Science.gov

Sample records for medium-sized spiny neurons

  1. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens.

    PubMed

    Gangarossa, Giuseppe; Espallergues, Julie; de Kerchove d'Exaerde, Alban; El Mestikawy, Salah; Gerfen, Charles R; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2013-01-01

    The nucleus accumbens (NAc) is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs) constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP) or the Cre-recombinase (Cre) under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific extracellular signal-regulated kinase (ERK) phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist), quinpirole (a D2 receptors (D2R)-like agonist), apomorphine (a non-selective DA receptor agonist), raclopride (a D2R-like antagonist), and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.

  2. A model of dopamine regulation of glutamatergic synapse on medium size spiny neurons.

    PubMed

    Di Maio, Vito; Ventriglia, Francesco; Santillo, Silvia

    2016-01-01

    Spiny neurons of striatum receive glutamatergic synapses on dendritic spines on the neck of which project dopaminergic synapses. Dopamine modulates, by D1 type receptors, the glutamatergic synapses by inducing the phosphorylation of AMPA and NMDA receptors which produces an increased amplitude response. Herein we present a model where, in addition to phosphorylation, the direct modulation by dopamine of the spine resistance can cooperate in producing the observed effect on some of these synapses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in BAC transgenic mice.

    PubMed

    Matamales, Miriam; Bertran-Gonzalez, Jesus; Salomon, Lucas; Degos, Bertrand; Deniau, Jean-Michel; Valjent, Emmanuel; Hervé, Denis; Girault, Jean-Antoine

    2009-01-01

    Precise identification of neuronal populations is a major challenge in neuroscience. In the striatum, more than 95% of neurons are GABAergic medium-sized spiny neurons (MSNs), which form two intermingled populations distinguished by their projections and protein content. Those expressing dopamine D(1)-receptors (D1Rs) project preferentially to the substantia nigra pars reticulata (SNr), whereas those expressing dopamine D(2)- receptors (D2Rs) project preferentially to the lateral part of the globus pallidus (LGP). The degree of segregation of these populations has been a continuous subject of debate, and the recent introduction of bacterial artificial chromosome (BAC) transgenic mice expressing fluorescent proteins driven by specific promoters was a major progress to facilitate striatal neuron identification. However, the fraction of MSNs labeled in these mice has been recently called into question, casting doubt on the generality of results obtained with such approaches. Here, we performed an in-depth quantitative analysis of striatal neurons in drd1a-EGFP and drd2-EGFP mice. We first quantified neuronal and non-neuronal populations in the striatum, based on nuclear staining with TO-PRO-3, and immunolabeling for NeuN, DARPP-32 (dopamine- and cAMP-regulated phosphoprotein Mr approximately 32,000), and various markers for interneurons. TO-PRO-3 staining was sufficient to identify MSNs by their typical nuclear morphology and, with a good probability, interneuron populations. In drd1a-EGFP/drd2-EGFP double transgenic mice all MSNs expressed EGFP, which was driven in about half of them by drd1a promoter. Retrograde labeling showed that all MSNs projecting to the SNr expressed D1R and very few D2R (<1%). In contrast, our results were compatible with the existence of some D1R-EGFP-expressing fibers giving off terminals in the LGP. Thus, our study shows that nuclear staining is a simple method for identifying MSNs and other striatal neurons. It also unambiguously confirms

  4. Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons.

    PubMed

    Delli Carri, Alessia; Onorati, Marco; Lelos, Mariah J; Castiglioni, Valentina; Faedo, Andrea; Menon, Ramesh; Camnasio, Stefano; Vuono, Romina; Spaiardi, Paolo; Talpo, Francesca; Toselli, Mauro; Martino, Gianvito; Barker, Roger A; Dunnett, Stephen B; Biella, Gerardo; Cattaneo, Elena

    2013-01-15

    Medium-sized spiny neurons (MSNs) are the only neostriatum projection neurons, and their degeneration underlies some of the clinical features of Huntington's disease. Using knowledge of human developmental biology and exposure to key neurodevelopmental molecules, human pluripotent stem (hPS) cells were induced to differentiate into MSNs. In a feeder-free adherent culture, ventral telencephalic specification is induced by BMP/TGFβ inhibition and subsequent SHH/DKK1 treatment. The emerging FOXG1(+)/GSX2(+) telencephalic progenitors are then terminally differentiated, resulting in the systematic line-independent generation of FOXP1(+)/FOXP2(+)/CTIP2(+)/calbindin(+)/DARPP-32(+) MSNs. Similar to mature MSNs, these neurons carry dopamine and A2a receptors, elicit a typical firing pattern and show inhibitory postsynaptic currents, as well as dopamine neuromodulation and synaptic integration ability in vivo. When transplanted into the striatum of quinolinic acid-lesioned rats, hPS-derived neurons survive and differentiate into DARPP-32(+) neurons, leading to a restoration of apomorphine-induced rotation behavior. In summary, hPS cells can be efficiently driven to acquire a functional striatal fate using an ontogeny-recapitulating stepwise method that represents a platform for in vitro human developmental neurobiology studies and drug screening approaches.

  5. L-Phosphinothricin modulation of inwardly rectifying K(+) channels increased excitability in striatal medium-sized spiny neurons.

    PubMed

    Domingos, Laetitia; Desrus, Agnès; Même, Sandra; Même, William

    2016-07-01

    Phosphinotricin (L-PPT) is the active compound of a broad-spectrum herbicide. Acute poisoning with L-PPT has various clinical manifestations, including seizures and convulsions. However, the exact mechanism of L-PPT toxicity remains unclear. The present study addressed the role of L-PPT, in the excitability of striatal medium-sized spiny neurons (MSNs). In whole-cell current-clamp experiments, L-PPT increased the input resistance (Ri), decreased the rheobase and increased the firing frequency of action potentials. In voltage-clamp experiments, L-PPT inhibited the inward-rectifying potassium (Kir) currents. Finally, the effects of L-PPT mimicked the inhibition of Kir channels with Ba(2+) on neuronal excitability. Altogether, these results suggest that the herbicide L-PPT is a modulator of Kir channels in MSNs. Thereby, Kir channels are potent regulators of the excitability of MSNs and reduced open probability of these channels would generate a powerful upregulation of neuronal output. This effect may represent a possible mechanism for L-PPT dependent neuronal toxicity.

  6. Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum.

    PubMed

    Doig, Natalie M; Moss, Jonathan; Bolam, J Paul

    2010-11-03

    The striatum receives major excitatory inputs from the cortex and thalamus that predominantly target the spines of medium-sized spiny neurons (MSNs). We aimed to determine whether there is any selectivity of these two excitatory afferents in their innervation of direct and indirect pathway MSNs. To address this, we used bacterial artificial chromosome transgenic mice, in which enhanced green fluorescent protein (EGFP) reports the presence of D(1) or D(2) dopamine receptor subtypes, markers of direct and indirect pathway MSNs, respectively. Excitatory afferents were identified by the selective expression of vesicular glutamate transporter type 1 (VGluT1) by corticostriatal afferents and vesicular glutamate transporter type 2 (VGluT2) by thalamostriatal afferents. A quantitative electron microscopic analysis was performed on striatal tissue from D(1) and D(2) mice that was double immunolabeled to reveal the EGFP and VGluT1 or VGluT2. We found that the proportion of synapses formed by terminals derived from the cortex and thalamus was similar for both direct and indirect pathway MSNs. Furthermore, qualitative analysis revealed that individual cortical or thalamic terminals form synapses with both direct and indirect pathway MSNs. Similarly, we observed a convergence of cortical and thalamic inputs onto individual MSNs of both direct and indirect pathway: individual EGFP-positive structures received input from both VGluT2-positive and VGluT2-negative terminals. These findings demonstrate that direct and indirect pathway MSNs are similarly innervated by cortical and thalamic afferents; both projections are thus likely to be critical in the control of MSNs and hence play fundamental roles in the expression of basal ganglia function.

  7. Altered excitatory and inhibitory inputs to striatal medium-sized spiny neurons and cortical pyramidal neurons in the Q175 mouse model of Huntington's disease.

    PubMed

    Indersmitten, Tim; Tran, Conny H; Cepeda, Carlos; Levine, Michael S

    2015-04-01

    The Q175 knockin mouse model of Huntington's disease (HD) carries a CAG trinucleotide expansion of the human mutant huntingtin allele in its native mouse genomic context and recapitulates the genotype more closely than transgenic models. In this study we examined the progression of changes in intrinsic membrane properties and excitatory and inhibitory synaptic transmission, using whole cell patch-clamp recordings of medium-sized spiny neurons (MSNs) in the dorsolateral striatum and cortical pyramidal neurons (CPNs) in layers 2/3 of the primary motor cortex in brain slices from heterozygous (Q175(+/-)) and homozygous (Q175(+/+)) mice. Input resistance in MSNs from Q175(+/+) and Q175(+/-) mice was significantly increased compared with wild-type (WT) littermates beginning at 2 mo. Furthermore, the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) was significantly reduced in MSNs from Q175(+/+) and Q175(+/-) mice compared with WTs beginning at 7 mo. In contrast, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and IPSC-to-EPSC ratios were increased in MSNs from Q175(+/+) mice beginning at 2 mo. Morphologically, significant decreases in spine density of MSNs from Q175(+/-) and Q175(+/+) mice occurred at 7 and 12 mo. In CPNs, sIPSC frequencies and IPSC-to-EPSC ratios were significantly increased in Q175(+/-) mice compared with WTs at 12 mo. There were no changes in intrinsic membrane properties or morphology. In summary, we show a number of alterations in electrophysiological and morphological properties of MSNs in Q175 mice that are similar to other HD mouse models. However, unlike other models, CPN inhibitory activity is increased in Q175(+/-) mice, indicating reduced cortical excitability.

  8. PKA-dependent phosphorylation of ribosomal protein S6 does not correlate with translation efficiency in striatonigral and striatopallidal medium-sized spiny neurons.

    PubMed

    Biever, Anne; Puighermanal, Emma; Nishi, Akinori; David, Alexandre; Panciatici, Claire; Longueville, Sophie; Xirodimas, Dimitris; Gangarossa, Giuseppe; Meyuhas, Oded; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2015-03-11

    Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is phosphorylated on several residues in response to numerous stimuli. Although commonly used as a marker for neuronal activity, its upstream mechanisms of regulation are poorly studied and its role in protein synthesis remains largely debated. Here, we demonstrate that the psychostimulant d-amphetamine (d-amph) markedly increases rpS6 phosphorylation at Ser235/236 sites in both crude and synaptoneurosomal preparations of the mouse striatum. This effect occurs selectively in D1R-expressing medium-sized spiny neurons (MSNs) and requires the cAMP/PKA/DARPP-32/PP-1 cascade, whereas it is independent of mTORC1/p70S6K, PKC, and ERK signaling. By developing a novel assay to label nascent peptidic chains, we show that the rpS6 phosphorylation induced in striatonigral MSNs by d-amph, as well as in striatopallidal MSNs by the antipsychotic haloperidol or in both subtypes by papaverine, is not correlated with the translation of global or 5' terminal oligopyrimidine tract mRNAs. Together, these results provide novel mechanistic insights into the in vivo regulation of the post-translational modification of rpS6 in the striatum and point out the lack of a relationship between PKA-dependent rpS6 phosphorylation and translation efficiency.

  9. Drug-primed reinstatement of cocaine seeking in mice: increased excitability of medium-sized spiny neurons in the nucleus accumbens.

    PubMed

    Ma, Yao-Ying; Henley, Sandy M; Toll, Jeff; Jentsch, James D; Evans, Christopher J; Levine, Michael S; Cepeda, Carlos

    2013-10-02

    To examine the mechanisms of drug relapse, we first established a model for cocaine IVSA (intravenous self-administration) in mice, and subsequently examined electrophysiological alterations of MSNs (medium-sized spiny neurons) in the NAc (nucleus accumbens) before and after acute application of cocaine in slices. Three groups were included: master mice trained by AL (active lever) pressings followed by IV (intravenous) cocaine delivery, yoked mice that received passive IV cocaine administration initiated by paired master mice, and saline controls. MSNs recorded in the NAc shell in master mice exhibited higher membrane input resistances but lower frequencies and smaller amplitudes of sEPSCs (spontaneous excitatory postsynaptic currents) compared with neurons recorded from saline control mice, whereas cells in the NAc core had higher sEPSCs frequencies and larger amplitudes. Furthermore, sEPSCs in MSNs of the shell compartment displayed longer decay times, suggesting that both pre- and postsynaptic mechanisms were involved. After acute re-exposure to a low-dose of cocaine in vitro, an AP (action potential)-dependent, persistent increase in sEPSC frequency was observed in both NAc shell and core MSNs from master, but not yoked or saline control mice. Furthermore, re-exposure to cocaine induced membrane hyperpolarization, but concomitantly increased excitability of MSNs from master mice, as evidenced by increased membrane input resistance, decreased depolarizing current to generate APs, and a more negative Thr (threshold) for firing. These data demonstrate functional differences in NAc MSNs after chronic contingent versus non-contingent IV cocaine administration in mice, as well as synaptic adaptations of MSNs before and after acute re-exposure to cocaine. Reversing these functional alterations in NAc could represent a rational target for the treatment of some reward-related behaviors, including drug addiction.

  10. Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington's Disease Mice.

    PubMed

    Botelho, Eliã P; Wang, Elizabeth; Chen, Jane Y; Holley, Sandra; Andre, Veronique; Cepeda, Carlos; Levine, Michael S

    2014-05-01

    Huntington's disease (HD) is a late-onset, slowly progressing neurodegenerative disorder caused by an expansion of glutamine repeats. The YAC128 mouse model has been widely used to study the progression of HD symptoms, but little is known about synaptic alterations in very old animals. The present experiments examined synaptic properties of striatal medium-sized spiny neurons (MSNs) in 16 month-old YAC128 mice. These mice were crossed with mice expressing enhanced green fluorescent protein (EGFP) under the control of either D1 or D2 dopamine receptor promoters to identify MSNs originating the direct and indirect pathways, respectively. The input-output curves of evoked excitatory postsynaptic currents mediated by activation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors were reduced in MSNs in both pathways. In the presence of DL-threo-β-Benzyloxyaspartic acid (DL-TBOA), a glutamate transporter blocker used to increase activation of extrasynaptic receptors, NMDA receptor-mediated currents displayed altered amplitudes, longer decay times, and greater charge (response areas) in both direct and indirect pathway MSNs in YAC128 mice compared to wildtype controls. Amplitudes were significantly increased, primarily in direct pathway MSNs while normalized areas were significantly increased only in indirect pathway MSNs, suggesting that the two types of MSNs are affected in different ways. It may be that indirect pathway neurons are more susceptible to changes in glutamate transport. Taken together, the present findings demonstrate differential alterations in synaptic versus extrasynaptic NMDA receptors in both direct and indirect pathway MSNs in late HD, which may contribute to the dysfunction and degeneration in both pathways.

  11. Regional and cell-type-specific effects of DAMGO on striatal D1 and D2 dopamine receptor-expressing medium-sized spiny neurons.

    PubMed

    Ma, Yao-Ying; Cepeda, Carlos; Chatta, Payush; Franklin, Lana; Evans, Christopher J; Levine, Michael S

    2012-03-08

    The striatum can be divided into the DLS (dorsolateral striatum) and the VMS (ventromedial striatum), which includes NAcC (nucleus accumbens core) and NAcS (nucleus accumbens shell). Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons) based on their location, expression of DA (dopamine) D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala(2)-MePhe(4)-Gly(ol)(5)]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS. RMPs (resting membrane potentials) were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials). Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

  12. Three-dimensional organization of dendrites and local axon collaterals of shell and core medium-sized spiny projection neurons of the rat nucleus accumbens.

