviours that contributed to the death of Elaine Bromiley may be latent within our organisations and teams, and may continue to contribute to failures that affect patient safety. PMID:27400489

  20. The dissolution of metallic zinc in D2EHPA

    SciTech Connect

    Chia, L.M.; Neira, M.P.; O`Keefe, T.J.

    1995-07-01

    The direct dissolution of zinc in an organic solution of di-(2-ethylhexyl) phosphoric acid (D2EHPA) and kerosene was studied. The objective was to gain a better understanding of the fundamentals involved in the anodic step of the galvanic stripping process. Results showed that metallic zinc does dissolve spontaneously at ambient temperature by an electrochemical mechanism and the presence of additional oxygen activated the process. When oxygen was removed by prior nitrogen sparging, dissolution did not occur indicating a depolarizing cathodic reaction is necessary. The concentration of water in the organic also affected the rate of dissolution. A factorially designed experiment was made using four variables at two levels selected by evaluating results from previous screening tests. D2EHPA concentration, surface area and agitation were all found to be significant for the values chosen. Temperature was less significant and it was found that zinc dissolution is probably a diffusion or mixed controlled process, as indicated by the calculated activation energy of 6 kcal/mole.

  1. Marginal fluctuations as instantons on M2/D2-branes

    NASA Astrophysics Data System (ADS)

    Naghdi, M.

    2014-03-01

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over spaces, where we use and for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis-Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of and , and it agrees with a marginal boundary operator of the conformal dimension of . However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all supersymmetries to , while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations and for the supercharges and scalars, respectively, while the fermions remain fixed in of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full gauge group along the same lines with a similar situation to the one faced in the AdS/CFT correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for as well.

  2. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS... LABELING RULEâ) Pt. 305, App. D2 Appendix D2 to Part 305—Water Heaters—Electric Range Information...

  3. The Emerging Role of D-2-Hydroxyglutarate as an Oncometabolite in Hematolymphoid and Central Nervous System Neoplasms

    PubMed Central

    Rakheja, Dinesh; Medeiros, L. Jeffrey; Bevan, Scott; Chen, Weina

    2013-01-01

    Approximately 20% of unselected cases and 30% cytogenetically diploid cases of acute myeloid leukemia (AML) and 80% of grade II–III gliomas and secondary glioblastomas carry mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes. IDH1/2 mutations prevent oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) and modulate the function of IDH (neomorphic activity) thereby facilitating reduction of α-KG to D-2-hydroxyglutarate (D-2HG), a putative oncometabolite. D-2HG is thought to act as a competitive inhibitor of α-KG-dependent dioxygenases that include prolyl hydroxylases and chromatin-modifying enzymes. The end result is a global increase of cellular DNA hypermethylation and alterations of the cellular epigenetic state, which has been proposed to play a role in the development of a variety of tumors. In this review, we provide an update on potential molecular mechanisms linking IDH1/2 mutations and the resulting oncometabolite, D-2HG, with malignant transformation. In addition, in patients with AML and glioma we focus on the associations between IDH1/2 mutations and clinical, morphologic, cytogenetic, and molecular characteristics. PMID:23847760

  4. All the solutions of the form M2 × WΣd - 2 for Lovelock gravity in vacuum in the Chern-Simons case

    NASA Astrophysics Data System (ADS)

    Oliva, Julio

    2013-04-01

    In this paper we classify a certain family of solutions of Lovelock gravity in the Chern-Simons (CS) case, in arbitrary (odd) dimension, d ⩾ 5. The spacetime is characterized by admitting a metric that is a warped product of a two-dimensional spacetime M2 and an (a priori) arbitrary Euclidean manifold Σd-2 of dimension d - 2. We show that the solutions are naturally classified in terms of the equations that restrict Σd-2. According to the strength of such constraints we found the following branches in which Σd-2 has to fulfill: a Lovelock equation with a single vacuum (Euclidean Lovelock Chern-Simons in dimension d - 2), a single scalar equation that is the trace of an Euclidean Lovelock CS equation in dimension d - 2, or finally a degenerate case in which Σd-2 is not restricted at all. We show that all the cases have some degeneracy in the sense that the metric functions are not completely fixed by the field equations. This result extends the static five-dimensional case previously discussed in Dotti et al. [Phys. Rev. D 76, 064038 (2007)], 10.1103/PhysRevD.76.064038, and it shows that in the CS case, the inclusion of higher powers in the curvature does not introduce new branches of solutions in Lovelock gravity. Finally, we comment on how the inclusion of a non-vanishing torsion may modify this analysis.

  5. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats.

    PubMed

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  6. Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mPFC of Adult Rats

    PubMed Central

    Castillo-Gómez, Esther; Varea, Emilio; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Nacher, Juan

    2016-01-01

    Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal neurons, two additional features affected in schizophrenia. To evaluate these parameters, we have chronically treated adult rats with PPHT (a D2R agonist) after enzymatic removal of PSA with Endo-N. Both treatments decreased spine density in apical dendrites of pyramidal neurons without affecting their inhibitory innervation. Endo-N also reduced the expression of vesicular glutamate transporter-1. These results indicate that D2R and PSA-NCAM are important players in the regulation of the structural plasticity of mPFC excitatory neurons. This is relevant to our understanding of the neurobiological basis of schizophrenia, in which structural alterations of pyramidal neurons and altered expression of D2R and PSA-NCAM have been found. PMID:27110404

  7. Cost-utility of routine cataract surgery

    PubMed Central

    Räsänen, Pirjo; Krootila, Kari; Sintonen, Harri; Leivo, Tiina; Koivisto, Anna-Maija; Ryynänen, Olli-Pekka; Blom, Marja; Roine, Risto P

    2006-01-01

    Background If decisions on health care spending are to be as rational and objective as possible, knowledge on cost-effectiveness of routine care is essential. Our aim, therefore, was to evaluate the cost-utility of routine cataract surgery in a real-world setting. Methods Prospective assessment of health-related quality of life (HRQoL) of patients undergoing cataract surgery. 219 patients (mean (SD) age 71 (11) years) entering cataract surgery (in 87 only first eye operated, in 73 both eyes operated, in 59 first eye had been operated earlier) filled in the 15D HRQoL questionnaire before and six months after operation. Direct hospital costs were obtained from a clinical patient administration database and cost-utility analysis performed from the perspective of the secondary care provider extrapolating benefits of surgery to the remaining statistical life-expectancy of the patients. Results Mean (SD) utility score (on a 0–1 scale) increased statistically insignificantly from 0.82 (0.13) to 0.83 (0.14). Of the 15 dimensions of the HRQoL instrument, only seeing improved significantly after operation. Mean utility score improved statistically significantly only in patients reporting significant or major preoperative seeing problems. Of the subgroups, only those whose both eyes were operated during follow-up showed a statistically significant (p < 0.001) improvement. Cost per quality-adjusted life year (QALY) gained was €5128 for patients whose both eyes were operated and €8212 for patients with only one eye operated during the 6-month follow-up. In patients whose first eye had been operated earlier mean HRQoL deteriorated after surgery precluding the establishment of the cost per QALY. Conclusion Mean utility gain after routine cataract surgery in a real-world setting was relatively small and confined mostly to patients whose both eyes were operated. The cost of cataract surgery per quality-adjusted life year gained was much higher than previously reported and

  8. Thermal and flow analysis subroutines for the SINDA-version 9 computer routine

    NASA Technical Reports Server (NTRS)

    Oren, J. A.; Williams, D. R.

    1973-01-01

    Fluid flow analysis, special thermal analysis and input/output capabilities of the MOTAR routine were incorporated into the SINDA routine. All the capabilities were added in the form of user subroutines so that they may be added to different versions of SINDA with a minimum of programmer effort. Two modifications were made to the existing subroutines of SINDA/8 to incorporate the above subroutines. These were: (1) A modification to the preprocessor to permit actual values of array numbers, conductor numbers, node numbers or constant numbers supplied as array data to be converted to relative numbers. (2) Modifications to execution subroutine CNFAST to make it compatible with the radiant interchange user subroutine, RADIR. This modified version of SINDA has been designated SINDA/version 9. A detailed discussion of the methods used for the capabilities added is presented. The modifications for the SINDA subroutines are described, as well as user subroutines. All subroutines added or modified are listed.

  9. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

    PubMed

    Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

    2011-11-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards. PMID:21803530

  10. Routine dyspnea assessment on unit admission.

    PubMed

    Baker, Kathy; Barsamian, Jennifer; Leone, Danielle; Donovan, Barbara C; Williams, Donna; Carnevale, Kerry; Lansing, Robert; Banzett, Robert

    2013-11-01

    Dyspnea assessment is valuable in diagnosis, prognosis, symptom management, and targeted intervention, and in the allotment and management of patient care resources. The assessment of dyspnea, like that of pain, depends on patient self-report. Expert consensus panels have called for dyspnea to be measured quantitatively and documented on a routine basis, as is the practice with pain. But little information is available on how to measure and record dyspnea ratings systematically. Consequently, the prevalence of dyspnea in hospital settings may be greater than is generally recognized, and dyspnea may be insufficiently managed. This article describes a pilot study that sought to test the feasibility of measuring dyspnea as part of the initial patient assessment performed by nurses within several inpatient units of a large urban hospital. PMID:24113531

  11. Recommendations on routine screening pelvic examination

    PubMed Central

    Tonelli, Marcello; Gorber, Sarah Connor; Moore, Ainsley; Thombs, Brett D.

    2016-01-01

    Abstract Objective To review the 2014 American College of Physicians (ACP) guideline on the use of pelvic examinations to screen for cancer (other than cervical), pelvic inflammatory disease, or other benign gynecologic conditions to determine whether the ACP guideline on routine pelvic examinations was consistent with Canadian Task Force on Preventive Health Care (CTFPHC) standards and could be adapted or adopted. Methods The SNAP-IT (Smooth National Adaptation and Presentation of Guidelines to Improve Thrombosis Treatment) method was used to determine whether the ACP guideline was consistent with CTFPHC standards and could be adapted or adopted. Recommendations The CTFPHC recommends not performing a screening pelvic examination to screen for noncervical cancer, pelvic inflammatory disease, or other gynecological conditions in asymptomatic women. This is a strong recommendation with moderate-quality evidence. Conclusion The CTFPHC adopts the recommendation on screening pelvic examination as published by the ACP in 2014. PMID:26975912

  12. [Routine hematologic parameters for thalassemia screening].

    PubMed

    Schubert, S; Christofi, Y; Papadatou, A

    1990-01-01

    There is an evaluation of routine examination of the blood film for the recognition of Thalassaemia (Th.). The results of 100 blood films from each group--Th. major, Th. minor, healthy persons (centre for Thalassaemia "Bishop Makarios"/Nikosia--Cypros)-were analyzed. MCV and MCH were most useful for the recognition of Th. minor. The constellation of increased red blood cells and normal hemoglobin seems to be typical for Th. minor. Haemoglobin and haematocrit are not suited because they were widely normal. Target cells also are not sufficient for screening--they were present only in 10% of Th. minor. To the contrary most values were clearly decreased in Th. major, and target cells were present here in almost 90%. PMID:1713894

  13. The routinization of hospice: charisma and bureaucratization.

    PubMed

    James, N; Field, D

    1992-06-01

    In 25 years the number of hospices in Britain has multiplied from under 15 in 1965 to over 430 in 1991. During this period, often working out with the mainstream health system, the hospices actively sought to transform terminal care. More recently a process of diversification and legitimation has meant that hospices have become increasingly subject to mainstream influence. Using Weber's concept of charisma we examine the development of the hospice movement during this period of expansion. We suggest there are a number of factors leading to the routinization of hospice care including the ways in which it was sponsored and developed at the local level, and pressures toward bureaucratization and professionalization. We make links with recent developments in the health services. Finally we consider whether it is possible for the hospice movement to sustain its founding ideals. PMID:1529374

  14. Effects of the d 2 dwarfing gene in pearl millet.

    PubMed

    Bidinger, F R; Raju, D S

    1990-04-01

    Dwarf varieties have had virtually no impact on the production of pearl millet, in contrast to the case of wheat, rice, and sorghum. This research compared tall and dwarf near-isogenic F1 hybrids to attempt to determine if there were deleterious effects of the d 2 dwarfing gene that might account for the lack of release/cultivation of dwarf pearl millet cultivars. Dwarf isohybrids on average yielded less than the tails, because of a smaller average seed size combined with a similar grain number per unit area. There was, however, a larger contribution of background genetic variation (pollinator, male-sterile, and interaction effects) to hybrid variation for nearly all characters measured, including seed size, than there was of the dwarfing gene. Selection of dwarf parents capable of producing hybrids with equal seed size and yield to that of tall parents should not be difficult. PMID:24226457

  15. When Routines Are Not so Routine: Exploring Coordination Work in Hospitals

    ERIC Educational Resources Information Center

    Haque, Saira Naim

    2010-01-01

    Many work processes take place through routines, or recurrent patterns of action. These activities involve individuals from several occupations working across spatial, temporal, and organizational boundaries. Crossing these professional, temporal and spatial boundaries has unique challenges which can lead to coordination failures. In these…

  16. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  17. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  18. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  19. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  20. 42 CFR 493.1210 - Condition: Routine chemistry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, §...

  1. Rituals and Routines: Supporting Infants and Toddlers and Their Families

    ERIC Educational Resources Information Center

    Gillespie, Linda; Petersen, Sandra

    2012-01-01

    The words "routine" and "ritual" are sometimes used interchangeably. Yet there are some important differences. Routines are repeated, predictable events that provide a foundation for the daily tasks in a child's life. Teachers can create a predictable routine in early childhood settings for infants and toddlers, and they can individualize those…

  2. The effects of fast-off-D2 receptor antagonism on L-DOPA-induced dyskinesia and psychosis in parkinsonian macaques.

    PubMed

    Koprich, James B; Huot, Philippe; Fox, Susan H; Jarvie, Keith; Lang, Anthony E; Seeman, Philip; Brotchie, Jonathan M

    2013-06-01

    3,4-Dihydroxyphenylalanine (L-DOPA) treatment of Parkinson's disease (PD) is compromised by motor side effects, such as dyskinesia and non-motor problems, including psychosis. Because of the marked reduction in brain dopamine in PD and the resultant dopamine D2 receptor supersensitivity, it is impossible to use standard potent dopamine D2 receptor antagonists such as haloperidol to alleviate side effects without compromising the anti-parkinsonian benefits of L-DOPA. Haloperidol antagonizes D2 receptors with high affinity and slowly dissociates from D2 receptors (50% dissociation at 38min). We hypothesized that a rapidly dissociating D2 antagonist might allow some functional dopaminergic transmission and thus have a profile, with respect to reduction of dyskinesia and anti-parkinsonian effects, that was more useful therapeutically. The present study tested the principle of using a fast-off-D2 drug, CLR151 (50% dissociation at 23s) to modify L-DOPA actions in cynomolgus macaques with MPTP-parkinsonism. CLR151 (100mg/kg p.o.) reduced L-DOPA-induced dyskinesia and activity in the parkinsonian macaque by 86% and 52% respectively during peak action. CLR151 (100mg/kg) also reduced psychosis-like behaviour (i.e. reduced apparent visual hallucinations by 78%). Nevertheless, this dose of CLR151 significantly reduced the duration of anti-parkinsonian action of L-DOPA, ON-time (by 90%), and increased parkinsonian disability (by 57%). These data suggest that fast-off-D2 dopamine receptor antagonists, with D2-off-rate values close to those for CLR151, are unlikely to be useful in the treatment of dyskinesia and psychosis in PD. However, fast-off-D2 drugs could provide benefit if new congeners would have an even faster dissociation rate. Such drugs are now becoming available. PMID:23306217

  3. Plant d-2-Hydroxyglutarate Dehydrogenase Participates in the Catabolism of Lysine Especially during Senescence*

    PubMed Central

    Engqvist, Martin K. M.; Kuhn, Anke; Wienstroer, Judith; Weber, Katrin; Jansen, Erwin E. W.; Jakobs, Cornelis; Weber, Andreas P. M.; Maurino, Veronica G.

    2011-01-01

    d-2-Hydroxyglutarate dehydrogenase (d-2HGDH) catalyzes the specific and efficient oxidation of d-2-hydroxyglutarate (d-2HG) to 2-oxoglutarate using FAD as a cofactor. In this work, we demonstrate that d-2HGDH localizes to plant mitochondria and that its expression increases gradually during developmental and dark-induced senescence in Arabidopsis thaliana, indicating an enhanced demand of respiration of alternative substrates through this enzymatic system under these conditions. Using loss-of-function mutants in d-2HGDH (d2hgdh1) and stable isotope dilution LC-MS/MS, we found that the d-isomer of 2HG accumulated in leaves of d2hgdh1 during both forms of carbon starvation. In addition to this, d2hgdh1 presented enhanced levels of most TCA cycle intermediates and free amino acids. In contrast to the deleterious effects caused by a deficiency in d-2HGDH in humans, d2hgdh1 and overexpressing lines of d-2HGDH showed normal developmental and senescence phenotypes, indicating a mild role of d-2HGDH in the tested conditions. Moreover, metabolic fingerprinting of leaves of plants grown in media supplemented with putative precursors indicated that d-2HG most probably originates during the catabolism of lysine. Finally, the l-isomer of 2HG was also detected in leaf extracts, indicating that both chiral forms of 2HG participate in plant metabolism. PMID:21296880

  4. Development of Message Passing Routines for High Performance Parallel Computations

    NASA Technical Reports Server (NTRS)

    Summers, Edward K.

    2004-01-01

    Computational Fluid Dynamics (CFD) calculations require a great deal of computing power for completing the detailed computations involved. In an effort shorten the time it takes to complete such calculations they are implemented on a parallel computer. In the case of a parallel computer some sort of message passing structure must be used to communicate between the computers because, unlike a single machine, each computer in a parallel computing cluster does not have access to all the data or run all the parts of the total program. Thus, message passing is used to divide up the data and send instructions to each machine. The nature of my work this summer involves programming the "message passing" aspect of the parallel computer. I am working on modifying an existing program, which was written with OpenMP, and does not use a multi-machine parallel computing structure, to work with Message Passing Interface (MPI) routines. The actual code is being written in the FORTRAN 90 programming language. My goal is to write a parameterized message passing structure that could be used for a variety of individual applications and implement it on Silicon Graphics Incorporated s (SGI) IRIX operating system. With this new parameterized structure engineers would be able to speed up computations for a wide variety of purposes without having to use larger and more expensive computing equipment from another division or another NASA center.

  5. [Premature ejaculation in urological routine practice].

    PubMed

    Mathers, M J; Sommer, F; Degener, S; Brandt, A S; Roth, S

    2013-01-01

    Premature ejaculation is a frequent male sexual complaint or sexual disturbance found in urological practices and outpatient units. The frequency in the individual practices varies considerably. In large studies the prevalence is strongly dependent on the definition and ranges between 3% and 25%. Subjectively, the inability to delay ejaculation and the distress resulting from it, is relevant for the patient and his partner. Intravaginal ejaculation latency time (IELT) is used as an objective parameter. Nevertheless, in the everyday routine practice this objective parameter is not practical. Clinically 2 questionnaires have asserted themselves (Premature Ejaculation Profile and Index of Premature Ejaculation). Studies have shown that the self-assessment of patients correlates relatively well with the objective IELT measured by means of a stopwatch. Beside topical anaesthetics and elective serotonin reuptake inhibitors (SSRI), especially Dapexetine which has been approved in Germany since 2009, are treatment options. These drugs differ particularly in their use (daily or on-demand) and their effectiveness (measured by x-fold increase of IELT). This article deals with the clinical approach to EP. Beside the definition, prevalence, aetiology and neurophysiology of EP, the different pharmacological therapies as well as the guidelines of the International Society for Sexual Medicine are discussed. PMID:23381878

  6. Peri-colonic haematoma following routine colonoscopy

    PubMed Central

    Page, Felicity; Adedeji, Olfunso

    2015-01-01

    Introduction We present a case of an extra-luminal haematoma following routine colonoscopy. This case highlights an uncommon but potentially life threatening complication in which there is little published literature to date. Presentation of case A 73 year old male presented with abdominal pain and a reduction in haemoglobin following an uneventful colonoscopy. The imaging had been required as part of colorectal cancer follow up. Initial differential diagnosis included colonic perforation and the patient was admitted for further investigations. Same day CT scan imaging revealed an extra-luminal haematoma in the mid descending colon. The patient was managed non-operatively and was discharged with antibiotics following a period of observation. Discussion Colonoscopy is a highly effective imaging modality for direct visualisation of the lower gastrointestinal tract and for simultaneous diagnostic or therapeutic interventions. In recent years the use of colonoscopy has increased greatly, this is largely due to an increasingly aging population, increased availability of the resource and as a consequence of the implementation of the Bowel Cancer Screening Programme. Extra-colonic bleeding following colonoscopy is rare. Causes that have been identified in the literature include splenic injury, mesenteric tears, hepatic injury and retroperitoneal haemorrhage. To the authors' knowledge, there is very little published literature specifically on isolated peri-colonic haematomas following colonoscopy. Conclusion This case highlights an unusual but potentially life threatening complication following colonoscopy. Endoscopists and clinicians should be aware of the diagnosis to allow for early recognition and appropriate management. PMID:26900460

  7. Closed cycle refrigeration for routine magnetotransport measurements

    NASA Astrophysics Data System (ADS)

    Gunawardana, Binuka; Ye, Tianyu; Wegscheider, Werner; Mani, Ramesh

    2015-03-01

    Condensed matter physics is often interested in the behavior of materials at very low temperatures. Low temperatures have traditionally been realized using liquid helium. However, the recent scarcity of liquid helium and the rapid rise in its cost has encouraged the development of alternative approaches, based on closed cycle refrigerators, for realizing low temperatures. Here, we convey our experiences in developing a home-made, low cost, variable temperature closed cycle refrigeration system for routine magnetotransport measurements down to 10K, and present measurements obtained with this system relating to the electronic properties of the high mobility GaAs/AlGaAs 2D semiconductors system. The setup was constructed to examine 0.5cm × 0.5cm semiconductor chips including up to 49 leads and reach ~ 10K within 3 hours. A computer controlled data acquisition system was assembled to collect resistivity and Hall effect data, and extract the carrier Hall mobility and density as a function of the temperature.

  8. Don't neglect routine staff meetings.

    PubMed

    Board, H K

    1982-03-01

    Staff meetings are essential to good staff communication. Meetings help keep the grapevine from growing so big that it strangles the group with its rumors. By holding regular meetings with your staff, you create a consistency in your communications that helps prevent problems that you don't even suspect from cropping up. All personnel should attend the meetings. This way everyone hears news at the same time. Be consistent in your use of meetings. Meetings are more effective if you have a planned agenda and a firm time schedule. Encourage your staff to use meetings to talk out problems that affect the group. Once the meeting is over, encourage them to leave their feelings in the room. Many leaders are reluctant, for a variety of reasons, to hold meetings with their staffs. But it's like dieting and exercise; the more you do it, the easier it becomes. This type of meeting will pay rich dividends in staff personal and professional growth and in improved communication. The sense of participation that can be gained by the effective use of staff meetings can lead to high morale and effective staff performance. As you begin to see the results of a cohesive staff functioning together well, you will realize the routine staff meeting is a management tool that should not be overlooked or underused. PMID:6917733

  9. Routine ultrasound surveillance after carotid endarterectomy.

    PubMed

    Pratesi, C; Pulli, R; Ferlaino, E; Michelagnoli, S; Bernacchi, R; Borgioloi, F; Nuzzaci, G

    1996-02-01

    Ultrasounds (US) are employed in preoperative carotid disease diagnosis and in carotid endarterectomy (CEA) follow-up. The authors present their experience about postoperative modifications in CEA site with US evaluation with particular interest in restenosis. Clinical and instrumental examinations were performed at intervals 1, 3, 6, 12, and 24 months following surgery. Follow-up data were available on 189 CEAs. In 58 cases a primary closure was performed, whereas in the other 131 cases, a patch was applied. 15 restenosis (7.9%) were seen during the follow-up control period with 2 cases of haemodynamic restenosis (1%). Good results were recorded with PTFE patch angioplasty (restenosis 4.4%), instead of vein (restenosis 14.2%) and a biosynthetic material called Omniflow (restenosis 9.5%). A vein patch dilatation was encountered in 13 applications (30.9%). In conclusion the routine application of US after carotid endarterectomy allowed us to monitor the evolution of the repair processes and of the stenotic lesions from the very beginning. PMID:8606212

  10. CULA: hybrid GPU accelerated linear algebra routines

    NASA Astrophysics Data System (ADS)

    Humphrey, John R.; Price, Daniel K.; Spagnoli, Kyle E.; Paolini, Aaron L.; Kelmelis, Eric J.

    2010-04-01

    The modern graphics processing unit (GPU) found in many standard personal computers is a highly parallel math processor capable of nearly 1 TFLOPS peak throughput at a cost similar to a high-end CPU and an excellent FLOPS/watt ratio. High-level linear algebra operations are computationally intense, often requiring O(N3) operations and would seem a natural fit for the processing power of the GPU. Our work is on CULA, a GPU accelerated implementation of linear algebra routines. We present results from factorizations such as LU decomposition, singular value decomposition and QR decomposition along with applications like system solution and least squares. The GPU execution model featured by NVIDIA GPUs based on CUDA demands very strong parallelism, requiring between hundreds and thousands of simultaneous operations to achieve high performance. Some constructs from linear algebra map extremely well to the GPU and others map poorly. CPUs, on the other hand, do well at smaller order parallelism and perform acceptably during low-parallelism code segments. Our work addresses this via hybrid a processing model, in which the CPU and GPU work simultaneously to produce results. In many cases, this is accomplished by allowing each platform to do the work it performs most naturally.

  11. CYB5D2 displays tumor suppression activities towards cervical cancer.

    PubMed

    Xie, Yanyun; Shen, Yen Ting; Kapoor, Anil; Ojo, Diane; Wei, Fengxiang; De Melo, Jason; Lin, Xiaozeng; Wong, Nicholas; Yan, Judy; Tao, Lijian; Major, Pierre; Tang, Damu

    2016-04-01

    Cervical cancer is caused by infections with human papillomaviruses (HPV) and genetic alternations in the cervical epithelium. While the former is well studied, the latter remains unclear. We report here that CYB5D2/Neuferricin possesses tumor suppressing activity towards cervical tumorigenesis. Ectopic expression of CYB5D2 did not affect HeLa cell proliferation and the cell's ability to form xenograft tumors, but significantly inhibited HeLa cell invasion in vitro and the cell-produced lung metastasis in NOD/SCID mice. Knockdown of CYB5D2 enhanced HeLa cell invasion. Two mutations in CYB5D2, the substitutions of arginine (R) 7 with either proline (P) or glycine (G), were reported in colon cancer. Both CYB5D2(R7P) and CYB5D2(R7G) were incapable of inhibiting HeLa cell invasion. CYB5D2 binds heme, in which aspartate (D) 86 is required. While CYB5D2(D86G) is heme-binding defective, it inhibited HeLa cell invasion. On the other hand, CYB5D2(R7P) and CYB5D2(R7G) bound heme but did not inhibit HeLa cell invasion. Collectively, CYB5D2 inhibits HeLa cell invasion independently of its heme binding. Furthermore, immunohistochemistry examination of CYB5D2 expression in 20 normal cervical tissues and 40 cervical squamous cell carcinomas (SCC) revealed a CYB5D2 reduction in 87.5% (35/40) of SCC. Analysis of CYB5D2 gene expression and genomic alteration data available from Oncomeine™ detected significant reductions of CYB5D2 mRNA in 40 SCCs and CYB5D2 gene copy number in 107 SCCs. Collectively, we provide evidence that CYB5D2 is a candidate tumor suppressor of cervical tumorigenesis. PMID:26692170

  12. Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking and Stability.

    PubMed

    Ebersole, Brittany; Petko, Jessica; Woll, Matthew; Murakami, Shoko; Sokolina, Kate; Wong, Victoria; Stagljar, Igor; Lüscher, Bernhard; Levenson, Robert

    2015-01-01

    We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R. PMID:26535572

  13. Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking and Stability

    PubMed Central

    Ebersole, Brittany; Petko, Jessica; Woll, Matthew; Murakami, Shoko; Sokolina, Kate; Wong, Victoria; Stagljar, Igor; Lüscher, Bernhard; Levenson, Robert

    2015-01-01

    We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R. PMID:26535572

  14. Color constancy in 3D-2D face recognition

    NASA Astrophysics Data System (ADS)

    Meyer, Manuel; Riess, Christian; Angelopoulou, Elli; Evangelopoulos, Georgios; Kakadiaris, Ioannis A.

    2013-05-01

    Face is one of the most popular biometric modalities. However, up to now, color is rarely actively used in face recognition. Yet, it is well-known that when a person recognizes a face, color cues can become as important as shape, especially when combined with the ability of people to identify the color of objects independent of illuminant color variations. In this paper, we examine the feasibility and effect of explicitly embedding illuminant color information in face recognition systems. We empirically examine the theoretical maximum gain of including known illuminant color to a 3D-2D face recognition system. We also investigate the impact of using computational color constancy methods for estimating the illuminant color, which is then incorporated into the face recognition framework. Our experiments show that under close-to-ideal illumination estimates, one can improve face recognition rates by 16%. When the illuminant color is algorithmically estimated, the improvement is approximately 5%. These results suggest that color constancy has a positive impact on face recognition, but the accuracy of the illuminant color estimate has a considerable effect on its benefits.

  15. Higher derivative massive spin-3 models in D =2 +1

    NASA Astrophysics Data System (ADS)

    Dalmazi, D.; Mendonça, E. L.

    2016-07-01

    We find new higher derivative models describing a parity doublet of massive spin-3 modes in D =2 +1 dimensions. One of them is of fourth order in derivatives while the other one is of sixth order. They are complete, in the sense that they contain the auxiliary scalar field required to remove spurious degrees of freedom. Both of them are obtained through the master action technique starting with the usual (second-order) spin-3 Singh-Hagen model, which guarantees that they are ghost free. The fourth- and sixth-order terms are both invariant under (transverse) Weyl transformations, quite similarly to the fourth-order K -term of the "new massive gravity." The sixth-order term slightly differs from the product of the Schouten by the Einstein tensor, both of third order in derivatives. It is also possible to write down the fourth-order term as a product of a Schouten-like by an Einstein-like tensor (both of second order in derivatives) in close analogy with the K -term.

  16. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects. PMID:26143263

  17. Opposing roles of Prostaglandin D2 receptors in ulcerative colitis

    PubMed Central

    Sturm, Eva M.; Radnai, Balazs; Jandl, Katharina; Stančić, Angela; Parzmair, Gerald P.; Högenauer, Christoph; Kump, Patrizia; Wenzl, Heimo; Petritsch, Wolfgang; Pieber, Thomas R.; Schuligoi, Rufina; Marsche, Gunther; Ferreirós, Nerea; Heinemann, Akos; Schicho, Rudolf

    2014-01-01

    Pro-resolution functions were reported for Prostaglandin D2 (PGD2) in colitis, but the role of its two receptors, DP and in particular CRTH2 are less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes, and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of DSS colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared to control subjects. In contrast, CRTH2 was decreased in eosinophils, NK and CD3+ T cells but not in monocytes and CD3+/CD4+ T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydroTXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved while the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue where it may contribute to inflammation whereas DP likely promotes anti-inflammatory actions. PMID:24929001

  18. Mechanisms of agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Lin, Hong; Strange, Philip G

    2004-12-01

    In this study, we investigated the biochemical mechanisms of agonist action at the G protein-coupled D2 dopamine receptor expressed in Chinese hamster ovary cells. Stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding by full and partial agonists was determined at different concentrations of [35S]GTPgammaS (0.1 and 10 nM) and in the presence of different concentrations of GDP. At both concentrations of [35S]GTPgammaS, increasing GDP decreased the [35S]GTPgammaS binding observed with maximally stimulating concentrations of agonist, with partial agonists exhibiting greater sensitivity to the effects of GDP than full agonists. The relative efficacy of partial agonists was greater at the lower GDP concentrations. Concentration-response experiments were performed for a range of agonists at the two [35S]GTPgammaS concentrations and with different concentrations of GDP. At 0.1 nM [35S]GTPgammaS, the potency of both full and partial agonists was dependent on the GDP concentration in the assays. At 10 nM [35S]GTPgammaS, the potency of full agonists exhibited a greater dependence on the GDP concentration, whereas the potency of partial agonists was virtually independent of GDP. We concluded that at the lower [35S]GTPgammaS concentration, the rate-determining step in G protein activation is the binding of [35S]GTPgammaS to the G protein. At the higher [35S]GTPgammaS concentration, for full agonists, [35S]GTPgammaS binding remains the slowest step, whereas for partial agonists, another (GDP-independent) step, probably ternary complex breakdown, becomes rate-determining. PMID:15340043

  19. Mechanisms of inverse agonist action at D2 dopamine receptors.

    PubMed

    Roberts, David J; Strange, Philip G

    2005-05-01

    Mechanisms of inverse agonist action at the D2(short) dopamine receptor have been examined. Discrimination of G-protein-coupled and -uncoupled forms of the receptor by inverse agonists was examined in competition ligand-binding studies versus the agonist [3H]NPA at a concentration labelling both G-protein-coupled and -uncoupled receptors. Competition of inverse agonists versus [3H]NPA gave data that were fitted best by a two-binding site model in the absence of GTP but by a one-binding site model in the presence of GTP. K(i) values were derived from the competition data for binding of the inverse agonists to G-protein-uncoupled and -coupled receptors. K(coupled) and K(uncoupled) were statistically different for the set of compounds tested (ANOVA) but the individual values were different in a post hoc test only for (+)-butaclamol. These observations were supported by simulations of these competition experiments according to the extended ternary complex model. Inverse agonist efficacy of the ligands was assessed from their ability to reduce agonist-independent [35S]GTP gamma S binding to varying degrees in concentration-response curves. Inverse agonism by (+)-butaclamol and spiperone occurred at higher potency when GDP was added to assays, whereas the potency of (-)-sulpiride was unaffected. These data show that some inverse agonists ((+)-butaclamol, spiperone) achieve inverse agonism by stabilising the uncoupled form of the receptor at the expense of the coupled form. For other compounds tested, we were unable to define the mechanism. PMID:15735658

  20. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  1. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  2. D2R DNA Transfer Into the Nucleus Accumbens Attenuates Cocaine Self-Administration in Rats

    PubMed Central

    THANOS, PANAYOTIS K.; MICHAELIDES, MICHAEL; UMEGAKI, HIROYUKI; VOLKOW, NORA D.