    PubMed

    van Dongen, Yvette C; Mailly, Philippe; Thierry, Anne-Marie; Groenewegen, Henk J; Deniau, Jean-Michel

    2008-09-01

    Medium-sized spiny projection neurons (MSN) in the head of the primate caudate nucleus are thought to have preferred dendritic orientations that tend to parallel the orientations of the striosomes. Moreover, recurrent axon collaterals of MSN in the rat dorsal striatum have been categorized into two types, i.e., restricted and widespread. The nucleus accumbens (Acb) has a highly complex compartmental organization, and the spatial organization of dendritic and axonal arbors of MSN has not yet been systematically studied. In this study, using single-cell juxtacellular labeling with neurobiotin as well as anterograde neuroanatomical tracing with biotinylated dextran amine, we investigated the three-dimensional (3D) organization of dendrites and axons of MSN of the rat Acb in relation to subregional (shell-core) and compartmental (patch-matrix) boundaries. Our results show that dendritic arbors of MSN in both the Acb shell and core subregions are preferentially oriented, i.e., they are flattened in at least one of the 3D-planes. The preferred orientations are influenced by shell-core and patch-matrix boundaries, suggesting parallel and independent processing of information. Dendritic orientations of MSN of the Acb core are more heterogeneous than those of the shell and the dorsal striatum, suggesting a more complex distribution of striatal inputs within the core. Although dendrites respect the shell-core and patch-matrix boundaries, recurrent axon collaterals may cross these boundaries. Finally, different degrees of overlap between dendritic and axonal arborizations of individual MSN were identified, suggesting various possibilities of lateral inhibitory interactions within and between, functionally distinct territories of the Acb.

  13. Spatial distribution of D1R- and D2R-expressing medium-sized spiny neurons differs along the rostro-caudal axis of the mouse dorsal striatum.

    PubMed

    Gangarossa, Giuseppe; Espallergues, Julie; Mailly, Philippe; De Bundel, Dimitri; de Kerchove d'Exaerde, Alban; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel; Krieger, Patrik

    2013-01-01

    The striatum projection neurons are striatonigral and striatopallidal medium-sized spiny neurons (MSNs) that preferentially express D1 (D1R) and D2 (D2R) dopamine receptors, respectively. It is generally assumed that these neurons are physically intermingled, without cytoarchitectural organization although this has not been tested. To address this question we used BAC transgenic mice expressing enhanced green fluorescence (EGFP) under the control of Drd1a or Drd2 promoter and spatial point pattern statistics. We demonstrate that D1R- and D2R-expressing MSNs are randomly distributed in most of the dorsal striatum, whereas a specific region in the caudal striatum, adjacent to the GPe, lacks neurons expressing markers for indirect pathway neurons. This area comprises almost exclusively D1R-expressing MSNs. These neurons receive excitatory inputs from the primary auditory cortex and the medial geniculate thalamic nucleus and a rich dopamine innervation. This area contains cholinergic and GABAergic interneurons but apparently no D2R/A2aR modulation because no fluorescence was detected in the neuropil of Drd2-EGFP or Drd2-Cre, and Adora-Cre BAC transgenic mice crossed with reporter mice. This striatal area that expresses calbindin D28k, VGluT1 and 2, is poor in μ opiate receptors and preproenkephalin. Altogether, the differences observed in D1R-MSNs, D2R-MSNs, and interneurons densities, as well as the anatomical segregation of D1R- and D2R/A2aR-expressing MSNs suggest that there are regional differences in the organization of the striatum.

  14. Functional connectome of the striatal medium spiny neuron.

    PubMed

    Chuhma, Nao; Tanaka, Kenji F; Hen, René; Rayport, Stephen

    2011-01-26

    Dopamine system disorders ranging from movement disorders to addiction and schizophrenia involve striatal medium spiny neurons (MSNs), yet their functional connectivity has been difficult to determine comprehensively. We generated a mouse with conditional channelrhodopsin-2 expression restricted to medium spiny neurons and assessed the specificity and strength of their intrinsic connections in the striatum and their projections to the globus pallidus and the substantia nigra. In the striatum, medium spiny neurons connected with other MSNs and tonically active cholinergic interneurons, but not with fast-spiking GABA interneurons. In the globus pallidus, medium spiny neurons connected strongly with one class of electrophysiologically identified neurons, but weakly with the other. In the substantia nigra, medium spiny neurons connected strongly with GABA, but not with dopamine neurons. Projections to the globus pallidus showed solely D2-mediated presynaptic inhibition, whereas projections to the substantia nigra showed solely D1-mediated presynaptic facilitation. This optogenetic approach defines the functional connectome of the striatal medium spiny neuron.

  15. Fractional Cable Models for Spiny Neuronal Dendrites

    NASA Astrophysics Data System (ADS)

    Henry, B. I.; Langlands, T. A. M.; Wearne, S. L.

    2008-03-01

    Cable equations with fractional order temporal operators are introduced to model electrotonic properties of spiny neuronal dendrites. These equations are derived from Nernst-Planck equations with fractional order operators to model the anomalous subdiffusion that arises from trapping properties of dendritic spines. The fractional cable models predict that postsynaptic potentials propagating along dendrites with larger spine densities can arrive at the soma faster and be sustained at higher levels over longer times. Calibration and validation of the models should provide new insight into the functional implications of altered neuronal spine densities, a hallmark of normal aging and many neurodegenerative disorders.

  16. Detection of phasic dopamine by D1 and D2 striatal medium spiny neurons.

    PubMed

    Yapo, Cedric; Nair, Anu G; Clement, Lorna; Castro, Liliana R; Hellgren Kotaleski, Jeanette; Vincent, Pierre

    2017-08-07

    Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall

  17. Huntington's disease and the striatal medium spiny neuron: cell-autonomous and non-cell-autonomous mechanisms of disease.

    PubMed

    Ehrlich, Michelle E

    2012-04-01

    Huntington's disease is an autosomal dominant disorder caused by a mutation in the gene encoding the protein huntingtin on chromosome 4. The mutation is an expanded CAG repeat in the first exon, encoding a polyglutamine tract. If the polyglutamine tract is > 40, penetrance is 100% and death is inevitable. Despite the widespread expression of huntingtin, HD has long been considered primarily as a disease of the striatum. It is characterized by selective vulnerability with dysfunction followed by death of the medium size spiny neuron. Considerable effort is being expended to determine whether striatal damage is cell-autonomous, non-cell-autonomous, requiring cell-cell and region to region communication, or both. We review data supporting both mechanisms. We also attempt to organize the data into common mechanisms that may arise outside the medium, spiny neuron, but ultimately have their greatest impact in the striatum.

  18. Striatal plasticity and medium spiny neuron dendritic remodeling in parkinsonism.

    PubMed

    Deutch, Ariel Y; Colbran, Roger J; Winder, Danny J

    2007-01-01

    Current approaches to Parkinson's Disease (PD) are largely based on our current understanding of the mechanisms that contribute to the death of nigrostriatal dopamine neurons. However, our understanding of the consequences of the loss of dopamine on the striatal target cells of nigrostriatal neurons is much less advanced. In particular, the compensatory changes that occur in striatal medium spiny neurons (MSNs) that have lost their normal dopamine input remains poorly understood. The compensatory changes may have either positive or negative effects. Among the alterations that occur in striatal cells of the dopamine-denervated striatum are dystrophic changes in the dendrites of MSNs, with a loss of dendritic length and dendritic spine number. Dendritic spines are the targets of convergent nigrostriatal dopamine and corticostriatal glutamate axons, and integrate these convergent signals to determine the nature of striatal output. The loss of these spines in the dopamine-denervated state may protect the MSN from overt excitotoxic death, but at the price of compromising MSN function. The loss of dendritic spines is thought be responsible for the gradual decrease in levodopa efficacy in late-stage PD, suggesting that therapeutic interventions need to be developed that target key downstream signaling complexes in medium spiny neurons.

  19. Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

    PubMed Central

    Andjelic, Sofija; Gallopin, Thierry; Cauli, Bruno; Hill, Elisa L.; Roux, Lisa; Badr, Sammy; Hu, Emilie; Tamás, Gábor; Lambolez, Bertrand

    2009-01-01

    The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity. PMID:19052106

  20. Glutamatergic nonpyramidal neurons from neocortical layer VI and their comparison with pyramidal and spiny stellate neurons.

    PubMed

    Andjelic, Sofija; Gallopin, Thierry; Cauli, Bruno; Hill, Elisa L; Roux, Lisa; Badr, Sammy; Hu, Emilie; Tamás, Gábor; Lambolez, Bertrand

    2009-02-01

    The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription-polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

  1. Nitric oxide regulates synaptic transmission between spiny projection neurons.

    PubMed

    Sagi, Yotam; Heiman, Myriam; Peterson, Jayms D; Musatov, Sergei; Scarduzio, Mariangela; Logan, Stephen M; Kaplitt, Michael G; Surmeier, Dalton J; Heintz, Nathaniel; Greengard, Paul

    2014-12-09

    Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection.

  2. Opioid self-administration results in cell-type specific adaptations of striatal medium spiny neurons.

    PubMed

    James, Alex S; Chen, Jane Y; Cepeda, Carlos; Mittal, Nitish; Jentsch, James David; Levine, Michael S; Evans, Christopher J; Walwyn, Wendy

    2013-11-01

    Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters. Mice learned to self-administer 0.1mg/kg/infusion of the opioid remifentanil during 2h sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1- and D2-MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (μOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors.

  3. Opioid self-administration results in cell-type specific adaptations of striatal medium spiny neurons

    PubMed Central

    James, Alex S.; Chen, Jane Y.; Cepeda, Carlos; Mittal, Nitish; Jentsch, James David; Levine, Michael S.; Evans, Christopher J.; Walwyn, Wendy

    2013-01-01

    Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing Green Fluorescent Protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters and trained to self-administer the opioid remifentanil. D1- and D2-GFP mice learned to self-administer 0.1 mg/kg/infusion remifentanil during 2hr sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1 and D2 MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (µOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors. PMID:23968589

  4. The underside of the cerebral cortex: layer V/VI spiny inverted neurons

    PubMed Central

    Mendizabal-Zubiaga, Juan L; Reblet, Concepcion; Bueno-Lopez, Jose L

    2007-01-01

    This paper presents an account of past and current research on spiny inverted neurons – alternatively also known as ‘inverted pyramidal neurons’– in rats, rabbits and cats. In our laboratory, we have studied these cells with a battery of techniques suited for light and electron microscopy, including Nissl staining, Golgi impregnation, dye intracellular filling and axon retrograde track-tracing. Our results show that spiny inverted neurons make up less than 8.5 and 5.5% of all cortical neurons in the primary and secondary rabbit visual cortex, respectively. Infragranular spiny inverted neurons constitute 15 and 8.5% of infragranular neurons in the same animal and areas. Spiny inverted neurons congregate at layers V–VI in all studied species. Studies have also revealed that spiny inverted neurons are excitatory neurons which furnish axons for various cortico-cortical, cortico-claustral and cortico-striatal projections, but not for non-telencephalic centres such as the lateral and medial geniculate nuclei, the colliculi or the pons. As a group, each subset of inverted cells contributing to a given projection is located below the pyramidal neurons whose axons furnish the same centre. Spiny inverted neurons are particularly conspicuous as a source of the backward cortico-cortical projection to primary visual cortex and from this to the claustrum. Indeed, they constitute up to 82% of the infragranular cells that furnish these projections. Spiny inverted neurons may be classified into three subtypes according to the point of origin of the axon on the cell: the somatic basal pole which faces the cortical outer surface, the somatic flank and the reverse apical dendrite. As seen with electron microscopy, the axon initial segments of these subtypes are distinct from one another, not only in length and thickness, but also in the number of received synaptic boutons. All of these anatomical features together may support a synaptic-input integration which is peculiar to

  5. Fractional cable model for signal conduction in spiny neuronal dendrites

    NASA Astrophysics Data System (ADS)

    Vitali, Silvia; Mainardi, Francesco

    2017-06-01

    The cable model is widely used in several fields of science to describe the propagation of signals. A relevant medical and biological example is the anomalous subdiffusion in spiny neuronal dendrites observed in several studies of the last decade. Anomalous subdiffusion can be modelled in several ways introducing some fractional component into the classical cable model. The Chauchy problem associated to these kind of models has been investigated by many authors, but up to our knowledge an explicit solution for the signalling problem has not yet been published. Here we propose how this solution can be derived applying the generalized convolution theorem (known as Efros theorem) for Laplace transforms. The fractional cable model considered in this paper is defined by replacing the first order time derivative with a fractional derivative of order α ∈ (0, 1) of Caputo type. The signalling problem is solved for any input function applied to the accessible end of a semi-infinite cable, which satisfies the requirements of the Efros theorem. The solutions corresponding to the simple cases of impulsive and step inputs are explicitly calculated in integral form containing Wright functions. Thanks to the variability of the parameter α, the corresponding solutions are expected to adapt to the qualitative behaviour of the membrane potential observed in experiments better than in the standard case α = 1.