    2009-01-01

    Dopamine (DA) D2 receptor (D2R) agonists and antagonists can modulate self-administration behavior, conditioned place preference, and locomotor responses to cocaine. Low levels of D2R have also been observed in cocaine addicted subjects and in non human primates after chronic cocaine exposures. Prior studies had shown that D2R upregulation in the nucleus accumbens (NAc) in rodents trained to self-administer alcohol markedly attenuated alcohol preference and intake. Here we assess the effects of D2R upregulation in the NAc on cocaine intake in rats trained to self-administer cocaine. Following 2 weeks of i.v. cocaine self-administration (CSA), rats were stereotaxically treated with an adenovirus that carried the D2R gene to upregulate D2R in the NAc. D2R vector treatment resulted in a significant decrease (75%) in cocaine infusions and lever presses (70%) for cocaine. This effect lasted 6 days before cocaine consumption returned to baseline levels, which corresponds roughly to the time it takes D2R to return to baseline levels. These findings show that CSA and D2R in the NAc are negatively correlated and suggest that cocaine intake is modulated in part by D2R levels in NAc. Thus strategies aimed at increasing D2R expression in NAc may be beneficial in treating cocaine abuse and addiction. PMID:18418874

  3. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2.

    PubMed

    Lin, An-Ping; Abbas, Saman; Kim, Sang-Woo; Ortega, Manoela; Bouamar, Hakim; Escobedo, Yissela; Varadarajan, Prakash; Qin, Yuejuan; Sudderth, Jessica; Schulz, Eduard; Deutsch, Alexander; Mohan, Sumitra; Ulz, Peter; Neumeister, Peter; Rakheja, Dinesh; Gao, Xiaoli; Hinck, Andrew; Weintraub, Susan T; DeBerardinis, Ralph J; Sill, Heinz; Dahia, Patricia L M; Aguiar, Ricardo C T

    2015-01-01

    Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases. PMID:26178471

  4. 26 CFR 301.6104(d)-2 - Making applications and returns widely available.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from public disclosure. (See section 6104(d)(3) and § 301.6104(d)-3(b)(3) and (4)); and (C) any... available. 301.6104(d)-2 Section 301.6104(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Returns and Records § 301.6104(d)-2 Making applications and returns widely available. (a) In general....

  5. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2

    PubMed Central

    Lin, An-Ping; Abbas, Saman; Kim, Sang-Woo; Ortega, Manoela; Bouamar, Hakim; Escobedo, Yissela; Varadarajan, Prakash; Qin, Yuejuan; Sudderth, Jessica; Schulz, Eduard; Deutsch, Alexander; Mohan, Sumitra; Ulz, Peter; Neumeister, Peter; Rakheja, Dinesh; Gao, Xiaoli; Hinck, Andrew; Weintraub, Susan T.; DeBerardinis, Ralph J.; Sill, Heinz; Dahia, Patricia L. M.; Aguiar, Ricardo C. T.

    2015-01-01

    Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases. PMID:26178471

  6. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; discontinuance of contributions. 1.411(d)-2 Section 1.411(d)-2 Internal Revenue INTERNAL REVENUE SERVICE...-Sharing, Stock Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of... appropriate) to satisfy the requirements of section 4044 or section 403(d)(1) of the Employee...

  7. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; discontinuance of contributions. 1.411(d)-2 Section 1.411(d)-2 Internal Revenue INTERNAL REVENUE SERVICE...-Sharing, Stock Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of... appropriate) to satisfy the requirements of section 4044 or section 403(d)(1) of the Employee...

  8. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Termination or partial termination; discontinuance of contributions. 1.411(d)-2 Section 1.411(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.411(d)-2 Termination...

  9. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; discontinuance of contributions. 1.411(d)-2 Section 1.411(d)-2 Internal Revenue INTERNAL REVENUE SERVICE...-Sharing, Stock Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of... appropriate) to satisfy the requirements of section 4044 or section 403(d)(1) of the Employee...

  10. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...; discontinuance of contributions. 1.411(d)-2 Section 1.411(d)-2 Internal Revenue INTERNAL REVENUE SERVICE...-Sharing, Stock Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of... appropriate) to satisfy the requirements of section 4044 or section 403(d)(1) of the Employee...

  11. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  12. Preliminary abatement device evaluation: 1D-2D KGM cyclone design

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclones are predominately used in controlling cotton gin particulate matter (PM) emissions. The most commonly used cyclone designs are the 2D-2D and 1D-3D; however other designs such as the 1D-2D KGM have or are currently being used. A 1D-2D cyclone has a barrel length equal to the barrel diamete...

  13. Implantation of Energetic D+ Ions into Carbon Dioxide Ices and Implications for our Solar System: Formation of D2O and D2CO3

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-10-01

    Carbon dioxide (CO2) ices were irradiated with energetic D+ ions to simulate the exposure of oxygen-bearing solar system ices to energetic protons from the solar wind and magnetospheric sources. The formation of species was observed online and in situ by exploiting FTIR spectroscopy. Molecular products include ozone (O3), carbon oxides (CO3(C 2v , D 3h ), CO4, CO5, CO6), D2-water (D2O), and D2-carbonic acid (D2CO3). Species released into the gas phase were sampled via a quadrupole mass spectrometer, and possible minor contributions from D2-formaldehyde (D2CO), D4-methanol (CD3OD), and D2-formic acid (DCOOD) were additionally identified. The feasibility of several reaction networks was investigated by determining their ability to fit the observed temporal column densities of 10 key species that were quantified during the irradiation period. Directly relevant to the CO2-bearing ices of comets, icy satellites in the outer solar system, and the ice caps on Mars, this work illustrates for the first time that D2-water is formed as a product of the exposure of CO2 ices to D+ ions. These findings provide strong support for water formation from oxygen-bearing materials via non-thermal hydrogen atoms, and predict reaction pathways that are likely to be unfolding on the surfaces of asteroids and the Moon.

  14. Targets of deuterides TiD2, ZrD2, NbD, and CrD2 with different structures used in experiments on the study of pd and dd reactions at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Bystritsky, V. M.; Dudkin, G. N.; Filipowicz, M.; Tuleushev, Yu. Zh.; Zhakanbaev, E. A.

    2016-02-01

    Methods for depositing thin layers of deuterides TiD2, ZrD2, NbD, and CrD2 on stainless steel substrates are described. Magnetron sputtering of nanolayers of the above deuterides with different textures is considered. A technology for making titanium, zirconium, niobium, and chromium deuteride targets is proposed, which will definitely verify the hypothesis of the enhancement of the dd and pd reactions due to the channeling of the deuterons in the crystals of the above deuterides.

  15. Textured targets of deuterides TiD2, ZrD2, NbD, and CrD2 in experiments to study the pd and dd reaction mechanisms at astrophysical energies

    NASA Astrophysics Data System (ADS)

    Bystritsky, V. M.; Dudkin, G. N.; Filipowicz, M.; Tuleushev, Yu. Zh.; Zhakanbaev, E. A.

    2016-01-01

    Various methods for depositing thin layers of deuterides (hydrides) TiD2 (TiH2), ZrD2 (ZrH2), NbD (NbH), and CrD2 (CrH2) on stainless steel, copper, and silicon substrates are described. The method for magnetron sputtering of nanolayers of these deuterides (hydrides) with various textures is considered. A technology for producing titanium, zirconium, niobium, and chromium deuteride (hydride) targets is proposed, which will allow the hypothesis of dd and pd reaction enhancement through the channeling of deuterons (protons) in crystals of these deuterides to be unambiguously tested.

  16. Performance Analysis of Apollo Navigational Starter Routine

    NASA Technical Reports Server (NTRS)

    Ivanov, Stoyan I.; Holt, Greg

    2010-01-01

    The focus of this project is to recreate and analyze the effectiveness of the original Apollo Starter Routine (ASR) which was used to generate the state vector of the Apollo spacecraft based on a series of radiometric observations. The original Apollo navigation software is unavailable in a modern programming language and the original coding has not been preserved. This necessitates its recreation using the original software documentation. Space Shuttle navigation software does not typically use the ASR or an algorithm like it since the Shuttle s state vector is easily deduced from GPS information or other sources. However, this tactic will be ineffective when trying to determine the state vector of a craft approaching, departing or in orbit around the Moon since the GPS network faces the surface of the Earth, not outer space. The recreation of the ASR from the original documentation is therefore vital as a simulation baseline for the navigation software under development for the Constellation program. The algorithms that make up the ASR will be extracted from the original documentation and adapted for and then implemented in a modern programming language; the majority of it will be coded in Matlab. The ASR s effectiveness will then be tested using simulated tracking data. The ability of the ASR to handle realistically noisy data and the accuracy with which it generates state vectors were analyzed. The ASR proved to be robust enough to process data with range and angle noise as large as 10,000 meters and 10(exp -6) radians together and 300,000 meters and 5x10(exp -4) radians separately at Lunar distances. The ASR was able to handle marginally more noise at distances closer to the Earth where the angle noise was less significant. The ASR is capable of effectively processing 40-80 data points gathered at a rate of one per 20 seconds at close Earth orbit and up to 28-40 data points gathered at a rate of one per minute at distant Earth orbit and Lunar orbit.

  17. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes.

    PubMed

    Werneck-de-Castro, Joao P; Fonseca, Tatiana L; Ignacio, Daniele L; Fernandes, Gustavo W; Andrade-Feraud, Cristina M; Lartey, Lattoya J; Ribeiro, Marcelo B; Ribeiro, Miriam O; Gereben, Balazs; Bianco, Antonio C

    2015-10-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

  18. For Earth into space: The German Spacelab Mission D-2

    NASA Astrophysics Data System (ADS)

    Sahm, P. R.; Keller, M. H.; Schiewe, B.

    The Spacelab Mission D-2 successfully lifted off from Kennedy Space Center on April 26, 1993. With 88 experiments on board covering eleven different research disciplines it was a very ambitious mission. Besides materials and life science subjects, the mission also encompassed astronomy, earth observation, radiation physics and biology, telecommunication, automation and robotics. Notable results were obtained in almost all cases. To give some examples of the scientific output, building upon results obtained in previous missions (FSLP, D1) diffusion in melts was broadly represented delivering most precise data on the atomic mobility within various liquids, and crystal growth experiments (the largest gallium arsenide crystal grown by the floating zone technique, so far obtained anywhere, was one of the results), biological cell growth experiments were continued (for example, beer yeast cultures, continuing their growth on earth, delivered a qualitatively superior brewery result), the human physiology miniclinic configuration ANTHRORACK gave novel insights concerning cardiovascular, pulmonary, and renal (fluid volume determining) factors. Astronomical experiments yielded insights into our own galaxy within the ultra violet spectrum, earth observation experiments delivered the most precise resolution data superimposed by thematic mapping of many areas of the Earth, and the robotics experiment brought a remarkable feature in that a flying object was caught by the space robot, which was only achieved through several innovative advances during the time of experiment preparation. The eight years of preparation were also beneficial in another sense. Several discoveries have been made, and various technology transfers into ground-based processes were verified. To name the outstanding ones, in the materials science a novel bearing materials production process was developped, a patent granted for an improved high temperature heating chamber; with life sciences a new hormone

  19. Pharmacological evidence that dopamine inhibits the cardioaccelerator sympathetic outflow via D2-like receptors in pithed rats.

    PubMed

    Alcántara-Vázquez, Oscar; Villamil-Hernández, Ma Trinidad; Sánchez-López, Araceli; Centurión, David

    2013-01-01

    It has been suggested that N,N-di-n-propyl-dopamine (dopamine analogue) decreased heart rate in rats through stimulation of dopamine receptors. Nevertheless, the role of prejunctional dopamine D1/2-like receptors or even α2-adrenoceptors to mediate cardiac sympatho-inhibition induced by dopamine remains unclear. Hence, this study identified the pharmacological profile of the cardiac sympatho-inhibition to dopamine in pithed rats. Male Wistar rats were pithed and prepared to stimulate the cardiac sympathetic outflow or to receive i.v. bolus of exogenous noradrenaline. I.v. continuous infusions of dopamine (endogenous ligand) or quinpirole (D2-like agonist) dose-dependently inhibited the tachycardic responses to sympathetic stimulation, but not those to exogenous noradrenaline. In contrast, SKF-38393 (100 μg/kg∙min, D1-like agonist) failed to modify both of these responses. The sympatho-inhibition to dopamine (1.8 μg/kg∙min) or quinpirole (100 μg/kg∙min): i) remained unaltered after saline or the antagonists SCH-23390 (D1-like, 300 μg/kg) and rauwolscine (α2-adrenoceptors, 300 μg/kg); and ii) was significantly antagonized by raclopride (D2-like, 300 μg/kg). These antagonists, at the above doses, failed to modify the sympathetically-induced tachycardic responses. The above results suggest that the inhibition of the cardiac sympathetic outflow to dopamine and quinpirole is primarily mediated by prejunctional D2-like receptors but not D1-like receptors or α2-adrenoceptors. PMID:24225403

  20. Support Routines for In Situ Image Processing

    NASA Technical Reports Server (NTRS)

    Deen, Robert G.; Pariser, Oleg; Yeates, Matthew C.; Lee, Hyun H.; Lorre, Jean

    2013-01-01

    This software consists of a set of application programs that support ground-based image processing for in situ missions. These programs represent a collection of utility routines that perform miscellaneous functions in the context of the ground data system. Each one fulfills some specific need as determined via operational experience. The most unique aspect to these programs is that they are integrated into the large, in situ image processing system via the PIG (Planetary Image Geometry) library. They work directly with space in situ data, understanding the appropriate image meta-data fields and updating them properly. The programs themselves are completely multimission; all mission dependencies are handled by PIG. This suite of programs consists of: (1)marscahv: Generates a linearized, epi-polar aligned image given a stereo pair of images. These images are optimized for 1-D stereo correlations, (2) marscheckcm: Compares the camera model in an image label with one derived via kinematics modeling on the ground, (3) marschkovl: Checks the overlaps between a list of images in order to determine which might be stereo pairs. This is useful for non-traditional stereo images like long-baseline or those from an articulating arm camera, (4) marscoordtrans: Translates mosaic coordinates from one form into another, (5) marsdispcompare: Checks a Left Right stereo disparity image against a Right Left disparity image to ensure they are consistent with each other, (6) marsdispwarp: Takes one image of a stereo pair and warps it through a disparity map to create a synthetic opposite- eye image. For example, a right eye image could be transformed to look like it was taken from the left eye via this program, (7) marsfidfinder: Finds fiducial markers in an image by projecting their approximate location and then using correlation to locate the markers to subpixel accuracy. These fiducial markets are small targets attached to the spacecraft surface. This helps verify, or improve, the

  1. Source characterization refinements for routine modeling applications

    NASA Astrophysics Data System (ADS)

    Paine, Robert; Warren, Laura L.; Moore, Gary E.

    2016-03-01

    Steady-state dispersion models recommended by various environmental agencies worldwide have generally been evaluated with traditional stack release databases, including tracer studies. The sources associated with these field data are generally those with isolated stacks or release points under relatively ideal conditions. Many modeling applications, however, involve sources that act to modify the local dispersion environment as well as the conditions associated with plume buoyancy and final plume rise. The source characterizations affecting plume rise that are introduced and discussed in this paper include: 1) sources with large fugitive heat releases that result in a local urbanized effect, 2) stacks on or near individual buildings with large fugitive heat releases that tend to result in buoyant "liftoff" effects counteracting aerodynamic downwash effects, 3) stacks with considerable moisture content, which leads to additional heat of condensation during plume rise - an effect that is not considered by most dispersion models, and 4) stacks in a line that result in at least partial plume merging and buoyancy enhancement under certain conditions. One or more of these effects are appropriate for a given modeling application. We present examples of specific applications for one or more of these procedures in the paper. This paper describes methods to introduce the four source characterization approaches to more accurately simulate plume rise to a variety of dispersion models. The authors have focused upon applying these methods to the AERMOD modeling system, which is the United States Environmental Protection Agency's preferred model in addition to being used internationally, but the techniques are applicable to dispersion models worldwide. While the methods could be installed directly into specific models such as AERMOD, the advantage of implementing them outside the model is to allow them to be applicable to numerous models immediately and also to allow them to

  2. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist.

    PubMed

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P; Newman, Amy Hauck; Ferré, Sergi; Yano, Hideaki

    2016-04-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR > D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180

  3. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist

    PubMed Central

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P.; Newman, Amy Hauck

    2016-01-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180

  4. Prescriptive Package. Improving Patrol Productivity. Volume I. Routine Patrol.

    ERIC Educational Resources Information Center

    Gay, William G.; Schack, Stephen

    Designed to assist police departments in improving the productivity of their patrol operations, this volume on routine patrol and a companion volume on specialized patrol operations are intended for use by various sizes of departments. The volume on routine patrol focuses on the major issues of patrol productivity and recommends a number of…

  5. Routine Activities and Victimization at School: The Significance of Gender

    ERIC Educational Resources Information Center

    Popp, Ann Marie; Peguero, Anthony A.

    2011-01-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a…

  6. See, Say, Write: A Writing Routine for the Preschool Classroom

    ERIC Educational Resources Information Center

    Copp, Stefanie B.; Cabell, Sonia Q.; Tortorelli, Laura S.

    2016-01-01

    See, Say, Write is an adaptable classroom writing routine that teachers can use across a range of activities in the preschool classroom. This preschool writing routine offers an opportunity for teachers to build on a shared experience through engagement in rich conversation and writing. After a shared experience, teachers will provide a visual…

  7. 32 CFR 318.14 - Blanket routine uses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Blanket routine uses. 318.14 Section 318.14 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) PRIVACY PROGRAM DEFENSE THREAT REDUCTION AGENCY PRIVACY PROGRAM § 318.14 Blanket routine uses. (a) Blanket...

  8. Routines in School Organizations: Creating Stability and Change

    ERIC Educational Resources Information Center

    Conley, Sharon; Enomoto, Ernestine K.

    2005-01-01

    Purpose: This paper presents routinized action theory as a way to examine the regular, habitual activities that occur in school organizations. Using this theoretical lens, school routines were analyzed in order to understand organizational stability and change. Design/methodology/approach: Using case study methods, three discrete cases are…

  9. Thinking Routines: Replicating Classroom Practices within Museum Settings

    ERIC Educational Resources Information Center

    Wolberg, Rochelle Ibanez; Goff, Allison

    2012-01-01

    This article describes thinking routines as tools to guide and support young children's thinking. These learning strategies, developed by Harvard University's Project Zero Classroom, actively engage students in constructing meaning while also understanding their own thinking process. The authors discuss how thinking routines can be used in both…

  10. 42 CFR 493.1267 - Standard: Routine chemistry.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard: Routine chemistry. 493.1267 Section 493.1267 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1267 Standard: Routine chemistry. For blood gas analyses, the laboratory must perform...

  11. 42 CFR 493.1267 - Standard: Routine chemistry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard: Routine chemistry. 493.1267 Section 493.1267 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1267 Standard: Routine chemistry. For blood gas analyses, the laboratory must perform...

  12. 42 CFR 493.841 - Standard; Routine chemistry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Routine chemistry. 493.841 Section 493.841 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.841 Standard; Routine chemistry. (a) Failure to attain a score of at least 80...

  13. 42 CFR 493.841 - Standard; Routine chemistry.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard; Routine chemistry. 493.841 Section 493.841 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.841 Standard; Routine chemistry. (a) Failure to attain a score of at least 80...

  14. 42 CFR 493.841 - Standard; Routine chemistry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard; Routine chemistry. 493.841 Section 493.841 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.841 Standard; Routine chemistry. (a) Failure to attain a score of at least 80...

  15. 42 CFR 493.841 - Standard; Routine chemistry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard; Routine chemistry. 493.841 Section 493.841 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.841 Standard; Routine chemistry. (a) Failure to attain a score of at least 80...

  16. 42 CFR 493.1267 - Standard: Routine chemistry.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard: Routine chemistry. 493.1267 Section 493.1267 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1267 Standard: Routine chemistry. For blood gas analyses, the laboratory must perform...

  17. 42 CFR 493.1267 - Standard: Routine chemistry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Routine chemistry. 493.1267 Section 493.1267 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1267 Standard: Routine chemistry. For blood gas analyses, the laboratory must perform...

  18. 42 CFR 493.1267 - Standard: Routine chemistry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard: Routine chemistry. 493.1267 Section 493.1267 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1267 Standard: Routine chemistry. For blood gas analyses, the laboratory must perform...

  19. 42 CFR 493.841 - Standard; Routine chemistry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Routine chemistry. 493.841 Section 493.841 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.841 Standard; Routine chemistry. (a) Failure to attain a score of at least 80...

  20. 32 CFR 1701.31 - General routine uses.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTELLIGENCE ADMINISTRATION OF RECORDS UNDER THE PRIVACY ACT OF 1974 Routine Uses Applicable to More Than One... of Congressional intelligence oversight committees in connection with the exercise of the committees... disclosed as a routine use pursuant to Executive Order to the President's Foreign Intelligence...

  1. 32 CFR 1701.31 - General routine uses.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... INTELLIGENCE ADMINISTRATION OF RECORDS UNDER THE PRIVACY ACT OF 1974 Routine Uses Applicable to More Than One... of Congressional intelligence oversight committees in connection with the exercise of the committees... disclosed as a routine use pursuant to Executive Order to the President's Foreign Intelligence...

  2. 32 CFR 1701.31 - General routine uses.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... INTELLIGENCE ADMINISTRATION OF RECORDS UNDER THE PRIVACY ACT OF 1974 Routine Uses Applicable to More Than One... of Congressional intelligence oversight committees in connection with the exercise of the committees... disclosed as a routine use pursuant to Executive Order to the President's Foreign Intelligence...

  3. An Element of Practical Knowledge in Education: Professional Routines

    ERIC Educational Resources Information Center

    Lacourse, France

    2011-01-01

    The question of practical knowledge and its teaching has arisen more perceptibly since the appearance of the aim to professionalize teachers. How can imperceptible knowledge such as professional routines be taught? To establish a social fabric and effective class management, it is essential to call on creative and adaptive professional routines.…

  4. Helping Children Understand Routines and Classroom Schedules. What Works Briefs.

    ERIC Educational Resources Information Center

    Ostrosky, M. M.; Jung, E. Y.; Hemmeter, M. L.; Thomas, D.

    Studies have documented that schedules and routines influence children's emotional, cognitive, and social development. Predictable and consistent schedules in preschool classrooms help children feel secure and comfortable. Also, schedules and routines help children understand the expectations of the environment and reduce the frequency of behavior…

  5. The Association between Routinization and Cognitive Resources in Later Life

    ERIC Educational Resources Information Center

    Tournier, Isabelle; Mathey, Stephanie; Postal, Virginie

    2012-01-01

    The aim of this study was to investigate the association between routinization of daily life activities and cognitive resources during aging. Routinization could increase excessively during aging and become maladaptative in reducing individual resources. Fifty-two young participants (M = 20.8 years) and 62 older participants (M = 66.9 years)…

  6. 15 CFR 923.84 - Routine program changes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... a routine program change. Failure to notify a State in writing within 4 weeks of receipt of notice... Programs § 923.84 Routine program changes. (a) Further detailing of a State's program that is the result of implementing provisions approved as part of a State's approved management program, that does not result in...

  7. Parental Involvement Routines and Former Head Start Children's Literacy Outcomes

    ERIC Educational Resources Information Center

    Dove, Meghan Kicklighter; Neuharth-Pritchett, Stacey; Wright, David W.; Wallinga, Charlotte

    2015-01-01

    This study examined the relationship between parental involvement routines and former Head Start children's literacy outcomes. Former Head Start children (n = 3, 808) from the National Head Start/Public School Transition Demonstration Research Project comprised the sample. Family routines and literacy outcomes in kindergarten were examined,…

  8. Changing Urban Bureaucracies: How New Practices Become Routinized.

    ERIC Educational Resources Information Center

    Yin, Robert K.; And Others

    The goal of this report is to describe the process by which new service practices in urban bureaucracies become routinized. The routinization process is studied by examining the life histories of six types of innovations: computer-assisted instruction; police computer systems; mobile intensive care units; closed circuit television systems; breath…

  9. Computer routine adds plotting capabilities to existing programs

    NASA Technical Reports Server (NTRS)

    Harris, J. C.; Linnekin, J. S.

    1966-01-01

    PLOTAN, a generalized plot analysis routine written for the IBM 7094 computer, minimizes the difficulties in adding plot capabilities to large existing programs. PLOTAN is used in conjunction with a binary tape writing routine and has the ability to plot any variable on the intermediate binary tape as a function of any other.

  10. Factors for Radical Creativity, Incremental Creativity, and Routine, Noncreative Performance

    ERIC Educational Resources Information Center

    Madjar, Nora; Greenberg, Ellen; Chen, Zheng

    2011-01-01

    This study extends theory and research by differentiating between routine, noncreative performance and 2 distinct types of creativity: radical and incremental. We also use a sensemaking perspective to examine the interplay of social and personal factors that may influence a person's engagement in a certain level of creative action versus routine,…

  11. Recapturing Desired Family Routines: A Parent-Professional Behavioral Collaboration

    ERIC Educational Resources Information Center

    Buschbacher, Pamelazita; Fox, Lise; Clarke, Shelley

    2004-01-01

    Children with complex disabilities such as autism spectrum disorders and Landau Kleffner syndrome often lack means to participate in everyday family routines. Serious problem behaviors may result from their challenges in responding to and initiating communicative interactions. These behaviors can change routine family activities such that the…

  12. User manual for two simple postscript output FORTRAN plotting routines

    NASA Technical Reports Server (NTRS)

    Nguyen, T. X.

    1991-01-01

    Graphics is one of the important tools in engineering analysis and design. However, plotting routines that generate output on high quality laser printers normally come in graphics packages, which tend to be expensive and system dependent. These factors become important for small computer systems or desktop computers, especially when only some form of a simple plotting routine is sufficient. With the Postscript language becoming popular, there are more and more Postscript laser printers now available. Simple, versatile, low cost plotting routines that can generate output on high quality laser printers are needed and standard FORTRAN language plotting routines using output in Postscript language seems logical. The purpose here is to explain two simple FORTRAN plotting routines that generate output in Postscript language.

  13. Cellular localization of dopamine D2 receptor messenger RNA in the rat trigeminal ganglion.

    PubMed

    Peterfreund, R A; Kosofsky, B E; Fink, J S

    1995-12-01

    The actions of dopamine are mediated by specific, high-affinity, G protein-coupled receptors. Multiple subtypes of dopamine receptors have been characterized, including the D2 subtype (D2R). Cells within the dorsal root and petrosal ganglia of the rat express D2R messenger RNA (mRNA) consistent with D2R expression by primary sensory neurons. We hypothesized that neurons of the trigeminal ganglion express D2R mRNA. Total cellular RNA from rat trigeminal ganglia was analyzed on Northern blots under high stringency conditions. Hybridization of trigeminal ganglion RNA resulted in a signal which comigrated with striatal, pituitary, and hypothalamic D2R mRNA. To determine the distribution of D2R expressing cells in the trigeminal ganglion, cryostat sections were analyzed by in situ hybridization followed by emulsion autoradiography. We identified a population of clustered cells labeled with dense grain concentrations over their cytoplasms. These findings demonstrate the expression of D2 dopamine receptor mRNA in discrete subpopulations of neurons in the rat trigeminal ganglion. Our observations suggest that drugs active at dopamine receptors of the D2 subtype are potential modulators of sensory activity of neurons whose cell bodies reside in the trigeminal ganglion. D2 dopamine receptors may thus have a role in clinical pain syndromes involving the head and neck. PMID:7486101

  14. Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory.

    PubMed

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D; Riklund, Katrine; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars

    2016-07-12

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [(11)C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

  15. Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

    PubMed Central

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

    2016-01-01

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

  16. 78 FR 72693 - Information Collection Activities: Application for Permit To Modify; Proposed Collection; Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ...; 134E1700D2 EEEE500000 ET1SF0000.DAQ000] Information Collection Activities: Application for Permit To Modify... data and information that is submitted with an Application for Permit to Modify (APM) under the.... SUPPLEMENTARY INFORMATION: Title: 30 CFR 250, Application for Permit to Modify (APM), BSEE- 0124. Form:...

  17. An evaluation of LSU rDNA D1-D2 sequences for their use in species identification

    PubMed Central

    Sonnenberg, Rainer; Nolte, Arne W; Tautz, Diethard

    2007-01-01

    natural hybrids among cyprinid fish species (Alburnus alburnus and Rutilus rutilus) that this is indeed possible. Conclusion The D1-D2 LSU region is a suitable marker region for applications in DNA based species identification and should be considered to be routinely used as a marker complementing broad scale studies based on mitochondrial markers. PMID:17306026

  18. Results of an attempt to measure increased rates of the reaction D-2 + D-2 yields He-3 + n in a nonelectrochemical cold fusion experiment

    NASA Technical Reports Server (NTRS)

    Fralick, Gustave C.; Decker, Arthur J.; Blue, James W.

    1989-01-01

    An experiment was performed to look for evidence of deuterium fusion in palladium. The experiment, which involved introducing deuterium into the palladium filter of a hydrogen purifier, was designed to detect neutrons produced in the reaction D-2 + D-2 yields He-3 + n as well as heat production. The neutron counts for deuterium did not differ significantly from background or from the counts for a hydrogen control. Heat production was detected when deuterium, but not hydrogen, was pumped from the purifier.

  19. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

    PubMed Central

    Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

    2016-01-01

    The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of

  20. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia.

    PubMed

    Borroto-Escuela, Dasiel O; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

    2016-04-01

    The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A-D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor-receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A-D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2-N-methyl-d-aspartate (NMDA) and A2A-D2-metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)-D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological

  1. SINDA/SINFLO computer routine, volume 1, revision A. [for fluid flow system analysis

    NASA Technical Reports Server (NTRS)

    Oren, J. A.; Williams, D. R.

    1975-01-01

    The SINFLO package was developed to modify the SINDA preprocessor to accept and store the input data for fluid flow systems analysis and adding the FLOSOL user subroutine to perform the flow solution. This reduced and simplified the user input required for analysis of flow problems. A temperature calculation method, the flow-hybrid method which was developed in previous VSD thermal simulator routines, was incorporated for calculating fluid temperatures. The calculation method accuracy was improved by using fluid enthalpy rather than specific heat for the convective term of the fluid temperature equation. Subroutines and data input requirements are described along with user subroutines, flow data storage, and usage of the plot program.

  2. Effect of pd and dd reactions enhancement in deuterides TiD2, ZrD2 and Ta2D in the astrophysical energy range

    NASA Astrophysics Data System (ADS)

    Bystritskii, V. M.; Dudkin, G. N.; Filipowicz, M.; Huran, J.; Krylov, A. R.; Nechayev, B. A.; Padalko, V. N.; Pen'kov, F. M.; Philippov, A. V.; Tuleushev, Yu. Zh.

    2016-01-01

    Investigation of the pd-and dd-reactions in the ultralow energy (~keV) range is of great interest in the aspect of nuclear physics and astrophysics for developing of correct models of burning and evolution of stars. This report presents compendium of experimental results obtained at the pulsed plasma Hall accelerator (TPU, Tomsk). Most of those results are new, such as • temperature dependence of the neutron yield in the D( d, n)3He reaction in the ZrD2, Ta2D, TiD2 • potentials of electron screening and respective dependence of astrophysical S-factors in the dd-reaction for the deuteron collision energy in the range of 3-6 keV, with ZrD2, Ta2D temperature in the range of 20-200°C [1] • characteristics of the reaction d( p, γ)3He in the ultralow collision proton-deuterons energy range of 4-13 keV [2, 3] in ZrD2, Ta2D and TiD2 • observation of the neutron yield enhancement in the reaction D( d, n)3He at the ultralow deuteron collision energy due to channeling of deuterons in microscopic TiD2 with a face-centered cubic lattice type TiD1.73, oriented in the [100] direction [4]. The report includes discussion and comparison of the collected experimental results with the global data and calculations.

  3. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia

    PubMed Central

    Abi-Dargham, Anissa; Rodenhiser, Janine; Printz, David; Zea-Ponce, Yolanda; Gil, Roberto; Kegeles, Lawrence S.; Weiss, Richard; Cooper, Thomas B.; Mann, J. John; Van Heertum, Ronald L.; Gorman, Jack M.; Laruelle, Marc

    2000-01-01

    The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D2 receptor. We measured in vivo occupancy of striatal D2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D2 receptor availability in patients with schizophrenia (19% ± 11%) compared with control subjects (9% ± 7%, P = 0.003). The increased occupancy of D2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons. PMID:10884434

  4. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  5. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  6. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome.

    PubMed Central

    Blum, K; Sheridan, P J; Wood, R C; Braverman, E R; Chen, T J; Cull, J G; Comings, D E

    1996-01-01

    The dopaminergic system, and in particular the dopamine D2 receptor, has been profoundly implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine receptors leads to aberrant substance seeking behaviour (alcohol, drug, tobacco, and food) and other related behaviours (pathological gambling, Tourette's syndrome, and attention deficit hyperactivity disorder). We propose that variants of the D2 dopamine receptor gene are important common genetic determinants of the 'reward deficiency syndrome'. PMID:8774539

  7. The Implementation of C-ID, R2D2 Model on Learning Reading Comprehension

    ERIC Educational Resources Information Center

    Rayanto, Yudi Hari; Rusmawan, Putu Ngurah

    2016-01-01

    The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

  8. New generation dopaminergic agents. 1. Discovery of a novel scaffold which embraces the D2 agonist pharmacophore. Structure-activity relationships of a series of 2-(aminomethyl)chromans.

    PubMed

    Mewshaw, R E; Kavanagh, J; Stack, G; Marquis, K L; Shi, X; Kagan, M Z; Webb, M B; Katz, A H; Park, A; Kang, Y H; Abou-Gharbia, M; Scerni, R; Wasik, T; Cortes-Burgos, L; Spangler, T; Brennan, J A; Piesla, M; Mazandarani, H; Cockett, M I; Ochalski, R; Coupet, J; Andree, T H

    1997-12-19

    A series of 2-(aminomethyl)chromans (2-AMCs) was synthesized and evaluated for their affinity and selectivity for both the high- and low-affinity agonist states (D2High and D2Low, respectively) of the dopamine (DA) D2 receptor. The 7-hydroxy-2-(aminomethyl)chroman moiety was observed to be the primary D2 agonist pharmacophore. The 2-methylchroman moiety was discovered to be an entirely novel scaffold which could be used to access the D2 agonist pharmacophore. Attaching various simple alkyl and arylalkyl side chains to the 7-hydroxy 2-AMC nucleus had significant effects on selectivity for the D2High receptor vs the 5HT1A and alpha 1 receptors. A novel DA partial agonist, (R)-(-)-2-(benzylamino)methyl)chroman-7-ol [R-(-)-35c], was identified as having the highest affinity and best selectivity for the D2High receptor vs the alpha 1 and 5HT1A receptors. Several regions of the 2-AMC nucleus were modified and recognized as potential sites to modulate the level of intrinsic activity. The global minimum conformer of the 7-hydroxy-2-AMC moiety was identified as fulfilling the McDermed model D2 agonist pharmacophoric criteria and was proposed as the D2 receptor-bound conformation. Structure-activity relationships gained from these studies have aided in the synthesis of D2 partial agonists of varying intrinsic activity levels. These agents should be of therapeutic value in treating disorders resulting from hypo- and hyperdopaminergic activity, without the side effects associated with complete D2 agonism or antagonism. PMID:9435894

  9. STS-55 German payload specialists pose in front of SL-D2 module at KSC

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, German payload specialists pose in front of the Spacelab Deutsche 2 (SL-D2) science module at a Kennedy Space Center (KSC) processing facility. These two Germans have been assigned to support the STS-55/SL-D2 mission. They are Payload Specialist 2 Hans Schlegel (left) and Payload Specialist 1 Ulrich Walter. Walter and Schlegel are scheduled to fly aboard OV-102 for the mission, joining five NASA astronauts. Clearly visible on the SL-D2 module are the European Space Agency (ESA) insignia, the feedthrough plate, and the D2 insignia.

  10. TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer.

    PubMed

    Liang, Fang; Li, Qiao; Li, Xiayu; Li, Zheng; Gong, Zhaojian; Deng, Hao; Xiang, Bo; Zhou, Ming; Li, Xiaoling; Li, Guiyuan; Zeng, Zhaoyang; Xiong, Wei

    2016-09-01

    We previously identified TSC22D2 (transforming growth factor β-stimulated clone 22 domain family, member 2) as a novel cancer-associated gene in a rare multi-cancer family. However, its role in tumor development remains completely unknown. In this study, we found that TSC22D2 was significantly downregulated in colorectal cancer (CRC) and that TSC22D2 overexpression inhibited cell growth. Using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting proteins, we demonstrated that TSC22D2 interacts with pyruvate kinase isoform M2 (PKM2). These findings were confirmed by the results of immunoprecipitation and immunofluorescence assays. Moreover, overexpression of TSC22D2 reduced the level of nuclear PKM2 and suppressed cyclin D1 expression. Collectively, our study reveals a growth suppressor function of TSC22D2 that is at least partially dependent on the TSC22D2-PKM2-cyclinD1 regulatory axis. In addition, our data provide important clues that might contribute to future studies evaluating the role of TSC22D2. PMID:27573352

  11. Distribution of dopamine D2-like receptors in the human thalamus: autoradiographic and PET studies.

    PubMed

    Rieck, Richard W; Ansari, M S; Whetsell, William O; Deutch, Ariel Y; Kessler, Robert M

    2004-02-01

    The distribution of dopamine (DA) D(2)-like receptors in the human thalamus was studied using in vitro autoradiographic techniques and in vivo positron emission tomography in normal control subjects. [(125)I]Epidepride, which binds with high affinity to DA D(2) and D(3) receptors, was used in autoradiographic studies to determine the distribution and density of D(2)-like receptors, and the epidepride analogue [(18)F]fallypride positron was used for positron emission tomography studies to delineate D(2)-like receptors in vivo. Both approaches revealed a heterogeneous distribution of thalamic D(2/3) receptors, with relatively high densities in the intralaminar and midline thalamic nuclei, including the paraventricular, parataenial, paracentral, centrolateral, and centromedian/parafascicular nuclei. Moderate densities of D(2/3) sites were seen in the mediodorsal and anterior nuclei, while other thalamic nuclei expressed lower levels of D(2)-like receptors. Most thalamic nuclei that express high densities of D(2)-like receptors project to forebrain DA terminal fields, suggesting that both the thalamic neurons expressing D(2)-like receptors and the projection targets of these neurons are regulated by DA. Because the midline/intralaminar nuclei receive prominent projections from both the ascending reticular activating core and the hypothalamus, these thalamic nuclei may integrate activity conveying both interoceptive and exteroceptive information to telencephalic DA systems involved in reward and cognition. PMID:14627996

  12. De novo expression of dopamine D2 receptors on microglia after stroke.

    PubMed

    Huck, Jojanneke H J; Freyer, Dorette; Böttcher, Chotima; Mladinov, Mihovil; Muselmann-Genschow, Claudia; Thielke, Mareike; Gladow, Nadine; Bloomquist, Dana; Mergenthaler, Philipp; Priller, Josef

    2015-11-01

    Dopamine is the predominant catecholamine in the brain and functions as a neurotransmitter. Dopamine is also a potent immune modulator. In this study, we have characterized the expression of dopamine receptors on murine microglia. We found that cultured primary microglia express dopamine D1, D2, D3, D4, and D5 receptors. We specifically focused on the D2 receptor (D2R), a major target of antipsychotic drugs. Whereas D2Rs were strongly expressed on striatal neurons in vivo, we did not detect any D2R expression on resident microglia in the healthy brains of wild-type mice or transgenic mice expressing the green fluorescent protein (GFP) under the control of the Drd2 promoter. However, cerebral ischemia induced the expression of D2R on Iba1-immunoreactive inflammatory cells in the infarct core and penumbra. Notably, D2R expression was confined to CD45(hi) cells, and GFP BM chimeras revealed that D2R was expressed on activated resident microglia as well as on peripherally derived macrophages in the ischemic brain. Importantly, the D2/3R agonist, pramipexole, enhanced the secretion of nitrite by cultured microglia in response to proinflammatory stimuli. Thus, dopamine may serve as a modulator of microglia function during neuroinflammation. PMID:26104289

  13. Cocaine self-administration produces a persistent increase in dopamine D2 High receptors.

    PubMed

    Briand, Lisa A; Flagel, Shelly B; Seeman, Philip; Robinson, Terry E

    2008-08-01

    Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high-affinity state, and dopamine exerts its effects via the more functionally relevant high-affinity D2 receptor (D2 High). We report here that cocaine self-administration experience produces a large (approximately 150%) increase in the proportion of D2 High receptors in the striatum with no change in the total number of D2 receptors, and this effect is evident both 3 and 30 days after the discontinuation of cocaine self-administration. Changes in D2 High receptors would not be evident with the probes used in human (and non-human primate) imaging studies. We suggest, therefore, that cocaine addicts and animals previously treated with cocaine may be hyper-responsive to dopaminergic drugs in part because an increase in D2 High receptors results in dopamine supersensitivity. This may also help explain why stimuli that increase dopamine neurotransmission, including drugs themselves, are so effective in producing relapse in individuals with a history of exposure to cocaine. PMID:18284941

  14. Immunohistochemical localization of dopamine D2 receptor in the rat carotid body.

    PubMed

    Wakai, Jun; Takayama, Anna; Yokoyama, Takuya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-10-01

    Dopamine modulates the chemosensitivity of arterial chemoreceptors, and dopamine D2 receptor (D2R) is expected to localize in the glomus cells and/or sensory nerve endings of the carotid body. In the present study, the localization of D2R in the rat carotid body was examined using double immunofluorescence for D2R with various cell markers. D2R immunoreactivity was mainly localized in glomus cells immunoreactive to tyrosine hydroxylase or dopamine β-hydroxylase (DBH), but not in S100B-immunoreactive sustentacular cells. Furthermore, D2R immunoreactivity was observed in petrosal ganglion cells and nerve bundles in the carotid body, but not in the nerve endings with P2X2 immunoreactivity. In the carotid ganglion, a few punctate D2R-immunoreactive products were detected in DBH-immunoreactive nerve cell bodies. These results showed that D2R was mainly distributed in glomus cells, and suggested that D2R plays a role in the inhibitory modulation of chemosensory activity in a paracrine and/or autocrine manner. PMID:26272445

  15. Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists.

    PubMed

    Urbanek, Rebecca A; Xiong, Hui; Wu, Ye; Blackwell, William; Steelman, Gary; Rosamond, Jim; Wesolowski, Steven S; Campbell, James B; Zhang, Minli; Brockel, Becky; Widzowski, Daniel V

    2013-01-15

    Dopamine (D(2)) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D(2) partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D(2) partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model. PMID:23237836

  16. Protein Kinase C Beta Regulates the D2-Like Dopamine Autoreceptor

    PubMed Central

    Luderman, Kathryn D.; Chen, Rong; Ferris, Mark J.; Jones, Sara R.; Gnegy, Margaret E.

    2014-01-01

    The focus of this study was the regulation of the D2-like dopamine autoreceptor (D2 autoreceptor) by protein kinase Cβ, a member of the protein kinase C (PKC) family. Together with the dopamine transporter, the D2 autoreceptor regulates the level of extracellular dopamine and thus dopaminergic signaling. PKC regulates neuronal signaling via several mechanisms, including desensitizing autoreceptors to increase the release of several different neurotransmitters. Here, using both PKCβ−/− mice and specific PKCβ inhibitors, we demonstrated that a lack of PKCβ activity enhanced the D2 autoreceptor-stimulated decrease in dopamine release following both chemical and electrical stimulations. Inhibition of PKCβ increased surface localization of D2R in mouse striatal synaptosomes, which could underlie the greater sensitivity to quinpirole following inhibition of PKCβ. PKCβ−/− mice displayed greater sensitivity to the quinpirole-induced suppression of locomotor activity, demonstrating that the regulation of the D2 autoreceptor by PKCβ is physiologically significant. Overall, we have found that PKCβ downregulates the D2 autoreceptor, providing an additional layer of regulation for dopaminergic signaling. We propose that in the absence of PKCβ activity, surface D2 autoreceptor localization and thus D2 autoreceptor signaling is increased, leading to less dopamine in the extracellular space and attenuated dopaminergic signaling. PMID:25446677

  17. Floating-point function generation routines for 16-bit microcomputers

    NASA Technical Reports Server (NTRS)

    Mackin, M. A.; Soeder, J. F.

    1984-01-01

    Several computer subroutines have been developed that interpolate three types of nonanalytic functions: univariate, bivariate, and map. The routines use data in floating-point form. However, because they are written for use on a 16-bit Intel 8086 system with an 8087 mathematical coprocessor, they execute as fast as routines using data in scaled integer form. Although all of the routines are written in assembly language, they have been implemented in a modular fashion so as to facilitate their use with high-level languages.

  18. Factors for radical creativity, incremental creativity, and routine, noncreative performance.

    PubMed

    Madjar, Nora; Greenberg, Ellen; Chen, Zheng

    2011-07-01

    This study extends theory and research by differentiating between routine, noncreative performance and 2 distinct types of creativity: radical and incremental. We also use a sensemaking perspective to examine the interplay of social and personal factors that may influence a person's engagement in a certain level of creative action versus routine, noncreative work. Results demonstrate that willingness to take risks, resources for creativity, and career commitment are associated primarily with radical creativity; that the presence of creative coworkers and organizational identification are associated with incremental creativity; and that conformity and organizational identification are linked with routine performance. Theoretical and managerial implications are discussed. PMID:21319879

  19. [Routine episiotomy in modern obstetrics. Is it necessary?].

    PubMed

    Korczyński, Jerzy

    2002-01-01

    The study presents a literature review on the benefits and risk of the routine episiotomy during the second stage of labour. Perineal trauma complications as well as perinatal outcomes are discussed. The risk of stress incontinence and sexual dysfunction are described. New techniques for improve of perinatal outcomes and prevention of post partum incontinence are described. Routine episiotomy gives poor effects in many cases. Perineal massage during pregnancy, waterbirth, are most interesting methods to avoid routine episiotomy and improve the quality of life in post partum women. PMID:12152258

  20. Photodesorption of H2O, HDO, and D2O ice and its impact on fractionation

    NASA Astrophysics Data System (ADS)

    Arasa, Carina; Koning, Jesper; Kroes, Geert-Jan; Walsh, Catherine; van Dishoeck, Ewine F.

    2015-03-01

    The HDO/H2O ratio measured in interstellar gas is often used to draw conclusions on the formation and evolution of water in star-forming regions and, by comparison with cometary data, on the origin of water on Earth. In cold cores and in the outer regions of protoplanetary disks, an important source of gas-phase water comes from photodesorption of water ice. This research note presents fitting formulae for implementation in astrochemical models using previously computed photodesorption efficiencies for all water ice isotopologues obtained with classical molecular dynamics simulations. The results are used to investigate to what extent the gas-phase HDO/H2O ratio reflects that present in the ice or whether fractionation can occur during the photodesorption process. Probabilities for the top four monolayers are presented for photodesorption of X (X = H, D) atoms, OX radicals, and X2O and HDO molecules following photodissociation of H2O, D2O, and HDO in H2O amorphous ice at ice temperatures from 10-100 K. Significant isotope effects are found for all possible products: (1) H atom photodesorption probabilities from H2O ice are larger than those for D atom photodesorption from D2O ice by a factor of 1.1; the ratio of H and D photodesorbed upon HDO photodissociation is a factor of 2. This process will enrich the ice in deuterium atoms over time; (2) the OD/OH photodesorption ratio upon D2O and H2O photodissociation is on average a factor of 2, but the OD/OH photodesorption ratio upon HDO photodissociation is almost constant at unity for all ice temperatures; (3) D atoms are more effective in kicking out neighbouring water molecules than H atoms. However, the ratio of the photodesorbed HDO and H2O molecules is equal to the HDO/H2O ratio in the ice, therefore, there is no isotope fractionation when HDO and H2O photodesorb from the ice. Nevertheless, the enrichment of the ice in D atoms due to photodesorption can over time lead to an enhanced HDO/H2O ratio in the ice, and

  1. Experimental Studies on the Formation of D2O and D2O2 by Implantation of Energetic D+ Ions into Oxygen Ices

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-02-01

    The formation of water (H2O) in the interstellar medium is intrinsically linked to grain-surface chemistry; thought to involve reactions between atomic (or molecular) hydrogen with atomic oxygen (O), molecular oxygen (O2), and ozone (O3). Laboratory precedent suggests that H2O is produced efficiently when O2 ices are exposed to H atoms (~100 K). This leads to the sequential generation of the hydroxyperoxyl radical (HO2), then hydrogen peroxide (H2O2), and finally H2O and a hydroxyl radical (OH); despite a barrier of ~2300 K for the last step. Recent detection of the four involved species toward ρ Oph A supports this general scenario; however, the precise formation mechanism remains undetermined. Here, solid O2 ice held at 12 K is exposed to a monoenergetic beam of 5 keV D+ ions. Products formed during the irradiation period are monitored through FTIR spectroscopy. O3 is observed through seven archetypal absorptions. Three additional bands found at 2583, 2707, and 1195 cm -1 correspond to matrix isolated DO2 (ν1) and D2O2 (ν1, ν5), and D2O (ν2), respectively. During subsequent warming, the O2 ice sublimates, revealing a broad band at 2472 cm-1 characteristic of amorphous D2O (ν1, ν3). Sublimating D2, D2O, D2O2, and O3 products were confirmed through their subsequent detection via quadrupole mass spectrometry. Reaction schemes based on both thermally accessible and suprathermally induced chemistries were developed to fit the observed temporal profiles are used to elucidate possible reaction pathways for the formation of D2-water. Several alternative schemes to the hydrogenation pathway (O2→HO2→H2O2→H2O) were identified; their astrophysical implications are briefly discussed.

  2. Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

    PubMed Central

    Czoty, Paul W.; Gage, H. Donald; Garg, Pradeep K.; Garg, Sudha; Nader, Michael A.

    2013-01-01

    Rationale Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. Objective We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n=5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n=9). Methods Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and four days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. Results ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. Conclusions The results indicate that repeated treatment with a low efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity. PMID:24077804

  3. Routine oxygen consumption in different sizes of a tilapia, Oreochromis niloticus (Trewavas) using the closed chamber respiratory method.

    PubMed

    Kisia, S M; Hughes, G M

    1993-01-01

    Routine oxygen consumption (Vo2) measurements on 54 specimens (0.055-190.4 g) of a tilapia, Oreochromis niloticus (Trewavas) were carried out using two different types of closed respirometers: a modified cuvette for fish weighing 0.055-0.91 g and ordinary closed chamber respirometer for fish weighing more than 1 g. Vo2 values over the weight range studied had a scaling value of 0.743 which relates closely to the values for the gill respiratory surface area and morphometric oxygen diffusing capacity of O. niloticus in a previous study /13/. This shows that a close relationship exists between changes in structural parameters involved in oxygen uptake and the routine metabolism of O. niloticus with development. The values for routine Vo2 of 1.38 and 7.65 ml/h for 10 g and 100 g fish, respectively (calculated from the regression equation) show that O. niloticus is a moderately active fish. PMID:7871925

  4. Prostaglandin D2: A dominant mediator of aspirin exacerbated respiratory disease

    PubMed Central

    Cahill, Katherine N.; Bensko, Jillian C.; Boyce, Joshua A.; Laidlaw, Tanya M.

    2014-01-01

    Background Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy. Objective We investigated differences in urinary eicosanoid metabolites and blood eosinophils in subjects with AERD who tolerate and those who fail aspirin desensitization, and also in AERD subjects who were successfully treated with high-dose aspirin therapy. Methods 29 subjects with AERD were stratified into those who tolerated aspirin desensitization (Group I) and those who did not (Group II). Urine was analyzed for eicosanoid metabolites at baseline, during aspirin reactions, and on high-dose aspirin therapy. Blood was analyzed for cell differentials at baseline and on aspirin therapy. Results Basal prostaglandin D2 metabolite (PGD-M) (13.6±2.7 vs. 7.0±0.8 pmol/mg Cr; P<.05), and thromboxane metabolite (TX-M) levels (1.4±0.3 vs. 0.9±0.1 pmol/mg Cr; P<.01) were higher in Group II than in Group I. During aspirin reactions, PGD-M remained unchanged while TX-M (0.7±0.1 pmol/mg Cr; P=.07) tended to decrease in Group I. In contrast, PGD-M rose dramatically in Group II (61.3±19.9 pmol/mg Cr; P<.05), while TX-M did not change. The decrease in FEV1 inversely correlated with basal urinary levels of both LTE4 and PGD-M. Blood eosinophil and basophil levels rose while urinary PGD-M (2.2±0.8 pmol/mg Cr, P<.001) decreased on two months of high-dose aspirin therapy in Group I. Conclusion Failure to tolerate aspirin desensitization in a subset of subjects with AERD is associated with PGD2 overproduction. The increase in blood eosinophils and basophils while on high-dose aspirin therapy may reflect the functional consequences of decreased PGD2 release and the therapeutic benefit of aspirin. PMID:25218285

  5. Dopamine D2 receptors are organized in bands in normal human temporal cortex.

    PubMed

    Goldsmith, S K; Joyce, J N

    1996-09-01

    Previous studies have documented a highly compartmentalized and laminar organization of dopamine D2 receptors in human hippocampus, entorhinal and perirhinal cortices. These areas receive input from regions of polysensory association cortices of the superior and inferior temporal sulci that evidence functional modules identified by other techniques. We examined the isocortical regions of temporal lobe for an equally well-differentiated pattern of D2 receptor expression as observed in their paleocortical temporal lobe targets. Using quantitative autoradiography we identified an organization of three-dimensional bands of high concentrations of dopamine D2 receptors throughout the rostral-caudal extent of the normal human temporal cortex. In the coronal plane, these D2 receptor-enriched bands had a columnar appearance with the concentration of D2 receptors almost two-fold higher within the bands than in the immediately adjacent cortex. These D2 receptor-enriched bands had a distinct laminar appearance with a paucity of [125I]epidepride binding to D2 receptors over the granule cell layer and higher concentrations of D2 receptors in laminae III and V than in the immediately adjacent cortex. They had a consistent width (mean width of 2.83 +/- 0.62 mm) in the coronal plane, but had their long axes in the rostrocaudal plane (some were at least 2500 microns in length). Hence, they exist as three-dimensional D2 receptor-enriched and receptor-poor modules with their long axes in the rostrocaudal plane. Tyrosine hydroxylase-immunoreactive fibers were observed to cross orthogonally to the long axes of the D2 receptor enriched bands. Other monoamine receptors (beta-adrenergic, 5-hydroxytryptamine2), and markers for myelin (anti-myelin basic protein immunohistochemistry), glia (5'-nucleotidase), and energy metabolism (cytochrome oxidase) showed a laminar organization but failed to demarcate the D2 receptor-enriched bands. The majority of these D2 receptor-enriched bands were

  6. Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys

    PubMed Central

    Rommelfanger, Karen S.; Masilamoni, Gunasingh J.; Smith, Yoland; Wichmann, Thomas

    2012-01-01

    According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the “indirect” pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions. PMID:22131382

  7. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  8. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.

    PubMed

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  9. Prostaglandin D2 induces the production of human beta-defensin-3 in human keratinocytes.

    PubMed

    Kanda, Naoko; Ishikawa, Takeko; Watanabe, Shinichi

    2010-04-01

    The antimicrobial peptide human beta-defensin-3 (hBD-3) is produced by epidermal keratinocytes and protects the skin from infections. This peptide induces the release of a lipid mediator, prostaglandin D(2) from dermal mast cells. Prostaglandin D(2) binds to cell-surface G protein-coupled receptors, D prostanoid receptor, and chemoattractant receptor-homologous molecule expressed on T helper cell type 2 (CRTH2). Both receptors are detected on epidermal keratinocytes. It is reported that prostaglandin D(2) is involved in cutaneous allergy, however, its role in antimicrobial defense is unknown. We examined the in vitro effects of prostaglandin D(2) on hBD-3 production in normal human keratinocytes. Prostaglandin D(2) enhanced hBD-3 secretion and mRNA expression in human keratinocytes. Prostaglandin D(2)-induced hBD-3 production was suppressed by the CRTH2 antagonist ramatroban and by antisense oligonucleotides against c-Jun and c-Fos, components of a transcription factor, activator protein-1 (AP-1). Prostaglandin D(2) enhanced the transcriptional activity and DNA binding of AP-1, expression, phosphorylation, and DNA binding of c-Fos proteins in keratinocytes. Prostaglandin D(2)-induced hBD-3 production, AP-1 activity, and c-Fos expression and phosphorylation were suppressed by U0126, PP2, and pertussis toxin, which are inhibitors of mitogen-activated protein kinase kinase (MEK), src, and G(i) proteins, respectively. The phosphorylation of extracellular signal-regulated kinase (ERK), downstream kinase of MEK, was induced by prostaglandin D(2), and suppressed by ramatroban, pertussis toxin, PP2, and U0126. These results suggest that prostaglandin D(2) induces hBD-3 production in human keratinocytes by activating AP-1 through the expression and phosphorylation of c-Fos via the CRTH2/G(i)/src/MEK/ERK pathway. Prostaglandin D(2) may promote cutaneous antimicrobial activity via hBD-3. PMID:19925780

  10. Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

    PubMed

    Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

    2016-08-01

    Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. PMID:27302109

  11. Task Force: Routine Genital Herpes Screening Not Recommended

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160205.html Task Force: Routine Genital Herpes Screening Not Recommended Unless someone ... 2, 2016 (HealthDay News) -- A U.S. federal task force is prepared to recommend that teens, adults and ...

  12. Thromboembolism Prophylaxis in Hip Arthroplasty: Routine and High Risk Patients.

    PubMed

    Nam, Denis; Nunley, Ryan M; Johnson, Staci R; Keeney, James A; Clohisy, John C; Barrack, Robert L

    2015-12-01

    This study's purpose was to present the use of a risk stratification protocol in which "routine" risk patients receive a mobile compression device with aspirin and "high" risk patients receive warfarin for thromboprophylaxis after hip arthroplasty. 1859 hip arthroplasty patients were prospectively enrolled (1402 routine risk--75.4%, 457 high risk--24.6%). The cumulative rate of venous thromboembolism events was 0.5% in the routine versus 0.5% in the high-risk cohort within 6weeks postoperatively (P=1.00). Patients in the routine risk cohort had a lower rate of major bleeding (0.5% versus 2.0%, P=0.006) and wound complications (0.2% versus 1.2%, P=0.01). Use of our risk stratification protocol allowed the avoidance of more aggressive anticoagulation in 75% of patients while achieving a low overall incidence of symptomatic VTE. PMID:26182980

  13. User's Manual: Routines for Radiative Heat Transfer and Thermometry

    NASA Technical Reports Server (NTRS)

    Risch, Timothy K.

    2016-01-01

    Determining the intensity and spectral distribution of radiation emanating from a heated surface has applications in many areas of science and engineering. Areas of research in which the quantification of spectral radiation is used routinely include thermal radiation heat transfer, infrared signature analysis, and radiation thermometry. In the analysis of radiation, it is helpful to be able to predict the radiative intensity and the spectral distribution of the emitted energy. Presented in this report is a set of routines written in Microsoft Visual Basic for Applications (VBA) (Microsoft Corporation, Redmond, Washington) and incorporating functions specific to Microsoft Excel (Microsoft Corporation, Redmond, Washington) that are useful for predicting the radiative behavior of heated surfaces. These routines include functions for calculating quantities of primary importance to engineers and scientists. In addition, the routines also provide the capability to use such information to determine surface temperatures from spectral intensities and for calculating the sensitivity of the surface temperature measurements to unknowns in the input parameters.

  14. A crystal routine for collimation studies in circular proton accelerators

    NASA Astrophysics Data System (ADS)

    Mirarchi, D.; Hall, G.; Redaelli, S.; Scandale, W.

    2015-07-01

    A routine has been developed to simulate interactions of protons with bent crystals in a version of SixTrack for collimation studies. This routine is optimized to produce high-statistics tracking simulations for a highly efficient collimation system, like the one of the CERN Large Hadron Collider (LHC). The routine has recently been reviewed and improved through a comparison with experimental data, benchmarked against other codes and updated by adding better models of low-probability interactions. In this paper, data taken with 400 GeV/c proton beams at the CERN-SPS North Area are used to verify the prediction of the routine, including the results of a more recent analysis.

  15. Unsupervised daily routine and activity discovery in smart homes.

    PubMed

    Jie Yin; Qing Zhang; Karunanithi, Mohan

    2015-08-01

    The ability to accurately recognize daily activities of residents is a core premise of smart homes to assist with remote health monitoring. Most of the existing methods rely on a supervised model trained from a preselected and manually labeled set of activities, which are often time-consuming and costly to obtain in practice. In contrast, this paper presents an unsupervised method for discovering daily routines and activities for smart home residents. Our proposed method first uses a Markov chain to model a resident's locomotion patterns at different times of day and discover clusters of daily routines at the macro level. For each routine cluster, it then drills down to further discover room-level activities at the micro level. The automatic identification of daily routines and activities is useful for understanding indicators of functional decline of elderly people and suggesting timely interventions. PMID:26737536

  16. Routine Eye Exams See Vision Problems You Miss

    MedlinePlus

    ... news/fullstory_159863.html Routine Eye Exams See Vision Problems You Miss Older people and those who ... half of people with no new symptoms or vision problems receive new prescriptions or treatment changes as ...

  17. Hypoxic ventilatory response after dopamine D2 receptor blockade in unilateral rat model of Parkinson's disease.

    PubMed

    Andrzejewski, K; Budzińska, K; Zaremba, M; Kaczyńska, K

    2016-03-01

    Modified non-motor brainstem ventilatory control might be involved in Parkinson's disease. Our study was designed to investigate the impact of degeneration of the nigrostriatal dopaminergic pathway on resting breathing and hypoxic ventilatory response in conscious rats. The role of central and peripheral dopamine D2 receptors in the modulation of the hypoxic ventilatory response in conditions of dopamine shortage was examined. Adult Wistar rats received a unilateral double 6-hydroxydopamine lesion of the right medial forebrain bundle. After surgery, animals were placed in whole-body plethysmographic chamber and exposed to hypoxia (8% O2). One group of animals received inraperitoneal injections of either haloperidol or domperidone before hypoxia. Levels of dopamine and its metabolite in the brainstem and striatum were assessed. Neurotoxin treatment evoked limb use asymmetry. No effect on the resting normoxic respiration was observed. An increase in tidal volume and a decrease in respiratory rate during respiratory response to hypoxia with short magnification of minute ventilation were predominant effects. Domperidone treatment in intact animals evoked a significant increase in normoxic tidal volume, while haloperidol potentiated tidal volume increase in response to hypoxia. After the lesion, the effects of both antagonists were absent. In rats with Parkinson's, the content of dopamine and its metabolite decreased substantially in the injured striatum. Augmentation of a tidal volume response to hypoxia, and the absence of stimulatory effect of intraperitoneal domperidone on normoxic and haloperidol on hypoxic tidal volume, in lesioned rats indicated altered control of breathing. This could be the result of a dopamine deficiency in the striatum and an increased turnover of DOPAC/DA in the brainstem. PMID:26705738

  18. Survey of US Correctional Institutions for Routine HCV Testing.

    PubMed

    Beckwith, Curt G; Kurth, Ann E; Bazerman, Lauri; Solomon, Liza; Patry, Emily; Rich, Josiah D; Kuo, Irene

    2015-01-01

    To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment. PMID:25393180

  19. Adoption of routine telemedicine in Norway: the current picture

    PubMed Central

    Zanaboni, Paolo; Knarvik, Undine; Wootton, Richard

    2014-01-01

    Background Telemedicine appears to be ready for wider adoption. Although existing research evidence is useful, the adoption of routine telemedicine in healthcare systems has been slow. Objective We conducted a study to explore the current use of routine telemedicine in Norway, at national, regional, and local levels, to provide objective and up-to-date information and to estimate the potential for wider adoption of telemedicine. Design A top-down approach was used to collect official data on the national use of telemedicine from the Norwegian Patient Register. A bottom-up approach was used to collect complementary information on the routine use of telemedicine through a survey conducted at the five largest publicly funded hospitals. Results Results show that routine telemedicine has been adopted in all health regions in Norway and in 68% of hospitals. Despite being widely adopted, the current level of use of telemedicine is low compared to the number of face-to-face visits. Examples of routine telemedicine can be found in several clinical specialties. Most services connect different hospitals in secondary care, and they are mostly delivered as teleconsultations via videoconference. Conclusions Routine telemedicine in Norway has been widely adopted, probably for geographical reasons, as in other settings. However, the level of use of telemedicine in Norway is rather low, and it has significant potential for further development as an alternative to face-to-face outpatient visits. This study is a first attempt to map routine telemedicine at regional, institutional, and clinical levels, and it provides useful information to understand the adoption of telemedicine in routine healthcare and to measure change in future updates. PMID:24433942

  20. Unusual Foreign Body in a Routine Lateral Cephalogram

    PubMed Central

    James, Jean; S, Praveen; V.P, Latheef; S, Sreehari

    2015-01-01

    Routine radiographs made in the orthodontic office can often give way to detection and diagnosis of unusual syndromes, signs or foreign bodies. A case report of one such accidental detection of a very unusual foreign body within the nasal cavity of an orthodontic patient has been presented here to emphasize the importance of routine radiographic views, which over and above aiding in Orthodontic diagnosis, can also often detect potentially life threatening problems in the Oro-facial region. PMID:25859532

  1. Survey of US Correctional Institutions for Routine HCV Testing

    PubMed Central

    Kurth, Ann E.; Bazerman, Lauri; Solomon, Liza; Patry, Emily; Rich, Josiah D.; Kuo, Irene

    2015-01-01

    To ascertain HCV testing practices among US prisons and jails, we conducted a survey study in 2012, consisting of medical directors of all US state prisons and 40 of the largest US jails, that demonstrated a minority of US prisons and jails conduct routine HCV testing. Routine voluntary HCV testing in correctional facilities is urgently needed to increase diagnosis, enable risk-reduction counseling and preventive health care, and facilitate evaluation for antiviral treatment. PMID:25393180

  2. Routine activities and victimization at school: the significance of gender.

    PubMed

    Popp, Ann Marie; Peguero, Anthony A

    2011-08-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a gender-specific relationship with victimization. This article explores the importance of gender in understanding the relationship between student's participation in extracurricular routine activities (e.g., student government, clubs, sports, and etc.) and the risk of victimization. From the Education Longitudinal Study of 2002, a sample of 10th-grade students was drawn for analyses. Hierarchical Generalized Linear Modeling was employed to explore the role of gender in the relationship between extracurricular routine activities and victimization at school. The results reveal that students' gender indeed interacts with several of the extracurricular routine activities creating gender-specific risks of victimization. This article highlights the importance of gender in explaining victimization and suggests researchers should consider how gender may interact with other routine activities and victimization. PMID:20956442

  3. Routine HIV Testing in Indiana Community Health Centers.

    PubMed

    Meyerson, Beth E; Navale, Shalini M; Gillespie, Anthony; Ohmit, Anita

    2015-01-01

    Objectives. We assessed routine HIV testing in Indiana community health centers (CHCs). Methods. CHC medical directors reported HIV services, testing behaviors, barriers, and health center characteristics via survey from April to May 2013. Standard of care testing was measured by the extent to which CHCs complied with national guidelines for routine HIV testing in clinical settings. Results. Most (85.7%) CHCs reported HIV testing, primarily at patient request or if the patient was symptomatic. Routine HIV testing was provided for pregnant women by 60.7% of CHCs. Only 10.7% provided routine testing for adolescents to adults up to age 65 years. Routine testing was reported by 14.3% for gay and bisexual men, although 46.4% of CHCs reported asking patients about sexual orientation. Linkage to care services for HIV-positive patients, counseling for HIV treatment adherence, and partner testing generally was not provided. Conclusions. Most CHCs reported HIV testing, but such testing did not reflect the standard of care, because it depended on patient request or symptoms. One approach in future studies may be to allow respondents to compare current testing with standard of care and then reflect on barriers to and facilitators of adoption and implementation of routine HIV testing. PMID:25393186

  4. Work routinization and implications for ergonomic exposure assessment.

    PubMed

    Gold, Judith E; Park, Jung-Soon; Punnett, Laura

    2006-01-15

    Jobs in many modern settings, including manufacturing, service, agriculture and construction, are variable in their content and timing. This prompts the need for exposure assessment methods that do not assume regular work cycles. A scheme is presented for classifying levels of routinization to inform development of an appropriate exposure assessment strategy for a given occupational setting. Five levels of routinization have been defined based on the tasks of which the job is composed: 1) a single scheduled task with a regular work cycle; 2) multiple cyclical tasks; 3) a mix of cyclical and non-cyclical tasks; 4) one non-cyclical task; 5) multiple non-cyclical tasks. This classification, based primarily on job observation, is illustrated through data from a study of automobile manufacturing workers (n = 1200), from which self-assessed exposures to physical and psychosocial stressors were also obtained. In this cohort, decision latitude was greater with higher routinization level (p < 0.0001), and the least routinized jobs showed the lowest self-reported exposure to physical ergonomic stressors. The job analysis checklist developed for non-routinized jobs is presented, and limitations of the task analysis method utilized in the study are discussed. A work sampling approach to job analysis is recommended as the most efficient way to obtain a comparable unbiased exposure estimate across all routinization levels. PMID:16393801

  5. UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is not required.

    PubMed

    Williams, Alan; Güthlein, Carolin; Beresford, Nicola; Böttger, Erik C; Springer, Burkhard; Davis, Elaine O

    2011-09-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2 at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement. PMID:21725019

  6. 40 CFR 721.10270 - [5,6]Fullerene-C84-D2d.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fullerene-C84-D2d. 721.10270 Section 721.10270 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10270 Fullerene-C84-D2d. (a)...