  6. Optimal balance of the striatal medium spiny neuron network.

    PubMed

    Ponzi, Adam; Wickens, Jeffery R

    2013-04-01

    Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of 10 ~ 20% and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around 15% connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics - it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is

  7. Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA synapses in vitro

    PubMed Central

    Geldwert, Daron; Norris, J Madison; Feldman, Igor G; Schulman, Joshua J; Joyce, Myra P; Rayport, Stephen

    2006-01-01

    Background The striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make autaptic connections that provide access to single, identified medium-spiny to medium-spiny neuron synaptic connections. Results We examined medium-spiny neuron autaptic connections in postnatal cultures from the nucleus accumbens, the ventral part of the striatal complex. These connections were subject to presynaptic dopamine modulation. D1-like receptors mediated either inhibition or facilitation, while D2-like receptors predominantly mediated inhibition. Many connections showed both D1 and D2 modulation, consistent with a significant functional colocalization of D1 and D2-like receptors at presynaptic sites. These same connections were subject to GABAA, GABAB, norepinephrine and serotonin modulation, revealing a multiplicity of modulatory autoreceptors and heteroreceptors on individual varicosities. In some instances, autaptic connections had two components that were differentially modulated by dopamine agonists, suggesting that dopamine receptors could be distributed heterogeneously on the presynaptic varicosities making up a single synaptic (i.e. autaptic) connection. Conclusion Differential trafficking of dopamine receptors to different presynaptic varicosities could explain the many controversial studies reporting widely varying degrees of dopamine receptor colocalization in medium-spiny neurons, as well as more generally the diversity of dopamine actions in target areas. Longer-term changes in the modulatory actions of dopamine in the striatal complex could be due to plasticity in the presynaptic distribution of dopamine receptors on medium-spiny neuron varicosities. PMID:16813648

  8. Morphology of spiny neurons in the human entorhinal cortex: intracellular filling with lucifer yellow.

    PubMed

    Mikkonen, M; Pitkänen, A; Soininen, H; Alafuzoff, I; Miettinen, R

    2000-01-01

    The present study was designed to investigate the morphology of spiny neurons in the human entorhinal cortex. Coronal entorhinal slices (n = 67; 200 microm thick) were obtained from autopsies of three subjects. Spiny neurons (n = 132) filled with Lucifer Yellow were analysed in different subfields and layers of the entorhinal cortex. Based on the shape of the somata and primary dendritic trees, spiny neurons were divided into four morphological categories; (i) classical pyramidal, (ii) stellate, (iii) modified stellate, and (iv) horizontal tripolar cells. The morphology of filled neurons varied more in different layers than in the different subfields of the entorhinal cortex. In layer II, the majority (81%) of spiny neurons had stellate or modified stellate morphology, but in the rostromedial subfields (olfactory subfield and rostral subfield) there were also horizontal tripolar neurons. Dendritic branches of layer II neurons extended to layer I (94%) and to layer III (83%). Unlike in layer II, most (74%) of the filled neurons in layers III, V and VI were classical pyramidal cells. The majority of pyramidal cells in the superficial portion of layer III had dendrites that extended up to layer II, occupying the space between the neuronal clusters. Some dendrites reached down to the deep portion of layer III. Apical dendrites of layer V and VI pyramidal cells traveled up to the deep portion of layer III.Our data indicate that the morphology of spiny neurons in different layers of the human entorhinal cortex is variable. Vertical extension of dendritic branches to adjacent layers supports the idea that inputs terminating in a specific lamina influence target cells located in various entorhinal layers. There appears to be more overlap in the dendritic fields between superficial layers II and III than between the superficial (II/III) and deep (V/VI) layers, thus supporting the idea of segregation of information flow targeted to the superficial or deep layers in the human

  9. MEF-2 regulates activity-dependent spine loss in striatopallidal medium spiny neurons.

    PubMed

    Tian, Xinyong; Kai, Li; Hockberger, Philip E; Wokosin, David L; Surmeier, D James

    2010-05-01

    Striatal dopamine depletion profoundly reduces the density of spines and corticostriatal glutamatergic synapses formed on D(2) dopamine receptor expressing striatopallidal medium spiny neurons, leaving D(1) receptor expressing striatonigral medium spiny neurons relatively intact. Because D(2) dopamine receptors diminish the excitability of striatopallidal MSNs, the pruning of synapses could be a form of homeostatic plasticity aimed at restoring activity into a preferred range. To characterize the homeostatic mechanisms controlling synapse density in striatal medium spiny neurons, striatum from transgenic mice expressing a D(2) receptor reporter construct was co-cultured with wild-type cerebral cortex. Sustained depolarization of these co-cultures induced a profound pruning of glutamatergic synapses and spines in striatopallidal medium spiny neurons. This pruning was dependent upon Ca(2+) entry through Cav1.2 L-type Ca(2+) channels, activation of the Ca(2+)-dependent protein phosphatase calcineurin and up-regulation of myocyte enhancer factor 2 (MEF2) transcriptional activity. Depolarization and MEF2 up-regulation increased the expression of two genes linked to synaptic remodeling-Nur77 and Arc. Taken together, these studies establish a translational framework within which striatal adaptations linked to the symptoms of Parkinson's disease can be explored.

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  11. MEF-2 regulates activity-dependent spine loss in striatopallidal medium spiny neurons

    PubMed Central

    Tian, Xinyong; Kai, Li; Hockberger, Philip E.; Wokosin, David L.; Surmeier, D. James

    2010-01-01

    Striatal dopamine depletion profoundly reduces the density of spines and corticostriatal glutamatergic synapses formed on D2 dopamine receptor expressing striatopallidal medium spiny neurons, leaving D1 receptor expressing striatonigral medium spiny neurons relatively intact. Because D2 dopamine receptors diminish the excitability of striatopallidal MSNs, the pruning of synapses could be a form of homeostatic plasticity aimed at restoring activity into a preferred range. To characterize the homeostatic mechanisms controlling synapse density in striatal medium spiny neurons, striatum from transgenic mice expressing a D2 receptor reporter construct was co-cultured with wild-type cerebral cortex. Sustained depolarization of these co-cultures induced a profound pruning of glutamatergic synapses and spines in striatopallidal medium spiny neurons. This pruning was dependent upon Ca2+ entry through Cav1.2 L-type Ca2+ channels, activation of the Ca2+-dependent protein phosphatase calcineurin and up-regulation of myocyte enhancer factor 2 (MEF2) transcriptional activity. Depolarization and MEF2 up-regulation increased the expression of two genes linked to synaptic remodeling – Nur77 and Arc. Taken together, these studies establish a translational framework within with striatal adaptations linked to the symptoms of Parkinson's disease can be explored. PMID:20197093

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  13. Dopaminergic modulation of axon collaterals interconnecting spiny neurons of the rat striatum.

    PubMed

    Guzmán, Jaime N; Hernández, Adán; Galarraga, Elvira; Tapia, Dagoberto; Laville, Antonio; Vergara, Ramiro; Aceves, Jorge; Bargas, José

    2003-10-01

    Dopamine is a critical modulator of striatal function; its absence produces Parkinson's disease. Most cellular actions of dopamine are still unknown. This work describes the presynaptic actions of dopaminergic receptor agonists on GABAergic transmission between neostriatal projection neurons. Axon collaterals interconnect projection neurons, the main axons of which project to other basal ganglia nuclei. Most if not all of these projecting axons pass through the globus pallidus. Thus, we lesioned the intrinsic neurons of the globus pallidus and stimulated neostriatal efferent axons antidromically with a bipolar electrode located in this nucleus. This maneuver revealed a bicuculline-sensitive synaptic current while recording in spiny cells. D1 receptor agonists facilitated whereas D2 receptor agonists depressed this synaptic current. In contrast, a bicuculline-sensitive synaptic current evoked by field stimulation inside the neostriatum was not consistently modulated, in agreement with previous studies. The data are discussed in light of the most recent experimental and modeling results. The conclusion was that inhibition of spiny cells by axon collaterals of other spiny cells is quantitatively important; however, to be functionally important, this inhibition might be conditioned to the synchronized firing of spiny neurons. Finally, dopamine exerts a potentially important role regulating the extent of lateral inhibition.

  14. Somatostatinergic modulation of firing pattern and calcium-activated potassium currents in medium spiny neostriatal neurons.

    PubMed

    Galarraga, E; Vilchis, C; Tkatch, T; Salgado, H; Tecuapetla, F; Perez-Rosello, T; Perez-Garci, E; Hernandez-Echeagaray, E; Surmeier, D J; Bargas, J

    2007-05-11

    Somatostatin is synthesized and released by aspiny GABAergic interneurons of the neostriatum, some of them identified as low threshold spike generating neurons (LTS-interneurons). These neurons make synaptic contacts with spiny neostriatal projection neurons. However, very few somatostatin actions on projection neurons have been described. The present work reports that somatostatin modulates the Ca(2+) activated K(+) currents (K(Ca) currents) expressed by projection cells. These actions contribute in designing the firing pattern of the spiny projection neuron; which is the output of the neostriatum. Small conductance (SK) and large conductance (BK) K(Ca) currents represent between 30% and 50% of the sustained outward current in spiny cells. Somatostatin reduces SK-type K(+) currents and at the same time enhances BK-type K(+) currents. This dual effect enhances the fast component of the after hyperpolarizing potential while reducing the slow component. Somatostatin then modifies the firing pattern of spiny neurons which changed from a tonic regular pattern to an interrupted "stuttering"-like pattern. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) tissue expression analysis of dorsal striatal somatostatinergic receptors (SSTR) mRNA revealed that all five SSTR mRNAs are present. However, single cell RT-PCR profiling suggests that the most probable receptor in charge of this modulation is the SSTR2 receptor. Interestingly, aspiny interneurons may exhibit a "stuttering"-like firing pattern. Therefore, somatostatin actions appear to be the entrainment of projection neurons to the rhythms generated by some interneurons. Somatostatin is then capable of modifying the processing and output of the neostriatum.

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

    PubMed

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

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

  16. Behavioral and transcriptome alterations in male and female mice with postnatal deletion of TrkB in dorsal striatal medium spiny neurons

    PubMed Central

    2013-01-01

    Background The high affinity tyrosine kinase receptor, TrkB, is the primary receptor for brain derived neurotrophic factor (BDNF) and plays an important role in development, maintenance and plasticity of the striatal output medium size spiny neuron. The striatal BDNF/TrkB system is thereby implicated in many physiologic and pathophysiologic processes, the latter including mood disorders, addiction, and Huntington’s disease. We crossed a mouse harboring a transgene directing cre-recombinase expression primarily to postnatal, dorsal striatal medium spiny neurons, to a mouse containing a floxed TrkB allele (fB) mouse designed for deletion of TrkB to determine its role in the adult striatum. Results We found that there were sexually dimorphic alterations in behaviors in response to stressful situations and drugs of abuse. Significant sex and/or genotype differences were found in the forced swim test of depression-like behaviors, anxiety-like behaviors on the elevated plus maze, and cocaine conditioned reward. Microarray analysis of dorsal striatum revealed significant dysregulation in individual and groups of genes that may contribute to the observed behavioral responses and in some cases, represent previously unidentified downstream targets of TrkB. Conclusions The data point to a set of behaviors and changes in gene expression following postnatal deletion of TrkB in the dorsal striatum distinct from those in other brain regions. PMID:24369067

  17. P2Y1 receptor modulation of Ca2+-activated K+ currents in medium-sized neurons from neonatal rat striatal slices

    PubMed Central

    Coppi, E.; Pedata, F.

    2012-01-01

    ATP signaling to neurons and glia in the nervous system occurs via activation of both P2Y and P2X receptors. Here, we investigated the effects of P2Y1 receptor stimulation in developing striatal medium-sized neurons using patch-clamp recordings from acute brain slices of 7- and 28-day-old rats. Application of the selective P2Y1 receptor agonist 2-(Methylthio) ADP trisodium salt (2-MeSADP; 250 nM) increased outward K+ currents evoked by a ramp depolarization protocol in voltage-clamp recordings. This effect was observed in 59 out of 82 cells (72%) and was blocked completely by the P2Y1 antagonist, 2′-deoxy-N6-methyl adenosine 3′,5′-diphosphate. The averaged 2-MeSADP-sensitive conductance was fitted by the sum of a linear conductance and a Boltzmann relation, giving one-half activation voltage of −14.2 mV and an equivalent charge of 2.91. The 2MeSADP-mediated effect was sensitive to submillimolar concentrations of tetraethylammonium (TEA; 200 μM), to 200 nM iberiotoxin and to 100 nM apamin, suggesting the involvement of both big and small potassium (BK and SK, respectively) calcium-activated channels. In current-clamp experiments, 2-MeSADP decreased depolarization-evoked action potential (AP) firing in all 26 cells investigated, and this effect was reversed by TEA and by apamin but not by iberiotoxin. We conclude that the stimulation of P2Y1 receptors in developing striatal neurons leads to activation of calcium-activated potassium channels [IK(Ca)] of both BK and SK subtypes, the latter responsible for decreasing the frequency of AP firing in response to current injection. Therefore, P2Y1 signaling leading to activation of IK(Ca) may be important in regulating the activity of medium-sized neurons in the striatum. PMID:22131374

  18. Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia

    PubMed Central

    Heiman, Myriam; Heilbut, Adrian; Francardo, Veronica; Kulicke, Ruth; Fenster, Robert J.; Kolaczyk, Eric D.; Mesirov, Jill P.; Surmeier, Dalton J.; Cenci, M. Angela; Greengard, Paul

    2014-01-01

    Levodopa treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). Although it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type–specific gene-expression changes that occur in subclasses of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes, the expression of which is correlated with levodopa dose, many of which are under the control of activator protein-1 and ERK signaling. Despite homeostatic adaptations involving several signaling modulators, activator protein-1–dependent gene expression remains highly dysregulated in direct pathway SPNs upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease. PMID:24599591

  19. Severely impaired learning and altered neuronal morphology in mice lacking NMDA receptors in medium spiny neurons.

    PubMed

    Beutler, Lisa R; Eldred, Kiara C; Quintana, Albert; Keene, C Dirk; Rose, Shannon E; Postupna, Nadia; Montine, Thomas J; Palmiter, Richard D

    2011-01-01

    The striatum is composed predominantly of medium spiny neurons (MSNs) that integrate excitatory, glutamatergic inputs from the cortex and thalamus, and modulatory dopaminergic inputs from the ventral midbrain to influence behavior. Glutamatergic activation of AMPA, NMDA, and metabotropic receptors on MSNs is important for striatal development and function, but the roles of each of these receptor classes remain incompletely understood. Signaling through NMDA-type glutamate receptors (NMDARs) in the striatum has been implicated in various motor and appetitive learning paradigms. In addition, signaling through NMDARs influences neuronal morphology, which could underlie their role in mediating learned behaviors. To study the role of NMDARs on MSNs in learning and in morphological development, we generated mice lacking the essential NR1 subunit, encoded by the Grin1 gene, selectively in MSNs. Although these knockout mice appear normal and display normal 24-hour locomotion, they have severe deficits in motor learning, operant conditioning and active avoidance. In addition, the MSNs from these knockout mice have smaller cell bodies and decreased dendritic length compared to littermate controls. We conclude that NMDAR signaling in MSNs is critical for normal MSN morphology and many forms of learning.

  20. Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

    PubMed

    González-Burgos, I; García-Martínez, S; Velázquez-Zamora, D A; Ponce-Rolón, R

    2010-10-01

    Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

  1. Loss of escape-related giant neurons in a spiny lobster, Panulirus argus.

    PubMed

    Espinoza, Sandra Y; Breen, Lana; Varghese, Nisha; Faulkes, Zen

    2006-12-01

    When attacked, many decapod crustaceans perform tailflips, which are triggered by a neural circuit that includes lateral giant interneurons, medial giant interneurons, and fast flexor motor giant neurons (MoGs). Slipper lobsters (Scyllaridae) lack these giant neurons, and it has been hypothesized that behavioral (e.g., digging) and morphological (e.g., flattening and armor) specializations in this group caused the loss of escape-related giant neurons. To test this hypothesis, we examined a species of spiny lobster, Panulirus argus. Spiny lobsters belong to the sister taxon of the scyllarids, but they have a more crayfish-like morphology than scyllarids and were predicted to have escape-related giant neurons. Ventral nerve cords of P. argus were examined using paraffin-embedded sections and cobalt backfills. We found no escape-related giant neurons and no large axon profiles in the dorsal region of the nerve cord of P. argus. Cobalt backfills showed one fewer fast flexor motor neuron than in species with MoGs and none of the fast flexor motor neurons show any of the anatomical specializations of MoGs. This suggests that all palinuran species lack this giant escape circuit, and that the loss of rapid escape behavior preceded, and may have driven, alternative predator avoidance and anti-predator strategies in palinurans.