  7. 40 CFR 721.10269 - [5,6]Fullerene-C84-D2.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fullerene-C84-D2. 721.10269 Section 721.10269 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10269 Fullerene-C84-D2. (a)...

  8. Neural Substrates of Dopamine D2 Receptor Modulated Executive Functions in the Monkey Prefrontal Cortex.

    PubMed

    Puig, M Victoria; Miller, Earl K

    2015-09-01

    Dopamine D2 receptors (D2R) play a major role in cognition, mood and motor movements. Their blockade by antipsychotic drugs reduces hallucinatory and delusional behaviors in schizophrenia, but often fails to alleviate affective and cognitive dysfunctions. The prefrontal cortex (PFC) expresses D2R and is altered in schizophrenia. We investigated how D2R modulate behavior and PFC function in monkeys. Two monkeys learned new and performed highly familiar visuomotor associations, where each cue was associated with a saccade to a right or left target. We recorded neural spikes and local field potentials from multiple electrodes while injecting the D2R antagonist eticlopride in the lateral PFC. Blocking prefrontal D2R impaired associative learning and cognitive flexibility, reduced motivation, but left the performance of familiar associations intact. Eticlopride reduced saccade-direction selectivity of prefrontal neurons, leading to a decrease in neural information about the associations, and an increase in alpha oscillations. These results, together with our recent study using a D1R antagonist, suggest that D1R and D2R in the primate lateral PFC cooperate to modulate several executive functions. Our findings help to gain insight into why antipsychotic drugs, with strong antagonistic actions on D2R, fail to ameliorate cognitive and emotional deficits in schizophrenia. PMID:24814093

  9. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App....

  10. Striatal Dopamine D2/3 Receptor Availability in Treatment Resistant Depression

    PubMed Central

    Ruhé, Eric H. G.; van Wingen, Guido A.; Booij, Jan; Denys, Damiaan

    2014-01-01

    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 D2/3 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. PMID:25411966

  11. ISCCP-D2like-Day Terra Ed3A

    Atmospheric Science Data Center

    2016-06-08

    ... and Order:  Reverb   Reverb Tutorial Subset/Visualization Tool:  CERES Order Tool Order Data:  ... Detailed CERES ISCCP-D2like Product Information Data Products Catalog:  DPC_ISCCP-D2like-Day-Nit_R5V3 ...

  12. Regulation of dopamine D2 receptors in a novel cell line (SUP1)

    SciTech Connect

    Ivins, K.J.; Luedtke, R.R.; Artymyshyn, R.P.; Molinoff, P.B. )

    1991-04-01

    A prolactin-secreting cell line, SUP1, has been established from rat pituitary tumor 7315a. In radioligand binding experiments, the D2 receptor antagonist (S)-(-)-3-{sup 125}I iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2- pyrrolidinyl)methyl)benzamide ({sup 125}I IBZM) labeled a single class of sites in homogenates of SUP1 cells (Kd = 0.6 nM; Bmax = 45 fmol/mg of protein). The sites displayed a pharmacological profile consistent with that of D2 receptors. Inhibition of the binding of {sup 125}I IBZM by dopamine was sensitive to GTP, suggesting that D2 receptors in SUP1 cells are coupled to guanine nucleotide-binding protein(s). In the presence of isobutylmethylxanthine, dopamine decreased the level of cAMP accumulation in SUP1 cells. Dopamine also inhibited prolactin secretion from SUP1 cells. Both the inhibition of cAMP accumulation and the inhibition of prolactin secretion were blocked by D2 receptor antagonists, suggesting that these effects of dopamine were mediated by an interaction with D2 receptors. The regulation of D2 receptors in SUP1 cells by D2 receptor agonists was investigated. Exposure of SUP1 cells to dopamine or to the D2 receptor agonist N-propylnorapomorphine led to increased expression of D2 receptors, with no change in the affinity of the receptors for {sup 125}I IBZM. An increase in the density of D2 receptors in SUP1 cells was evident within 7 hr of exposure to dopamine. Spiroperidol, a D2 receptor antagonist, blocked the effect of dopamine on receptor density. These results suggest that exposure of D2 receptors in SUP1 cells to agonists leads to an up-regulation of D2 receptors. Dopamine retained the ability to inhibit cAMP accumulation in SUP1 cells exposed to dopamine for 24 hr, suggesting that D2 receptors in SUP1 cells are not desensitized by prolonged exposure to agonist.

  13. Differential contributions of dopamine D1, D2, and D3 receptors to MDMA-induced effects on locomotor behavior patterns in mice.

    PubMed

    Risbrough, Victoria B; Masten, Virginia L; Caldwell, Sorana; Paulus, Martin P; Low, Malcolm J; Geyer, Mark A

    2006-11-01

    MDMA or 'ecstasy' (3,4-methylenedioxymethamphetamine) is a commonly used psychoactive drug that has unusual and distinctive behavioral effects in both humans and animals. In rodents, MDMA administration produces a unique locomotor activity pattern, with high activity characterized by smooth locomotor paths and perseverative thigmotaxis. Although considerable evidence supports a major role for serotonin release in MDMA-induced locomotor activity, dopamine (DA) receptor antagonists have recently been shown to attenuate these effects. Here, we tested the hypothesis that DA D1, D2, and D3 receptors contribute to MDMA-induced alterations in locomotor activity and motor patterns. DA D1, D2, or D3 receptor knockout (KO) and wild-type (WT) mice received vehicle or (+/-)-MDMA and were tested for 60 min in the behavioral pattern monitor (BPM). D1 KO mice exhibited significant increases in MDMA-induced hyperactivity in the late testing phase as well as an overall increase in straight path movements. In contrast, D2 KO mice exhibited reductions in MDMA-induced hyperactivity in the late testing phase, and exhibited significantly less sensitivity to MDMA-induced perseverative thigmotaxis. At baseline, D2 KO mice also exhibited reduced activity and more circumscribed movements compared to WT mice. Female D3 KO mice showed a slight reduction in MDMA-induced hyperactivity. These results confirm differential modulatory roles for D1 and D2 and perhaps D3 receptors in MDMA-induced hyperactivity. More specifically, D1 receptor activation appears to modify the type of activity (linear vs circumscribed), whereas D2 receptor activation appears to contribute to the repetitive circling behavior produced by MDMA. PMID:16855533

  14. Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.

    PubMed

    Shimoda, Yoko; Okada, Shuichi; Yamada, Eijiro; Pessin, Jeffrey E; Yamada, Masanobu

    2015-10-01

    Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a functionally unknown protein that contains a Tctex1 domain found in dynein light chain family members. Examination of gene expression during adipogenesis demonstrated a marked increase in Tctex1d2 protein expression that was essentially undetectable in preadipocytes and markedly induced during 3T3-L1 adipocyte differentiation. Tctex1d2 overexpression significantly inhibited insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose uptake. In contrast, Tctex1d2 knockdown significantly increased insulin-stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction target required for GLUT4 translocation. Although overexpression of Tctex1d2 had no significant effect on GLUT4 internalization, Tctex1d2 was found to associate with syntaxin 4 in an insulin-dependent manner and inhibit Doc2b binding to syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions. Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin 4 binding protein that functions as a negative regulator of GLUT4 plasma membrane translocation through inhibition of the Doc2b-syntaxin 4 interaction. PMID:26200093

  15. Drug-induced up-regulation of dopamine D2 receptors on cultured cells.

    PubMed

    Starr, S; Kozell, L B; Neve, K A

    1995-08-01

    Ligand-induced up-regulation of recombinant dopamine D2 receptors was assessed using C6 glioma cells stably expressing the short (415-amino-acid; D2s) and long (444-amino-acid; D2L) forms of the receptor. Overnight treatment of C6-D2L cells with N-propylnorapomorphine (NPA) caused a time- and concentration-dependent increase in the density of receptors, as assessed by the binding of radioligand to membranes prepared from the cells, with no change in the affinity of the receptors for the radioligand. The effect of 10 microM NPA was maximal after 10 h, at which time the density of D2L receptors was more than doubled. The agonists dopamine and quinpirole also increased the density of D2L receptors. The receptor up-regulation was not specific for agonists, because the antagonists epidepride, sulpiride, and domperidone caused smaller (30-60%) increases in receptor density. Prolonged treatment with 10 microM NPA desensitized D2L receptors, as evidenced by a reduced ability of dopamine to inhibit adenylyl cyclase, whereas treatment with sulpiride was associated with an enhanced responsiveness to dopamine. The magnitude of NPA-induced receptor up-regulation in each of four clonal lines of C6-D2L cells (mean increase, 80%) was greater than in all four lines of C6-D2S cells (33%). Inactivation of pertussis toxin-sensitive G proteins had no effect on the basal density of D2L receptors or on the NPA-induced receptor up-regulation. Treatment with 5 micrograms/ml of cycloheximide, on the other hand, decreased the basal density of receptors and attenuated, but did not prevent, the NPA-induced increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7616211

  16. Identification of resolvin D2 receptor mediating resolution of infections and organ protection

    PubMed Central

    Chiang, Nan; Dalli, Jesmond; Colas, Romain A.

    2015-01-01

    Endogenous mechanisms that orchestrate resolution of acute inflammation are essential in host defense and the return to homeostasis. Resolvin (Rv)D2 is a potent immunoresolvent biosynthesized during active resolution that stereoselectively stimulates resolution of acute inflammation. Here, using an unbiased G protein–coupled receptor-β-arrestin–based screening and functional sensing systems, we identified a receptor for RvD2, namely GPR18, that is expressed on human leukocytes, including polymorphonuclear neutrophils (PMN), monocytes, and macrophages (MΦ). In human MΦ, RvD2-stimulated intracellular cyclic AMP was dependent on GPR18. RvD2-stimulated phagocytosis of Escherichia coli and apoptotic PMN (efferocytosis) were enhanced with GPR18 overexpression and significantly reduced by shRNA knockdown. Specific binding of RvD2 to recombinant GPR18 was confirmed using a synthetic 3H-labeled-RvD2. Scatchard analysis gave a Kd of ∼10 nM consistent with RvD2 bioactive concentration range. In both E. coli and Staphylococcus aureus infections, RvD2 limited PMN infiltration, enhanced phagocyte clearance of bacteria, and accelerated resolution. These actions were lost in GPR18-deficient mice. During PMN-mediated second organ injury, RvD2’s protective actions were also significantly diminished in GPR18-deficient mice. Together, these results provide evidence for a novel RvD2–GPR18 resolution axis that stimulates human and mouse phagocyte functions to control bacterial infections and promote organ protection. PMID:26195725

  17. Developing a Mobile Electronic D2B Checklist for Treatment of ST Elevation Myocardial Infarction Patients Who Need a Primary Coronary Intervention

    PubMed Central

    Lin, Hung-Jung; Hsu, Min-Huei; Huang, Chien-Cheng; Tan, Che-Kim; Chou, Shu-Lien; Huang, Shou-Yung; Chen, Chia-Jung

    2015-01-01

    Abstract ST elevation myocardial infarction (STEMI), one main type of acute myocardial infarction with high mortality, requires percutaneous coronary intervention (PCI) with balloon inflation. Current guidelines recommend a door-to-balloon (D2B) interval (i.e., starts with the patient's arrival in the emergency department and ends when PCI with a catheter guidewire and balloon inflation crosses the culprit lesion) of no more than 90 min. However, promptly implementing PCI requires coordinating various medical teams. Checklists can be used to ensure consistency and operating sequences when executing complex tasks in a clinical routine. Developing an effective D2B checklist would enhance the care of STEMI patients who need PCI. Mobile information and communication technologies have the potential to greatly improve communication, facilitate access to information, and eliminate duplicated documentation without the limitations of space and time. In a research project by the Chi Mei Medical Center, “Developing a Mobile Electronic D2B Checklist for Managing the Treatment of STEMI Patients Who Need Primary Coronary Intervention,” a prototype version of a mobile checklist was developed. This study describes the research project and the four phases of the system development life cycle, comprising system planning and selection, analysis, design, and implementation and operation. Face-to-face interviews with 16 potential users were conducted and revealed highly positive user perception and use intention toward the prototype. Discussion and directions for future research are also presented. PMID:25615278

  18. Developing a mobile electronic D2B checklist for treatment of ST elevation myocardial infarction patients who need a primary coronary intervention.

    PubMed

    Lin, Hung-Jung; Hsu, Min-Huei; Huang, Chien-Cheng; Liu, Chung-Feng; Tan, Che-Kim; Chou, Shu-Lien; Huang, Shou-Yung; Chen, Chia-Jung

    2015-04-01

    ST elevation myocardial infarction (STEMI), one main type of acute myocardial infarction with high mortality, requires percutaneous coronary intervention (PCI) with balloon inflation. Current guidelines recommend a door-to-balloon (D2B) interval (i.e., starts with the patient's arrival in the emergency department and ends when PCI with a catheter guidewire and balloon inflation crosses the culprit lesion) of no more than 90 min. However, promptly implementing PCI requires coordinating various medical teams. Checklists can be used to ensure consistency and operating sequences when executing complex tasks in a clinical routine. Developing an effective D2B checklist would enhance the care of STEMI patients who need PCI. Mobile information and communication technologies have the potential to greatly improve communication, facilitate access to information, and eliminate duplicated documentation without the limitations of space and time. In a research project by the Chi Mei Medical Center, "Developing a Mobile Electronic D2B Checklist for Managing the Treatment of STEMI Patients Who Need Primary Coronary Intervention," a prototype version of a mobile checklist was developed. This study describes the research project and the four phases of the system development life cycle, comprising system planning and selection, analysis, design, and implementation and operation. Face-to-face interviews with 16 potential users were conducted and revealed highly positive user perception and use intention toward the prototype. Discussion and directions for future research are also presented. PMID:25615278

  19. Routine or targeted HIV screening of Indonesian prisoners.

    PubMed

    Nelwan, Erni Juwita; Isa, Ahmad; Alisjahbana, Bachti; Triani, Nurlita; Djamaris, Iqbal; Djaja, Ilham; Pohan, Herdiman T; Zwanikken, Prisca; Crevel, Reinout van; van der Ven, Andre; Meheus, Andre

    2016-03-14

    Purpose - Routine HIV screening of prisoners is generally recommended, but rarely implemented in low-resource settings. Targeted screening can be used as an alternative. Both strategies may provide an opportunity to start HIV treatment but no formal comparisons have been done of these two strategies. The paper aims to discuss these issues. Design/methodology/approach - The authors compared yield and costs of routine and targeted screening in a narcotic prison in Indonesia. Routine HIV screening was done for all incoming prisoners from August 2007-February 2009, after it was switched for budgetary reasons to targeted ("opt-out") HIV screening of inmates classified as people who inject drugs (PWIDs), and "opt-in" HIV testing for all non-PWIDs. Findings - During routine screening 662 inmates were included. All 115 PWIDs and 93.2 percent of non-PWIDs agreed to be tested, 37.4 percent and 0.4 percent respectively were HIV-positive. During targeted screening (March 2009-October 2010), of 888 inmates who entered prison, 107 reported injecting drug use and were offered HIV testing, of whom 31 (29 percent) chose not to be tested and 25.0 percent of those tested were HIV-positive. Of 781 non-PWIDs, 187 (24 percent) came for testing (opt-in), and 2.1 percent were infected. During targeted screening fewer people admitted drug use (12.0 vs 17.4 percent). Routine screening yielded twice as many HIV-infected subjects (45 vs 23). The estimated cost per detected HIV infection was 338 USD for routine and 263 USD for targeted screening. Originality/value - In a resource limited setting like Indonesia, routine HIV screening in prison is feasible and more effective than targeted screening, which may be stigmatizing. HIV infections that remain unrecognized can fuel ongoing transmission in prison and lead to unnecessary disease progression and deaths. PMID:26933989

  20. 79 FR 13540 - Food Additives Permitted for Direct Addition to Food for Human Consumption; Vitamin D2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2014-03-11

    ... to Food for Human Consumption; Vitamin D 2 Bakers Yeast AGENCY: Food and Drug Administration, HHS... authorizing the use of vitamin D 2 bakers yeast as a source of vitamin D 2 and as a leavening agent in yeast-leavened baked products at levels not to exceed 400 International Units (IU) of vitamin D 2 per 100...

  1. Reversible Chromatic Response of Polydiacetylene Derivative Vesicles in D2O Solvent.

    PubMed

    Shin, Min Jae; Kim, Jong-Duk

    2016-01-26

    The thermal chromatic sensitivity of polydiacetylenes (PDAs) with 10,12-pentacosadiynoic acid (PCDA) derivatives, which have a hydroxyl group (HEEPCDA) and an amine group (APPCDA), were investigated using D2O and H2O as solvents. The vesicle solution with polymerized HEEPCDA exhibited a reversible chromatic response during the heating and cooling cycle in D2O, but not in H2O. On the other hand, the vesicle solution with the polymerized APPCDA exhibited a reversible chromatic response in H2O during the heating and cooling cycle, but the color of the solution did not change much in D2O. The critical vesicle concentration of HEEPCDA was lower in D2O than in H2O, and the chromatic sensitivity of the polymerized vesicles to temperature was slower in D2O than in H2O. We think that it is due to D2O being a more highly structured solvent than H2O with the hydrogen bonding in D2O stronger than that in H2O. PMID:26730887

  2. Structure-Based Virtual Screening for Dopamine D2 Receptor Ligands as Potential Antipsychotics.

    PubMed

    Kaczor, Agnieszka A; Silva, Andrea G; Loza, María I; Kolb, Peter; Castro, Marián; Poso, Antti

    2016-04-01

    Structure-based virtual screening using a D2 receptor homology model was performed to identify dopamine D2 receptor ligands as potential antipsychotics. From screening a library of 6.5 million compounds, 21 were selected and were subjected to experimental validation. From these 21 compounds tested, ten D2 ligands were identified (47.6 % success rate, among them D2 receptor antagonists, as expected) that have additional affinity for other receptors tested, in particular 5-HT2A receptors. The affinity (Ki values) of the compounds ranged from 58 nm to about 24 μm. Similarity and fragment analysis indicated a significant degree of structural novelty among the identified compounds. We found one D2 receptor antagonist that did not have a protonatable nitrogen atom, which is a key structural element of the classical D2 pharmacophore model necessary for interaction with the conserved Asp(3.32) residue. This compound exhibited greater than 20-fold binding selectivity for the D2 receptor over the D3 receptor. We provide additional evidence that the amide hydrogen atom of this compound forms a hydrogen bond with Asp(3.32), as determined by tests of its derivatives that cannot maintain this interaction. PMID:26990027

  3. Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

    PubMed

    Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

    2015-03-01

    The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. PMID:25740537

  4. Dopamine D2/3 receptor antagonism reduces activity-based anorexia.

    PubMed

    Klenotich, S J; Ho, E V; McMurray, M S; Server, C H; Dulawa, S C

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT(2A/2C), 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted. PMID:26241351

  5. Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

    PubMed Central

    Yoon, Ye Ran

    2015-01-01

    Background The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. Methods We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. Results In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. Conclusion We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors. PMID:26790386

  6. Dopamine D2/3 receptor antagonism reduces activity-based anorexia

    PubMed Central

    Klenotich, S J; Ho, E V; McMurray, M S; Server, C H; Dulawa, S C

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT2A/2C, 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted. PMID:26241351

  7. NeuroD2 regulates the development of hippocampal mossy fiber synapses

    PubMed Central

    2012-01-01

    Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo. PMID:22369234

  8. Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

    PubMed Central

    de Jong, Johannes W; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E; Luijendijk, Mieneke C M; van der Eerden, Harrie A M; Garner, Keith M; Vanderschuren, Louk J M J; Adan, Roger A H

    2015-01-01

    Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior. PMID:25735756

  9. EZVIDEO, FORTRAN graphics routines for the IBM AT

    SciTech Connect

    Patterson, M.R.; Holdeman, J.T.; Ward, R.C.; Jackson, W.L.

    1989-10-01

    A set of IBM PC-based FORTRAN plotting routines called EZVIDEO is described in this report. These routines are written in FORTRAN and can be called from FORTRAN programs. EZVIDEO simulates a subset of the well-known DISSPLA graphics calls and makes plots directly on the IBM AT display screen. Screen dumps can also be made to an attached LaserJet or Epson printer to make hard copy without using terminal emulators. More than forty DISSPLA calls are simulated by the EZVIDEO routines. Typical screen plots require about 10 seconds (s), and good hard copy of the screen image on a laser printer requires less than 2 minutes (min). This higher-resolution hard copy is adequate for most purposes because of the enhanced resolution of the screen in the EGA and VGA modes. These EZVIDEO routines give the IB, AT user a stand-alone capability to make useful scientific or engineering plots directly on the AT, using data generated in FORTRAN programs. The routines will also work on the IBM PC or XT in CGA mode, but they require more time and yield less resolution. 7 refs., 4 figs.

  10. The role of routine follow-up after gynecological malignancy.

    PubMed

    Kew, F M; Roberts, A P; Cruickshank, D J

    2005-01-01

    The objective of this article was to determine the evidence base for routine follow-up after gynecological malignancy. Only articles with a survival analysis were included. Relevant articles were identified by a comprehensive literature search of the main biomedical databases, hand searching of references of selected articles, and expert spotting of relevant journals and proceedings of international meetings. A two-stage extraction of data was undertaken. No prospective trials were identified. Twenty-nine retrospective case series analyses and one poster presentation met the inclusion criteria. Eight articles and one letter on endometrial cancer, six articles and one poster presentation on cervical cancer, and two articles in vulval cancer were reviewed. Only one article in endometrial cancer showed any survival benefit from routine follow-up, but it was of very poor methodologic quality. Two articles found a survival benefit from routine follow-up after cervical cancer. The two articles on vulval cancer did not find any survival benefit from routine review. There is no prospective research on the benefits of routine follow-up after gynecological cancer. Retrospective evidence calls in to question the benefit of universal follow-up. Prospective research is urgently needed. PMID:15882163

  11. Clinician's Attitudes to the Introduction of Routine Weighing in Pregnancy

    PubMed Central

    Beckmann, Michael M.; Wilkinson, Shelley A.

    2016-01-01

    Background. Excessive gestational weight gain poses significant short- and long-term health risks to both mother and baby. Professional bodies and health services increasingly recommend greater attention be paid to weight gain in pregnancy. A large Australian tertiary maternity hospital plans to facilitate the (re)introduction of routine weighing of all women at every antenatal visit. Objective. To identify clinicians' perspectives of barriers and enablers to routinely weighing pregnant women and variations in current practice, knowledge, and attitudes between different staff groups. Method. Forty-four maternity staff from three professional groups were interviewed in four focus groups. Staff included midwives; medical staff; and dietitians. Transcripts underwent qualitative content analysis to identify and examine barriers and enablers to the routine weighing of women throughout pregnancy. Results. While most staff supported routine weighing, various concerns were raised. Issues included access to resources and staff; the ability to provide appropriate counselling and evidence-based interventions; and the impact of weighing on patients and the therapeutic relationship. Conclusion. Many clinicians supported the practice of routine weighing in pregnancy, but barriers were also identified. Implementation strategies will be tailored to the discrete professional groups and will address identified gaps in knowledge, resources, and clinician skills and confidence. PMID:27446614

  12. Social and Demographic Predictors of Preschoolers’ Bedtime Routines

    PubMed Central

    Hale, Lauren; Berger, Lawrence M.; LeBourgeois, Monique K.; Brooks-Gunn, Jeanne

    2009-01-01

    Objective To examine associations of child and family sociodemographic characteristics with preschooler bedtime routines. Method We use parent-report data on 3,217 3-year-old children (48% black; 26% Hispanic; 26% white) from the Fragile Families and Child Wellbeing Study to examine whether child and family characteristics are associated with the presence, time, and consistency of bedtime routines. Results Over 80% of sample children have a bedtime yet only two-thirds follow it. After extensive controls for maternal education, family structure, and other household characteristics, Black and Hispanic children have later bedtimes than white children and reduced odds of using regular bedtimes (by 22% and 29%, respectively) and using bedtime routines (by 47% and 33%, respectively). Low maternal education, increased household size, and poverty are associated with decreased use of parent-child interactive and hygiene-related bedtime routines. Conclusion Children from disadvantaged households are less likely to have consistent bedtime routines than their more advantaged counterparts. This may contribute to later disparities in sleep quality, duration and timing, factors known to be associated with adverse behavioral, cognitive, and health outcomes. PMID:19745760

  13. Clinician's Attitudes to the Introduction of Routine Weighing in Pregnancy.

    PubMed

    Hasted, Tim; Stapleton, Helen; Beckmann, Michael M; Wilkinson, Shelley A

    2016-01-01

    Background. Excessive gestational weight gain poses significant short- and long-term health risks to both mother and baby. Professional bodies and health services increasingly recommend greater attention be paid to weight gain in pregnancy. A large Australian tertiary maternity hospital plans to facilitate the (re)introduction of routine weighing of all women at every antenatal visit. Objective. To identify clinicians' perspectives of barriers and enablers to routinely weighing pregnant women and variations in current practice, knowledge, and attitudes between different staff groups. Method. Forty-four maternity staff from three professional groups were interviewed in four focus groups. Staff included midwives; medical staff; and dietitians. Transcripts underwent qualitative content analysis to identify and examine barriers and enablers to the routine weighing of women throughout pregnancy. Results. While most staff supported routine weighing, various concerns were raised. Issues included access to resources and staff; the ability to provide appropriate counselling and evidence-based interventions; and the impact of weighing on patients and the therapeutic relationship. Conclusion. Many clinicians supported the practice of routine weighing in pregnancy, but barriers were also identified. Implementation strategies will be tailored to the discrete professional groups and will address identified gaps in knowledge, resources, and clinician skills and confidence. PMID:27446614

  14. Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    PubMed

    Pepino, Marta Y; Eisenstein, Sarah A; Bischoff, Allison N; Klein, Samuel; Moerlein, Stephen M; Perlmutter, Joel S; Black, Kevin J; Hershey, Tamara

    2016-09-01

    Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships between these variables and the impact of obesity on these relationships may reveal insight into the neurobiological basis of sweet preferences. We evaluated sucrose preferences, perception of sweetness intensity, and striatal D2R binding potential (D2R BPND) using positron emission tomography with a D2R-selective radioligand insensitive to endogenous dopamine, (N-[(11)C] methyl)benperidol, in 20 subjects without obesity (BMI 22.5 ± 2.4 kg/m(2); age 28.3 ± 5.4 years) and 24 subjects with obesity (BMI 40.3 ± 5.0 kg/m(2); age 31.2 ± 6.3 years). The groups had similar sucrose preferences, sweetness intensity perception, striatal D2R BPND, and age-related D2R BPND declines. However, both striatal D2R BPND and age correlated with sucrose preferences in subjects without obesity, explaining 52% of their variance in sucrose preference. In contrast, these associations were absent in the obese group. In conclusion, the age-related decline in D2R was not linked to the age-related decline in sweetness preferences, suggesting that other, as-yet-unknown mechanisms play a role and that these mechanisms are disrupted in obesity. PMID:27307220

  15. Impact of D2 Receptor Internalization on Binding Affinity of Neuroimaging Radiotracers

    PubMed Central

    Guo, Ningning; Guo, Wen; Kralikova, Michaela; Jiang, Man; Schieren, Ira; Narendran, Raj; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc; Javitch, Jonathan A; Rayport, Stephen

    2010-01-01

    Synaptic dopamine (DA) levels seem to affect the in vivo binding of many D2 receptor radioligands. Thus, release of endogenous DA induced by the administration of amphetamine decreases ligand binding, whereas DA depletion increases binding. This is generally thought to be due to competition between endogenous DA and the radioligands for D2 receptors. However, the temporal discrepancy between amphetamine-induced increases in DA as measured by microdialysis, which last on the order of 2 h, and the prolonged decrease in ligand binding, which lasts up to a day, has suggested that agonist-induced D2 receptor internalization may contribute to the sustained decrease in D2 receptor-binding potential seen following a DA surge. To test this hypothesis, we developed an in vitro system showing robust agonist-induced D2 receptor internalization following treatment with the agonist quinpirole. Human embryonic kidney 293 (HEK293) cells were stably co-transfected with human D2 receptor, G-protein-coupled receptor kinase 2 and arrestin 3. Agonist-induced D2 receptor internalization was demonstrated by fluorescence microscopy, flow cytometry, and radioligand competition binding. The binding of seven D2 antagonists and four agonists to the surface and internalized receptors was measured in intact cells. All the imaging ligands bound with high affinity to both surface and internalized D2 receptors. Affinity of most of the ligands to internalized receptors was modestly lower, indicating that internalization would reduce the binding potential measured in imaging studies carried out with these ligands. However, between-ligand differences in the magnitude of the internalization-associated affinity shift only partly accounted for the data obtained in neuroimaging experiments, suggesting the involvement of mechanisms beyond competition and internalization. PMID:19956086

  16. Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique

    PubMed Central

    Voelxen, Nadine F.; Walenta, Stefan; Proescholdt, Martin; Dettmer, Katja; Pusch, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    Patients with malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of-function” mutations in the isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other tumor entities, including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (<0.1 mM), but its concentration increases up to 35 mM in malignant tumor tissues. Consequently, the “oncometabolite” D2HG has gained increasing interest in the field of tumor metabolism. To facilitate its quantitative measurement without loss of spatial resolution at a microscopical level, we have developed a novel bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0–10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension. PMID:27014623

  17. Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease.

    PubMed

    Joyce, J N; Kaeger, C; Ryoo, H; Goldsmith, S

    1993-05-14

    Receptor autoradiography was used to quantify the number of dopamine D2 receptors labeled with [125I]epidepride in the medial temporal lobe of seven cases of Alzheimer's disease in comparison to eight cases of neurologically intact controls. The Alzheimer's disease cases showed the greatest losses of D2 receptors in the basolateral nucleus of the amygdala and molecular layer of the dentate gyrus and the smallest differences from controls in the perirhinal region and subiculum. The loss of D2 receptors in the hippocampus and amygdala of cases with Alzheimer's disease in concert with alterations in dopaminergic innervation could contribute to the clinical symptoms of this disorder. PMID:8361636

  18. Chimeric D1/D2 dopamine receptors. Distinct determinants of selective efficacy, potency, and signal transduction.

    PubMed

    Kozell, L B; Machida, C A; Neve, R L; Neve, K A

    1994-12-01

    D1/D2 chimeras were constructed that had D1 dopamine receptor sequence at the amino-terminal end and D2 dopamine receptor sequence at the carboxyl-terminal end. The chimeras with the first four, five and six transmembrane domains of the D1 receptor (CH2, CH3, CH4, respectively) bound the D1 receptor antagonist [3H]SCH 23390 with high affinity. Reciprocal chimeras constructed with D2 receptor sequence at the amino-terminal end displayed no detectable specific binding of [3H]SCH 23390, [125I]epidepride, or [3H]spiperone. CH2, CH3, and CH4 had lower affinity than either D1 or D2 dopamine receptors for the nonselective antagonists and agonists and D2-selective antagonists tested. The chimeric receptors had affinities for three D1-selective ligands and the D2-selective agonist, quinpirole, that were intermediate between D1 and D2 receptor affinities for the drugs. The substantial loss or gain of affinity for three ligands upon replacement of D1 transmembrane VII with D2 sequence (CH4) suggests an important role for this region in the selectivity of these drugs. Stimulation of adenylyl cyclase activity by D1 agonists occurred in cells expressing CH3 and CH4, both of which included the D1 third cytoplasmic loop, but not in cells expressing CH1 or CH2, both with the D2 third cytoplasmic loop. However, only CH3 was able to mediate stimulation of adenylyl cyclase by quinpirole, implying that D2 receptor transmembrane domain VI was an important determinant of the selective efficacy of quinpirole. On the other hand, transmembrane domain VII was particularly important for the selective potency of quinpirole. Inhibition of beta-adrenergic receptor-stimulated adenylyl cyclase activity by dopamine was seen in cells expressing D2 receptors and CH1, but not CH2, CH3, or CH4. Thus, the third cytoplasmic loop of D1 dopamine receptors was crucial for the coupling of the receptors to Gs, but inhibition of adenylyl cyclase via Gi required structural features, such as the second

  19. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport.