  2. Increased excitability of medium-sized dorsal root ganglion neurons by prolonged interleukin-1β exposure is K+ channel dependent and reversible

    PubMed Central

    Stemkowski, Patrick L; Noh, Myung-chul; Chen, Yishen; Smith, Peter A

    2015-01-01

    Chronic constriction injury of rat sciatic nerve promotes signs of neuropathic pain. This is associated with an increase in the level of interleukin 1β (IL-1β) in primary afferents that peaks at 7 days. This initial cytokine exposure has been proposed to trigger an enduring alteration in neuronal phenotype that underlies chronic hyper-excitability in sensory nerves, which initiates and maintains chronic neuropathic pain. We have shown previously that 5–6 days of exposure of rat dorsal root ganglia (DRGs) to 100 pm IL-1β increases the excitability of medium-sized neurons. We have now found using whole-cell recording that this increased excitability reverts to control levels within 3–4 days of cytokine removal. The effects of IL-1β were dominated by changes in K+ currents. Thus, the amplitudes of A-current, delayed rectifier and Ca2+-sensitive K+ currents were reduced by ∼68%, ∼64% and ∼36%, respectively. Effects of IL-1β on other cation currents were modest by comparison. There was thus a slight decrease in availability of high voltage-activated Ca2+ channel current, a small increase in rates of activation of hyperpolarization-activated cyclic nucleotide-gated channel current (IH), and a shift in the voltage dependence of activation of tetrodotoxin-sensitive sodium current (TTX-S INa) to more negative potentials. It is unlikely, therefore, that direct interaction of IL-1β with DRG neurons initiates an enduring phenotypic shift in their electrophysiological properties following sciatic nerve injury. Persistent increases in primary afferent excitability following nerve injury may instead depend on altered K+ channel function and on the continued presence of slightly elevated levels IL-1β and other cytokines. PMID:26110238

  3. Striatal plasticity in parkinsonism: dystrophic changes in medium spiny neurons and progression in Parkinson's disease.

    PubMed

    Deutch, A Y

    2006-01-01

    Striatal dopamine loss in Parkinson's Disease (PD) sets into play a variety of compensatory responses to help counter dopamine depletion. Most of these changes involve surviving dopamine neurons, but there are also changes in striatal medium spiny neurons (MSNs), which are the major target of dopamine axons. Among these changes are decreases in MSN dendritic length and spine density, which may dampen excessive corticostriatal glutamatergic drive onto MSNs that occurs secondary to dopamine loss. An increasing knowledge of dendritic changes in PD suggests strategies for tracking progressive worsening of symptoms and is opening new ideas on novel therapeutic strategies for PD.

  4. Muscarinic enhancement of persistent sodium current synchronizes striatal medium spiny neurons.

    PubMed

    Carrillo-Reid, Luis; Tecuapetla, Fatuel; Vautrelle, Nicolas; Hernández, Adán; Vergara, Ramiro; Galarraga, Elvira; Bargas, José

    2009-08-01

    Network dynamics denoted by synchronous firing of neuronal pools rely on synaptic interactions and intrinsic properties. In striatal medium spiny neurons, N-methyl-d-aspartate (NMDA) receptor activation endows neurons with nonlinear capabilities by inducing a negative-slope conductance region (NSCR) in the current-voltage relationship. Nonlinearities underlie associative learning, procedural memory, and the sequential organization of behavior in basal ganglia nuclei. The cholinergic system modulates the function of medium spiny projection neurons through the activation of muscarinic receptors, increasing the NMDA-induced NSCR. This enhancement is reflected as a change in the NMDA-induced network dynamics, making it more synchronous. Nevertheless, little is known about the contribution of intrinsic properties that promote this activity. To investigate the mechanisms underlying the cholinergic modulation of bistable behavior in the striatum, we used whole cell and calcium-imaging techniques. A persistent sodium current modulated by muscarinic receptor activation participated in the enhancement of the NSCR and the increased network synchrony. These experiments provide evidence that persistent sodium current generates bistable behavior in striatal neurons and contributes to the regulation of synchronous network activity. The neuromodulation of bistable properties could represent a cellular and network mechanism for cholinergic actions in the striatum.

  5. New rules governing synaptic plasticity in core nucleus accumbens medium spiny neurons.

    PubMed

    Ji, Xincai; Martin, Gilles E

    2012-12-01

    The nucleus accumbens is a forebrain region responsible for drug reward and goal-directed behaviors. It has long been believed that drugs of abuse exert their addictive properties on behavior by altering the strength of synaptic communication over long periods of time. To date, attempts at understanding the relationship between drugs of abuse and synaptic plasticity have relied on the high-frequency long-term potentiation model of T.V. Bliss & T. Lømo [(1973) Journal of Physiology, 232, 331-356]. We examined synaptic plasticity using spike-timing-dependent plasticity, a stimulation paradigm that reflects more closely the in vivo firing patterns of mouse core nucleus accumbens medium spiny neurons and their afferents. In contrast to other brain regions, the same stimulation paradigm evoked bidirectional long-term plasticity. The magnitude of spike-timing-dependent long-term potentiation (tLTP) changed with the delay between action potentials and excitatory post-synaptic potentials, and frequency, whereas that of spike-timing-dependent long-term depression (tLTD) remained unchanged. We showed that tLTP depended on N-methyl-d-aspartate receptors, whereas tLTD relied on action potentials. Importantly, the intracellular calcium signaling pathways mobilised during tLTP and tLTD were different. Thus, calcium-induced calcium release underlies tLTD but not tLTP. Finally, we found that the firing pattern of a subset of medium spiny neurons was strongly inhibited by dopamine receptor agonists. Surprisingly, these neurons were exclusively associated with tLTP but not with tLTD. Taken together, these data point to the existence of two subgroups of medium spiny neurons with distinct properties, each displaying unique abilities to undergo synaptic plasticity.

  6. Dopamine DARPP-32-Dependent Modulation of Prefrontal Cortical Input and Intercellular Coupling in Mouse Accumbens Spiny and Aspiny Neurons

    PubMed Central

    Onn, S-P; Lin, M; Liu, J; Grace, AA

    2010-01-01

    The roles of DARPP-32 in mediating dopamine (DA)-dependent modulation of corticoaccumbens transmission and intercellular coupling were examined in mouse accumbens (NAC) neurons by both intracellular sharp electrode and whole cell recordings. In wildtype (WT) mice bath application of the D2-like agonist quinpirole resulted in 73% coupling incidence in NAC spiny neurons, compared to baseline (9%), whereas quinpirole failed to affect the basal coupling (24%) in slices from DARPP-32 knockout (KO) mice. Thus, D2 stimulation attenuated DARPP-32-mediated suppression of coupling in WT spiny neurons, but this modulation was absent in KO mice. Further, whole cell recordings revealed that quinpirole reversibly decreased the amplitude of cortical-evoked EPSPs in spiny neurons of WT mice, but this reduction was markedly attenuated in KO mice. Bath application of the D1/D5 agonist SKF 38393 did not alter evoked EPSP amplitude in WT or KO spiny neurons. Therefore, DA D2 receptor regulation of both cortical synaptic (chemical) and local non-synaptic (dye coupling) communications in NAC spiny neurons is critically dependent on intracellular DARPP-32 cascades. Conversely, in fast-spiking interneurons, blockade of D1/D5 receptors produced a substantial decrease in EPSP amplitude in WT, but not in KO mice. Lastly, in putative cholinergic interneurons, cortical-evoked disynaptic IPSPs were attenuated by D2-like receptor stimulation in WT but not KO slices. These data indicate that DARPP-32 plays a central role in 1) modulating intercellular coupling, 2) cortical excitatory drive of spiny and aspiny GABAergic neurons, and 3) local feedforward inhibitory drive of cholinergic-like interneurons within accumbens circuits PMID:18155847

  7. Subsets of Spiny Striosomal Striatal Neurons Revealed in the Gad1-GFP BAC Transgenic Mouse.

    PubMed

    Cuzon Carlson, Verginia C; Mathur, Brian N; Davis, Margaret I; Lovinger, David M

    2011-11-01

    OBJECTIVE: To characterize GFP-expressing cells in the striatum of Cb6-Tg(Gad1-EGFP)G42Zjh/J mice, in which the Gad1 (also referred to as GAD67) promoter drives GFP expression (Gad1-GFP mouse). BACKGROUND: GFP-expressing cells of the GAD1-GFP mouse have been described to be a population of parvalbumin-positive basket interneurons residing in the cerebral cortex and the cerebellum. However, the cells in the dorsal striatum of these mice have not been characterized. METHODS: Using a combination of immunohistochemistry, electrophysiology, DiI labeling, and retrograde tracing, we investigated the phenotypes of GFP-expressing cells in the GAD1-GFP mice. RESULTS: A small number of striatal neurons express GFP in these mice. In the mature striatum, these cells are preferentially located in the lateral striatum with a strong expression in the lateral striatal streak. The GAD1-GFP positive neurons are distinct from the standard fast-spiking and low-threshold-spiking GAD-67 expressing striatal interneurons and appear to be a subset of medium spiny neurons. These neurons are generally colocalized with striosomal markers such as dynorphin, mu-opioid receptors, as well as CB1 and calretinin-immunopositive fibers. Striatal Gad1-GFP neurons can be separated into two groups based on the shape of the somata and patterns of action potential firing. Retrograde labeling indicated that a proportion of these cells are projection neurons. CONCLUSIONS: The examination of GAD1-GFP cells in these mice revealed 2 subpopulations of ventral striosomal striatal medium spiny neurons, based on morphology, patch-matrix segregation and membrane properties.

  8. Quantitative analysis of spiny neurons in the adult human caudate nucleus: can it confirm the current qualitative cell classification?

    PubMed

    Krstonošić, Bojana; Milošević, Nebojša T; Marić, Dušica L; Babović, Siniša S

    2015-09-01

    The caudate nucleus, as a part of the striatum (neostriatum or dorsal striatum), is involved in the control of cognitive, motor and limbic functions. The majority of the caudate nucleus cells are projection spiny neurons, whose activity is determined by excitatory inputs from the cortex, thalamus, globus pallidus and brainstem. A qualitative analysis of human caudate nucleus neurons involves the description of the structure and features of cells, and accordingly, their classification into an appropriate type. The aim of this study is to determine the justification of the current qualitative classification of spiny neurons in the precommissural head of the human caudate nucleus by quantifying morphological properties of neurons. After the qualitative analysis of microscopic images of the Golgi-impregnated caudate nucleus neurons, five morphological properties of cells were measured/quantified. In terms of the dendritic field area, caudate nucleus neurons were divided into two subgroups: small and large neurons. In our sample of 251 projection nerve cells, 58.17 % (146) were small and 41.83 % (105) were large neurons. These data show that suggested groups of spiny neurons in the human caudate nucleus differ in their morphology. Since the structure and function of cells are closely correlated, it is possible that these morphologically different types of neurons may represent different functional groups.

  9. Inhibitory collaterals in genetically identified medium spiny neurons in mouse primary corticostriatal cultures.

    PubMed

    Lalchandani, Rupa R; Vicini, Stefano

    2013-11-01

    Inhibitory collaterals between striatal medium spiny neuron (MSN) subtypes have been shown to critically influence striatal output. However, the low rate of inhibitory collateral detection between striatal MSNs in conventional ex vivo slice recordings has made the study of these connections challenging. Furthermore, most studies on MSN collaterals have been conducted either blind or in models, in which only one MSN subtype can be distinguished. Here, we describe a dissociated culture system using striatal and cortical neurons harvested from genetically modified mice at postnatal day 0. These mice express tdTomato and enhanced green fluorescent protein (EGFP) downstream of the dopamine D1 and D2 receptor promoters, respectively, allowing for simultaneous distinction between the two major subtypes of MSNs. In vitro, these neurons develop spines, hyperpolarized resting membrane potentials and exhibit up-and-down states, while also maintaining expression of both fluorophores through time. Using paired whole-cell patch-clamp recordings from identified MSNs at 14 days in vitro, we are able to detect a much higher rate of inhibitory functional synapses than what has been previously reported in slice recordings. These collateral synapses release γ-Aminobutyric acid (GABA) and shape the firing patters of other MSNs. Although reduced in vitro models have a number of inherent limitations, the cultures described here provide a unique opportunity to study frequently observed functional collaterals between identifiable MSNs. Additionally, cultured neurons allow for control of the extracellular environment, with the potential to investigate pharmacological regulation of inhibitory MSNs collaterals.

  10. Intrinsic excitability varies by sex in prepubertal striatal medium spiny neurons

    PubMed Central

    Dorris, David M.; Cao, Jinyan; Willett, Jaime A.; Hauser, Caitlin A.

    2014-01-01

    Sex differences in neuron electrophysiological properties were traditionally associated with brain regions directly involved in reproduction in adult, postpubertal animals. There is growing acknowledgement that sex differences can exist in other developmental periods and brain regions as well. This includes the dorsal striatum (caudate/putamen), which shows robust sex differences in gene expression, neuromodulator action (including dopamine and 17β-estradiol), and relevant sensorimotor behaviors and pathologies such as the responsiveness to drugs of abuse. Here we examine whether these sex differences extend to striatal neuron electrophysiology. We test the hypothesis that passive and active medium spiny neuron (MSN) electrophysiological properties in prepubertal rat dorsal striatum differ by sex. We made whole cell recordings from male and females MSNs from acute brain slices. The slope of the evoked firing rate to current injection curve was increased in MSNs recorded from females compared with males. The initial action potential firing rate was increased in MSNs recorded from females compared with males. Action potential after-hyperpolarization peak was decreased, and threshold was hyperpolarized in MSNs recorded from females compared with males. No sex differences in passive electrophysiological properties or miniature excitatory synaptic currents were detected. These findings indicate that MSN excitability is increased in prepubertal females compared with males, providing a new mechanism that potentially contributes to generating sex differences in striatal-mediated processes. Broadly, these findings demonstrate that sex differences in neuron electrophysiological properties can exist prepuberty in brain regions not directly related to reproduction. PMID:25376786

  11. Cell-type-specific inhibition of the dendritic plateau potential in striatal spiny projection neurons.

    PubMed

    Du, Kai; Wu, Yu-Wei; Lindroos, Robert; Liu, Yu; Rózsa, Balázs; Katona, Gergely; Ding, Jun B; Kotaleski, Jeanette Hellgren

    2017-09-05

    Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dual-color uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a cell-type-specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg(2+) block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.

  12. Characterization of acid-sensing ion channels in medium spiny neurons of mouse striatum.

    PubMed

    Jiang, Q; Li, M-H; Papasian, C J; Branigan, D; Xiong, Z-G; Wang, J Q; Chu, X-P

    2009-08-04

    Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in neurodegenerative diseases. They are highly expressed in the striatum, where medium spiny neurons (MSNs) are a major population. Given that the properties of ASICs in MSNs are unknown, in this study, we characterized ASICs in MSNs of the mouse striatum. A rapid drop in extracellular pH induced transient inward currents in all MSNs. The pH value for half-maximal activation was 6.25, close to that obtained in homomeric ASIC1a channels. Based on psalmotoxin 1 and zinc sensitivity, ASIC1a (70.5% of neurons) and heteromeric ASIC1a-2 channels (29.5% of neurons) appeared responsible for the acid-induced currents in MSNs. ASIC currents were diminished in MSNs from ASIC1, but not ASIC2, null mice. Furthermore, a drop in pH induced calcium influx by activating homomeric ASIC1a channels. Activation of ASICs increased the membrane excitability of MSNs and lowering extracellular Ca2+ potentiated ASIC currents. Our data suggest that the homomeric ASIC1a channel represents a majority of the ASIC isoform in MSNs. The potential function of ASICs in the striatum requires further investigation.

  13. Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons.

    PubMed

    Martín-Ibáñez, Raquel; Pardo, Mónica; Giralt, Albert; Miguez, Andrés; Guardia, Inés; Marion-Poll, Lucile; Herranz, Cristina; Esgleas, Miriam; Garcia-Díaz Barriga, Gerardo; Edel, Michael J; Vicario-Abejón, Carlos; Alberch, Jordi; Girault, Jean-Antoine; Chan, Susan; Kastner, Philippe; Canals, Josep M

    2017-04-15

    Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G1/G0 phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, He(-/-) mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.

  14. Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal medium spiny neurons.

    PubMed

    Neely, M D; Schmidt, D E; Deutch, A Y

    2007-10-26

    The proximate cause of Parkinson's disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson's disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures composed of ventral mesencephalon, striatum, and cortex of the neonatal rat, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson's disease.

  15. Effects of dopaminergic modulation on the integrative properties of the ventral striatal medium spiny neuron.

    PubMed

    Moyer, Jason T; Wolf, John A; Finkel, Leif H

    2007-12-01

    Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor-mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.

  16. Cortical Regulation of Dopamine Depletion-Induced Dendritic Spine Loss in Striatal Medium Spiny Neurons

    PubMed Central

    Neely, M. Diana; Schmidt, Dennis E.; Deutch, Ariel Y.

    2007-01-01

    The proximate cause of Parkinson’s Disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson’s Disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures comprised of ventral mesencephalon, striatum, and cortex, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin MPP+ or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson’s Disease. PMID:17888581

  17. Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation

    PubMed Central

    Tsutsui-Kimura, Iku; Takiue, Hiroyuki; Yoshida, Keitaro; Xu, Ming; Yano, Ryutaro; Ohta, Hiroyuki; Nishida, Hiroshi; Bouchekioua, Youcef; Okano, Hideyuki; Uchigashima, Motokazu; Watanabe, Masahiko; Takata, Norio; Drew, Michael R.; Sano, Hiromi; Mimura, Masaru; Tanaka, Kenji F.

    2017-01-01

    Impaired motivation is present in a variety of neurological disorders, suggesting that decreased motivation is caused by broad dysfunction of the nervous system across a variety of circuits. Based on evidence that impaired motivation is a major symptom in the early stages of Huntington's disease, when dopamine receptor type 2-expressing striatal medium spiny neurons (D2-MSNs) are particularly affected, we hypothesize that degeneration of these neurons would be a key node regulating motivational status. Using a progressive, time-controllable, diphtheria toxin-mediated cell ablation/dysfunction technique, we find that loss-of-function of D2-MSNs within ventrolateral striatum (VLS) is sufficient to reduce goal-directed behaviours without impairing reward preference or spontaneous behaviour. Moreover, optogenetic inhibition and ablation of VLS D2-MSNs causes, respectively, transient and chronic reductions of goal-directed behaviours. Our data demonstrate that the circuitry containing VLS D2-MSNs control motivated behaviours and that VLS D2-MSN loss-of-function is a possible cause of motivation deficits in neurodegenerative diseases. PMID:28145402

  18. Dopamine-deprived striatal GABAergic interneurons burst and generate repetitive gigantic IPSCs in medium spiny neurons.

    PubMed

    Dehorter, Nathalie; Guigoni, Celine; Lopez, Catherine; Hirsch, June; Eusebio, Alexandre; Ben-Ari, Yehezkel; Hammond, Constance

    2009-06-17

    Striatal GABAergic microcircuits modulate cortical responses and movement execution in part by controlling the activity of medium spiny neurons (MSNs). How this is altered by chronic dopamine depletion, such as in Parkinson's disease, is not presently understood. We now report that, in dopamine-depleted slices of the striatum, MSNs generate giant spontaneous postsynaptic GABAergic currents (single or in bursts at 60 Hz) interspersed with silent episodes, rather than the continuous, low-frequency GABAergic drive (5 Hz) observed in control MSNs. This shift was observed in one-half of the MSN population, including both "D(1)-negative" and "D(1)-positive" MSNs. Single GABA and NMDA channel recordings revealed that the resting membrane potential and reversal potential of GABA were similar in control and dopamine-depleted MSNs, and depolarizing, but not excitatory, actions of GABA were observed. Glutamatergic and cholinergic antagonists did not block the GABAergic oscillations, suggesting that they were generated by GABAergic neurons. In support of this, cell-attached recordings revealed that a subpopulation of intrastriatal GABAergic interneurons generated bursts of spikes in dopamine-deprived conditions. This subpopulation included low-threshold spike interneurons but not fast-spiking interneurons, cholinergic interneurons, or MSNs. Therefore, a population of local GABAergic interneurons shifts from tonic to oscillatory mode when dopamine deprived and gives rise to spontaneous repetitive giant GABAergic currents in one-half the MSNs. We suggest that this may in turn alter integration of cortical signals by MSNs.

  19. Dopamine D2 Receptors Regulate Collateral Inhibition between Striatal Medium Spiny Neurons

    PubMed Central

    van der Goes, Marie-Sophie; Partridge, John G.; Vicini, Stefano

    2013-01-01

    The principle neurons of the striatum are GABAergic medium spiny neurons (MSNs), whose collateral synapses onto neighboring neurons play critical roles in striatal function. MSNs can be divided by dopamine receptor expression into D1-class and D2-class MSNs, and alterations in D2 MSNs are associated with various pathological states. Despite overwhelming evidence for D2 receptors (D2Rs) in maintaining proper striatal function, it remains unclear how MSN collaterals are specifically altered by D2R activation. Here, we report that chronic D2R stimulation regulates MSN collaterals in vitro by presynaptic and postsynaptic mechanisms. We used corticostriatal cultures from mice in which MSN subtypes were distinguished by fluorophore expression. Quinpirole, an agonist for D2/3 receptors, was used to chronically activate D2Rs. Quinpirole increased the rate and strength of collateral formation onto D2R-containing MSNs as measured by dual whole-cell patch-clamp recordings. Additionally, these neurons were more sensitive to low concentrations of GABA and exhibited an increase in gephyrin puncta density, suggesting increased postsynaptic GABAA receptors. Last, quinpirole treatment increased presynaptic GABA release sites, as shown by increased frequency of sIPSCs and mIPSCs, correlating with increased VGAT (vesicular GABA transporter) puncta. Combined with the observation that there were no detectable differences in sensitivity to specific GABAA receptor modulators, we provide evidence that D2R activation powerfully transforms MSN collaterals via coordinated presynaptic and postsynaptic alterations. As the D2 class of MSNs is highly implicated in Parkinson's disease and other neurological disorders, our findings may contribute to understanding and treating the changes that occur in these pathological states. PMID:23986243

  20. Genetic deletion of PDE10A selectively impairs incentive salience attribution and decreases medium spiny neuron excitability.

    PubMed

    Piccart, Elisabeth; De Backer, Jean-François; Gall, David; Lambot, Laurie; Raes, Adam; Vanhoof, Greet; Schiffmann, Serge; D'Hooge, Rudi

    2014-07-15

    The striatum is the main input structure to the basal ganglia and consists mainly out of medium spiny neurons. The numerous spines on their dendrites render them capable of integrating cortical glutamatergic inputs with a motivational dopaminergic signal that originates in the midbrain. This integrative function is thought to underly attribution of incentive salience, a process that is severely disrupted in schizophrenic patients. Phosphodiesterase 10A (PDE10A) is located mainly to the striatal medium spiny neurons and hydrolyses cAMP and cGMP, key determinants of MSN signaling. We show here that genetic depletion of PDE10A critically mediates attribution of salience to reward-predicting cues, evident in impaired performance in PDE10A knockout mice in an instrumentally conditioned reinforcement task. We furthermore report modest impairment of latent inhibition in PDE10A knockout mice, and unaltered prepulse inhibition. We suggest that the lack of effect on PPI is due to the pre-attentional nature of this task. Finally, we performed whole-cell patch clamp recordings and confirm suggested changes in intrinsic membrane excitability. A decrease in spontaneous firing in striatal medium spiny neurons was found. These data show that PDE10A plays a pivotal role in striatal signaling and striatum-mediated salience attribution.

  1. Dopaminergic treatment weakens medium spiny neuron collateral inhibition in the parkinsonian striatum.

    PubMed

    Wei, Wei; Ding, Shengyuan; Zhou, Fu-Ming

    2017-03-01

    The striatal medium spiny neurons (MSNs) are critical to both motor and cognitive functions. A potential regulator of MSN activity is the GABAergic collateral axonal input from neighboring MSNs. These collateral axon terminals are further under the regulation of presynaptic dopamine (DA) receptors that may become dysfunctional when the intense striatal DA innervation is lost in Parkinson's disease (PD). We show that DA D1 receptor-expressing MSNs (D1-MSNs) and D2 receptor-expressing MSNs (D2-MSNs) each formed high-rate, one-way collateral connections with a homotypic preference in both normal and DA-denervated mouse striatum. Furthermore, whereas the homotypic preference, one-way directionality and the basal inhibitory strength were preserved, DA inhibited GABA release at the D2-MSN→D2-MSN collateral synapse in a supersensitive manner in the DA-denervated striatum. In contrast, for D1-MSN-originated collateral connections, whereas D1 agonism facilitated D1-MSN→D1-MSN collateral inhibition in the normal striatum, this presynaptic D1R facilitation of GABA release was lost in the parkinsonian striatum. These results indicate that in the parkinsonian striatum, dopaminergic treatment can presynaptically weaken the D2-MSN→D2-MSN collateral inhibition and disinhibit the surrounding D2-MSNs, whereas the D1-MSN→D1-MSN collateral inhibition is weakened by the loss of the presynaptic D1 receptor facilitation, disinhibiting the surrounding D1-MSNs. Together, these newly discovered effects can disrupt the MSN circuits in the parkinsonian striatum and may contribute to dopaminergic treatment-induced aberrant motor and nonmotor behaviors in PD.NEW & NOTEWORTHY With the use of a large database, this study establishes that neighboring homotypic striatal spiny projection neurons have a 50% chance to form one-way collateral inhibitory connection, a substantially higher rate than previous estimates. This study also shows that dopamine denervation may alter presynaptic dopamine

  2. Developmental alterations in motor coordination and medium spiny neuron markers in mice lacking pgc-1α.

    PubMed

    Lucas, Elizabeth K; Dougherty, Sarah E; McMeekin, Laura J; Trinh, Alisa T; Reid, Courtney S; Cowell, Rita M

    2012-01-01

    Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of Huntington Disease (HD). Adult PGC-1α (-/-) mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α (-/-) mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α (-/-) mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α (-/-) mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α (-/-) striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α (-/-) mice show increases in the expression of medium spiny neuron (MSN) markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning.

  3. Different Corticostriatal Integration in Spiny Projection Neurons from Direct and Indirect Pathways

    PubMed Central

    Flores-Barrera, Edén; Vizcarra-Chacón, Bianca J.; Tapia, Dagoberto; Bargas, José; Galarraga, Elvira

    2010-01-01

    The striatum is the principal input structure of the basal ganglia. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs) and interneurons. Also: glutamatergic afferents to the striatum come from the thalamus. Despite differences in axonal projections, dopamine (DA) receptors expression and differences in excitability between MSNs from “direct” and “indirect” basal ganglia pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with bacterial artificial chromosome (BAC) transgenic mice, here it is shown that corticostriatal responses in D1- and D2-receptor expressing MSNs (D1- and D2-MSNs) are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P > 0.9), in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin (ENK) immunoreactive. Responses are more prolonged and evoke more action potentials in D1-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D2-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response. Inhibition always depressed corticostriatal depolarization in D2-MSNs, while it helped in sustaining prolonged depolarizations in D1-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA depletion in 6-hydroxy-dopamine (6-OHDA) lesioned animals: a response reduction was seen in substance P (SP)+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion. PMID:20589098

  4. Developmental Alterations in Motor Coordination and Medium Spiny Neuron Markers in Mice Lacking PGC-1α

    PubMed Central

    Lucas, Elizabeth K.; Dougherty, Sarah E.; McMeekin, Laura J.; Trinh, Alisa T.; Reid, Courtney S.; Cowell, Rita M.

    2012-01-01

    Accumulating evidence implicates the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) in the pathophysiology of Huntington Disease (HD). Adult PGC-1α −/− mice exhibit striatal neurodegeneration, and reductions in the expression of PGC-1α have been observed in striatum and muscle of HD patients as well as in animal models of the disease. However, it is unknown whether decreased expression of PGC-1α alone is sufficient to lead to the motor phenotype and striatal pathology characteristic of HD. For the first time, we show that young PGC-1α −/− mice exhibit severe rotarod deficits, decreased rearing behavior, and increased occurrence of tremor in addition to the previously described hindlimb clasping. Motor impairment and striatal vacuolation are apparent in PGC-1α −/− mice by four weeks of age and do not improve or decline by twelve weeks of age. The behavioral and pathological phenotype of PGC-1α −/− mice can be completely recapitulated by conditional nervous system deletion of PGC-1α, indicating that peripheral effects are not responsible for the observed abnormalities. Evaluation of the transcriptional profile of PGC-1α −/− striatal neuron populations and comparison to striatal neuron profiles of R6/2 HD mice revealed that PGC-1α deficiency alone is not sufficient to cause the transcriptional changes observed in this HD mouse model. In contrast to R6/2 HD mice, PGC-1α −/− mice show increases in the expression of medium spiny neuron (MSN) markers with age, suggesting that the observed behavioral and structural abnormalities are not primarily due to MSN loss, the defining pathological feature of HD. These results indicate that PGC-1α is required for the proper development of motor circuitry and transcriptional homeostasis in MSNs and that developmental disruption of PGC-1α leads to long-term alterations in motor functioning. PMID:22916173

  5. Short-Latency Activation of Striatal Spiny Neurons via Subcortical Visual Pathways

    PubMed Central

    Schulz, Jan M.; Redgrave, Peter; Mehring, Carsten; Aertsen, Ad; Clements, Koreen M.; Wickens, Jeff R.; Reynolds, John N. J.

    2011-01-01

    The striatum is a site of integration of neural pathways involved in reinforcement learning. Traditionally, inputs from cerebral cortex are thought to be reinforced by dopaminergic afferents signaling the occurrence of biologically salient sensory events. Here, we detail an alternative route for short-latency sensory-evoked input to the striatum requiring neither dopamine nor the cortex. Using intracellular recording techniques, we measured subthreshold inputs to spiny projection neurons (SPNs) in urethane-anesthetized rats. Contralateral whole-field light flashes evoked weak membrane potential responses in approximately two-thirds of neurons. However, after local disinhibitory injections of the GABAA antagonist bicuculline into the deep layers of the superior colliculus (SC), but not the overlying visual cortex, strong, light-evoked, depolarizations to the up state emerged at short latency (115 ± 14 ms) in all neurons tested. Dopamine depletion using α-methyl-para-tyrosine had no detectable effect on striatal visual responses during SC disinhibition. In contrast, local inhibitory injections of GABA agonists, muscimol and baclofen, into the parafascicular nucleus of the thalamus blocked the early, visual-evoked up-state transitions in SPNs. Comparable muscimol-induced inhibition of the visual cortex failed to suppress the visual responsiveness of SPNs induced by SC disinhibition. Together, these results suggest that short-latency, preattentive visual input can reach the striatum not only via the tecto-nigro-striatal route but also through tecto-thalamo-striatal projections. Thus, after the onset of a biologically significant visual event, closely timed short-latency thalamostriatal (glutamate) and nigrostriatal (dopamine) inputs are likely to converge on striatal SPNs, providing depolarizing and neuromodulator signals necessary for synaptic plasticity mechanisms. PMID:19439610

  6. GABAA receptor activity shapes the formation of inhibitory synapses between developing medium spiny neurons

    PubMed Central

    Arama, Jessica; Abitbol, Karine; Goffin, Darren; Fuchs, Celine; Sihra, Talvinder S.; Thomson, Alex M.; Jovanovic, Jasmina N.