    PubMed

    Schmidts, Miriam; Hou, Yuqing; Cortés, Claudio R; Mans, Dorus A; Huber, Celine; Boldt, Karsten; Patel, Mitali; van Reeuwijk, Jeroen; Plaza, Jean-Marc; van Beersum, Sylvia E C; Yap, Zhi Min; Letteboer, Stef J F; Taylor, S Paige; Herridge, Warren; Johnson, Colin A; Scambler, Peter J; Ueffing, Marius; Kayserili, Hulya; Krakow, Deborah; King, Stephen M; Beales, Philip L; Al-Gazali, Lihadh; Wicking, Carol; Cormier-Daire, Valerie; Roepman, Ronald; Mitchison, Hannah M; Witman, George B

    2015-01-01

    The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions. PMID:26044572

  20. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

    PubMed Central

    Schmidts, Miriam; Hou, Yuqing; Cortés, Claudio R.; Mans, Dorus A.; Huber, Celine; Boldt, Karsten; Patel, Mitali; van Reeuwijk, Jeroen; Plaza, Jean-Marc; van Beersum, Sylvia E. C.; Yap, Zhi Min; Letteboer, Stef J. F.; Taylor, S. Paige; Herridge, Warren; Johnson, Colin A.; Scambler, Peter J.; Ueffing, Marius; Kayserili, Hulya; Krakow, Deborah; King, Stephen M.; Beales, Philip L.; Al-Gazali, Lihadh; Wicking, Carol; Cormier-Daire, Valerie; Roepman, Ronald; Mitchison, Hannah M.; Witman, George B.; Al-Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Asimit, Jennifer; Ayub, Mohammad; Barrett, Jeff; Barroso, Inês; Bentham, Jamie; Bhattacharya, Shoumo; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Boustred, Chris; Breen, Gerome; Brion, Marie-Jo; Brown, Andrew; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Daly, Allan; Danecek, Petr; Smith, George Davey; Day-Williams, Aaron; Day, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Farooqi, I. Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David; Flicek, Paul; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geschwind, Daniel; Greenwood, Celia; Grozeva, Detelina; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Huang, Jie; Humphries, Steve E.; Hurles, Matt; Hysi, Pirro; Jackson, David; Jamshidi, Yalda; Jewell, David; Chris, Joyce; Kaye, Jane; Keane, Thomas; Kemp, John; Kennedy, Karen; Kent, Alastair; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lee, Irene; Li, Rui; Li, Yingrui; Ryan, Liu; Lönnqvist, Jouko; Lopes, Margarida; MacArthur, Daniel G.; Massimo, Mangino; Marchini, Jonathan; Maslen, John; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donovan, Michael; O'Rahilly, Stephen; Onoufriadis, Alexandros; Oualkacha, Karim; Owen, Michael; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quail, Michael A.; Quaye, Lydia; Raymond, Lucy; Rehnström, Karola; Brent Richards, J.; Ring, Sue; Ritchie, Graham R S; Savage, David B.; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Shihab, Hashem; Shin, So-Youn; Skuse, David; Small, Kerrin; Smee, Carol; Soler, Artigas María; Soranzo, Nicole; Southam, Lorraine; Spector, Tim; St Pourcain, Beate; St. Clair, David; Stalker, Jim; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ioanna; Tian, Jing; Timpson, Nic; Tobin, Martin; Valdes, Ana; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Wain, Louise; Walter, Klaudia; Wang, Jun; Ward, Kirsten; Wheeler, Ellie; Whittall, Ros; Williams, Hywel; Williamson, Kathy; Wilson, Scott G.; Wong, Kim; Whyte, Tamieka; ChangJiang, Xu; Zeggini, Eleftheria; Zhang, Feng; Zheng, Hou-Feng

    2015-01-01

    The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions. PMID:26044572

  1. Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

    PubMed

    Bagalkot, T R; Jin, H-M; Prabhu, V V; Muna, S S; Cui, Y; Yadav, B K; Chae, H-J; Chung, Y-C

    2015-12-17

    The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice. PMID:26484605

  2. Master schedule for CY-1982 Hanford environmental surveillance routine program

    SciTech Connect

    Blumer, P.J.; Sula, M.J.; Eddy, P.A.

    1981-12-01

    This report provides the current schedule of data collection for the routine environmental surveillance program at the Hanford Site. The environmental surveillance program objectives are to evaluate and report the levels of radioactive and nonradioactive pollutants in the Hanford environs, as required in DOE Order 5484.1. The routine sampling schedule provided does not include samples which are planned to be collected during FY-1982 in support of special studies or for quality control purposes. In addition, the routine program outlined in this schedule is subject to modification during the year in response to changes in Site operations, program requirements, or unusual sample results. Sampling schedules are presented for the following: air; Columbia River; sanitary water; surface water; ground water; foodstuffs; wildlife; soil and vegetation; external radiation measurements; portable instrument surveys; and surveillance of waste disposal sites. (ATT)

  3. Guide to good practices for shift routines and operating practices

    SciTech Connect

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, ``Shift Routines and Operating Practices,`` Chapter 2 of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing shift routines and operating practices. ``Shift Routines and Operating Practices`` is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for a high standard of professional conduct and sound operating practices to promote safe and efficient operations. Recently, guidance pertaining to this element has been strengthened for nuclear power reactors. This additional guidance is given in Appendix C for information purposes. Though this guidance and good practices pertain to nuclear power reactors, DOE sites may choose to use a graded approach for implementing these in nuclear facilities.

  4. Pulse processing routines for neutron time-of-flight data

    NASA Astrophysics Data System (ADS)

    Žugec, P.; Weiß, C.; Guerrero, C.; Gunsing, F.; Vlachoudis, V.; Sabate-Gilarte, M.; Stamatopoulos, A.; Wright, T.; Lerendegui-Marco, J.; Mingrone, F.; Ryan, J. A.; Warren, S. G.; Tsinganis, A.; Barbagallo, M.

    2016-03-01

    A pulse shape analysis framework is described, which was developed for n_TOF-Phase3, the third phase in the operation of the n_TOF facility at CERN. The most notable feature of this new framework is the adoption of generic pulse shape analysis routines, characterized by a minimal number of explicit assumptions about the nature of pulses. The aim of these routines is to be applicable to a wide variety of detectors, thus facilitating the introduction of the new detectors or types of detectors into the analysis framework. The operational details of the routines are suited to the specific requirements of particular detectors by adjusting the set of external input parameters. Pulse recognition, baseline calculation and the pulse shape fitting procedure are described. Special emphasis is put on their computational efficiency, since the most basic implementations of these conceptually simple methods are often computationally inefficient.

  5. Computer routines for probability distributions, random numbers, and related functions

    USGS Publications Warehouse

    Kirby, W.

    1983-01-01

    Use of previously coded and tested subroutines simplifies and speeds up program development and testing. This report presents routines that can be used to calculate various probability distributions and other functions of importance in statistical hydrology. The routines are designed as general-purpose Fortran subroutines and functions to be called from user-written main progress. The probability distributions provided include the beta, chi-square, gamma, Gaussian (normal), Pearson Type III (tables and approximation), and Weibull. Also provided are the distributions of the Grubbs-Beck outlier test, Kolmogorov 's and Smirnov 's D, Student 's t, noncentral t (approximate), and Snedecor F. Other mathematical functions include the Bessel function, I sub o, gamma and log-gamma functions, error functions, and exponential integral. Auxiliary services include sorting and printer-plotting. Random number generators for uniform and normal numbers are provided and may be used with some of the above routines to generate numbers from other distributions. (USGS)

  6. Computer routines for probability distributions, random numbers, and related functions

    USGS Publications Warehouse

    Kirby, W.H.

    1980-01-01

    Use of previously codes and tested subroutines simplifies and speeds up program development and testing. This report presents routines that can be used to calculate various probability distributions and other functions of importance in statistical hydrology. The routines are designed as general-purpose Fortran subroutines and functions to be called from user-written main programs. The probability distributions provided include the beta, chisquare, gamma, Gaussian (normal), Pearson Type III (tables and approximation), and Weibull. Also provided are the distributions of the Grubbs-Beck outlier test, Kolmogorov 's and Smirnov 's D, Student 's t, noncentral t (approximate), and Snedecor F tests. Other mathematical functions include the Bessel function I (subzero), gamma and log-gamma functions, error functions and exponential integral. Auxiliary services include sorting and printer plotting. Random number generators for uniform and normal numbers are provided and may be used with some of the above routines to generate numbers from other distributions. (USGS)

  7. Routine Activities Preceding Adolescent Sexual Abuse of Younger Children.

    PubMed

    Leclerc, Benoit; Felson, Marcus

    2016-03-01

    Adolescent abuse of younger children has long been recognized, but empirical research on the circumstances of this phenomenon is rare. This article examines how adolescent offenders find and gain access to victims, work out time alone with them, and set up or exploit settings for sexual contact. Prior researchers learned that adult sex offenders use certain routine activities to perform these tasks. The current research inquires whether adolescent offenders are similar. We administered Kaufman's Modus Operandi Questionnaire to a sample of 116 Canadian adolescent males undergoing treatment for a sexual offense against a child. Adolescent offenders follow routines similar to adults but are better able to use games and activities as a prelude to sexual abuse. We discuss how routine legal activities set the stage for activities and should be considered when devising situational prevention strategies. PMID:25060598

  8. Monochromatic, Rosseland mean, and Planck mean opacity routine

    NASA Astrophysics Data System (ADS)

    Semenov, D.

    2006-11-01

    Several FORTRAN77 codes were developed to compute frequency-dependent, Rosseland and Planck mean opacities of gas and dust in protoplanetary disks. The opacities can be computed for an ensemble of dust grains having various compositions (ices, silicates, organics, etc), sizes, topologies (homogeneous/composite aggregates, homogeneous/layered/composite spheres, etc.), porosities, and dust-to-gas ratio. Several examples are available. In addition, a very fast opacity routine to be used in modeling of the radiative transfer in hydro simulations of disks is available upon request (10^8 routine calls require about 30s on Pentium 4 3.0GHz).

  9. Value of routine histopathological examination of appendices in Hong Kong.

    PubMed Central

    Chan, W; Fu, K H

    1987-01-01

    A retrospective study of the histopathological findings of more than 11,443 appendices submitted as surgical specimens over 14 years was performed in this department. In most cases routine histopathological examination added little clinically important information to other clinical and operative gross findings, but a variety of interesting and uncommon lesions were identified. In 85 cases clinically important pathological findings were first discovered on routine histopathological examination. These included enterobiasis, schistosomiasis, mucocele, trichuriasis, tuberculosis, ascariasis, endometriosis, mucinous cystadenoma, granuloma, carcinoid tumour, neuroma, clonorchiasis, primary adenocarcinoma and secondary carcinoma. PMID:3584486

  10. Antipsychotic-induced alterations in D2 dopamine receptor interacting proteins within the cortex.

    PubMed

    Kabbani, Nadine; Levenson, Robert

    2006-02-27

    Current antipsychotic treatment involves the regulation of D2 dopamine receptor activity in the brain. Here, we examined the effects of chronic haloperidol and clozapine on cortical D2 dopamine receptors and six different dopamine receptor interacting proteins. Using comparative immunoblot analysis, we found that treatment with either haloperidol or clozapine increased D2 dopamine receptors, calcium activator protein for secretion, protein 4.1N, and neuronal calcium sensor-1 expression. Treatment with clozapine increased calmodulin and spinophilin expression, while treatment with haloperidol decreased expression of these two dopamine receptor interacting proteins. Neither antipsychotic drug was found to have an effect on filamin-A expression. These findings underscore a role for cortical D2 dopamine receptor in the mechanism of antipsychotic drug action, and suggest dopamine receptor interacting proteins as novel targets in antipsychotic drug development. PMID:16462601

  11. Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent pathway.

    PubMed

    Czyzyk-Krzeska, M F; Lawson, E E; Millhorn, D E

    1992-11-01

    Dopamine is a major neurotransmitter in the arterial chemoreceptor pathway. In the present study we wished to determine if messenger RNAs for dopamine D1 and D2 receptor are expressed in carotid body (type I cells), in sensory neurons of the petrosal ganglion which innervate the carotid body and in sympathetic neurons of the superior cervical ganglion. We failed to detect D1 receptor mRNA in any of these tissues. However, we found that D2 receptor mRNA was expressed by dopaminergic carotid body type I cells. D2 receptor mRNA was also found in petrosal ganglion neurons that innervated the carotid sinus and carotid body. In addition, a large number of sympathetic postganglionic neurons in the superior cervical ganglion expressed D2 receptor mRNA. PMID:1362730

  12. Dopamine D2 receptor bands in normal human temporal cortex are absent in Alzheimer's disease.

    PubMed

    Joyce, J N; Myers, A J; Gurevich, E

    1998-02-16

    A modular organization of bands enriched in high concentrations of D2 receptors are observed throughout the rostral to caudal aspects of the temporal cortex of the normal human at postmortem, but are most frequently observed in the inferior and superior temporal cortices [S. Goldsmith, J.N. Joyce, Dopamine D2 receptors are organized in bands in normal human temporal cortex, Neuroscience 74 (1996) 435-451]. In the tissue derived at postmortem from Alzheimer's disease cases (AD), these D2 receptor-enriched modules were found to be largely absent at rostral and mid-levels of the temporal cortex. Regions exhibiting this loss of receptor binding also showed a marked reduction in the number of pyramidal neurons stained for D2 mRNA. In addition, the AD material exhibited numerous thioflavin-positive plaques and tangle-filled extraneuronal (ghost) pyramidal neurons that were D2 mRNA-negative. Regions that are the earliest affected and most susceptible to classical AD pathology are also most sensitive to the loss of D2 receptors. These results, along with our previous data [J.N. Joyce, C. Kaeger, H. Ryoo, S. Goldsmith, Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease, Neurosci. Lett. 154 (1993) 171-174; H. Ryoo, J. N. Joyce, The loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in Alzheimer's disease, J. Comp. Neurol. 348 (1994) 94-110], indicate that specific pathways enriched with D2 receptors, including that within modules of higher order association cortices of the temporal lobe and continued through segregated pathways within the parahippocampus and hippocampus, are particularly susceptible to the loss in AD. These dopamine D2 receptor-enriched modules may play an important role in the reciprocal activity of large groups of neurons in these high-order association cortical regions. Hence, the loss of the D2 receptor-enriched modules in Alzheimer's disease contributes to disturbances in information

  13. Domain requirements for DNA unwinding by mycobacterial UvrD2, an essential DNA helicase.

    PubMed

    Sinha, Krishna Murari; Stephanou, Nicolas C; Unciuleac, Mihaela-Carmen; Glickman, Michael S; Shuman, Stewart

    2008-09-01

    Mycobacterial UvrD2 is a DNA-dependent ATPase with 3' to 5' helicase activity. UvrD2 is an atypical helicase, insofar as its N-terminal ATPase domain resembles the superfamily I helicases UvrD/PcrA, yet it has a C-terminal HRDC domain, which is a feature of RecQ-type superfamily II helicases. The ATPase and HRDC domains are connected by a CxxC-(14)-CxxC tetracysteine module that defines a new clade of UvrD2-like bacterial helicases found only in Actinomycetales. By characterizing truncated versions of Mycobacterium smegmatis UvrD2, we show that whereas the HRDC domain is not required for ATPase or helicase activities in vitro, deletion of the tetracysteine module abolishes duplex unwinding while preserving ATP hydrolysis. Replacing each of the CxxC motifs with a double-alanine variant AxxA had no effect on duplex unwinding, signifying that the domain module, not the cysteines, is crucial for function. The helicase activity of a truncated UvrD2 lacking the tetracysteine and HRDC domains was restored by the DNA-binding protein Ku, a component of the mycobacterial NHEJ system and a cofactor for DNA unwinding by the paralogous mycobacterial helicase UvrD1. Our findings indicate that coupling of ATP hydrolysis to duplex unwinding can be achieved by protein domains acting in cis or trans. Attempts to disrupt the M. smegmatis uvrD2 gene were unsuccessful unless a second copy of uvrD2 was present elsewhere in the chromosome, indicating that UvrD2 is essential for growth of M. smegmatis. PMID:18702526

  14. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer.

    PubMed

    Ferré, Sergi; Bonaventura, Jordi; Tomasi, Dardo; Navarro, Gemma; Moreno, Estefanía; Cortés, Antonio; Lluís, Carme; Casadó, Vicent; Volkow, Nora D

    2016-05-01

    The structure constituted by a G protein coupled receptor (GPCR) homodimer and a G protein provides a main functional unit and oligomeric entities can be viewed as multiples of dimers. For GPCR heteromers, experimental evidence supports a tetrameric structure, comprised of two different homodimers, each able to signal with its preferred G protein. GPCR homomers and heteromers can act as the conduit of allosteric interactions between orthosteric ligands. The well-known agonist/agonist allosteric interaction in the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer, by which A2AR agonists decrease the affinity of D2R agonists, gave the first rationale for the use of A2AR antagonists in Parkinson's disease. We review new pharmacological findings that can be explained in the frame of a tetrameric structure of the A2AR-D2R heteromer: first, ligand-independent allosteric modulations by the D2R that result in changes of the binding properties of A2AR ligands; second, differential modulation of the intrinsic efficacy of D2R ligands for G protein-dependent and independent signaling; third, the canonical antagonistic Gs-Gi interaction within the frame of the heteromer; and fourth, the ability of A2AR antagonists, including caffeine, to also exert the same allosteric modulations of D2R ligands than A2AR agonists, while A2AR agonists and antagonists counteract each other's effects. These findings can have important clinical implications when evaluating the use of A2AR antagonists. They also call for the need of monitoring caffeine intake when evaluating the effect of D2R ligands, when used as therapeutic agents in neuropsychiatric disorders or as probes in imaging studies. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:26051403

  15. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    PubMed Central

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-01-01

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

  16. Dopaminergic isoquinolines with hexahydrocyclopenta[ij]-isoquinolines as D2-like selective ligands.

    PubMed

    Párraga, Javier; Andujar, Sebastián A; Rojas, Sebastián; Gutierrez, Lucas J; El Aouad, Noureddine; Sanz, M Jesús; Enriz, Ricardo D; Cabedo, Nuria; Cortes, Diego

    2016-10-21

    Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the β-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR. PMID:27343851

  17. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    DOE PAGESBeta

    Volkow, N. D.; Wang, G. -J.; Logan, J.; Alexoff, D.; Fowler, J. S.; Thanos, P. K.; Wong, C.; Casado, V.; Ferre, S.; Tomasi, D.

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release inmore » striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.« less

  18. Vitamin D2 Supplementation Amplifies Eccentric Exercise-Induced Muscle Damage in NASCAR Pit Crew Athletes

    PubMed Central

    Nieman, David C.; Gillitt, Nicholas D.; Shanely, R. Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-01-01

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n = 13) and placebo (n = 15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p < 0.001, p = 0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p = 0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p < 0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

  19. Separating curium and californium on experimental batches of solid extractants containing D2EHPA

    SciTech Connect

    Dedov, V.B.; Trukhlyaev, P.S.; Kalinichenko, B.S.; Shvetsov, I.K.

    1987-05-01

    Data are given on the extraction parameters for D2EHPA-impregnated solids made by a new method of binding the reagent to the matrix in the synthesis of a styrene-divinylbenzene copolymer by suspension polymerization. Results are given on separating curium and californium with these D2EHPA materials under dynamic conditions. The optimum separation conditions are given, where one obtains virtually pure fractions of the two elements.

  20. Bacterial Ice Nucleation in Monodisperse D2O and H2O-in-Oil Emulsions.

    PubMed

    Weng, Lindong; Tessier, Shannon N; Smith, Kyle; Edd, Jon F; Stott, Shannon L; Toner, Mehmet

    2016-09-13

    Ice nucleation is of fundamental significance in many areas, including atmospheric science, food technology, and cryobiology. In this study, we investigated the ice-nucleation characteristics of picoliter-sized drops consisting of different D2O and H2O mixtures with and without the ice-nucleating bacteria Pseudomonas syringae. We also studied the effects of commonly used cryoprotectants such as ethylene glycol, propylene glycol, and trehalose on the nucleation characteristics of D2O and H2O mixtures. The results show that the median freezing temperature of the suspension containing 1 mg/mL of a lyophilized preparation of P. syringae is as high as -4.6 °C for 100% D2O, compared to -8.9 °C for 100% H2O. As the D2O concentration increases every 25% (v/v), the profile of the ice-nucleation kinetics of D2O + H2O mixtures containing 1 mg/mL Snomax shifts by about 1 °C, suggesting an ideal mixing behavior of D2O and H2O. Furthermore, all of the cryoprotectants investigated in this study are found to depress the freezing phenomenon. Both the homogeneous and heterogeneous freezing temperatures of these aqueous solutions depend on the water activity and are independent of the nature of the solute. These findings enrich our fundamental knowledge of D2O-related ice nucleation and suggest that the combination of D2O and ice-nucleating agents could be a potential self-ice-nucleating formulation. The implications of self-nucleation include a higher, precisely controlled ice seeding temperature for slow freezing that would significantly improve the viability of many ice-assisted cryopreservation protocols. PMID:27495973

  1. Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat1

    PubMed Central

    Clària, Joan; Dalli, Jesmond; Yacoubian, Stephanie; Gao, Fei; Serhan, Charles N.

    2012-01-01

    The unprecedented rise in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. Here, with inflamed adipose, we investigated the biosynthesis, conversion and actions of Resolvin (Rv) D1 and RvD2, potent anti-inflammatory and pro-resolving lipid mediators (LM), and their ability to regulate monocyte interactions with adipocytes. LM-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified pro-resolving receptors (i.e. ALX/FPR2, ChemR23 and GPR32) in these tissues. Compared to lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner while decreasing pro-inflammatory adipokine production including leptin, TNFα, IL-6 and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B4-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins to novel oxo-resolvins. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series resolvins (RvD1 and RvD2) are potent pro-resolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation. PMID:22844113

  2. Dopamine D2 receptor overexpression alters behavior and physiology in Drd2-EGFP mice.

    PubMed

    Kramer, Paul F; Christensen, Christine H; Hazelwood, Lisa A; Dobi, Alice; Bock, Roland; Sibley, David R; Mateo, Yolanda; Alvarez, Veronica A

    2011-01-01

    Bacteria artificial chromosome (BAC) transgenic mice expressing the reporter protein enhanced green fluorescent protein (EGFP) under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological functions of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display an ∼40% increase in membrane expression of the dopamine D2 receptor (D2R) and a twofold increase in D2R mRNA levels in the striatum when compared with wild-type and Drd1-EGFP mice. D2R overexpression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. Dopamine (DA) transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice, and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice overexpress D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice. PMID:21209197

  3. Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.

    PubMed

    Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2014-01-01

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

  4. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

    SciTech Connect

    Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. )

    1991-07-01

    The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

  5. Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

    SciTech Connect

    Busk, Peter K. . E-mail: pkbu@novonordisk.com; Hinrichsen, Rebecca; Bartkova, Jirina; Hansen, Ane H.; Christoffersen, Tue E.H.; Bartek, Jiri; Haunso, Stig

    2005-03-10

    The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21{sup Waf1/Cip1} and p27{sup Kip1}. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic under such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27{sup Kip1}. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2.

  6. Transcriptional Inhibition of REST by NeuroD2 during Neuronal Differentiation

    PubMed Central

    Ravanpay, Ali C.; Hansen, Stacey J.; Olson, James M.

    2010-01-01

    For a progenitor cell to become a neuron, three activities must occur: neuronal differentiation program must be activated, elements repressing neuronal differentiation must be deactivated and competing differentiation programs must be silenced. It is known that NeuroD2 and related bHLH transcription factors induce neuronal differentiation, REST represses neuronal differentiation, and Zfhx1a prevents myogenic gene expression. We demonstrate that NeuroD2 suppresses REST during differentiation in culture. In the hippocampus of NeuroD2 knockout mice, higher level of REST is detected. Functional significance of NeuroD2-REST interplay is uncovered by showing that forced expression of REST interferes with neuronal differentiation in culture. NeuroD2 inhibits REST indirectly by involving the inhibitor of myogenic genes, Zfhx1a, which binds response elements in REST 5′-UTR. Our study supports a model wherein NeuroD2 induces transcription of neuronal genes and Zfhx1a, which in turn de-represses neuronal differentiation by down-regulating REST, and suppresses competing myogenic fate. PMID:20346398

  7. Phasic dopamine release drives rapid activation of striatal D2-receptors

    PubMed Central

    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

  8. Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex.

    PubMed

    Graham, Devon L; Durai, Heather H; Garden, Jamie D; Cohen, Evan L; Echevarria, Franklin D; Stanwood, Gregg D

    2015-02-18

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  9. Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex

    PubMed Central

    2015-01-01

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  10. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys.

    PubMed

    Nader, Michael A; Morgan, Drake; Gage, H Donald; Nader, Susan H; Calhoun, Tonya L; Buchheimer, Nancy; Ehrenkaufer, Richard; Mach, Robert H

    2006-08-01

    Dopamine neurotransmission is associated with high susceptibility to cocaine abuse. Positron emission tomography was used in 12 rhesus macaques to determine if dopamine D2 receptor availability was associated with the rate of cocaine reinforcement, and to study changes in brain dopaminergic function during maintenance of and abstinence from cocaine. Baseline D2 receptor availability was negatively correlated with rates of cocaine self-administration. D2 receptor availability decreased by 15-20% within 1 week of initiating self-administration and remained reduced by approximately 20% during 1 year of exposure. Long-term reductions in D2 receptor availability were observed, with decreases persisting for up to 1 year of abstinence in some monkeys. These data provide evidence for a predisposition to self-administer cocaine based on D2 receptor availability, and demonstrate that the brain dopamine system responds rapidly following cocaine exposure. Individual differences in the rate of recovery of D2 receptor function during abstinence were noted. PMID:16829955

  11. Characterization of D2 receptors and dopamine levels in the thalamus of the rat

    SciTech Connect

    Young, K.A.; Wilcox, R.E. Univ. of Texas, Austin )

    1991-01-01

    The authors kinetically characterized D2 receptors in thalami pooled from a group of Sprague-Dawley rats and then determined thalamic levels of dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and norepinephrine (NE) in relation to a measure of thalamic DA D2 receptor densities in another group of rats. The equilibrium dissociation constant (kd) was estimated as 0.1 nM by three independent methods, while the Bmax for thalamic D2 receptors was found to be 6.4 fmol/mg p using {sup 3}H-spiperone as ligand and ketanserin to occlude 5HT2 binding. Kinetic constants were in agreement with previously reported kinetic data from rodent caudate-putamen. This suggests that thalamic D2 receptors are similar to D2 receptors from other brain areas. Mean thalamic levels of DA, DOPAC, and HVA concur with previous reports of a sparse distribution of thalamic DA neurons. D2 receptor densities were positively correlated with DA metabolites DOPAC and HVA, but not DA or NE. These results establish fundamental characteristics of thalamic DA neurotransmission to assist in the investigation of behavioral pharmacology of this area.

  12. CO and D2O chemistry on continuous and discontinuous samaria thin films on Pt(111)

    NASA Astrophysics Data System (ADS)

    Jhang, Jin-Hao; Keil, Simona; Schaefer, Andreas; Zielasek, Volkmar; Bäumer, Marcus

    2016-08-01

    The chemistry of CO and D2O, individually adsorbed or co-adsorbed, on epitaxial thin films of samaria on Pt(111) was studied by temperature-programmed desorption spectroscopy (TPD). Continuous thin films as well as discontinuous films composed of samaria islands on bare Pt(111) were prepared. Their comparative study indicates that Sm2O3 islands provide lattice oxygen at their perimeter for CO oxidation on adjacent exposed Pt area where CO adsorption takes place. CO2 production was observed only on as-prepared discontinuous films. While, in particular on thermally reduced samaria islands, TPD after D2O adsorption revealed D2 production which indicates a pathway for D2O dissociation, no evidence for the water gas shift reaction of CO and residual OD species on the surface was found after co-adsorption of CO and D2O. Instead, interaction between CO and OD species at the perimeter of islands on reduced discontinuous SmOx thin films obviously promotes D2 formation without yielding CO2 as desorbing product.

  13. Coexpressed D1- and D2-Like Dopamine Receptors Antagonistically Modulate Acetylcholine Release in Caenorhabditis elegans

    PubMed Central

    Allen, Andrew T.; Maher, Kathryn N.; Wani, Khursheed A.; Betts, Katherine E.; Chase, Daniel L.

    2011-01-01

    Dopamine acts through two classes of G protein-coupled receptor (D1-like and D2-like) to modulate neuron activity in the brain. While subtypes of D1- and D2-like receptors are coexpressed in many neurons of the mammalian brain, it is unclear how signaling by these coexpressed receptors interacts to modulate the activity of the neuron in which they are expressed. D1- and D2-like dopamine receptors are also coexpressed in the cholinergic ventral-cord motor neurons of Caenorhabditis elegans. To begin to understand how coexpressed dopamine receptors interact to modulate neuron activity, we performed a genetic screen in C. elegans and isolated mutants defective in dopamine response. These mutants were also defective in behaviors mediated by endogenous dopamine signaling, including basal slowing and swimming-induced paralysis. We used transgene rescue experiments to show that defects in these dopamine-specific behaviors were caused by abnormal signaling in the cholinergic motor neurons. To investigate the interaction between the D1- and D2-like receptors specifically in these cholinergic motor neurons, we measured the sensitivity of dopamine-signaling mutants and transgenic animals to the acetylcholinesterase inhibitor aldicarb. We found that D2 signaling inhibited acetylcholine release from the cholinergic motor neurons while D1 signaling stimulated release from these same cells. Thus, coexpressed D1- and D2-like dopamine receptors act antagonistically in vivo to modulate acetylcholine release from the cholinergic motor neurons of C. elegans. PMID:21515580

  14. The free routine postcatheterization urogram: a cost/benefit analysis

    SciTech Connect

    Waldman, J.D.; Kaplan, G.W.; Rummerfield, P.S.; Gilpin, E.A.; Kirkpatrick, S.E.

    1982-01-01

    Postangiography urography has become routine procedure in most centers performing cardiac catheterization in children. We analyzed the x-radiation dosage and clinical yield of this procedure. Using lithium fluoride thermoluminescent dosimeters, radiation exposure to the abdomen and gonads was measured in 35 children during postangiography urography. Results of 334 consecutive routine postangiography cine-urograms were evaluated based on clinical significance and compared to previous reports on this subject. Average absorbed abdominal radiation dosage was 241 mR +/- 240 from cine-urography, 16 mR +/- 13 from fluoroscopy, and 107 mR +/- 111 from a single abdominal roentgenogram. Gonadal dosage averaged 8 mR and was uniformly less than 27 mR. Of 334 routine postangiography cineurograms, 282 (84%) were normal, 30 (9%) were technically inadequate, 12 (3%) had abnormalities that were clinically insignificant or were falsely positive and in 10 (3%), clinically significant urologic conditions were confirmed. Because of the low yield of clinically significant anomalies and the added radiation exposure, we no longer perform routine postangiography cine-urography in children. Following cardiac angiography, the upper renal collecting systems are examined fluoroscopically. If abnormalities are suspected or fluoroscopy is equivocal, a single abdominal roentgenogram is performed. Using this procedure, mean average absorbed abdominal radiation dose can be reduced from 241 mR to 30.5 mR.

  15. Routine Metabolic Rate of Channel Catfish Ictalurus punctatus Fry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Channel catfish eggs are typically incubated at high density and are often subjected to sub-optimum dissolved oxygen (DO) concentrations while in the hatchery. Since DO plays an important role in the development, hatch rate, and growth of catfish eggs and fry, we measured routine metabolic rate of ...

  16. Back to Schooling: Challenging Implicit Routines and Change

    ERIC Educational Resources Information Center

    Gorodetsky, Malka; Barak, Judith

    2009-01-01

    Engestrom and others have suggested that major barriers towards school change are rooted in the hidden, implicit aspects of daily school life that are taken for granted. These constitute the school's taken-for-granted routines, which mold teachers' affordances and constraints within the school, without their awareness. The present paper provides…

  17. Classroom Ordering and the Situational Imperatives of Routine and Ritual

    ERIC Educational Resources Information Center

    Diehl, David; McFarland, Daniel A.

    2012-01-01

    This article contends that the problem of classroom order rests less in the roles and compositions of classrooms than in the multidimensional nature of their social situations. Classroom order arises from the dynamic relationship between distinct situational requirements: the coordination of interaction into institutionalized patterns (routine)…

  18. 32 CFR 552.109 - Routine security controls.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 true Routine security controls. 552.109 Section 552.109 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Regulation Controlling the Access to the Fort Lewis Main Cantonment Area...