    2015-01-01

    Basal ganglia play an essential role in motor coordination and cognitive functions. The GABAergic medium spiny neurons (MSNs) account for ~95% of all the neurons in this brain region. Central to the normal functioning of MSNs is integration of synaptic activity arriving from the glutamatergic corticostriatal and thalamostriatal afferents, with synaptic inhibition mediated by local interneurons and MSN axon collaterals. In this study we have investigated how the specific types of GABAergic synapses between the MSNs develop over time, and how the activity of GABAA receptors (GABAARs) influences this development. Isolated embryonic (E17) MSNs form a homogenous population in vitro and display spontaneous synaptic activity and functional properties similar to their in vivo counterparts. In dual whole-cell recordings of synaptically connected pairs of MSNs, action potential (AP)-activated synaptic events were detected between 7 and 14 days in vitro (DIV), which coincided with the shift in GABAAR operation from depolarization to hyperpolarization, as detected indirectly by intracellular calcium imaging. In parallel, the predominant subtypes of inhibitory synapses, which innervate dendrites of MSNs and contain GABAAR α1 or α2 subunits, underwent distinct changes in the size of postsynaptic clusters, with α1 becoming smaller and α2 larger over time, while both the percentage and the size of mixed α1/α2-postsynaptic clusters were increased. When activity of GABAARs was under chronic blockade between 4–7 DIV, the structural properties of these synapses remained unchanged. In contrast, chronic inhibition of GABAARs between 7–14 DIV led to reduction in size of α1- and α1/α2-postsynaptic clusters and a concomitant increase in number and size of α2-postsynaptic clusters. Thus, the main subtypes of GABAergic synapses formed by MSNs are regulated by GABAAR activity, but in opposite directions, and thus appear to be driven by different molecular mechanisms. PMID

  7. New Rules Governing Synaptic Plasticity In Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Martin, Gilles E.

    2012-01-01

    The nucleus accumbens is a forebrain region responsible for drug reward and goal directed behaviors. It has long been believed that drugs of abuse exert their addictive properties on behavior by altering the strength of synaptic communication over long periods of time. To date, attempts at understanding the relationship between drugs of abuse and synaptic plasticity have relied on the high-frequency long-term potentiation model of Bliss and LØmo (1973). We examined synaptic plasticity using spike-timing-dependent plasticity, a stimulation paradigm that reflects more closely in vivo firing patterns of core NAcc medium spiny neurons and their afferents. In contrast to other brain regions, the same stimulation paradigm evoked bidirectional long-term plasticity. Long-term potentiation (tLTP) magnitude changed with delay between action potentials (APs) and excitatory post-synaptic potentials (EPSPs), and frequency, while that of long-term depression (tLTD) remained unchanged. We showed that tLTP depended on NMDA receptors, whereas tLTD relied on action potentials. Importantly, intracellular calcium signaling pathways mobilized during tLTP and tLTD were different. Thus, calcium-induced calcium release underlies tLTD but not tLTP. Finally, we found that the firing pattern of a subset of MSNs was strongly inhibited by dopamine receptor agonists. Surprisingly, these neurons were exclusively associated with tLTP but not with tLTD. Taken together, these data point to the existence of two subgroups of MSNs with distinct properties, each displaying unique abilities to undergo synaptic plasticity. PMID:23013293

  8. Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

    PubMed Central

    Mizuno, Takeo; Schmauss, Claudia; Rayport, Stephen

    2007-01-01

    Background In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca2+ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results Presynaptic Ca2+ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of medium-spiny neuron varicosities

  9. Genetic Inhibition of CaMKII in Dorsal Striatal Medium Spiny Neurons Reduces Functional Excitatory Synapses and Enhances Intrinsic Excitability

    PubMed Central

    Klug, Jason R.; Mathur, Brian N.; Kash, Thomas L.; Wang, Hui-Dong; Matthews, Robert T.; Robison, A. J.; Anderson, Mark E.; Deutch, Ariel Y.; Lovinger, David M.; Colbran, Roger J.; Winder, Danny G.

    2012-01-01

    Ca2+/calmodulin-dependent protein kinase II (CaMKII) is abundant in striatal medium spiny neurons (MSNs). CaMKII is dynamically regulated by changes in dopamine signaling, as occurs in Parkinson's disease as well as addiction. Although CaMKII has been extensively studied in the hippocampus where it regulates excitatory synaptic transmission, relatively little is known about how it modulates neuronal function in the striatum. Therefore, we examined the impact of selectively overexpressing an EGFP-fused CaMKII inhibitory peptide (EAC3I) in striatal medium spiny neurons (MSNs) using a novel transgenic mouse model. EAC3I-expressing cells exhibited markedly decreased excitatory transmission, indicated by a decrease in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). This decrease was not accompanied by changes in the probability of release, levels of glutamate at the synapse, or changes in dendritic spine density. CaMKII regulation of the AMPA receptor subunit GluA1 is a major means by which the kinase regulates neuronal function in the hippocampus. We found that the decrease in striatal excitatory transmission seen in the EAC3I mice is mimicked by deletion of GluA1. Further, while CaMKII inhibition decreased excitatory transmission onto MSNs, it increased their intrinsic excitability. These data suggest that CaMKII plays a critical role in setting the excitability rheostat of striatal MSNs by coordinating excitatory synaptic drive and the resulting depolarization response. PMID:23028932

  10. Genetic inhibition of CaMKII in dorsal striatal medium spiny neurons reduces functional excitatory synapses and enhances intrinsic excitability.

    PubMed

    Klug, Jason R; Mathur, Brian N; Kash, Thomas L; Wang, Hui-Dong; Matthews, Robert T; Robison, A J; Anderson, Mark E; Deutch, Ariel Y; Lovinger, David M; Colbran, Roger J; Winder, Danny G

    2012-01-01

    Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is abundant in striatal medium spiny neurons (MSNs). CaMKII is dynamically regulated by changes in dopamine signaling, as occurs in Parkinson's disease as well as addiction. Although CaMKII has been extensively studied in the hippocampus where it regulates excitatory synaptic transmission, relatively little is known about how it modulates neuronal function in the striatum. Therefore, we examined the impact of selectively overexpressing an EGFP-fused CaMKII inhibitory peptide (EAC3I) in striatal medium spiny neurons (MSNs) using a novel transgenic mouse model. EAC3I-expressing cells exhibited markedly decreased excitatory transmission, indicated by a decrease in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). This decrease was not accompanied by changes in the probability of release, levels of glutamate at the synapse, or changes in dendritic spine density. CaMKII regulation of the AMPA receptor subunit GluA1 is a major means by which the kinase regulates neuronal function in the hippocampus. We found that the decrease in striatal excitatory transmission seen in the EAC3I mice is mimicked by deletion of GluA1. Further, while CaMKII inhibition decreased excitatory transmission onto MSNs, it increased their intrinsic excitability. These data suggest that CaMKII plays a critical role in setting the excitability rheostat of striatal MSNs by coordinating excitatory synaptic drive and the resulting depolarization response.

  11. Consistent injury to medium spiny neurons and white matter in the mouse striatum after prolonged transient global cerebral ischemia.

    PubMed

    Yoshioka, Hideyuki; Niizuma, Kuniyasu; Katsu, Masataka; Sakata, Hiroyuki; Okami, Nobuya; Chan, Pak H

    2011-04-01

    A reproducible transient global cerebral ischemia (tGCI) mouse model has not been fully established. Although striatal neurons and white matter are recognized to be vulnerable to ischemia, their injury after tGCI in mice has not been elucidated. The purpose of this study was to evaluate injuries to striatal neurons and white matter after tGCI in C57BL/6 mice, and to develop a reproducible tGCI model. Male C57BL/6 mice were subjected to tGCI by bilateral common carotid artery occlusion (BCCAO). Mice whose cortical cerebral blood flow after BCCAO decreased to less than 13% of the pre-ischemic value were used. Histological analysis showed that at 3 days after 22 min of BCCAO, striatal neurons were injured more consistently than those in other brain regions. Quantitative analysis of cytochrome c release into the cytosol and DNA fragmentation in the striatum showed consistent injury to the striatum. Immunohistochemistry and Western blot analysis revealed that DARPP-32-positive medium spiny neurons, the majority of striatal neurons, were the most vulnerable among the striatal neuronal subpopulations. The striatum (especially medium spiny neurons) was susceptible to oxidative stress after tGCI, which is probably one of the mechanisms of vulnerability. SMI-32 immunostaining showed that white matter in the striatum was also consistently injured 3 days after 22 min of BCCAO. We thus suggest that this is a tGCI model using C57BL/6 mice that consistently produces neuronal and white matter injury in the striatum by a simple technique. This model can be highly applicable for elucidating molecular mechanisms in the brain after global ischemia.

  12. Phenotype-dependent inhibition of glutamatergic transmission on nucleus accumbens medium spiny neurons by the abused inhalant toluene

    PubMed Central

    Beckley, Jacob T.; Randall, Patrick K.; Smith, Rachel J.; Hughes, Benjamin A.; Kalivas, Peter W.; Woodward, John J.

    2015-01-01

    Abused inhalants are voluntary inhaled at high concentrations to produce intoxicating effects. Results from animal studies show that the abused inhalant toluene triggers behaviors, such as self-administration and conditioned place preference that are commonly associated with addictive drugs. Little is known however about how toluene affects neurons within the nucleus accumbens (NAc), a brain region within the basal ganglia that mediates goal-directed behaviors and is implicated in the development and maintenance of addictive behaviors. Here, we report that toluene inhibits a component of the after-hyperpolarization potential (AHP), and dose-dependently inhibits NMDA-mediated currents in rat NAc medium spiny neurons (MSN). Moreover, using the multivariate statistical technique, partial least squares discriminative analysis (PLS-DA) to analyze electrophysiological measures from rat NAc MSNs, we show that toluene induces a persistent depression of AMPA-mediated currents in one subtype of NAc medium spiny neurons, and that the electrophysiological features of MSN neurons predicts their sensitivity to toluene. The CB1 receptor antagonist AM281 blocked the toluene-induced long-term depression of AMPA currents, indicating that this process is dependent on endocannabinoid signaling. The neuronal identity of recorded cells was examined using dual histochemistry and shows that toluene-sensitive NAc neurons are dopamine D2 MSNs that express preproenkephalin mRNA. Overall, the results from these studies indicate that physiological characteristics obtained from NAc MSNs during whole-cell patch clamp recordings reliably predict neuronal phenotype, and that the abused inhalant toluene differentially depresses excitatory neurotransmission in NAc neuronal subtypes. PMID:25752326

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

    PubMed

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

    2016-12-01

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

  14. Calcium dynamics predict direction of synaptic plasticity in striatal spiny projection neurons.

    PubMed

    Jędrzejewska-Szmek, Joanna; Damodaran, Sriraman; Dorman, Daniel B; Blackwell, Kim T

    2017-04-01

    The striatum is a major site of learning and memory formation for sensorimotor and cognitive association. One of the mechanisms used by the brain for memory storage is synaptic plasticity - the long-lasting, activity-dependent change in synaptic strength. All forms of synaptic plasticity require an elevation in intracellular calcium, and a common hypothesis is that the amplitude and duration of calcium transients can determine the direction of synaptic plasticity. The utility of this hypothesis in the striatum is unclear in part because dopamine is required for striatal plasticity and in part because of the diversity in stimulation protocols. To test whether calcium can predict plasticity direction, we developed a calcium-based plasticity rule using a spiny projection neuron model with sophisticated calcium dynamics including calcium diffusion, buffering and pump extrusion. We utilized three spike timing-dependent plasticity (STDP) induction protocols, in which postsynaptic potentials are paired with precisely timed action potentials and the timing of such pairing determines whether potentiation or depression will occur. Results show that despite the variation in calcium dynamics, a single, calcium-based plasticity rule, which explicitly considers duration of calcium elevations, can explain the direction of synaptic weight change for all three STDP protocols. Additional simulations show that the plasticity rule correctly predicts the NMDA receptor dependence of long-term potentiation and the L-type channel dependence of long-term depression. By utilizing realistic calcium dynamics, the model reveals mechanisms controlling synaptic plasticity direction, and shows that the dynamics of calcium, not just calcium amplitude, are crucial for synaptic plasticity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Dopamine and cyclic-AMP regulated phosphoprotein-32-dependent modulation of prefrontal cortical input and intercellular coupling in mouse accumbens spiny and aspiny neurons.

    PubMed

    Onn, S-P; Lin, M; Liu, J-J; Grace, A A

    2008-02-06

    The roles of dopamine and cyclic-AMP regulated phosphoprotein-32 (DARPP-32) in mediating dopamine (DA)-dependent modulation of corticoaccumbens transmission and intercellular coupling were examined in mouse accumbens (NAC) neurons by both intracellular sharp electrode and whole cell recordings. In wild-type (WT) mice bath application of the D2-like agonist quinpirole resulted in 73% coupling incidence in NAC spiny neurons, compared with baseline (9%), whereas quinpirole failed to affect the basal coupling (24%) in slices from DARPP-32 knockout (KO) mice. Thus, D2 stimulation attenuated DARPP-32-mediated suppression of coupling in WT spiny neurons, but this modulation was absent in KO mice. Further, whole cell recordings revealed that quinpirole reversibly decreased the amplitude of cortical-evoked excitatory postsynaptic potentials (EPSPs) in spiny neurons of WT mice, but this reduction was markedly attenuated in KO mice. Bath application of the D1/D5 agonist SKF 38393 did not alter evoked EPSP amplitude in WT or KO spiny neurons. Therefore, DA D2 receptor regulation of both cortical synaptic (chemical) and local non-synaptic (dye coupling) communications in NAC spiny neurons is critically dependent on intracellular DARPP-32 cascades. Conversely, in fast-spiking interneurons, blockade of D1/D5 receptors produced a substantial decrease in EPSP amplitude in WT, but not in KO mice. Lastly, in putative cholinergic interneurons, cortical-evoked disynaptic inhibitory potentials (IPSPs) were attenuated by D2-like receptor stimulation in WT but not KO slices. These data indicate that DARPP-32 plays a central role in 1) modulating intercellular coupling, 2) cortical excitatory drive of spiny and aspiny GABAergic neurons, and 3) local feedforward inhibitory drive of cholinergic-like interneurons within accumbens circuits.

  16. Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2.

    PubMed

    Sano, Hiromi; Nagai, Yumiko; Miyakawa, Tsuyoshi; Shigemoto, Ryuichi; Yokoi, Mineto

    2008-04-01

    Cyclic nucleotide phosphodiesterase 10A (PDE10A) is a member of phosphodiesterase families that degrade cAMP and/or cGMP in distinct intracellular sites. PDE10A has a dual activity on hydrolysis of both cAMP and cGMP, and is prominently expressed in the striatum and the testis. Previous studies suggested that PDE10A is involved in regulation of locomotor activity and potentially related to psychosis, but concrete physiological roles of PDE10A remains elusive yet. In this study, we genetically inactivated PDE10A2, a prominent isoform of PDE10A in the brain, in mice, and demonstrate that PDE10A2 deficiency results in increased social interaction without any major influence on different other behaviors, along with increased levels of striatal cAMP. We also demonstrate that PDE10A2 is selectively distributed in medium spiny neurons, but not interneurons, of the striatal complex. Thus, our results establish a physiological role for PDE10A2 in regulating cAMP pathway and social interaction, and suggest that cAMP signaling cascade in striatal medium spiny neurons might be involved in regulating social interaction behavior in mice.

  17. Marked differences in the number and type of synapses innervating the somata and primary dendrites of midbrain dopaminergic neurons, striatal cholinergic interneurons, and striatal spiny projection neurons in the rat.