  19. Cervical discospondylitis in 2 Great Dane puppies following routine surgery.

    PubMed

    Finnen, Andrea; Blond, Laurent; Parent, Joane

    2012-05-01

    Two Great Dane puppies developed cervical discospondylitis following routine surgery for sterilization. One animal was affected at C4-C5 and the other at C6-C7 intervertebral discs. Pseudomonas aeruginosa was obtained in pure culture from ultrasound-guided disc aspiration in 1 case. Both animals were successfully treated with long-term antibiotics. PMID:23115366

  20. Daily Routines and Sleep Disorders in Visually Impaired Children.

    ERIC Educational Resources Information Center

    Troster, Heinrich; And Others

    1996-01-01

    Assessed sleep disorders in 265 visually impaired and 67 non-disabled 10- to 72-month olds. Found that infants with visual impairments had more difficulties in falling asleep and in sleeping through the night than nonhandicapped children. Also found a relationship between sleep disorders and the regularity of children's daily routine and…

  1. Asymptomatic Gastric Band Erosion Detected during Routine Gastroduodenoscopy.

    PubMed

    Yun, Gee Young; Kim, Woo Sub; Kim, Hye Jin; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

    2016-05-01

    The incidence of gastric band erosion has decreased to 1%. Gastric band erosion can manifest with various clinical symptoms, although some patients remain asymptomatic. We present a case of a mostly asymptomatic patient who was diagnosed with gastric band erosion during a routine health check-up. A 32-year-old man without any underlying diseases except for non-alcoholic fatty liver underwent laparoscopic adjustable gastric band surgery in 2010. He had no significant complications postoperatively. He underwent routine health check-ups with near-normal gastroduodenoscopic findings through 2014. However, in 2015, routine gastroduodenoscopy showed that the gastric band had eroded into the stomach. His gastric band was removed laparoscopically, and the remaining gastric ulcer perforation was repaired using an omental patch. Due to the early diagnosis, the infection was not serious. The patient was discharged on postoperative day 3 with oral antibiotics. This patient was fortunately diagnosed early by virtue of a routine health check-up; thus, eliminating the possibility of serious complications. PMID:26867553

  2. Asymptomatic Gastric Band Erosion Detected during Routine Gastroduodenoscopy

    PubMed Central

    Yun, Gee Young; Kim, Woo Sub; Kim, Hye Jin; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

    2016-01-01

    The incidence of gastric band erosion has decreased to 1%. Gastric band erosion can manifest with various clinical symptoms, although some patients remain asymptomatic. We present a case of a mostly asymptomatic patient who was diagnosed with gastric band erosion during a routine health check-up. A 32-year-old man without any underlying diseases except for non-alcoholic fatty liver underwent laparoscopic adjustable gastric band surgery in 2010. He had no significant complications postoperatively. He underwent routine health check-ups with near-normal gastroduodenoscopic findings through 2014. However, in 2015, routine gastroduodenoscopy showed that the gastric band had eroded into the stomach. His gastric band was removed laparoscopically, and the remaining gastric ulcer perforation was repaired using an omental patch. Due to the early diagnosis, the infection was not serious. The patient was discharged on postoperative day 3 with oral antibiotics. This patient was fortunately diagnosed early by virtue of a routine health check-up; thus, eliminating the possibility of serious complications. PMID:26867553

  3. 32 CFR 552.109 - Routine security controls.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Routine security controls. 552.109 Section 552.109 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Regulation Controlling the Access to the Fort Lewis Main Cantonment Area...

  4. Creating Masterpieces: How Course Structures and Routines Enable Student Performance

    ERIC Educational Resources Information Center

    Dean, Kathy Lund; Fornaciari, Charles J.

    2014-01-01

    Over a five-year period, we made a persistent observation: Course structures and routines, such as assignment parameters, student group process rules, and grading schemes were being consistently ignored. As a result, we got distracted by correcting these structural issues and were spending less time on student assignment performance. In this…

  5. 32 CFR 552.109 - Routine security controls.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Routine security controls. 552.109 Section 552.109 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Regulation Controlling the...

  6. 32 CFR 552.109 - Routine security controls.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 3 2013-07-01 2013-07-01 false Routine security controls. 552.109 Section 552.109 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Regulation Controlling the...

  7. 32 CFR 552.109 - Routine security controls.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Routine security controls. 552.109 Section 552.109 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Regulation Controlling the...

  8. Developing Corpus-Based Materials to Teach Pragmatic Routines

    ERIC Educational Resources Information Center

    Bardovi-Harlig, Kathleen; Mossman, Sabrina; Vellenga, Heidi E.

    2015-01-01

    This article describes how to develop teaching materials for pragmatics based on authentic language by using a spoken corpus. The authors show how to use the corpus in conjunction with textbooks to identify pragmatic routines for speech acts and how to extract appropriate language samples and adapt them for classroom use. They demonstrate how to…

  9. 15 CFR 923.84 - Routine program changes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the routine program change and identify any enforceable policies to be added to the management program... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Amendments to and Termination of Approved Management... implementing provisions approved as part of a State's approved management program, that does not result in...

  10. 15 CFR 923.84 - Routine program changes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the routine program change and identify any enforceable policies to be added to the management program... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Amendments to and Termination of Approved Management... implementing provisions approved as part of a State's approved management program, that does not result in...

  11. Cervical discospondylitis in 2 Great Dane puppies following routine surgery

    PubMed Central

    Finnen, Andrea; Blond, Laurent; Parent, Joane

    2012-01-01

    Two Great Dane puppies developed cervical discospondylitis following routine surgery for sterilization. One animal was affected at C4–C5 and the other at C6–C7 intervertebral discs. Pseudomonas aeruginosa was obtained in pure culture from ultrasound-guided disc aspiration in 1 case. Both animals were successfully treated with long-term antibiotics. PMID:23115366

  12. Supporting Classroom Transitions between Daily Routines: Strategies and Tips

    ERIC Educational Resources Information Center

    Banerjee, Rashida; Horn, Eva

    2013-01-01

    The purpose of this article is to provide tools for preschool professionals to plan for transitions between daily routines, to identify challenging transitions during the day, and to offer strategies to support transitions in classrooms to prevent challenging behaviors from occurring due to frequent changes. Specifically, the authors answer three…

  13. Radioxenon retention in the skeleton on a routine ventilation study.

    PubMed

    Kramer, E L; Tiu, S; Sanger, J J; Benjamin, D D

    1983-07-01

    Marked retention of radioxenon by the skeletal structures during a routine ventilation scan is described. Xenon uptake by bones occurs largely in the intraosseous fat. Augmented uptake in this case may be related to the patient's prolonged steroid therapy. PMID:6617033

  14. Rasch Analysis of the Routines-Based Interview Implementation Checklist

    ERIC Educational Resources Information Center

    Boavida, Tânia; Akers, Kate; McWilliam, R. A.; Jung, Lee Ann

    2015-01-01

    The Routines-­Based Interview (RBI) is useful for developing functional outcomes/goals, for establishing strong relationships with families, and for assessing the family's true needs. In this study, the authors investigated the psychometric properties of the RBI Implementation Checklist, conducted by 120 early intervention professionals,…

  15. The Effect of Instruction on Pragmatic Routines in Academic Discussion

    ERIC Educational Resources Information Center

    Bardovi-Harlig, Kathleen; Mossman, Sabrina; Vellenga, Heidi E.

    2015-01-01

    This study investigates the effect of instruction on the acquisition of pragmatic routines used in academic discussion, specifically expressions of agreement, disagreement, and clarification. Thirty-seven learners, including an experimental group of 26 students and a control group of 11 students, participated in the study. Five intact classes…

  16. Rethinking the Hidden Curriculum: Daily Routine in Slovene Preschools

    ERIC Educational Resources Information Center

    Zorec, Marcela Batistic; Došler, Anita Jug

    2016-01-01

    In Slovenia there is a unitary system of early education for all preschool-aged children. Since the vast majority of children attend full-day programmes, the daily routine represents a significant part of life for children in kindergarten. When systemic and curricular reform of preschools was introduced at the end of the twentieth century, lot of…

  17. 42 CFR 414.220 - Inexpensive or routinely purchased items.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... routinely purchased items. (a) Definitions. (1) Inexpensive equipment means equipment the average purchase... purchased equipment means equipment that was acquired by purchase on a national basis at least 75 percent of... lump sum amount for purchase of the item based on the applicable fee schedule amount. (2)...

  18. 42 CFR 414.220 - Inexpensive or routinely purchased items.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... average purchase price of which did not exceed $150 during the period July 1986 through June 1987. (2) Routinely purchased equipment means equipment that was acquired by purchase on a national basis at least 75... basis or in a lump sum amount for purchase of the item based on the applicable fee schedule amount....

  19. 42 CFR 414.220 - Inexpensive or routinely purchased items.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... routinely purchased items. (a) Definitions. (1) Inexpensive equipment means equipment the average purchase... purchased equipment means equipment that was acquired by purchase on a national basis at least 75 percent of... lump sum amount for purchase of the item based on the applicable fee schedule amount. (2)...

  20. Routines, Roles, and Responsibilities for Aligning Scientific and Classroom Practices

    ERIC Educational Resources Information Center

    Ford, Michael J.; Wargo, Brian M.

    2007-01-01

    Reform efforts in science education have focused on engaging students in authentic scientific practices. For these efforts to succeed, detailed articulations of scientific practice need to be linked to understandings of classroom practice. Here we characterize engagement in practice generally in terms of "3Rs": routines, roles, and…

  1. Collection of parallel linear equations routines for the Denelcor HEP

    SciTech Connect

    Dongarra, J.J.; Hiromoto, R.E.

    1983-09-01

    This note describes the implementation and performance results for a few standard linear algebra routines on the Denelcor HEP computer. The algorithms used here are based on high-level modules which facilitate portability and perform efficiently in a wide range of environments.

  2. Nonanalytic function generation routines for 16-bit microprocessors

    NASA Technical Reports Server (NTRS)

    Soeder, J. F.; Shaufl, M.

    1980-01-01

    Interpolation techniques for three types (univariate, bivariate, and map) of nonanalytic functions are described. These interpolation techniques are then implemented in scaled fraction arithmetic on a representative 16 bit microprocessor. A FORTRAN program is described that facilitates the scaling, documentation, and organization of data for use by these routines. Listings of all these programs are included in an appendix.

  3. NASA/MSFC NASTRAN auxiliary I/O routines

    NASA Technical Reports Server (NTRS)

    Tagg, M.; Thornton, B.

    1983-01-01

    Since the initial installation of NASTRAN on the UNIVAC 1100/82 computer at the Marshall Space Flight Center (MSFC), a number of local codes have been incorporated as user routines. This paper describes four of these codes and how interested users may obtain additional information.

  4. Routine Activities and Sexual Harassment in the Workplace.

    ERIC Educational Resources Information Center

    De Coster, Stacy; Estes, Sarah Beth; Mueller, Charles W.

    1999-01-01

    In criminology, routine activities of potential victims can be used to predict victimization. Application to organizational sexual harassment data shows that organizational features (proximity in job location, supervisor or work group guardianship) and individual characteristics (target attractiveness) can predict sexual harassment victimization,…

  5. Infant/Toddler Caregiving: A Guide to Routines. Second Edition.

    ERIC Educational Resources Information Center

    Gonzalez-Mena, Janet

    Intended for use in conjunction with videos illustrating key concepts and caregiving techniques, this guide focuses on how the daily routines of caring for infants and toddlers can become opportunities for promoting the child's learning and development and for deepening the relationship between child and caregiver. Special attention is given to…

  6. School Bus Crash Rates on Routine and Nonroutine Routes

    ERIC Educational Resources Information Center

    O'Neal, Elizabeth; Ramirez, Marizen; Hamann, Cara; Young, Tracy; Stahlhut, Mary; Peek-Asa, Corinne

    2014-01-01

    Background: Although prior research has established that school buses are a safe form of transportation, crashes can produce catastrophic consequences. School buses have 2 types of routes: predictable, routine routes that take children to and from school and less predictable, nonroutine routes for school events. No studies have examined school bus…

  7. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2.

    PubMed

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C

    2006-07-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol x min(-1) x mol(-1) P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol x min(-1) x mol(-1). In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes). PMID:16817851

  8. Biological activity profiles of 1alpha,25-dihydroxyvitamin D2, D3, D4, D7, and 24-epi-1alpha,25-dihydroxyvitamin D2.

    PubMed

    Tsugawa, N; Nakagawa, K; Kawamoto, Y; Tachibana, Y; Hayashi, T; Ozono, K; Okano, T

    1999-04-01

    We have synthesized several 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D] derivatives and evaluated their biological activity in terms of their binding affinity for the vitamin D receptor (VDR) and vitamin D-binding protein (DBP), antiproliferative or differentiation-inducing effects on human promyelocytic leukemic HL-60 cells, and transcriptional activity on a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), and human osteocalcin gene promoter, including a VDRE in transfected human osteosarcoma MG-63 cells. Furthermore, human VDR- or retinoic acid X receptor alpha (RXR alpha)-mediated luciferase activities of the derivatives were also measured by a one-hybrid system in human epitheloid carcinoma, cervix HeLa cells and African green monkey kidney CV-1 cells. Binding affinity for VDR, bone-resorbing activity, antiproliferative and cell-differentiating effects, transactivation potencies on target genes and VDR- or RXR alpha-mediated gene regulations of 1alpha,25(OH)2D2 and 1alpha,25(OH)2D4 were almost comparable to the effects of 1alpha,25(OH)2D3 while 24-epi-1alpha,25(OH)2D2 and 1alpha,25(OH)2D7 were much less active than 1alpha,25(OH)2D3 in these respects. This is the first report concerning biological assessment of 1alpha,25(OH)2D2, 1alpha,25(OH)2D3, 1alpha,25(OH)2D4, 24-epi-1alpha,25(OH)2D2 and 1alpha,25(OH)2D7 at the molecular level, especially with regards to the structural differences at the 24R- or 24S-methyl group and a double bond between carbons 22 and 23 in the side chain of 1alpha,25(OH)2D derivatives. PMID:10328556

  9. Regulation of dopamine D2 receptors by sodium and pH.

    PubMed

    Neve, K A

    1991-04-01

    The role of Na+ and H+ in the regulation of D2 receptor affinity for ligands was studied to determine the molecular mechanisms of this phenomenon. The potency of substituted benzamide derivatives and agonists at D2 receptors depended on the concentration of Na+ and H+, whereas the potency of other antagonists was relatively unaltered by changes in pH or Na+ concentration. The potency of agonists was generally decreased in the presence of NaCl or lowered pH. For example, in the absence of sodium the affinity of D2 receptors for dopamine was decreased 17-fold by lowering of the pH from 8.0 to pH 6.8. Addition of NaCl caused 2-4-fold decreases in affinity for most agonists. The affinity of the receptors for two substituted benzamide derivatives, on the other hand, was reduced 6-44-fold by elevated concentrations of H+ but was enhanced 7-24-fold in the presence of Na+. The regulation by H+ of the potency of dopamine was selective for D2 receptors, because binding of dopamine to neostriatal D1 receptors was unaffected by changes in pH. Decreasing of the pH from 8.0 or 7.3 to 6.8 facilitated the dissociation of the substituted benzamide ligand [125I]epidepride from D2 receptors but inhibited dissociation of [3H]spiperone. Furthermore, the presence of NaCl or lowered pH slowed inactivation of D2 receptors by N-ethylmaleimide. Together, these data suggest that the conformation of D2 receptors is regulated by both Na+ and H+. The affinity of D2 receptors for agonists and substituted benzamide antagonists varies according to the conformational state of the receptors, whereas other antagonists bind to both forms with approximately equal potency. Amiloride is a compound that interacts with many sodium-binding macromolecules. At equilibrium, amiloride inhibited the binding of [3H]spiperone and [125I]epidepride in a manner suggesting a more complex interaction than simple competitive inhibition. The rate of dissociation of both radioligands was enhanced by amiloride, as would be

  10. Three amino acids in the D2 dopamine receptor regulate selective ligand function and affinity

    PubMed Central

    Cummings, David F.; Ericksen, Spencer S.; Schetz, John A.

    2016-01-01

    The D2 dopamine receptor is an important therapeutic target for the treatment of psychotic, agitated, and abnormal behavioral states. To better understand the specific interactions of subtype-selective ligands with dopamine receptor subtypes, seven ligands with high selectivity (>120-fold) for the D4 subtype of dopamine receptor were tested on wild-type and mutant D2 receptors. Five of the selective ligands were observed to have 21-fold to 293-fold increases in D2 receptor affinity when three non-conserved amino acids in TM2 and TM3 were mutated to the corresponding D4 amino acids. The two ligands with the greatest improvement in affinity for the D2 mutant receptor [i.e., 3-{[4-(4-iodophenyl) piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine (L-750,667) and 1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine (RBI-257)] were investigated in functional assays. Consistent with their higher affinity for the mutant than for the wild-type receptor, concentrations of L-750,667 or RBI-257 that produced large reductions in the potency of quinpirole’s functional response in the mutant did not significantly reduce quinpirole’s functional response in the wild-type D2 receptor. In contrast to RBI-257 which is an antagonist at all receptors, L-750,667 is a partial agonist at the wild-type D2 but an antagonist at both the mutant D2 and wild-type D4 receptors. Our study demonstrates for the first time that the TM2/3 microdomain of the D2 dopamine receptor not only regulates the selective affinity of ligands, but in selected cases can also regulate their function. Utilizing a new docking technique that incorporates receptor backbone flexibility, the three non-conserved amino acids that encompass the TM2/3 microdomain were found to account in large part for the differences in intermolecular steric contacts between the ligands and receptors. Consistent with the experimental data, this model illustrates the interactions between a variety of subtype

  11. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies.

    PubMed

    Levey, A I; Hersch, S M; Rye, D B; Sunahara, R K; Niznik, H B; Kitt, C A; Price, D L; Maggio, R; Brann, M R; Ciliax, B J

    1993-10-01

    Five or more dopamine receptor genes are expressed in brain. However, the pharmacological similarities of the encoded D1-D5 receptors have hindered studies of the localization and functions of the subtypes. To better understand the roles of the individual receptors, antibodies were raised against recombinant D1 and D2 proteins and were shown to bind to the receptor subtypes specifically in Western blot and immunoprecipitation studies. Each antibody reacted selectively with the respective receptor protein expressed both in cells transfected with the cDNAs and in brain. By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra. Within each region, however, the precise distributions of each subtype were distinct and often complementary. D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the olfactory bulb, and in either substantia nigra pars compacta or reticulata. Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions. In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum. Presynaptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release. D1 was also present in axon terminals in the substantia nigra. These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain. PMID:8415621

  12. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    PubMed

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. PMID:26970582

  13. H2O and D2 mixtures under pressure: Spectroscopy and proton exchange kinetics

    NASA Astrophysics Data System (ADS)

    Borstad, Gustav M.; Yoo, Choong-Shik

    2011-11-01

    We have investigated the pressure-induced spectral changes and the proton exchange reactions of D2-H2O mixtures to 64 GPa using micro-Raman spectroscopy. The results show the profound difference in the rotational and vibrational Raman spectra of hydrogen isotopes from those of the pure samples, showing the vibrational modes at higher frequencies and continuing to increase with pressure without apparent turnover. This indicates the repulsive nature of D2-H2O interaction without hydrogen bonds between the two and, thus, interstitial fillings of D2 molecules into the bcc-like ice lattice. The spectral analysis using the Morse potential yields a hydrogen bond distance of 0.734 Å at 6 GPa—slightly shorter than that in pure—attributed to the repulsive interaction. The pressure-dependent spectral changes suggest that the proton-ordering transition in the ice lattice occurs over a large pressure range between 28 and 50 GPa, which is substantially lower than that of pure ice (40-80 GPa). This again indicates the presence of high internal pressure arising from the repulsive interaction. The Raman spectra show evidences that the proton exchange occurs in various phases including in solid D2 and H2O mixtures. Based on the time-dependent spectral changes, we obtained the proton exchange rates of k ˜ 0.085 h-1 at 0.2 GPa in fluid D2 and water mixtures, k ˜ 0.03 h-1 and 0.003 h-1 at 2 GPa and 4 GPa, respectively, in fluid D2-ice mixtures, and k ˜ 10-3 h-1 at 8 GPa in solid D2 and ice mixtures.

  14. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Logan, J. ||

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  15. In vivo and in vitro detection of dopamine d2 receptors in uveal melanomas.

    PubMed

    Bodei, Lisa; Hofland, Leo J; Ferone, Diego; Mooy, Cornelia M; Kros, Johan M; Paridaens, Dion A; Baarsma, Seerp G; Ferdeghini, Marco; Van Hagen, Martin P; Krenning, Eric P; Kwekkeboom, Dik J

    2003-12-01

    Scintigraphy with radiolabeled benzamides was used in melanoma patients. Studies with a newer benzamide called 123I-epidepride, a high-affinity D2 receptor (D2R) antagonist, showed high sensitivity in D2R-positive pituitary adenomas. We evaluated the presence of D2R in patients with uveal melanomas in vivo with 123I-epidepride, and in vitro in melanomas, using immunohistochemistry (IHC) and 125I-epidepride autoradiography. We studied the in vivo tumor-to-background (TB) ratios in six patients with posterior uveal melanoma (one previously enucleated). IHC was performed in 3 of 6 tumors after enucleation and in another 20 uveal melanomas, 7 metastatic lymph nodes from skin melanoma, and 2 normal specimens. 125I-epidepride autoradiography was performed in 10 uveal melanomas (3 of which were studied in vivo), 7 metastases, and 2 normal samples. Radioligand uptake was present in the affected eye of 5 patients with uveal melanoma (TB = 3.1-6.1) and absent in the operated one (TB = 1). Eight uveal tumors were positive at IHC (35%), 14 weakly positive (61%), and 1 negative (4%). Two metastases were positive (29%), 2 weakly positive (29%), and 3 negative (42%). Two uveal tumors were positive at autoradiography (20%), 7 had nonspecific binding (70%), and 1 was negative (10%). One metastasis was positive (14%), while 6 were negative (86%). 123I-epidepride scintigraphy in uveal melanomas seems promising for sensitivity and image quality. D2R was demonstrated in a significant proportion of the melanomas, although 123I-epidepride uptake might also be nonspecific and unrelated to D2R binding. Although further studies on larger series are needed, 123I-epidepride could represent a future tool to study the expression of D2R in other classes of neuroendocrine tumors. PMID:14969602

  16. Cell-free protein synthesis and purification of human dopamine D2 receptor long isoform.

    PubMed

    Basu, Dipannita; Castellano, Jessica M; Thomas, Nancy; Mishra, Ram K

    2013-01-01

    The human dopamine D2 receptor long isoform (D2L) has significant implications in neurological and neuropsychiatric disorders such as Parkinson's disease and schizophrenia. Detailed structural knowledge of this receptor is limited owing to its highly hydrophobic nature, which leads to protein aggregation and host toxicity when expressed in cellular systems. The newly emerging field of cell-free protein expression presents numerous advantages to overcome these challenges. This system utilizes protein synthesis machinery and exogenous DNA to synthesize functional proteins outside of intact cells. This study utilizes two different cell-free systems for the synthesis of human dopamine D2L receptor. These include the Escherichia coli lysate-based system and the wheat-germ lysate-based system. The bacterial cell-free method used pET 100/D-TOPO vector to synthesize hexa-histidine-tagged D2L receptor using a dialysis bag system; the resulting protein was purified using nickel-nitrilotriacetic acid affinity resin. The wheat germ system used pEU-glutathione-S-transferase (GST) vector to synthesize GST-tagged D2L receptor using a bilayer translation method; the resulting protein was purified using a GST affinity resin. The presence and binding capacity of the synthesized D2L receptor was confirmed by immunoblotting and radioligand competition assays, respectively. Additionally, in-gel protein sequencing via Nano LC-MS/MS was used to confirm protein synthesis via the wheat germ system. The results showed both systems to synthesize microgram quantities of the receptor. Improved expression of this highly challenging protein can improve research and understanding of the human dopamine D2L receptor. PMID:23424095

  17. Progress in Understanding the Infrared Spectra of He- and Ne-C_2D_2

    NASA Astrophysics Data System (ADS)

    Moazzen-Ahmadi, Nasser; McKellar, Bob

    2014-06-01

    Infrared spectra of He-C_2H_2 were recorded around 1990 in Roger Miller's lab, but detailed rotational assignment was apparently not possible even with the help of theoretical predictions. So there were no published experimental spectra of helium-acetylene van der Waals complexes until our recent work on He-C_2D_2 in the νb{3} region (˜2440 wn). The problem is that this complex lies close to the free rotor limit, so that most of the intensity in the spectrum piles up in tangles of closely spaced lines located close to the monomer rotational transitions, R(0), P(1), etc. Our previous He-C_2D_2 assignments were limited to the R(0) region, that is, the j = 1 ← 0 subband, where j represents C_2D_2 rotation. Here, we extend the analysis to j = 0 ← 1 and 2 ← 1 transitions with the help of new spectra obtained using a tunable OPO laser probe and a cooled supersonic jet nozzle. These subbands are weaker, not only because of the Boltzmann factor, but also the 2:1 nuclear spin statistics of j" = even:odd C_2D_2 levels. Moreover, the j = 0 ← 1 subband is overlapped by strong (C_2D_2)_2 transitions. We use a term value approach, obtaining a self-consistent set of ``experimental" energy levels which can be directly compared with theory or fitted in terms of a Coriolis model. Challenges also arise with Ne-C_2D_2, which is not quite so close to the free rotor limit, but still has many overlapping lines. Insights gained here help in assigning the tricky R(1) region for Ne-C_2D_2. M. Rezaei, N. Moazzen-Ahmadi, A.R.W. McKellar, B. Fernández, and D. Farrelly, Mol. Phys. 110, 2743 (2012).

  18. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    SciTech Connect

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  19. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    PubMed Central

    Carney, Amanda E.; Sanders, Rebecca D.; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W.; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ proximal sequence. The four non-coding sequence changes are unique to D2. The p.N314D substitution, however, is not; it is found together with a silent polymorphism, p.L218(TTA), on functionally normal Duarte-1 alleles (D1, also called Los Angeles or LA alleles). The HapMap database reveals that p.N314D is a common human variant, and cross-species comparisons implicate D314 as the ancestral allele. The p.N314D substitution is also functionally neutral in mammalian cell and yeast expression studies. In contrast, the 4 bp 5′ deletion characteristic of D2 alleles appears to be functionally impaired in reporter gene transfection studies. Here we present allele-specific qRT–PCR evidence that D2 alleles express less mRNA in vivo than their wild-type counterparts; the difference is small but statistically significant. Furthermore, we characterize the prevalence of the 4 bp deletion in GG, NN and DG populations; the deletion appears exclusive to D2 alleles. Combined, these data strongly implicate the 4 bp 5′ deletion as a causal mutation in Duarte galactosemia and suggest that direct tests for this deletion, as proposed here, could enhance or supplant current tests, which define D2 alleles on the basis of the presence and absence of linked coding sequence polymorphisms. PMID:19224951

  20. High affinity dopamine D2 receptor radioligands. 2. [125I]epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors.

    PubMed

    Kessler, R M; Ansari, M S; Schmidt, D E; de Paulis, T; Clanton, J A; Innis, R; al-Tikriti, M; Manning, R G; Gillespie, D

    1991-01-01

    Epidepride, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide+ ++, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25 degrees C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 mM MgCl2. Scatchard analysis of in vitro binding to striatal, medial frontal cortical, hippocampal and cerebellar membranes revealed a KD of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC50's for inhibition of [125I]epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 microM to greater than 10 microM. Partial displacement of [125I]epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to alpha 2 noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent KD of 9 nM. At an epidepride concentration equal to the KD for the D2 receptor, i.e. 25 pM, no striatal alpha 2 binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the alpha 2 site. Correlation of inhibition of [3H]spiperone and [125I]epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site. In vitro autoradiography revealed high densities of receptor binding in layers V and VI of prefrontal and cingulate cortices as well as in striatum. In vivo rat brain uptake revealed a hippocampal:cerebellar and frontal cortical:cerebellar ratio of 2.2:1 which fell to 1.1:1 following haloperidol pretreatment. These

  1. Changes in Routine Health Behaviors Following Late-life Bereavement: A Systematic Review

    PubMed Central

    Stahl, Sarah T.; Schulz, Richard

    2014-01-01

    This systematic review examines the relationship between late-life spousal bereavement and changes in routine health behaviors. We review six behavioral domains/modifiable risk factors that are important for maintaining health among elderly populations: physical activity, nutrition, sleep quality, alcohol consumption, tobacco use, and body weight status. Thirty-four articles were identified, derived from 32 studies. We found strong evidence for a relationship between bereavement and nutritional risk and involuntary weight loss, and moderate evidence for impaired sleep quality and increased alcohol consumption. There was mixed evidence for a relationship between bereavement and physical activity. We identify several methodological shortcomings, and describe the clinical implications of this review for the development of preventive intervention strategies. PMID:23881308

  2. Using 1D2D Hydrodynamic Modeling to Inform Restoration Planning in the Atchafalaya River Basin, Louisiana

    NASA Astrophysics Data System (ADS)

    Hayden-Lesmeister, A.; Remo, J. W.; Piazza, B.

    2015-12-01

    The Atchafalaya River (AR) in Louisiana is the principal distributary of the Mississippi River (MR), and its basin contains the largest contiguous area of baldcypress-water tupelo swamp forests in North America. After designation of the Atchafalaya River Basin (ARB) as a federal floodway following the destructive 1927 MR flood, it was extensively modified to accommodate a substantial portion of the MR flow (~25%) to mitigate flooding in southern Louisiana. These modifications and increased flows resulted in substantial incision along large portions of the AR, altering connectivity between the river and its associated waterbodies. As a result of incision, the hydroperiod has been substantially altered, which has contributed to a decline in ecological health of the ARB's baldcypress-water tupelo forests. While it is recognized that the altered hydroperiod has negatively affected natural baldcypress regeneration, it is unclear whether proposed projects designed to enhance flow connectivity will increase long-term survival of these forests. In this study, we have constructed a 1D2D hydrodynamic model using SOBEK 2.12 to realistically model key physical parameters such as residence times, inundation extent, water-surface elevations (WSELs), and flow velocities to increase our understanding of the ARB's altered hydroperiod and the consequences for baldcypress-water tupelo forests. While the model encompasses a majority of the ARB, our modeling effort is focused on the Flat Lake Water Management Unit located in the southern portion of the ARB, where it will also be used to evaluate flow connectivity enhancement projects within the management unit. We believe our 1D2D hybrid hydraulic modeling approach will provide the flexibility and accuracy needed to guide connectivity enhancement efforts in the ARB and may provide a model framework for guiding similar efforts along other highly-altered river systems.

  3. Dopamine D2-Like Receptors Modulate Unconditioned Fear: Role of the Inferior Colliculus

    PubMed Central

    de Oliveira, Amanda Ribeiro; Colombo, Ana Caroline; Muthuraju, Sangu; Almada, Rafael Carvalho; Brandão, Marcus Lira

    2014-01-01

    Background A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D2 receptor antagonist, into the inferior colliculus (IC) enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D2 receptors in the mediation of unconditioned and conditioned fear is still lacking. Methods The present study investigated the effects of intra-IC injections of the D2 receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC, fear-potentiated startle (FPS), and conditioned freezing. Results Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing. Conclusions Dopamine D2-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response. PMID:25133693

  4. Effect of D2O on growth properties and chemical structure of annual ryegrass (Lolium multiflorum)

    SciTech Connect

    Evans, Barbara R; Bali, Garima; Reeves, David T; O'Neill, Hugh Michael; Sun, Qining; Shah, Riddhi S; Ragauskas, Arthur

    2014-01-01

    In present paper, we report the production and detailed structural analysis of deuterium-enriched rye grass (Lolium multiflorum) for neutron scattering experiments. An efficient method to produce deuterated biomass was developed by designing hydroponic perfusion chambers. In preliminary studies, the partial deuterated rye samples were grown in increasing levels of D2O to study the seed germination and the level of deuterium incorporation as a function of D2O concentration. Solution NMR method indicated 36.9 % deuterium incorporation in 50 % D2O grown annual rye samples and further significant increase in the deuterium incorporation level was observed by germinating the rye seedlings in H2O and growing in 50 % D2O inside the perfusion chambers. Moreover, in an effort to compare the substrate characteristics related to enzymatic hydrolysis on deuterated and protiated version of biomass, annual rye grown in 50 % D2O was selected for detailed biomass characterization studies. The compositional analyses, degree of polymerization and cellulose crystallinity were compared with its protiated control. The cellulose molecular weight indicated slight variation with deuteration; however, hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration. Besides the minor differences in biomass components, the development of deuterated biomass for neutron scattering application is essential to understand the complex biomass conversion processes.

  5. The infrared spectrum of the Ne-C2D2 complex.

    PubMed

    Moazzen-Ahmadi, N; McKellar, A R W; Fernández, Berta; Farrelly, David

    2015-11-28

    Infrared spectra of Ne-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm(-1)) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Like helium-acetylene, this system lies close to the free rotor limit, making analysis tricky because stronger transitions tend to pile up close to monomer (C2D2) rotation-vibration transitions. Assignments are aided by predicted rotational energies calculated from a published ab initio intermolecular potential energy surface. The analysis extends up to the j = 3←2 band, where j labels C2D2 rotation within the dimer, and is much more complete than the limited infrared assignments previously reported for Ne-C2H2 and Ne-C2HD. Two previous microwave transitions within the j = 1 state of Ne-C2D2 are reassigned. Coriolis model fits to the theoretical levels and to the spectrum are compared. Since the variations observed as a function of C2D2 vibrational excitation are comparable to those noted between theory and experiment, it is evident that more detailed testing of theory will require vibrational averaging over the acetylene intramolecular modes. PMID:26627959

  6. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus.

    PubMed Central

    Iwatsuki, K; Song, P S

    1985-01-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same. PMID:3004613

  7. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus

    SciTech Connect

    Iwatsuki, K.; Song, P.S.

    1985-12-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same.

  8. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus.

    PubMed

    Iwatsuki, K; Song, P S

    1985-12-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same. PMID:3004613

  9. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    PubMed

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon. PMID:26314311

  10. Synthesis and characterization of selective dopamine D2 receptor ligands using aripiprazole as the lead compound

    PubMed Central

    Vangveravong, Suwanna; Zhang, Zhanbin; Taylor, Michelle; Bearden, Melissa; Xu, Jinbin; Cui, Jinquan; Wang, Wei; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D2 and D3 receptor subtype. PMID:21536445

  11. Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

    PubMed Central

    Wang, Xiong; Ma, Li; Zhang, En-jing; Zou, Ji-li; Guo, Hao; Peng, Si-wei; Wu, Jin-hu

    2014-01-01

    Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1–5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA. PMID:25254056

  12. Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients.

    PubMed

    Tuppurainen, H; Kuikka, J; Viinamäki, H; Husso-Saastamoinen, M; Bergström, K; Tiihonen, J

    2003-04-01

    Several lines of studies have suggested the importance of cortical dopamine (DA) transmission in the pathophysiology of schizophrenia. The putative alteration of striatal D(2) receptor density in schizophrenia has been studied intensely, although extrastriatal DA activity may be more relevant for behavioral symptoms. The aim of this study was to explore extrastriatal D(2/3) density in drug-naive schizophrenic patients. We studied the extrastriatal D(2/3) receptor binding with a novel high-affinity single-photon emission tomography ligand epidepride in seven drug-naive schizophrenic patients and seven matched controls. The symptoms were rated with Positive and Negative Syndrome Scale for Schizophrenia. The findings indicated an extremely low D(2/3) receptor binding among patients in temporal cortex in both hemispheres when compared with controls (effect size 2.0-2.3), and the D(2/3) levels had negative correlations with general psychopathological (r from -0.86 to -0.90) and negative (r from -0.37 to -0.55) schizophrenic symptoms. These results support the previous hypothesis on dysfunction of mesocortical DA function behind the cognitive and negative symptoms in schizophrenia. PMID:12740603

  13. Reactivity of Fe-0 atoms and clusters with D2O over FeO(111)

    SciTech Connect

    Parkinson, Gareth S.; Kim, Yu K.; Dohnalek, Zdenek; Smith, R. Scott; Kay, Bruce D.

    2009-03-26

    The interaction of Fe0 atoms with D2O layers on FeO(111) has been investigated using the “atom dropping” preparation technique and a combination of temperature programmed desorption, x-ray photoelectron spectroscopy, Auger electron spectroscopy, and infrared absorption spectroscopy. The data demonstrate that isolated Fe atoms form DFeOD insertion species upon deposition at 35 K, which then dissociate into FeOD and a surface hydroxyl above 200 K. Interestingly, even at very low Fe0 coverages the D2O is perturbed by the presence of the Fe, but only D2O desorption is observed. At higher (≥ 0.5 ML) coverages, clusters of Fe form which have molecular D2O and OD species adsorbed on the surface. Both molecular and recombinative desorption are observed in TPD. In contrast to the low coverage data, a second reaction pathway emerges at high coverage which leads to desorption of D2 and the formation of stable substoichiometric oxide. The mechanism for this minor channel is concluded to involve a reaction between two (or more) DFeOD complexes.

  14. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    SciTech Connect

    Brann, M.R.

    1985-12-31

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor.

  15. The infrared spectrum of the Ne-C2D2 complex

    NASA Astrophysics Data System (ADS)

    Moazzen-Ahmadi, N.; McKellar, A. R. W.; Fernández, Berta; Farrelly, David

    2015-11-01

    Infrared spectra of Ne-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm-1) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Like helium-acetylene, this system lies close to the free rotor limit, making analysis tricky because stronger transitions tend to pile up close to monomer (C2D2) rotation-vibration transitions. Assignments are aided by predicted rotational energies calculated from a published ab initio intermolecular potential energy surface. The analysis extends up to the j = 3←2 band, where j labels C2D2 rotation within the dimer, and is much more complete than the limited infrared assignments previously reported for Ne-C2H2 and Ne-C2HD. Two previous microwave transitions within the j = 1 state of Ne-C2D2 are reassigned. Coriolis model fits to the theoretical levels and to the spectrum are compared. Since the variations observed as a function of C2D2 vibrational excitation are comparable to those noted between theory and experiment, it is evident that more detailed testing of theory will require vibrational averaging over the acetylene intramolecular modes.

  16. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.

  17. D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function

    PubMed Central

    Sasaki, Masato; Knobbe, Christiane B.; Itsumi, Momoe; Elia, Andrew J.; Harris, Isaac S.; Chio, Iok In Christine; Cairns, Rob A.; McCracken, Susan; Wakeham, Andrew; Haight, Jillian; Ten, Annick You; Snow, Bryan; Ueda, Takeshi; Inoue, Satoshi; Yamamoto, Kazuo; Ko, Myunggon; Rao, Anjana; Yen, Katharine E.; Su, Shinsan M.; Mak, Tak Wah

    2012-01-01

    Isocitrate dehydrogenase-1 (IDH1) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knock-in (KI) mice. Idh1 mutation results in hemorrhage and perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated in Idh1-KI brain cells despite an apparent increase in the NADP+/NADPH ratio. Idh1-KI cells also show high levels of D-2-hydroxyglutarate (D2HG) that are associated with inhibited prolyl-hydroxylation of hypoxia-inducible transcription factor-1α (Hif1α) and up-regulated Hif1α target gene transcription. Intriguingly, D2HG also blocks prolyl-hydroxylation of collagen, causing a defect in collagen protein maturation. An endoplasmic reticulum (ER) stress response induced by the accumulation of immature collagens may account for the embryonic lethality of these mutants. Importantly, D2HG-mediated impairment of collagen maturation also led to basement membrane (BM) aberrations that could play a part in glioma progression. Our study presents strong in vivo evidence that the D2HG produced by the mutant Idh1 enzyme is responsible for the above effects. PMID:22925884

  18. Chromosomal aadD2 encodes an aminoglycoside nucleotidyltransferase in Bacillus clausii.

    PubMed

    Bozdogan, Bülent; Galopin, Sébastien; Gerbaud, Guy; Courvalin, Patrice; Leclercq, Roland

    2003-04-01

    Bacillus clausii SIN is one of the four strains of B. clausii composing a probiotic administered to humans for the prevention of gastrointestinal side effects due to oral antibiotic therapy. The strain is resistant to kanamycin, tobramycin, and amikacin. A gene conferring aminoglycoside resistance was cloned into Escherichia coli and sequenced. The gene, called aadD2, encoding a putative 246-amino acid protein, shared 47% identity with ant(4')-Ia from Staphylococcus aureus, which encodes an aminoglycoside 4'-O-nucleotidyltransferase. Phosphocellulose paper-binding assays indicated that the gene product was responsible for nucleotidylation of kanamycin, tobramycin, and amikacin. The aadD2 gene was detected by DNA-DNA hybridization in the three other strains of the probiotic mixture and in the reference strain B. clausii DSM8716, although it did not confer resistance in these strains. Mutations in the sequence of the putative promoter for aadD2 from B. clausii SIN resulted in higher identity with consensus promoter sequences and may account for aminoglycoside resistance in that strain. The aadD2 gene was chromosomally located in all strains and was not transferable by conjugation. These data indicate that chromosomal aadD2 is specific to B. clausii. PMID:12654668

  19. Dopamine D2 receptor agonists inhibit lung cancer progression by reducing angiogenesis and tumor infiltrating myeloid derived suppressor cells.

    PubMed

    Hoeppner, Luke H; Wang, Ying; Sharma, Anil; Javeed, Naureen; Van Keulen, Virginia P; Wang, Enfeng; Yang, Ping; Roden, Anja C; Peikert, Tobias; Molina, Julian R; Mukhopadhyay, Debabrata

    2015-01-01

    We sought to determine whether Dopamine D2 Receptor (D2R) agonists inhibit lung tumor progression and identify subpopulations of lung cancer patients that benefit most from D2R agonist therapy. We demonstrate D2R agonists abrogate lung tumor progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human lung cancer tissue revealed a positive correlation between endothelial D2R expression and tumor stage. Lung cancer patients with a smoking history exhibited greater levels of D2R in lung endothelium. Our results suggest D2R agonists may represent a promising individualized therapy for lung cancer patients with high levels of endothelial D2R expression and a smoking history. PMID:25226814

  20. Dopamine D2 Receptor Agonists Inhibit Lung Cancer Progression by Reducing Angiogenesis and Tumor Infiltrating Myeloid Derived Suppressor Cells

    PubMed Central

    Hoeppner, Luke H.; Wang, Ying; Sharma, Anil; Javeed, Naureen; Van Keulen, Virginia P.; Wang, Enfeng; Yang, Ping; Roden, Anja C.; Peikert, Tobias; Molina, Julian R.; Mukhopadhyay, Debabrata

    2014-01-01

    We sought to determine whether Dopamine D2 Receptor (D2R) agonists inhibit lung tumor progression and identify subpopulations of lung cancer patients that benefit most from D2R agonist therapy. We demonstrate D2R agonists abrogate lung tumor progression in syngeneic (LLC1) and human xenograft (A549) orthotopic murine models through inhibition of tumor angiogenesis and reduction of tumor infiltrating myeloid derived suppressor cells. Pathological examination of human lung cancer tissue revealed a positive correlation between endothelial D2R expression and tumor stage. Lung cancer patients with a smoking history exhibited greater levels of D2R in lung endothelium. Our results suggest D2R agonists may represent a promising individualized therapy for lung cancer patients with high levels of endothelial D2R expression and a smoking history. PMID:25226814

  1. The case for periodic OPV routine vaccination campaigns.

    PubMed

    Houy, Nicolas

    2016-01-21

    The possibility of periodic routine vaccination campaigns (PRVCs) is introduced in the context of a search for optimal oral poliovirus vaccine (OPV) administration strategies. Like the usual continuous routine vaccination campaign (CRVC), PRVCs target only newborns. However, they are not necessarily implemented continuously in time. Using a dynamic and compartmental polio transmission model in a stochastic context, it is shown that some PRVCs can achieve much greater efficiency than CRVC in terms of probability of wild poliovirus (WPV) eradication, even though they never outperform CRVC in terms of total number of paralytic infections. Moreover, these PRVCs results can be obtained at a lower price than CRVC. It is also shown that, even though PRVCs do not perform better than pulse vaccination campaigns (PVCs) when only epidemiological outputs are valued, they can do so when a cost-benefit analysis is preferred. PMID:26523796

  2. Cryogenic Neutron Protein Crystallography: routine methods and potential benefits

    SciTech Connect

    Weiss, Kevin L; Tomanicek, Stephen J; NG, Joseph D

    2014-01-01

    The use of cryocooling in neutron diffraction has been hampered by several technical challenges such as the need for specialized equipment and techniques. Recently we have developed and deployed equipment and strategies that allow for routine neutron data collection on cryocooled crystals using off the shelf components. This system has several advantages, compared to a closed displex cooling system such as fast cooling coupled with easier crystal mounting and centering. The ability to routinely collect cryogenic neutron data for analysis will significantly broaden the range of scientific questions that can be examined by neutron protein crystallography. Cryogenic neutron data collection for macromolecules has recently become available at the new Biological Diffractometer BIODIFF at FRM II and the Macromolecular Diffractometer (MaNDi) at the Spallation Neutron Source, Oak Ridge National Laboratory. To evaluate the benefits of a cryocooled neutron structure we collected a full neutron data set on the BIODIFF instrument on a Toho-1 lactamase structure at 100K.

  3. Master schedule for CY-1981 Hanford environmental surveillance routine program

    SciTech Connect

    Blumer, P.J.; Sula, M.J.; Eddy, P.A.

    1980-12-01

    The current schedule of data collection for the routine environmental surveillance program at the Hanford Site is provided. Questions about specific entries should be referred to the authors since modifications to the schedule are made during the year and special areas of study, usually of short duration, are not scheduled. The environmental surveillance program objectives are to evaluate the levels of radioactive and nonradioactive pollutants in the Hanford environs, as required in Manual Chapter 0513, and to monitor Hanford operations for compliance with applicable environmental criteria given in Manual Chapter 0524 and Washington State Water Quality Standards. Air quality data obtained in a separate program are also reported. The collection schedule for potable water is shown but it is not part of the routine environmental surveillance program. Schedules are presented for the following subjects: air, Columbia River, sanitary water, surface water, ground water, foodstuffs, wildlife, soil and vegetation, external radiation measurement, portable instrument surveys, and surveillance of waste disposal sites. (JGB)

  4. Routine health check-ups: A boon or a burden?

    PubMed

    Honnekeri, Bianca; Vyas, Aniruddha; Lokhandwala, Disha; Vaishnav, Avani; Vaishnav, Aditi; Singhal, Mayank; Barwad, Parag; Panicker, Gopi Krishna; Lokhandwala, Yash

    2016-01-01

    Healthcare provider institutions in India now offer structured health check-up 'packages' for routine screening of common diseases. While some tests included within their ambit are in keeping with international and Indian recommendations, some are entirely unwarranted. Unnecessary and inappropriate screening tests may cause more harm than benefit. Besides financial and resource burden, there may be over-diagnosis and over-treatment, psychological distress due to false-positive test results, harm from invasive follow-up tests, and false reassurance due to false-negative test results. Clinicians must ensure a net benefit from tests and interventions in order to efficiently deliver preventive services. We reviewed current screening guidelines for cardiovascular disease and common cancers, and surveyed multiple 'packages' provided at 8 centres in Mumbai, India. We put forth our recommendations for routine health screening in asymptomatic adults in India. PMID:27492031

  5. Analysis of routine communication in the air traffic control system

    NASA Technical Reports Server (NTRS)

    Clark, Herbert H.; Morrow, Daniel; Rodvoid, Michelle

    1990-01-01

    The present project has three related goals. The first is to describe the organization of routine controller-pilot communication. This includes identifying the basic units of communication and how they are organized into discourse, how controllers and pilots use language to achieve their goals, and what topics they discuss. The second goal is to identify the type and frequency of problems that interrupt routine information transfer and prompt pilots and controllers to focus on the communication itself. The authors analyze the costs of these problems in terms of communication efficiency, and the techniques used to resolve these problems. Third, the authors hope to identify factors associated with communication problems, such as deviations from conventional air traffic control procedures.

  6. Past radionuclide releases from routine operations at Rocky Flats.

    PubMed

    Ripple, S R; Widner, T E; Mongan, T R

    1996-10-01

    The Colorado Department of Public Health and Environment sponsored a study to reconstruct contaminant doses to the public from operations at the Rocky Flats nuclear weapons facility. This analysis of routine releases of plutonium and uranium, the principal radioactive materials used at the plant, was part of the Colorado Department of Public Health and Environment study. Historical radionuclide monitoring and data handling practices are characterized and uncertainties are quantified. Estimates of the annual release of plutonium and uranium are provided for the period from 1953 to 1989. Off-site airborne concentrations and deposition of plutonium and uranium associated with the releases are estimated, along with the highest doses for off-site populations. The predicted effective doses from the routine release of plutonium and uranium from Rocky Flats for a person residing near the plant boundary between 1953 and 1989 are very small. PMID:8830751

  7. Shifting responsibilities in organ procurement: a plan for routine referral.

    PubMed

    Prottas, J

    1988-08-12

    It is claimed that the primary factor affecting the supply of transplantable organs is the cooperation of health professionals. Organ procurement agencies (OPAs) must obtain timely access to potential donors who are mainly identified and contacted by the nurses and neurophysicians in intensive care units (ICUs). The discretion of medical personnel is limited to their judgment about medical suitability for donation while required request laws ensure that the family is offered the option of organ donation. Prottas argues that the hospital and its staff do not have a right to stand between the family and OPAs and that the principle of required request should be implemented through a policy of "routine referral." This policy would require hospitals routinely to inform OPAs of admissions of potential organ donors, thereby increasing OPA access independently of ICU staff behavior. Medical staff would still determine donor suitability and the time when the OPA could contact the family. PMID:3392816

  8. C-statistic fitting routines: User's manual and reference guide

    NASA Technical Reports Server (NTRS)

    Nousek, John A.; Farwana, Vida

    1991-01-01

    The computer program is discussed which can read several input files and provide a best set of values for the functions provided by the user, using either C-statistic or the chi(exp 2) statistic method. The program consists of one main routine and several functions and subroutines. Detail descriptions of each function and subroutine is presented. A brief description of the C-statistic and the reason for its application is also presented.

  9. Review of the status of the FASTBUS standard routine specification

    SciTech Connect

    Pordes, R.

    1986-11-01

    Within the next few months the FASTBUS Software Working group hopes to distribute the Specification for Standard Routines for FASTBUS. The draft specification will go to the members of the overseeing NIM committee for review. This paper presents the current status of the specification. It includes a list of the goals of the specification; some details of the concepts embedded in it; as well as an overview of the software implementations of the previously distributed draft versions of the specification.

  10. Optimization techniques for OpenCL-based linear algebra routines

    NASA Astrophysics Data System (ADS)

    Kozacik, Stephen; Fox, Paul; Humphrey, John; Kuller, Aryeh; Kelmelis, Eric; Prather, Dennis W.

    2014-06-01

    The OpenCL standard for general-purpose parallel programming allows a developer to target highly parallel computations towards graphics processing units (GPUs), CPUs, co-processing devices, and field programmable gate arrays (FPGAs). The computationally intense domains of linear algebra and image processing have shown significant speedups when implemented in the OpenCL environment. A major benefit of OpenCL is that a routine written for one device can be run across many different devices and architectures; however, a kernel optimized for one device may not exhibit high performance when executed on a different device. For this reason kernels must typically be hand-optimized for every target device family. Due to the large number of parameters that can affect performance, hand tuning for every possible device is impractical and often produces suboptimal results. For this work, we focused on optimizing the general matrix multiplication routine. General matrix multiplication is used as a building block for many linear algebra routines and often comprises a large portion of the run-time. Prior work has shown this routine to be a good candidate for high-performance implementation in OpenCL. We selected several candidate algorithms from the literature that are suitable for parameterization. We then developed parameterized kernels implementing these algorithms using only portable OpenCL features. Our implementation queries device information supplied by the OpenCL runtime and utilizes this as well as user input to generate a search space that satisfies device and algorithmic constraints. Preliminary results from our work confirm that optimizations are not portable from one device to the next, and show the benefits of automatic tuning. Using a standard set of tuning parameters seen in the literature for the NVIDIA Fermi architecture achieves a performance of 1.6 TFLOPS on an AMD 7970 device, while automatically tuning achieves a peak of 2.7 TFLOPS

  11. Getting through to circadian oscillators: why use constant routines?

    NASA Technical Reports Server (NTRS)

    Duffy, Jeanne F.; Dijk, Derk-Jan

    2002-01-01

    Overt 24-h rhythmicity is composed of both exogenous and endogenous components, reflecting the product of multiple (periodic) feedback loops with a core pacemaker at their center. Researchers attempting to reveal the endogenous circadian (near 24-h) component of rhythms commonly conduct their experiments under constant environmental conditions. However, even under constant environmental conditions, rhythmic changes in behavior, such as food intake or the sleep-wake cycle, can contribute to observed rhythmicity in many physiological and endocrine variables. Assessment of characteristics of the core circadian pacemaker and its direct contribution to rhythmicity in different variables, including rhythmicity in gene expression, may be more reliable when such periodic behaviors are eliminated or kept constant across all circadian phases. This is relevant for the assessment of the status of the circadian pacemaker in situations in which the sleep-wake cycle or food intake regimes are altered because of external conditions, such as in shift work or jet lag. It is also relevant for situations in which differences in overt rhythmicity could be due to changes in either sleep oscillatory processes or circadian rhythmicity, such as advanced or delayed sleep phase syndromes, in aging, or in particular clinical conditions. Researchers studying human circadian rhythms have developed constant routine protocols to assess the status of the circadian pacemaker in constant behavioral and environmental conditions, whereas this technique is often thought to be unnecessary in the study of animal rhythms. In this short review, the authors summarize constant routine methodology and what has been learned from constant routines and argue that animal and human circadian rhythm researchers should (continue to) use constant routines as a step on the road to getting through to central and peripheral circadian oscillators in the intact organism.

  12. Routine disinfection of the total dialysis fluid system.

    PubMed

    Gorke, A; Kittel, J

    2002-01-01

    The importance of bacteria and endotoxin free, sterile dialysis fluid for long term, high quality haemodialysis treatment is obvious and very much demanded (1,2). Dead spaces and connections between units (segments) of fluid production and delivery in elder systems are a continuous source for bacteria growth, biofilm generation and endotoxin release (3). After varying success with routine disinfection of system components showing partly fast recovery and growth of bacteria (i.e. < 48 hours) we changed to routine disinfection of the entire fluid production and distribution system. We call this'system disinfection'. We report the methods and results from observation of practice over 28 months of disinfection. The fluid system is composed of a soft water tank, reverse osmosis (double RO), RO fluid loop, central bicarbonate production and delivery system and dialysis stations with and without ultrafilter and citric-thermal disinfection before and after each haemodialysis. The system disinfection is carried out bimonthly with peracetic acid 3.5% in > 0.1% solution at a mean temperature of > 15 degrees C and at a minimum of 60 minutes of disinfection time. Samples for microbiological testing and endotoxin measurement were assessed 3-4 monthly at 7 measurement points. The tests were carried out 7 times on the 11th day (mean value [MV]) after routine system disinfection. The result was in 0.2 CFU/ml (MV) in 40 tests. The endotoxin levels (IU/L) were all < 0.25 except one at 0.325 in RO water. Endotoxin was assessed 5 times in 26 tests over 28 months. Samples were taken at 10.5 (MV) days after system disinfection. The Gel Clot or turbometric method was used. Efficient and preventive routine system disinfection of an entire dialysis fluid production and distribution system as standard in modern equipment - can support sufficient quality in dialysis fluid produced and distributed by elder and composed systems. PMID:12371736

  13. Changing the game: exploring infants' participation in early play routines

    PubMed Central

    Fantasia, Valentina; Fasulo, Alessandra; Costall, Alan; López, Beatriz

    2014-01-01

    Play has proved to have a central role in children's development, most notably in rule learning (Piaget, 1965; Sutton-Smith, 1979) and negotiation of roles and goals (Garvey, 1974; Bruner et al., 1976). Yet very little research has been done on early play. The present study focuses on early social games, i.e., vocal-kinetic play routines that mothers use to interact with infants from very early on. We explored 3-month-old infants and their mothers performing a routine game first in the usual way, then in two violated conditions: without gestures and without sound. The aim of the study is to investigate infants' participation and expectations in the game and whether this participation is affected by changes in the multimodal format of the game. Infants' facial expressions, gaze, and body movements were coded to measure levels of engagement and affective state across the three conditions. Results showed a significant decrease in Limbs Movements and expressions of Positive Affect, an increase in Gaze Away and in Stunned Expression when the game structure was violated. These results indicate that the violated game conditions were experienced as less engaging, either because of an unexpected break in the established joint routine, or simply because they were weaker versions of the same game. Overall, our results suggest that structured, multimodal play routines may constitute interactional contexts that only work as integrated units of auditory and motor resources, representing early communicative contexts which prepare the ground for later, more complex multimodal interactions, such as verbal exchanges. PMID:24936192

  14. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission.

    PubMed

    Ford, C P

    2014-12-12

    Dopamine D2-autoreceptors play a key role in regulating the activity of dopamine neurons and control the synthesis, release and uptake of dopamine. These Gi/o-coupled inhibitory receptors play a major part in shaping dopamine transmission. Found at both somatodendritic and axonal sites, autoreceptors regulate the firing patterns of dopamine neurons and control the timing and amount of dopamine released from their terminals in target regions. Alterations in the expression and activity of autoreceptors are thought to contribute to Parkinson's disease as well as schizophrenia, drug addiction and attention-deficit hyperactivity disorder (ADHD), which emphasizes the importance of D2-autoreceptors in regulating the dopamine system. This review will summarize the cellular actions of dopamine autoreceptors and discuss recent advances that have furthered our understanding of the mechanisms by which D2-receptors control dopamine transmission. PMID:24463000

  15. Adipocyte Mineralocorticoid Receptor Activation Leads to Metabolic Syndrome and Induction of Prostaglandin D2 Synthase.

    PubMed

    Urbanet, Riccardo; Nguyen Dinh Cat, Aurelie; Feraco, Alessandra; Venteclef, Nicolas; El Mogrhabi, Soumaya; Sierra-Ramos, Catalina; Alvarez de la Rosa, Diego; Adler, Gail K; Quilliot, Didier; Rossignol, Patrick; Fallo, Francesco; Touyz, Rhian M; Jaisser, Frédéric

    2015-07-01

    Metabolic syndrome is a major risk factor for the development of diabetes mellitus and cardiovascular diseases. Pharmacological antagonism of the mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits metabolic syndrome in preclinical models, but mechanistic studies are lacking to delineate the role of MR activation in adipose tissue. In this study, we report that MR expression is increased in visceral adipose tissue in a preclinical mouse model of metabolic syndrome and in obese patients. In vivo conditional upregulation of MR in mouse adipocytes led to increased weight and fat mass, insulin resistance, and metabolic syndrome features without affecting blood pressure. We identified prostaglandin D2 synthase as a novel MR target gene in adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects. Moreover, translational studies showed that expression of MR and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients. PMID:25966493

  16. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity

    PubMed Central

    Trifilieff, Pierre; Martinez, Diana

    2014-01-01

    Dependence to drugs of abuse is closely associated with impulsivity, or the propensity to choose a lower, but immediate, reward over a delayed, but more valuable outcome. Here, we review clinical and preclinical studies showing that striatal dopamine signaling and D2 receptor levels – which have been shown to be decreased in addiction - directly impact impulsivity, which is itself predictive of drug self-administration. Based on these studies, we propose that the alterations in D2 receptor binding and dopamine release seen in imaging studies of addiction constitute neurobiological markers of impulsivity. Recent studies in animals also show that higher striatal dopamine signaling at the D2 receptor is associated with a greater willingness to expend effort to reach goals, and we propose that this same relationship applies to humans, particularly with respect to recovery from addiction. PMID:23851257

  17. Presence of dopamine D-2 receptors in human tumoral cell lines

    SciTech Connect

    Sokoloff, P.; Riou, J.F.; Martres, M.P.; Schwartz, J.C. )

    1989-07-31

    ({sup 125}I) Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, ({sup 125}I) iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.

  18. UV photoreaction cross sections of CO and D2O on NiAl(110)

    NASA Astrophysics Data System (ADS)

    Nagai, Kenta; Watanabe, Kazuo

    2016-01-01

    Adsorption states and photoreactions of CO and D2O adsorbed on NiAl(110) at 90 K were studied by temperature-programmed desorption (TPD). Coverage dependence of TPD spectra showed growth behavior of adlayers of these molecules consistent with the literature, but a new path of thermal dissociation of D2O upon adsorption at 90 K was found. The photoreaction cross sections of CO and D2O at 4.7 eV were estimated in the order of 10- 21 cm2 and 10- 20 cm2, respectively. This result suggests that photoexcitation of the NiAl(110) substrate itself, a typical substrate used in supported model catalyst studies, will induce only negligible photoreactions of molecules adsorbed at surfaces of metal nanoparticles supported on ultrathin alumina films formed on NiAl(110).

  19. Reappraising striatal D1- and D2-neurons in reward and aversion.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; Sousa, Nuno; Rodrigues, Ana J

    2016-09-01

    The striatum has been involved in complex behaviors such as motor control, learning, decision-making, reward and aversion. The striatum is mainly composed of medium spiny neurons (MSNs), typically divided into those expressing dopamine receptor D1, forming the so-called direct pathway, and those expressing D2 receptor (indirect pathway). For decades it has been proposed that these two populations exhibit opposing control over motor output, and recently, the same dichotomy has been proposed for valenced behaviors. Whereas D1-MSNs mediate reinforcement and reward, D2-MSNs have been associated with punishment and aversion. In this review we will discuss pharmacological, genetic and optogenetic studies that indicate that there is still controversy to what concerns the role of striatal D1- and D2-MSNs in this type of behaviors, highlighting the need to reconsider the early view that they mediate solely opposing aspects of valenced behaviour. PMID:27235078

  20. Spectroscopic investigation of the 3d 2D → nf 2F transitions in lithium

    NASA Astrophysics Data System (ADS)

    Shahzada, S.; Shah, M.; Haq, S. U.; Nawaz, M.; Ahmed, M.; Nadeem, Ali

    2016-05-01

    We report term energies and effective quantum numbers of the odd parity 3d 2D → nf 2F series of lithium using multi-step and multi-photon laser excitation schemes. The experiments were performed using three dye lasers simultaneously pumped by the second harmonic (532 nm) of a Q-switched Nd:YAG laser in conjunction with an atomic beam apparatus and thermionic diode ion detector. The first ionization potential of lithium has been determined as 43,487.13 ± 0.02 cm- 1 from the much extended 3d 2D → nf 2F (17 ≤ n ≤ 70) series. In addition, the oscillator strengths of the 3d 2D → nf 2F (15 ≤ n ≤ 48) transitions have been determined, showing a decreasing trend with the increase in principal quantum number n.

  1. Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists.

    PubMed

    Weichert, Dietmar; Stanek, Markus; Hübner, Harald; Gmeiner, Peter

    2016-06-15

    Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describe the design, synthesis and biological investigation of a defined set of compounds leading to the identification of the benzoxazinone (R)-3, which shows agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D2 receptor. This directed approach yielded molecular probes with tuned dual activity. The congener desOH-3 devoid of the benzylic hydroxyl function was shown to be a β2 adrenergic antagonist/D2 receptor agonist with Ki values in the low nanomolar range. The compounds may serve as a promising starting point for the investigation and treatment of neurological disorders. PMID:27132867

  2. SHARON: a Simulator of Human Activities, ROutines and Needs.

    PubMed

    Veronese, Fabio; Proserpio, Daniele; Comai, Sara; Matteucci, Matteo; Salice, Fabio

    2015-01-01

    In a few decades, requests for assistance to the elderly will increase the already high health care costs. Within this context, a possible solution is represented by smart environments where services help dwellers' life. The development of smart technologies requires large datasets for training, validation or testing. Since the data collection from real smart homes has high costs the authors developed SHARON - a Simulator of Human Activity, ROutines and Needs. This software aims to support such projects, virtually reproducing environments and behaviors of the dwellers. This work proposes and validates a behavioral model able reproduce decisions and human habits, starting from an available data set or an interview. Physiological parameters and habits are merged with a probabilistic approach, choosing the most likely activity. With respect to other behavioral simulators available in the literature, SHARON is focused on routines and activities generation, based on user defined high level parameters. Within the evaluation phase it was applied a cross-validation approach, by simulating 300 days starting from a training set of 23 days and testing with the remaining 7 days validation set. As expected, results prove the simulated data correctly reproduce the activities routine distributions, in particular the more regular ones. PMID:26294528

  3. Experience with a routine fecal sampling program for plutonium workers

    SciTech Connect

    Bihl, D.E.; Buschbom, R.L.; Sula, M.J. )

    1993-11-01

    A quarterly fecal sampling program was conducted at the U. S. Department of Energy's Hanford site for congruent to 100 workers at risk for an intake of plutonium oxide and other forms of plutonium. To our surprise, we discovered that essentially all of the workers were excreting detectable activities of plutonium. Further investigation showed that the source was frequent, intermittent intakes at levels below detectability by normal workplace monitoring, indicating the extraordinary sensitivity of fecal sampling. However, the experience of this study also indicated that the increased sensitivity of routine fecal sampling relative to more common bioassay methods is offset by many problems. These include poor worker cooperation; difficulty in distinguishing low-level chronic intakes from a more significant, acute intake; difficulty in eliminating interference from ingested plutonium; and difficulty in interpreting what a single void means in terms of 24-h excretion. Recommendations for a routine fecal program include providing good communication to workers and management about reasons and logistics of fecal sampling prior to starting, using annual (instead of quarterly) fecal sampling for class Y plutonium, collecting samples after workers have been away from plutonium exposure for a least 3 d, and giving serious consideration to improving urinalysis sensitivity rather than going to routine fecal sampling.