    PubMed

    Sizemore, Rachel J; Zhang, Rong; Lin, Naili; Goddard, Liping; Wastney, Timothy; Parr-Brownlie, Louise C; Reynolds, John N J; Oorschot, Dorothy E

    2016-04-01

    Elucidating the link between cellular activity and goal-directed behavior requires a fuller understanding of the mechanisms underlying burst firing in midbrain dopaminergic neurons and those that suppress activity during aversive or non-rewarding events. We have characterized the afferent synaptic connections onto these neurons in the rat substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and compared these findings with cholinergic interneurons and spiny projection neurons in the striatum. We found that the average absolute number of synapses was three to three and one-half times greater onto the somata of dorsal striatal spiny projection neurons than onto the somata of dopaminergic neurons in the SNpc or dorsal striatal cholinergic interneurons. A similar comparison between populations of dopamine neurons revealed a two times greater number of somatic synapses on VTA dopaminergic neurons than SNpc dopaminergic neurons. The percentage of symmetrical, presumably inhibitory, synaptic inputs on somata was significantly higher on spiny projection neurons and cholinergic interneurons compared with SNpc dopaminergic neurons. Synaptic data on the primary dendrites yielded similar significant differences for the percentage of symmetrical synapses for VTA dopaminergic vs. striatal neurons. No differences in the absolute number or type of somatic synapses were evident for dopaminergic neurons in the SNpc of Wistar vs. Sprague-Dawley rat strains. These data from identified neurons are pivotal for interpreting their electrophysiological responses to afferent activity and for generating realistic computer models of neuronal networks of striatal and midbrain dopaminergic function.

  18. Integration of Biochemical and Electrical Signaling-Multiscale Model of the Medium Spiny Neuron of the Striatum

    PubMed Central

    Mattioni, Michele; Le Novère, Nicolas

    2013-01-01

    Neuron behavior results from the interplay between networks of biochemical processes and electrical signaling. Synaptic plasticity is one of the neuronal properties emerging from such an interaction. One of the current approaches to study plasticity is to model either its electrical aspects or its biochemical components. Among the chief reasons are the different time scales involved, electrical events happening in milliseconds while biochemical cascades respond in minutes or hours. In order to create multiscale models taking in consideration both aspects simultaneously, one needs to synchronize the two models, and exchange relevant variable values. We present a new event-driven algorithm to synchronize different neuronal models, which decreases computational time and avoids superfluous synchronizations. The algorithm is implemented in the TimeScales framework. We demonstrate its use by simulating a new multiscale model of the Medium Spiny Neuron of the Neostriatum. The model comprises over a thousand dendritic spines, where the electrical model interacts with the respective instances of a biochemical model. Our results show that a multiscale model is able to exhibit changes of synaptic plasticity as a result of the interaction between electrical and biochemical signaling. Our synchronization strategy is general enough to be used in simulations of other models with similar synchronization issues, such as networks of neurons. Moreover, the integration between the electrical and the biochemical models opens up the possibility to investigate multiscale process, like synaptic plasticity, in a more global manner, while taking into account a more realistic description of the underlying mechanisms. PMID:23843966

  19. Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

    PubMed

    Quintana, Albert; Sanz, Elisenda; Wang, Wengang; Storey, Granville P; Güler, Ali D; Wanat, Matthew J; Roller, Bryan A; La Torre, Anna; Amieux, Paul S; McKnight, G Stanley; Bamford, Nigel S; Palmiter, Richard D

    2012-11-01

    The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear. We found that, in the absence of GPR88, MSNs showed increased glutamatergic excitation and reduced GABAergic inhibition, which promoted enhanced firing rates in vivo, resulting in hyperactivity, poor motor coordination and impaired cue-based learning in mice. Targeted viral expression of GPR88 in MSNs rescued the molecular and electrophysiological properties and normalized behavior, suggesting that aberrant MSN activation in the absence of GPR88 underlies behavioral deficits and its dysfunction may contribute to behaviors observed in neuropsychiatric disease.

  20. Phenotype-dependent inhibition of glutamatergic transmission on nucleus accumbens medium spiny neurons by the abused inhalant toluene.

    PubMed

    Beckley, Jacob T; Randall, Patrick K; Smith, Rachel J; Hughes, Benjamin A; Kalivas, Peter W; Woodward, John J

    2016-05-01

    Abused inhalants are voluntarily inhaled at high concentrations to produce intoxicating effects. Results from animal studies show that the abused inhalant toluene triggers behaviors, such as self-administration and conditioned place preference, which are commonly associated with addictive drugs. However, little is known about how toluene affects neurons within the nucleus accumbens (NAc), a brain region within the basal ganglia that mediates goal-directed behaviors and is implicated in the development and maintenance of addictive behaviors. Here we report that toluene inhibits a component of the after-hyperpolarization potential, and dose-dependently inhibits N-methyl-D-aspartate (NMDA)-mediated currents in rat NAc medium spiny neurons (MSN). Moreover, using the multivariate statistical technique, partial least squares discriminative analysis to analyze electrophysiological measures from rat NAc MSNs, we show that toluene induces a persistent depression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated currents in one subtype of NAc MSNs, and that the electrophysiological features of MSN neurons predicts their sensitivity to toluene. The CB1 receptor antagonist AM281 blocked the toluene-induced long-term depression of AMPA currents, indicating that this process is dependent on endocannabinoid signaling. The neuronal identity of recorded cells was examined using dual histochemistry and shows that toluene-sensitive NAc neurons are dopamine D2 MSNs that express preproenkephalin mRNA. Overall, the results from these studies indicate that physiological characteristics obtained from NAc MSNs during whole-cell patch-clamp recordings reliably predict neuronal phenotype, and that the abused inhalant toluene differentially depresses excitatory neurotransmission in NAc neuronal subtypes.

  1. Extracerebellar role for Cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons.

    PubMed

    Kusnoor, S V; Parris, J; Muly, E C; Morgan, J I; Deutch, A Y

    2010-07-01

    Cerebellin1 (Cbln1) is a secreted glycoprotein that was originally isolated from the cerebellum and subsequently found to regulate synaptic development and stability. Cbln1 has a heterogeneous distribution in brain, but the only site in which it has been shown to have central effects is the cerebellar cortex, where loss of Cbln1 causes a reduction in granule cell-Purkinje cell synapses. Neurons of the thalamic parafascicular nucleus (PF), which provide glutamatergic projections to the striatum, also express high levels of Cbln1. We first examined Cbln1 in thalamostriatal neurons and then determined if cbln1 knockout mice exhibit structural deficits in striatal neurons. Virtually all PF neurons express Cbln1-immunoreactivity (-ir). In contrast, only rare Cbln1-ir neurons are present in the central medial complex, the other thalamic region that projects heavily to the dorsal striatum. In the striatum Cbln1-ir processes are apposed to medium spiny neuron (MSN) dendrites; ultrastructural studies revealed that Cbln1-ir axon terminals form axodendritic synapses with MSNs. Tract-tracing studies found that all PF cells retrogradely labeled from the striatum express Cbln1-ir. We then examined the dendritic structure of Golgi-impregnated MSNs in adult cbln1 knockout mice. MSN dendritic spine density was markedly increased in cbln1(-/-) mice relative to wildtype littermates, but total dendritic length was unchanged. Ultrastructural examination revealed an increase in the density of MSN axospinous synapses in cbln1(-/-) mice, with no change in postsynaptic density length. Thus, Cbln1 determines the dendritic structure of striatal MSNs, with effects distinct from those seen in the cerebellum.

  2. BDNF contributes to both rapid and homeostatic alterations in AMPA receptor surface expression in nucleus accumbens medium spiny neurons

    PubMed Central

    Reimers, Jeremy M.; Loweth, Jessica A.; Wolf, Marina E.

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in plasticity at glutamate synapses and the effects of repeated cocaine exposure. We recently showed that intracranial injection of BDNF into the rat nucleus accumbens (NAc), a key region for cocaine addiction, rapidly increases AMPA receptor (AMPAR) surface expression. To further characterize BDNF’s role in both rapid AMPAR trafficking and slower, homeostatic changes in AMPAR surface expression, we investigated the effects of acute (30 min) and long-term (24 h) treatment with BDNF on AMPAR distribution in NAc medium spiny neurons from postnatal rats co-cultured with mouse prefrontal cortex (PFC) neurons to restore excitatory inputs. Immunocytochemical studies showed that acute BDNF treatment increased cell surface GluA1 and GluA2 levels, as well as their co-localization, on NAc neurons. This effect of BDNF, confirmed using a protein crosslinking assay, was dependent on ERK but not AKT signaling. In contrast, long-term BDNF treatment decreased AMPAR surface expression on NAc neurons. Based on this latter result, we tested the hypothesis that BDNF plays a role in AMPAR “scaling down” in response to a prolonged increase in neuronal activity produced by bicuculline (24 h). Supporting this hypothesis, decreasing BDNF signaling with the extracellular BDNF scavenger TrkB-Fc prevented the scaling down of GluA1 and GluA2 surface levels in NAc neurons normally produced by bicuculline. In conclusion, BDNF exerts bidirectional effects on NAc AMPAR surface expression, depending on duration of exposure. Furthermore, BDNF’s involvement in synaptic scaling in the NAc differs from its previously described role in the visual cortex. PMID:24712995

  3. BDNF and Huntingtin protein modifications by manganese: implications for striatal medium spiny neuron pathology in manganese neurotoxicity.

    PubMed

    Stansfield, Kirstie H; Bichell, Terry Jo; Bowman, Aaron B; Guilarte, Tomás R

    2014-12-01

    High levels of manganese (Mn) exposure decrease striatal medium spiny neuron (MSN) dendritic length and spine density, but the mechanism(s) are not known. The Huntingtin (HTT) gene has been functionally linked to cortical brain-derived neurotrophic factor (BDNF) support of striatal MSNs via phosphorylation at serine 421. In Huntington's disease, pathogenic CAG repeat expansions of HTT decrease synthesis and disrupt transport of cortical-striatal BDNF, which may contribute to disease, and Mn is a putative environmental modifier of Huntington's disease pathology. Thus, we tested the hypothesis that changes in MSN dendritic morphology Mn due to exposure are associated with decreased BDNF levels and alterations in Htt protein. We report that BDNF levels are decreased in the striatum of Mn-exposed non-human primates and in the cerebral cortex and striatum of mice exposed to Mn. Furthermore, proBDNF and mature BDNF concentrations in primary cortical and hippocampal neuron cultures were decreased by exposure to Mn confirming the in vivo findings. Mn exposure decreased serine 421 phosphorylation of Htt in cortical and hippocampal neurons and increased total Htt levels. These data strongly support the hypothesis that Mn-exposure-related MSN pathology is associated with decreased BDNF trophic support via alterations in Htt.

  4. MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse

    PubMed Central

    Antzoulatos, Eleni; Jakowec, Michael W.; Petzinger, Giselle M.; Wood, Ruth I.

    2011-01-01

    Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4 × 20 mg/kg) or saline (n = 11-12/group). The right striatum was immunostained for tyrosine hydroxylase (TH). The left hemisphere was stained by Golgi Cox to quantify neuronal morphology in medium spiny neurons (MSNs) of the dorsolateral striatum. MPTP reduced TH, but there was no effect of castration and no interaction. For MSN dendritic morphology, MPTP decreased the highest branch order and increased spine density on 2nd-order dendrites. Castrated males had shorter 5th-order dendrites. However, there was no interaction between gonadal status and MPTP. Thus, castration and MPTP exert nonoverlapping effects on MSN morphology with castration acting on distal dendrites and MPTP acting proximally. PMID:21765998

  5. Effects of morphine withdrawal on the membrane properties of medium spiny neurons in the nucleus accumbens shell.

    PubMed

    Wu, Xiaobo; Shi, Meimei; Ling, Hengli; Wei, Chunling; Liu, Yihui; Liu, Zhiqiang; Ren, Wei

    2013-01-01

    Medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo persistent alterations in their biological and physiological characteristics upon exposure to drugs of abuse. Previous studies demonstrated that the biochemical, morphological, and intrinsic physiological properties of MSNs are heterogeneous and provided new insights into the physiological and molecular roles of individual MSNs in addictive behaviors. However, it remains unclear whether MSNs in the NAc shell (NAcSh), an important region for mediating behavioral sensitization, are electrophysiologically heterogeneous and how such heterogeneity is relevant to neuroadaptation associated with drug addiction. Here, the membrane properties, i.e., the intrinsic excitability and spike adaptation, of MSNs in the NAcSh from saline- or morphine-treated rats were investigated in vitro by whole-cell recording. In saline-treated rats, three distinct cell types were identified by their membrane properties: type I neurons showed high levels of intrinsic excitability and rapid spike adaptation; type II neurons showed moderate levels of intrinsic excitability and relatively slow spike frequency adaptation; type III neurons showed low levels of intrinsic excitability and putative strong spike adaptation. MSNs in rats undergoing withdrawal from chronic morphine treatment (10-14 days after the last injection) also exhibited the typical firing behaviors of these three types of neurons. However, the membrane properties of the MSNs were differentially altered after withdrawal. There was an enhancement in intrinsic excitability in type II MSNs and a promotion of spike adaptation in type I MSNs. The apamin-sensitive afterhyperpolarization current (I(AHP)) and the apamin-insensitive I(AHP) of the NAcSh MSNs were attenuated after chronic morphine withdrawal. These findings suggest that individual MSNs in the NAcSh manifest unique electrophysiological properties, which might contribute to psychostimulant-induced neuroadaptation.

  6. Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training

    PubMed Central

    Bello-Medina, Paola C.; Flores, Gonzalo; Quirarte, Gina L.; McGaugh, James L.; Prado Alcalá, Roberto A.

    2016-01-01

    A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis. PMID:27698138

  7. Mushroom spine dynamics in medium spiny neurons of dorsal striatum associated with memory of moderate and intense training.

    PubMed

    Bello-Medina, Paola C; Flores, Gonzalo; Quirarte, Gina L; McGaugh, James L; Prado Alcalá, Roberto A

    2016-10-18

    A growing body of evidence indicates that treatments that typically impair memory consolidation become ineffective when animals are given intense training. This effect has been obtained by treatments interfering with the neural activity of several brain structures, including the dorsal striatum. The mechanisms that mediate this phenomenon are unknown. One possibility is that intense training promotes the transfer of information derived from the enhanced training to a wider neuronal network. We now report that inhibitory avoidance (IA) induces mushroom spinogenesis in the medium spiny neurons (MSNs) of the dorsal striatum in rats, which is dependent upon the intensity of the foot-shock used for training; that is, the effect is seen only when high-intensity foot-shock is used in training. We also found that the relative density of thin spines was reduced. These changes were evident at 6 h after training and persisted for at least 24 h afterward. Importantly, foot-shock alone did not increase spinogenesis. Spine density in MSNs in the accumbens was also increased, but the increase did not correlate with the associative process involved in IA; rather, it resulted from the administration of the aversive stimulation alone. These findings suggest that mushroom spines of MSNs of the dorsal striatum receive afferent information that is involved in the integrative activity necessary for memory consolidation, and that intense training facilitates transfer of information from the dorsal striatum to other brain regions through augmented spinogenesis.

  8. Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons.

    PubMed

    Jedynak, Jakub; Hearing, Matthew; Ingebretson, Anna; Ebner, Stephanie R; Kelly, Matthew; Fischer, Rachel A; Kourrich, Saïd; Thomas, Mark J

    2016-01-01

    Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10-14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed 'challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs.