  4. Complexity reduction of clinical samples for routine mass spectrometric analysis.

    PubMed

    Mesmin, Cédric; van Oostrum, Jan; Domon, Bruno

    2016-04-01

    The precise measurement of protein abundance levels in highly complex biological samples such as plasma remains challenging. The wide range of protein concentrations impairs the detection of low-abundant species and the high number of peptide components to analyze results in interferences leading to erroneous quantitative results. The advances in MS instrumentation, with improved selectivity and sensitivity, partially address these issues, but sample preparation techniques remain the pivotal element to obtain robust routine mass spectrometric assays with a low LOD. A number of methodologies have been proposed and refined over the past two decades to reduce the range of protein concentrations and the number of peptide components. Whereas most of the methods have proven their utility for discovery studies, only a few are actually applicable to routine quantitative studies. In this account, common protein- and peptide-based fractionation methods are discussed, and illustrated with practical examples, with a focus on methods suited for clinical samples scheduled for biomarker validation assays and subsequent routine clinical mass spectrometric analyses. PMID:26680238

  5. Does Medical Evidence Support Routine Oronasopharyngeal Suction at Delivery?

    PubMed Central

    Evans, M. Blake

    2016-01-01

    Oronasopharyngeal suction (ONPS) is regularly performed in neonates at delivery in many hospitals across the country today. Although ONPS is a technique that has essentially become habitual for most obstetricians, its theorized usefulness to help promote expeditious lung aeration after delivery by removal of amniotic fluid, meconium, mucus and blood that may otherwise be aspirated by the newborn, is currently not recommended. ONPS can cause vagal stimulation-induced bradycardia and thus apnea, and can cause iatrogenic infection due to mucous membrane injury. Multiple studies that have been performed comparing routine use of ONPS to no intervention controls indicate that newborns receiving ONPS took a longer time to achieve normal oxygen saturations, caused apneic episodes, and caused disturbances in heart rate (mainly bradycardia) compared to the control groups. Although the ONPS groups revealed no significantly different APGAR scores at 1 and 5 minutes, the ONPS groups took longer than the control group to reach an arterial oxygen saturation greater than or equal to 92% in the first minutes of life. Currently, Neonatal Resuscitation Program guidelines discourage the use of routine OPNS during or after delivery with clear or meconium-stained amniotic fluid and in the absence of obvious obstruction. Furthermore, this manuscript highlights various literature sources revealing that the routine use of ONPS at the time of delivery can cause more harm than good, if any good at all. PMID:27328554

  6. K(3)EDTA Vacuum Tubes Validation for Routine Hematological Testing.

    PubMed

    Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Poli, Giovanni; Solero, Giovanni Pietro; Picheth, Geraldo; Guidi, Gian Cesare

    2012-01-01

    Background and Objective. Some in vitro diagnostic devices (e.g, blood collection vacuum tubes and syringes for blood analyses) are not validated before the quality laboratory managers decide to start using or to change the brand. Frequently, the laboratory or hospital managers select the vacuum tubes for blood collection based on cost considerations or on relevance of a brand. The aim of this study was to validate two dry K(3)EDTA vacuum tubes of different brands for routine hematological testing. Methods. Blood specimens from 100 volunteers in two different K(3)EDTA vacuum tubes were collected by a single, expert phlebotomist. The routine hematological testing was done on Advia 2120i hematology system. The significance of the differences between samples was assessed by paired Student's t-test after checking for normality. The level of statistical significance was set at P < 0.05. Results and Conclusions. Different brand's tubes evaluated can represent a clinically relevant source of variations only on mean platelet volume (MPV) and platelet distribution width (PDW). Basically, our validation will permit the laboratory or hospital managers to select the brand's vacuum tubes validated according to him/her technical or economical reasons for routine hematological tests. PMID:22888448

  7. K3EDTA Vacuum Tubes Validation for Routine Hematological Testing

    PubMed Central

    Lima-Oliveira, Gabriel; Lippi, Giuseppe; Salvagno, Gian Luca; Montagnana, Martina; Poli, Giovanni; Solero, Giovanni Pietro; Picheth, Geraldo; Guidi, Gian Cesare

    2012-01-01

    Background and Objective. Some in vitro diagnostic devices (e.g, blood collection vacuum tubes and syringes for blood analyses) are not validated before the quality laboratory managers decide to start using or to change the brand. Frequently, the laboratory or hospital managers select the vacuum tubes for blood collection based on cost considerations or on relevance of a brand. The aim of this study was to validate two dry K3EDTA vacuum tubes of different brands for routine hematological testing. Methods. Blood specimens from 100 volunteers in two different K3EDTA vacuum tubes were collected by a single, expert phlebotomist. The routine hematological testing was done on Advia 2120i hematology system. The significance of the differences between samples was assessed by paired Student's t-test after checking for normality. The level of statistical significance was set at P < 0.05. Results and Conclusions. Different brand's tubes evaluated can represent a clinically relevant source of variations only on mean platelet volume (MPV) and platelet distribution width (PDW). Basically, our validation will permit the laboratory or hospital managers to select the brand's vacuum tubes validated according to him/her technical or economical reasons for routine hematological tests. PMID:22888448

  8. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool. PMID:26864127

  9. R2d2 Drives Selfish Sweeps in the House Mouse

    PubMed Central

    Didion, John P.; Morgan, Andrew P.; Yadgary, Liran; Bell, Timothy A.; McMullan, Rachel C.; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J.; Campbell, Karl J.; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J.; Crowley, James J.; Chesler, Elissa J.; Förster, Daniel W.; French, John E.; Gabriel, Sofia I.; Gatti, Daniel M.; Garland, Theodore; Giagia-Athanasopoulou, Eva B.; Giménez, Mabel D.; Grize, Sofia A.; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C.; Herman, Jeremy S.; Holt, James M.; Hua, Kunjie; Jolley, Wesley J.; Lindholm, Anna K.; López-Fuster, María J.; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P.; Searle, Jeremy B.; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L.; Thomas-Laemont, Patricia; Threadgill, David W.; Ventura, Jacint; Weinstock, George M.; Pomp, Daniel; Churchill, Gary A.; Pardo-Manuel de Villena, Fernando

    2016-01-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

  10. Dopamine Transporters, D2 Receptors, and Dopamine Release in Generalized Social Anxiety Disorder

    PubMed Central

    Schneier, Franklin R.; Abi-Dargham, Anissa; Martinez, Diana; Slifstein, Mark; Hwang, Dah-Ren; Liebowitz, Michael R.; Laruelle, Marc

    2009-01-01

    Background Dopamine D2 receptor and dopamine transporter availability in the striatum have each been reported abnormal in generalized social anxiety disorder (GSAD) in studies using single photon computerized tomography (SPECT). D2 receptors and dopamine transporters have not previously been studied within the same GSAD subjects, however, and prior GSAD studies have not assessed dopamine release or subdivided striatum into functional subregions. Methods Unmedicated adults with GSAD (N=17) and matched healthy comparison subjects (HC, N=13) participated in this study. Of these, 15 GSAD and 13 HC subjects completed baseline assessment of D2 receptor availability using positron emission tomography (PET) with the radiotracer [11C] raclopride. Twelve GSAD and 13 HC subjects completed a repeat scan after intravenous administration of D-amphetamine, to study dopamine release. Twelve of the GSAD subjects and 10 of the HC subjects also completed SPECT with the radiotracer [123I] methyl 3ß-(4-iodophenyl) tropane-2ß-carboxylate ([123I] ß-CIT) to assess dopamine transporter availability. Results GSAD and HC groups did not differ significantly in striatal dopamine transporter availability, overall striatal or striatal subregion D2 receptor availability at baseline, or change in D2 receptor availability after D-amphetamine. Receptor availability and change after D-amphetamine were not significantly associated with severity of social anxiety or trait detachment. Conclusions These findings do not replicate previous findings of altered striatal dopamine transporter and D2 receptor availability in GSAD subjects assessed with SPECT. The differences from results of prior studies may be due to differences in imaging methods or characteristics of samples. PMID:19180583

  11. Obesity attenuates D2 autoreceptor‐mediated inhibition of putative ventral tegmental area dopaminergic neurons

    PubMed Central

    Koyama, Susumu; Mori, Masayoshi; Kanamaru, Syohei; Sazawa, Takuya; Miyazaki, Ayano; Terai, Hiroki; Hirose, Shinichi

    2014-01-01

    Abstract The ventral tegmental area (VTA) in the midbrain is important for food reward. High‐fat containing palatable foods have reinforcing effects and accelerate obesity. We have previously reported that diet‐induced obesity selectively decreased the spontaneous activity of VTA GABA neurons, but not dopamine neurons. The spontaneous activity of VTA dopamine neurons is regulated by D2 autoreceptors. In this study, we hypothesized that obesity would affect the excitability of VTA dopamine neurons via D2 autoreceptors. To examine this hypothesis, we compared D2 receptor‐mediated responses of VTA dopamine neurons between lean and obese mice. Mice fed on a high‐fat (45%) diet and mice fed on a standard diet were used as obese and lean models, respectively. Brain slice preparations were made from these two groups. Spontaneous activity of VTA neurons was recorded by extracellular recording. Putative VTA dopamine neurons were identified by firing inhibition with a D2 receptor agonist quinpirole, and electrophysiological criteria (firing frequency <5 Hz and action potential current duration >1.2 msec). Single‐dose application of quinpirole (3−100 nmol/L) exhibited similar firing inhibition of putative VTA dopamine neurons between lean and obese mice. In stepwise application by increasing quinpirole concentrations of 3, 10, 30, and 100 nmol/L subsequently, quinpirole‐induced inhibition of firing decreased in putative VTA dopamine neurons of obese mice compared with those of lean mice. In conclusion, high‐fat diet‐induced obesity attenuated D2 receptor‐mediated inhibition of putative VTA dopamine neurons due to the acceleration of D2 receptor desensitization. PMID:24793981

  12. Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons.

    PubMed

    Sciamanna, Giuseppe; Napolitano, Francesco; Pelosi, Barbara; Bonsi, Paola; Vitucci, Daniela; Nuzzo, Tommaso; Punzo, Daniela; Ghiglieri, Veronica; Ponterio, Giulia; Pasqualetti, Massimo; Pisani, Antonio; Usiello, Alessandro

    2015-06-01

    Ras homolog enriched in striatum (Rhes) is highly expressed in striatal medium spiny neurons (MSNs) of rodents. In the present study, we characterized the expression of Rhes mRNA across species, as well as its functional role in other striatal neuron subtypes. Double in situ hybridization analysis showed that Rhes transcript is selectively localized in striatal cholinergic interneurons (ChIs), but not in GABAergic parvalbumin- or in neuropeptide Y-positive cell populations. Rhes is closely linked to dopamine-dependent signaling. Therefore, we recorded ChIs activity in basal condition and following dopamine receptor activation. Surprisingly, instead of an expected dopamine D2 receptor (D2R)-mediated inhibition, we observed an aberrant excitatory response in ChIs from Rhes knockout mice. Conversely, the effect of D1R agonist on ChIs was less robust in Rhes mutants than in controls. Although Rhes deletion in mutants occurs throughout the striatum, we demonstrate that the D2R response is altered specifically in ChIs, since it was recorded in pharmacological isolation, and prevented either by intrapipette BAPTA or by GDP-β-S. Moreover, we show that blockade of Cav2.2 calcium channels prevented the abnormal D2R response. Finally, we found that the abnormal D2R activation in ChIs was rescued by selective PI3K inhibition thus suggesting that Rhes functionally modulates PI3K/Akt signaling pathway in these neurons. Our findings reveal that, besides its expression in MSNs, Rhes is localized also in striatal ChIs and, most importantly, lack of this G-protein, significantly alters D2R modulation of striatal cholinergic excitability. PMID:25818655

  13. Extrastriatal dopamine D2 receptors: distribution, pharmacological characterization and region-specific regulation by clozapine.

    PubMed

    Janowsky, A; Neve, K A; Kinzie, J M; Taylor, B; de Paulis, T; Belknap, J K

    1992-06-01

    The distribution of dopamine D2 receptors in the rat brain was determined by quantitative autoradiography of the binding of [125I]epidepride and the effects of chronic drug administration on regulation of receptors in striatal and extrastriatal brain regions were characterized. [125I]Epidepride (2200 Ci/mmol) bound with high affinity to coronal tissue sections from the rat brain (Kd = 78 pM), and specific binding was detected in a number of discrete layers, nuclei or regions of the hippocampus, thalamus, cerebellum and other extrastriatal sites. Pharmacological analysis of radioligand binding to hippocampal and cerebellar membranes indicated binding to dopamine D2 receptors, and approximately 10% of the binding appeared to represent low affinity idazoxan-displaceable binding to alpha-2 adrenoceptors. The binding to extrastriatal regions resembled previously reported radioligand binding to dopamine D2 receptors in striatal and cortical membranes. Chronic (14 day) administration of two dopamine D2 receptor antagonists, either the typical neuroleptic haloperidol (1.5 mg/kg i.p.) or the atypical neuroleptic clozapine (30 mg/kg i.p.), caused a significant increase in the density of [125I]epidepride binding sites in the medial prefrontal cortex and parietal cortex. Only haloperidol caused a significant increase in the density of [3H]spiperone and [125I]epidepride binding sites in the striatum and a slight increase in [125I]epidepride binding sites in the hippocampus. Similar administration of amphetamine (5 mg/kg i.p.) had no significant effect on the density of dopamine D2 receptors in any brain region examined. In addition, no drug-induced changes in the characteristics of dopamine D2 receptors in discrete areas of the cerebellum were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1534844

  14. R2d2 Drives Selfish Sweeps in the House Mouse.

    PubMed

    Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

    2016-06-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

  15. Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors.

    PubMed

    Fraser, Kurt M; Haight, Joshua L; Gardner, Eliot L; Flagel, Shelly B

    2016-05-15

    Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01-0.32mg/kg) or pramipexole (0.032-0.32mg/kg), the D2/D3 antagonist raclopride (0.1mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. PMID:26909847

  16. A new esterase EstD2 isolated from plant rhizosphere soil metagenome.

    PubMed

    Lee, Myung Hwan; Hong, Kyung Sik; Malhotra, Shweta; Park, Ji-Hye; Hwang, Eul Chul; Choi, Hong Kyu; Kim, Young Sup; Tao, Weixin; Lee, Seon-Woo

    2010-11-01

    Soil metagenome constitutes a reservoir for discovering novel enzymes from the unculturable microbial diversity. From three plant rhizosphere metagenomic libraries comprising a total of 142,900 members of recombinant plasmids, we obtained 14 recombinant fosmids that exhibited lipolytic activity. A selected recombinant plasmid, pFLP-2, which showed maximum lipolytic activity, was further analyzed. DNA sequence analysis of the subclone in pUC119, pELP-2, revealed an open reading frame of 1,191 bp encoding a 397-amino-acid protein. Purified EstD2 exhibited maximum enzymatic activity towards p-nitrophenyl butyrate, indicating that it is an esterase. Purified EstD2 showed optimal activity at 35 °C and at pH 8.0. The K(m) and K(cat) values were determined to be 79.4 μM and 120.5/s, respectively. The esterase exhibited an increase in enzymatic activity in the presence of 15% butanol and 15% methanol. Phylogenetic analysis revealed that the lipolytic protein EstD2 may be a member of a novel family of lipolytic enzymes. Several hypothetical protein homologs of EstD2 were found in the database. A hypothetical protein from Phenylobacterium zucineum HLK1, a close homolog of EstD2, displayed lipolytic activity when the corresponding gene was expressed in Escherichia coli. Our results suggest that the other hypothetical protein homologs of EstD2 might also be members of this novel family. PMID:20683720

  17. N-allyl epiderpride: An extremely potent SPECT radioligand for the dopamine D2 receptor

    SciTech Connect

    Kessler, R.M.; Mason, N.S.; Ansari, M.S.

    1994-05-01

    We have previously reported that epidepride is a potent (K{sub D} 24pM) and specific SPECT radioligand for the dopamine D2 receptor which can be used to study striatal and extrastriatal dopamine D2 receptors in man. We have synthesized and evaluated the N-allyl analogue of epiderpride (APID) as a potential SPECT radioligand for the dopamine D2 receptor. In comparison to epidepride it is even more potent at the dopamine D2 receptor, the K{sub D} for APID being 11 frontal cortical homogenate. The lipophilicity, evaluated using the log kw pH 7.5, was 2.9 versus 2.05 for epidepride. Competitive binding studies using rat striatal, hippocampal and frontal cortical homogenates showed high affinity for only dopamine D2 like cerebellar ratio of 275:1 at 320 minutes post injection-similar to that seen with epidepride, but with nearly four times higher brain uptake. Of interest was the off-rate from the dopamine D2 receptor; it was 0.0046 min{sup -1} in vitro at 25{degrees}C-corresponding to an t 1/2 of 150 minutes. Studies in rhesus monkeys show an in vivo off rate (following 2.5 mg/kg raclopride IV) of about 0.0082 min{sup -1} seen that with epidepride. SPECT studies in rhesus monkeys reveal APID is a promising SPECT radioligand that appears to be similar to epidepride, but with higher brain uptake due to its more optimal lipophilicity for entry into brain.

  18. Differential relationships between D1 and D2 dopamine receptor expression in the medial preoptic nucleus and sexually-motivated song in male European starlings (Sturnus vulgaris).

    PubMed

    DeVries, M S; Cordes, M A; Stevenson, S A; Riters, L V

    2015-08-20

    Converging data in songbirds support a central role for the medial preoptic nucleus (POM) in motivational aspects of vocal production. Recent data suggest that dopamine in the POM plays a complex modulatory role in the production of sexually-motivated song and that an optimal level of dopamine D1 receptor stimulation is required to facilitate singing behavior. To further explore this possibility, we used quantitative real-time PCR to examine relationships between mRNA expression of D1 as well as D2 receptors in the POM (and also the lateral septum and Area X) and sexually-motivated singing behavior in male European starlings. Results showed that both males with the highest and lowest D1 expression in the POM sang significantly less than males with intermediate levels of expression. Furthermore, singing behavior rose linearly in association with increasing levels of D1 expression in POM but dropped abruptly, such that individuals with D1 expression values higher than the mean sang very little. Analysis of birds with low and intermediate levels of D1 expression in POM revealed strong positive correlations between D1 expression and song but negative relationships between D2 receptor expression and song. These findings support prior work suggesting an optimal level of POM D1 receptor stimulation best facilitates sexually-motivated singing behavior. Results also suggest that D2 receptors may work in opposition to D1 receptors in POM to modify vocal production. PMID:26079111

  19. Locomotor hypoactivity and motor disturbances--behavioral effects induced by intracerebellar microinjections of dopaminergic DA-D2/D3 receptor agonists.

    PubMed

    Kolasiewicz, W; Maj, J

    2001-01-01

    In the light of recent findings, DA-D3 dopamine receptors with an unclear physiological function are present in the cerebellar cortex. Our preliminary results seem to indicate that bilateral injection of 7-OH-DPAT, a DA-D2/D3 receptor agonist (1 and 10 microg/0.5 microl), to lobule 9/10 of rat cerebellar cortex reduces spontaneous locomotor activity (hypolocomotor effects) and induces balance and motor coordination disturbances, respectively. Similar effects can be observed in the case of analogous microinjection of the DA-D3/D2 agonist pramipexole. In earlier studies, peripheral (ip) injection of nafadotride (0.6 mg/kg), a D3 receptor antagonist, neither affected per se spontaneous motor activity, nor modified the above described effects of 7-OH-DPAT. Participation of cerebellar DA-D3 and DA-D2 receptors in hypolocomotor effects, as well as putative participation of other receptors in the generation of motor disturbances, has been discussed. PMID:11990070

  20. MIE Lidar proposed for the German Space Shuttle Mission D2

    NASA Technical Reports Server (NTRS)

    Renger, W.; Endemann, M.; Quenzel, H.; Werner, C.

    1986-01-01

    Firm plans for a second German Spacelab mission (D2-mission), originally scheduled for late 1988 is basically a zero-g mission, but will also include earth observation experiments. On board the D2-facility will allow performance of a number of different measurements with the goal to obtain performance data (cloud top heights, height of the planetary boundary layer, optical thickness, and cloud base height of thin and medium thick clouds, ice/water phase discriminatin for clouds, tropopause height, tropaspheric height, tropospheric aerosols, and stratospheric aerosols.

  1. Melittin stimulates liver glycogenolysis and the release of prostaglandin D2 and thromboxane B2.

    PubMed Central

    García-Sáinz, J A; Hernández-Sotomayor, S M; Macías-Silva, M

    1990-01-01

    Melittin stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect was rapid and associated with production and release of prostaglandin D2 and thromboxane B2. Indomethacin blocked the release of these eicosanoids and the stimulation of glycogenolysis induced by melittin. Ibuprofen blocked the release of prostaglandin D2 induced by melittin and markedly attenuated that of thromboxane B2. Interestingly, the initial burst of glucose output induced by melittin was not inhibited by ibuprofen, although the duration of the glycogenolytic action of the peptide was greatly diminished. PMID:2375756

  2. Pion transfer from hydrogen to deuterium in H2+D2 gas mixtures

    NASA Astrophysics Data System (ADS)

    Weber, P.; Armstrong, D. S.; Measday, D. F.; Noble, A. J.; Stanislaus, S.; Harston, M. R.; Aniol, K. A.; Horváth, D.

    1990-01-01

    The transfer of negative pions from pionic hydrogen to deuterium has been investigated in gas mixtures of H2 and D2 as a function of the D2 concentration (C). The concentration dependence of the transfer rate was fitted using a phenomenological model with two parameters. For C-->∞ (32+/-3)% of the pions undergo transfer. The fitted parameters reflect the ratio of pion capture to pion transfer in collisions of pionic hydrogen with protons or deuterons. No pressure dependence for pion transfer was found.

  3. Adolescent Maturation of Dopamine D1 and D2 Receptor Function and Interactions in Rodents.

    PubMed

    Dwyer, Jennifer B; Leslie, Frances M

    2016-01-01

    Adolescence is a developmental period characterized by heightened vulnerability to illicit drug use and the onset of neuropsychiatric disorders. These clinical phenomena likely share common neurobiological substrates, as mesocorticolimbic dopamine systems actively mature during this period. Whereas prior studies have examined age-dependent changes in dopamine receptor binding, there have been fewer functional analyses. The aim of the present study was therefore to determine whether the functional consequences of D1 and D2-like activation are age-dependent. Adolescent and adult rats were given direct D1 and D2 agonists, alone and in combination. Locomotor and stereotypic behaviors were measured, and brains were collected for analysis of mRNA expression for the immediate early genes (IEGs), cfos and arc. Adolescents showed enhanced D2-like receptor control of locomotor and repetitive behaviors, which transitioned to dominant D1-like mechanisms in adulthood. When low doses of agonists were co-administered, adults showed supra-additive behavioral responses to D1/D2 combinations, whereas adolescents did not, which may suggest age differences in D1/D2 synergy. D1/D2-stimulated IEG expression was particularly prominent in the bed nucleus of the stria terminalis (BNST). Given the BNST's function as an integrator of corticostriatal, hippocampal, and stress-related circuitry, and the importance of neural network dynamics in producing behavior, an exploratory functional network analysis of regional IEG expression was performed. This data-driven analysis demonstrated similar developmental trajectories as those described in humans and suggested that dopaminergic drugs alter forebrain coordinated gene expression age dependently. D1/D2 recruitment of stress nuclei into functional networks was associated with low behavioral output in adolescents. Network analysis presents a novel tool to assess pharmacological action, and highlights critical developmental changes in functional

  4. Adolescent Maturation of Dopamine D1 and D2 Receptor Function and Interactions in Rodents

    PubMed Central

    Dwyer, Jennifer B.; Leslie, Frances M.

    2016-01-01

    Adolescence is a developmental period characterized by heightened vulnerability to illicit drug use and the onset of neuropsychiatric disorders. These clinical phenomena likely share common neurobiological substrates, as mesocorticolimbic dopamine systems actively mature during this period. Whereas prior studies have examined age-dependent changes in dopamine receptor binding, there have been fewer functional analyses. The aim of the present study was therefore to determine whether the functional consequences of D1 and D2-like activation are age-dependent. Adolescent and adult rats were given direct D1 and D2 agonists, alone and in combination. Locomotor and stereotypic behaviors were measured, and brains were collected for analysis of mRNA expression for the immediate early genes (IEGs), cfos and arc. Adolescents showed enhanced D2-like receptor control of locomotor and repetitive behaviors, which transitioned to dominant D1-like mechanisms in adulthood. When low doses of agonists were co-administered, adults showed supra-additive behavioral responses to D1/D2 combinations, whereas adolescents did not, which may suggest age differences in D1/D2 synergy. D1/D2-stimulated IEG expression was particularly prominent in the bed nucleus of the stria terminalis (BNST). Given the BNST’s function as an integrator of corticostriatal, hippocampal, and stress-related circuitry, and the importance of neural network dynamics in producing behavior, an exploratory functional network analysis of regional IEG expression was performed. This data-driven analysis demonstrated similar developmental trajectories as those described in humans and suggested that dopaminergic drugs alter forebrain coordinated gene expression age dependently. D1/D2 recruitment of stress nuclei into functional networks was associated with low behavioral output in adolescents. Network analysis presents a novel tool to assess pharmacological action, and highlights critical developmental changes in functional

  5. Visualization of extrastriatal dopamine D2 receptors in the human brain.

    PubMed

    Kessler, R M; Mason, N S; Votaw, J R; De Paulis, T; Clanton, J A; Ansari, M S; Schmidt, D E; Manning, R G; Bell, R L

    1992-11-13

    [123I]Epidepride, a potent and selective dopamine D2 radioligand, was administered to a 27 year old normal male volunteer. Single photon tomography revealed that peak striatal uptake occurred at 4 h after injection with a striatal:cerebellar ratio of 7.8 rising to over 100 at 18 h post injection. Uptake above the levels seen in cerebellum was also noted in the thalamus, pituitary, hypothalamus and temporal lobe, particularly medially. Single photon tomography with [123I]epidepride allows visualization of extrastriatal dopamine D2 receptors in man. PMID:1478255

  6. Temporal cortex dopamine D2/3 receptor binding in major depression.

    PubMed

    Lehto, Soili M; Kuikka, Jyrki; Tolmunen, Tommi; Hintikka, Jukka; Viinamäki, Heimo; Vanninen, Ritva; Haatainen, Kaisa; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Tiihonen, Jari

    2008-06-01

    The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [(123)I]epidepride to image D(2/3) receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D(2/3) receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives. PMID:18588596

  7. Genetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms.

    PubMed

    Frank, M J; Hutchison, K

    2009-11-24

    Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 function, respectively. Nevertheless, whereas the role for dopamine in positive learning is relatively well accepted, that in learning to avoid negative outcomes is more controversial. Here we further explore D2-receptor-related genetic contributions to probabilistic avoidance in humans, in light of recent data showing that particular DRD2 polymorphisms are associated with functional modulation of receptor expression [Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee M-LT, Xiao T, Papp A, Wang D, Sadée W (2007) Polymorphisms in human dopamine d2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A 104(51):20552-20557]. We find that a promoter polymorphism rs12364283 associated with transcription and D2 receptor density was strongly and selectively predictive of avoidance-based decisions. Two further polymorphisms (rs2283265 and rs1076560) associated with relatively reduced presynaptic relative to postsynaptic D2 receptor expression were predictive of relative impairments in negative compared to positive decisions. These previously undocumented effects of DRD2 polymorphisms were largely independent of those we reported previously for the C957T polymorphism (rs6277) associated with striatal D2 density. In contrast, effects of the commonly studied Taq1A polymorphism on reinforcement-based decisions were due to indirect association with C957T. Taken together these findings suggest multiple D2-dependent

  8. Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity

    PubMed Central

    Eisenstein, Sarah A.; Gredysa, Danuta M.; Antenor–Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M.; Black, Kevin J.; Perlmutter, Joel S.; Moerlein, Stephen M.; Hershey, Tamara

    2015-01-01

    Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic

  9. STS-55 crewmembers work in the SL-D2 module onboard OV-102

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Working in the shirt-sleeve research environment of the Spacelab Deutsche 2 (SL-D2) science module are STS-55 Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross, MS3 Bernard A. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and German Payload Specialist 1 Ulrich Walter. Ross examines sample tube at Rack 8 Werkstofflabor (WL) (left). Harris, holding his arm, waits to have his blood drawn by Schlegel (right). Wearing the baroreflex (BA) collar at Rack 12 Experiment Rack and waving is Walter. The SL-D2 module is located in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  10. DOPEX-1D2C: A one-dimensional, two-constraint radiation shield optimization code

    NASA Technical Reports Server (NTRS)

    Lahti, G. P.

    1973-01-01

    A one-dimensional, two-constraint radiation sheild weight optimization procedure and a computer program, DOPEX-1D2C, is described. The DOPEX-1D2C uses the steepest descent method to alter a set of initial (input) thicknesses of a spherical shield configuration to achieve a minimum weight while simultaneously satisfying two dose-rate constraints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. Code input instruction, a FORTRAN-4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is less than 1/2 minute on an IBM 7094.

  11. Dopamine binds calmodulin during autoregulation of dopaminergic D2 receptor signaling through CaMKIIα-calmodulin complex.

    PubMed

    Laoye, B J; Okurumeh, O A; Obagaye, O V; Olagunju, M O; Bankole, O O; Olubiyi, O O; Ogundele, O M

    2016-06-01

    The role of dopaminergic D2 receptor (D2R) autoregulation in dopamine (DA) neurotransmission cannot be overemphasized in cause and progression of disorders associated with complex behaviors. Although previous studies have shown that D2R is structurally and physiologically linked with calcium/calmodulin-dependent kinase II (CaMKIIα), however, the role of calmodulin in the CaMKIIα complex in D2R regulation remains elusive. In this study, using structural biology modeling softwares (iGEMDOCK and CueMol), we have shown the interaction between D2R, CaMKIIα, calmodulin, and DA under varying conditions. The outcomes of this study suggest that CaMKIIα causes a change in DA binding affinity to the D2R receptive site while the detached DA binds to calmodulin to stop the activity of D2R in the D2R-dopaminergic D1 receptor (D1R) heteromer. Ultimately, we concluded that D2R autoregulates to stop its heteromeric combination with D1R. D2R interacts with D1R to facilitate calcium movement that activates calmodulin, then CaMKIIα. The CaMKIIα-calmodulin complex changes the affinity of DA-D2R causing DA to break free and bind with calmodulin. PMID:26446938

  12. Roles of Dopamine D2 Receptor Subregions in Interactions with β-Arrestin2

    PubMed Central

    Zhang, Xiaohan; Choi, Bo-Gil; Kim, Kyeong-Man

    2016-01-01

    β-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of β-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with β-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with β-arrestin2. For this, we employed dopamine D2 and D3 receptors (D2R and D3R, respectively), since they display distinct agonist-induced interactions with β-arrestins. Our results showed that the second and third intracellular loops of D2R are involved in the agonist-induced translocation of β-arrestins toward plasma membranes. In contrast, the N- and C-termini of D2R exerted negative effects on the basal interaction with β-arrestins. PMID:27068263

  13. 17 CFR 240.12d2-1 - Suspension of trading.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Suspension of trading. 240... Securities Exchange Act of 1934 Suspension of Trading, Withdrawal, and Striking from Listing and Registration § 240.12d2-1 Suspension of trading. (a) A national securities exchange may suspend from trading...

  14. STS-55 German Payload Specialist Walter freefloats inside the SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter demonstrates the microgravity aboard the Spacelab Deutsche 2 (SL-D2) science module in Columbia's, Orbiter Vehicle (OV) 102's, payload bay (PLB). The module served as his space laboratory and that of his six crewmates for 10 days. Walter represents the German Aerospace Research Establishment (DLR).

  15. Podoplanin (D2-40) is a reliable marker of urinary bladder myofibroblasts (telocytes).

    PubMed

    Povýšil, C; Kaňa, M; Zámečník, L; Vaľová, Z; Hanuš, T

    2014-01-01

    Podoplanin, D2-40, has been described in a variety of normal and neoplastic tissues. It is often used for highlighting lymphatics. We evaluated the expression of podoplanin in α-smooth muscle actinpositive myofibroblasts producing the suburothelial layer in tunica propria of the urinary bladder that have some similar features with telocytes. Our results showed that these cells demonstrate distinct D2-40 immunoreactivity from telocytes occurring in the renal pelvis and ureter. We observed positive reaction not only in bioptic specimens from women with interstitial cystitis, but also in a control group of women and men treated for pathological bladder lesion different from interstitial cystitis. It is interesting that identical staining reaction was observed in the ureters only exceptionally. In addition, we examined samples from myofibroblastic tumoriform lesions of soft tissue such as nodular fascitis and fibromatosis (desmoid) and we obtained negative results. It means that the so-called myofibroblasts of urinary bladder tunica propria have a unique immunophenotype that has probably not been described until now. Our findings suggest that D2-40 can be used as a complementary immunostainer to α-smooth muscle actin on urinary bladder biopsies from patients with interstitial cystitis. The role of D2-40 as an immunohistochemical marker is still being investigated. PMID:25629270

  16. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

    PubMed

    Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

    2015-07-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. PMID:26048960

  17. Infralimbic D2 receptors are necessary for fear extinction and extinction-related tone responses

    PubMed Central

    Mueller, Devin; Bravo-Rivera, Christian; Quirk, Gregory J.

    2010-01-01

    Background Fear extinction is dependent on plasticity in the infralimbic prefrontal cortex (IL), an area heavily innervated by midbrain dopaminergic inputs. Dopamine D2 receptors are concentrated in infralimbic output neurons that are involved in the suppression of conditioned fear after extinction. Here we examined the specific role of the D2 receptor in mediating associative learning underlying fear extinction, using the selective D2 antagonist raclopride. Methods Raclopride was administered systemically or infused into IL prior to fear extinction, and extinction retention was tested the following day. Rats were also prepared for single unit recording in IL to assess the effect of raclopride on firing properties. Results We found that systemic injection of raclopride given prior to extinction impaired retrieval of extinction when tested drug free the next day, but also induced catalepsy during extinction training. To determine whether impaired extinction was due to impaired motor function or disruption of extinction consolidation, we infused raclopride directly into IL. Raclopride infused immediately before extinction training did not produce motor deficits, but impaired recall of extinction when tested drug free. Furthermore, in animals that underwent extinction training, systemic raclopride reduced the tone responsiveness of IL neurons in layers 5/6, with no changes in average firing rate. Conclusion We suggest that D2 receptors facilitate extinction by increasing the signal-to-noise of IL neurons that consolidate extinction. PMID:20926066

  18. 26 CFR 1.1244(d)-2 - Increases in basis of section 1244 stock.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Increases in basis of section 1244 stock. 1... Losses § 1.1244(d)-2 Increases in basis of section 1244 stock. (a) In general. If subsequent to the time... the basis of section 1244 stock, such increase shall be treated as allocable to stock which is...

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

    SciTech Connect

    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 (/sup 3/H)DA, modulation of (/sup 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 (/sup 3/H)spiperone binding assays. 31 references, 2 figures, 1 table.

  20. Immersive Input Display Device (I2D2) for tactical information viewing

    NASA Astrophysics Data System (ADS)

    Tremper, David E.; Burnett, Kevin P.; Malloy, Andrew R.; Wert, Robert

    2006-05-01

    Daylight readability of hand-held displays has been an ongoing issue for both commercial and military applications. In an effort to reduce the effects of ambient light on the readability of military displays, the Naval Research Laboratory (NRL) began investigating and developing advanced hand-held displays. Analysis and research of display technologies with consideration for vulnerability to environmental conditions resulted in the complete design and fabrication of the hand-held Immersive Input Display Device (I2D2) monocular. The I2D2 combines an Organic Light Emitting Diode (OLED) SVGA+ micro-display developed by eMagin Corporation with an optics configuration inside a cylindrical housing. A rubber pressure-eyecup allows view ability only when the eyecup is depressed, eliminating light from both entering and leaving the device. This feature allows the I2D2 to be used during the day, while not allowing ambient light to affect the readability. It simultaneously controls light leakage, effectively eliminating the illumination, and thus preserving the tactical position, of the user in the dark. This paper will examine the characteristics and introduce the design of the I2D2.