  9. Cocaine and Amphetamine Induce Overlapping but Distinct Patterns of AMPAR Plasticity in Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Jedynak, Jakub; Hearing, Matthew; Ingebretson, Anna; Ebner, Stephanie R; Kelly, Matthew; Fischer, Rachel A; Kourrich, Saïd; Thomas, Mark J

    2016-01-01

    Repeated exposure to psychostimulant drugs such as cocaine or amphetamine can promote drug-seeking and -taking behavior. In rodent addiction models, persistent changes in excitatory glutamatergic neurotransmission in the nucleus accumbens (NAc) appear to drive this drug-induced behavioral plasticity. To study whether changes in glutamatergic signaling are shared between or exclusive to specific psychostimulant drugs, we examined synaptic transmission from mice following repeated amphetamine or cocaine administration. Synaptic transmission mediated by AMPA-type glutamate receptors was potentiated in the NAc shell 10–14 days following repeated amphetamine or cocaine treatment. This synaptic enhancement was depotentiated by re-exposure to amphetamine or cocaine. By contrast, in the NAc core only repeated cocaine exposure enhanced synaptic transmission, which was subsequently depotentiated by an additional cocaine but not amphetamine injection during drug abstinence. To better understand the drug-induced depotentiation, we replicated these in vivo findings using an ex vivo model termed ‘challenge in the bath,' and showed that drug-induced decreases in synaptic strength occur rapidly (within 30 min) and require activation of metabotropic glutamate receptor 5 (mGluR5) and protein synthesis in the NAc shell, but not NAc core. Overall, these data demonstrate the specificity of neuronal circuit changes induced by amphetamine, introduce a novel method for studying drug challenge-induced plasticity, and define NAc shell medium spiny neurons as a primary site of persistent AMPA-type glutamate receptor plasticity by two widely used psychostimulant drugs. PMID:26068728

  10. The Sodium Channel β4 Auxiliary Subunit Selectively Controls Long-Term Depression in Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Saha, Sucharita; Gao, Guangping; Lasek, Amy W.; Homanics, Gregg E.; Guildford, Melissa; Tapper, Andrew R.; Martin, Gilles E.

    2017-01-01

    Voltage-gated sodium channels are essential for generating the initial rapid depolarization of neuronal membrane potential during action potentials (APs) that enable cell-to-cell communication, the propagation of signals throughout the brain, and the induction of synaptic plasticity. Although all brain neurons express one or several variants coding for the core pore-forming sodium channel α subunit, the expression of the β (β1–4) auxiliary subunits varies greatly. Of particular interest is the β4 subunit, encoded by the Scn4b gene, that is highly expressed in dorsal and ventral (i.e., nucleus accumbens – NAc) striata compared to other brain regions, and that endows sodium channels with unique gating properties. However, its role on neuronal activity, synaptic plasticity, and behaviors related to drugs of abuse remains poorly understood. Combining whole-cell patch-clamp recordings with two-photon calcium imaging in Scn4b knockout (KO) and knockdown mice, we found that Scn4b altered the properties of APs in core accumbens medium spiny neurons (MSNs). These alterations are associated with a reduction of the probability of MSNs to evoke spike-timing-dependent long-term depression (tLTD) and a reduced ability of backpropagating APs to evoke dendritic calcium transients. In contrast, long-term potentiation (tLTP) remained unaffected. Interestingly, we also showed that amphetamine-induced locomotor activity was significantly reduced in male Scn4b KO mice compared to wild-type controls. Taken together, these data indicate that the Scn4b subunit selectively controls tLTD by modulating dendritic calcium transients evoked by backpropagating APs. PMID:28243192

  11. BK Channels Mediate Dopamine Inhibition of Firing in a Subpopulation of Core Nucleus Accumbens Medium Spiny Neurons

    PubMed Central

    Ji, Xincai; Martin, Gilles E.

    2014-01-01

    Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5 μM A-77636 and 10 μM quinpirole, dopamine D1 (DR1s) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibited evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all MSNs expressed fast (IA), slowly inactivating delayed rectifier (Idr), and large conductance voltage- and calcium-activated potassium (BKs) channels . Although A-77636 and quinpirole enhanced IA, its selective blockade by 0.5 μM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10 μM paxilline, a selective BK channel blocker, prevented D1R agonist from inhibiting MSN firing. This result indicates that dopamine inhibits MSN firing through BK channels in a subpopulation of core accumbens MSNs exclusively associated with spike-timing-dependent long-term potentiation. PMID:25219484

  12. High- and low-conductance NMDA receptors are present in layer 4 spiny stellate and layer 2/3 pyramidal neurons of mouse barrel cortex.

    PubMed

    Scheppach, Christian

    2016-12-01

    N-Methyl-D-aspartate (NMDA) receptors are ion channels activated by the neurotransmitter glutamate in the mammalian brain and are important in synaptic function and plasticity, but are also found in extrasynaptic locations and influence neuronal excitability. There are different NMDA receptor subtypes which differ in their single-channel conductance. Recently, synaptic plasticity has been studied in the mouse barrel cortex, the primary sensory cortex for input from the animal's whiskers. Pharmacological data imply the presence of low-conductance NMDA receptors in spiny stellate neurons of cortical layer 4, but of high-conductance NMDA receptors in pyramidal neurons of layer 2/3. Here, to obtain complementary electrophysiological information on the functional NMDA receptors expressed in layer 4 and layer 2/3 neurons, single NMDA receptor currents were recorded with the patch-clamp method. Both cell types were found to contain high-conductance as well as low-conductance NMDA receptors. The results are consistent with the reported pharmacological data on synaptic plasticity, and with previous claims of a prominent role of low-conductance NMDA receptors in layer 4 spiny stellate neurons, including broad integration, amplification and distribution of excitation within the barrel in response to whisker stimulation, as well as modulation of excitability by ambient glutamate. However, layer 4 cells also expressed high-conductance NMDA receptors. The presence of low-conductance NMDA receptors in layer 2/3 pyramidal neurons suggests that some of these functions may be shared with layer 4 spiny stellate neurons.

  13. Tonic inhibition of accumbal spiny neurons by extrasynaptic α4βδ GABAA receptors modulates the actions of psychostimulants.

    PubMed

    Maguire, Edward P; Macpherson, Tom; Swinny, Jerome D; Dixon, Claire I; Herd, Murray B; Belelli, Delia; Stephens, David N; King, Sarah L; Lambert, Jeremy J

    2014-01-15

    Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ(-/-) or α4(-/-) mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4(-/-) mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4(D1-/-)) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4(-/-) or α4(D1-/-) mice, blocked cocaine enhancement of CPP. In comparison, α4(D2-/-) mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors.

  14. Synaptic scaling up in medium spiny neurons of aged BACHD mice: A slow-progression model of Huntington's disease.

    PubMed

    Rocher, Anne B; Gubellini, Paolo; Merienne, Nicolas; Boussicault, Lydie; Petit, Fanny; Gipchtein, Pauline; Jan, Caroline; Hantraye, Philippe; Brouillet, Emmanuel; Bonvento, Gilles

    2016-02-01

    Huntington's disease (HD) is an autosomal dominant disease that develops in midlife (~ 40 years-old at onset) and then progresses slowly. It is still unclear how striatal medium spiny neurons (MSNs), the most vulnerable neurons in HD, maintain their function for decades despite the chronic expression of mutant huntingtin (mHTT). In this study, we used aged BACHD mice, a HD model expressing the full-length human mHTT gene, to investigate the molecular, morphological and functional properties of striatal MSNs. We report that the density of dendritic spines in MSNs is substantially lower in aged BACHD mice than in wild-type (WT) mice, in the absence of major dendritic changes and neuronal loss. This spine loss is accompanied by changes in transcription, resulting in a low expression of the striatum-specific G protein-coupled receptor 88 (Gpr88) as well as a reorganization of the composition of AMPAR subunits (high Gria1/Gria2 mRNA ratio). We also detected functional changes in BACHD MSNs. Notably, BACHD MSNs were hyperexcitable and the amplitude of AMPAR-mediated synaptic currents was higher than in WT MSNs. Altogether, these data show that both the intrinsic properties and the strength of the remaining synapses are modified in MSNs with low dendritic spine density in aged BACHD mice. These homeostatic mechanisms may compensate for the substantial loss of synaptic inputs and thus alleviate the deleterious effects of mHTT expression on the activity of MSNs and also possibly on the motor phenotype in aged BACHD.

  15. Tonic Inhibition of Accumbal Spiny Neurons by Extrasynaptic α4βδ GABAA Receptors Modulates the Actions of Psychostimulants

    PubMed Central

    Maguire, Edward P.; Macpherson, Tom; Swinny, Jerome D.; Dixon, Claire I.; Herd, Murray B.; Belelli, Delia; Stephens, David N.

    2014-01-01

    Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors. PMID:24431441

  16. Inhibitory Synapse Formation in a Co-culture Model Incorporating GABAergic Medium Spiny Neurons and HEK293 Cells Stably Expressing GABAA Receptors

    PubMed Central

    Brown, Laura E.; Fuchs, Celine; Nicholson, Martin W.; Stephenson, F. Anne; Thomson, Alex M.; Jovanovic, Jasmina N.

    2014-01-01

    Inhibitory neurons act in the central nervous system to regulate the dynamics and spatio-temporal co-ordination of neuronal networks. GABA (γ-aminobutyric acid) is the predominant inhibitory neurotransmitter in the brain. It is released from the presynaptic terminals of inhibitory neurons within highly specialized intercellular junctions known as synapses, where it binds to GABAA receptors (GABAARs) present at the plasma membrane of the synapse-receiving, postsynaptic neurons. Activation of these GABA-gated ion channels leads to influx of chloride resulting in postsynaptic potential changes that decrease the probability that these neurons will generate action potentials. During development, diverse types of inhibitory neurons with distinct morphological, electrophysiological and neurochemical characteristics have the ability to recognize their target neurons and form synapses which incorporate specific GABAARs subtypes. This principle of selective innervation of neuronal targets raises the question as to how the appropriate synaptic partners identify each other. To elucidate the underlying molecular mechanisms, a novel in vitro co-culture model system was established, in which medium spiny GABAergic neurons, a highly homogenous population of neurons isolated from the embryonic striatum, were cultured with stably transfected HEK293 cell lines that express different GABAAR subtypes. Synapses form rapidly, efficiently and selectively in this system, and are easily accessible for quantification. Our results indicate that various GABAAR subtypes differ in their ability to promote synapse formation, suggesting that this reduced in vitro model system can be used to reproduce, at least in part, the in vivo conditions required for the recognition of the appropriate synaptic partners and formation of specific synapses. Here the protocols for culturing the medium spiny neurons and generating HEK293 cells lines expressing GABAARs are first described, followed by detailed

  17. Tetrahydrocarbazoles decrease elevated SOCE in medium spiny neurons from transgenic YAC128 mice, a model of Huntington's disease.

    PubMed

    Czeredys, Magdalena; Maciag, Filip; Methner, Axel; Kuznicki, Jacek

    2017-02-19

    Huntington's disease (HD) is a hereditary neurodegenerative disease caused by a polyglutamine expansion within the huntingtin (HTT) gene. One of the cellular functions that is dysregulated in HD is store-operated calcium entry (SOCE), a process in which the depletion of Ca(2+) from the endoplasmic reticulum (ER) induces Ca(2+) influx from the extracellular space. We detected an enhanced activity of SOC channels in medium spiny neurons (MSNs) from YAC128 mice, a transgenic model of HD, and investigated whether this could be reverted by tetrahydrocarbazoles. The compound 6-bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride was indeed able to restore the disturbed Ca(2+) homeostasis and stabilize SOCE in YAC128 MSN cultures. We also detected a beneficial effect of this compound on the mitochondrial membrane potential. Since dysregulated Ca(2+) homeostasis is believed to be one of the pathological hallmarks of HD, this compound might be a lead structure for HD treatment.

  18. Dysregulated information processing by medium spiny neurons in striatum of freely behaving mouse models of Huntington's disease.

    PubMed

    Miller, Benjamin R; Walker, Adam G; Shah, Anand S; Barton, Scott J; Rebec, George V

    2008-10-01

    Huntington's disease (HD) is an autosomal dominant condition that compromises behavioral output. Dysfunction of medium spiny neurons (MSNs), which are the sole output system of the striatum, is thought to underlie HD pathophysiology. What is not known is how HD alters MSN information processing during behavior, which likely drives the HD behavioral phenotype. We recorded from populations of MSNs in two freely behaving and symptomatic HD mouse models: R6/2 transgenics are based on a C57BL/6J*CBA/J background and show robust behavioral symptoms, whereas knock-in (KI) mice have a 129sv background and express relatively mild behavioral signs. At the single-unit level, we found that the MSN firing rate was elevated in R6/2 but not in KI mice compared with their respective wild-type (WT) controls. In contrast, burst activity, which corresponds to periods of high-frequency firing, was altered in both HD models compared with WT. At the population level, we found that correlated firing between pairs of MSNs was a prominent feature in WT that was reduced in both HD models. Similarly, coincident bursts, which are bursts between pairs of neurons that overlap in time and occur more often in pairs of MSNs that exhibit correlated firing, were decreased in HD mice. Our results indicate an important role in both bursting and correlated burst firing for information processing in MSNs. Dysregulation of this processing scheme, moreover, is a key component of HD pathophysiology regardless of the severity of HD symptoms, genetic construct, and background strain of the mouse models.

  19. Ultrastructural localization of 5'AMP odorant receptor sites on the dendrites of olfactory receptor neurons of the spiny lobster.

    PubMed

    Blaustein, D N; Simmons, R B; Burgess, M F; Derby, C D; Nishikawa, M; Olson, K S

    1993-07-01

    A unique probe--biotinylated adenosine-5'-monophosphate (5'AMP-biotin)--was used in transmission electron microscopic (TEM) studies to localize 5'AMP odorant binding sites on the dendrites of olfactory receptor neurons in the aesthetasc sensilla of the spiny lobster, Panulirus argus. This probe is capable of both binding to and exciting 5'AMP-sensitive olfactory receptor neurons, as revealed through biochemical and electrophysiological assays. TEM studies showed that 5'AMP-biotin binding sites are distributed along the entire dendritic region that is exposed to odorants, including the transitional zone (between the inner and outer dendritic segments, including the ciliary segment) and all of the outer dendritic segment. The density of 5'AMP binding sites per micron2 of membrane is similar along the length of the olfactory dendrite. However, the relative number of 5'AMP-biotin binding sites per micron2 of sensillar area diminishes in the distal 30% of the aesthetasc due to a decrease in the amount of dendritic membrane in that region. The distribution of these 5'AMP binding sites is therefore much more extensive than that of enzymes that inactivate 5'AMP--5'ectonucleotidase/phosphatase--which are restricted to the transitional zone (Gleeson et al., 1991). Taken together, these results suggest that 5'AMP-biotin is labeling 5'AMP-specific olfactory receptor sites that are located along the entire outer dendritic segment and that can be coupled to olfactory transduction. This study represents the first in situ localization of specific olfactory receptor sites using a specific, functionally defined ligand.

  20. Inositol 1,4,5-triphosphate drives glutamatergic and cholinergic inhibition selectively in spiny projection neurons in the striatum.

    PubMed

    Clements, Michael A; Swapna, Immani; Morikawa, Hitoshi

    2013-02-06

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluR1/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluR1 and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluR1 subtype. Ca(2+) release from intracellular stores specifically through inositol 1,4,5-triphospahte receptors (IP(3)Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca(2+)-activated K(+) channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca(2+) influx triggers Ca(2+) release solely through RyRs to generate SK-dependent slow afterhyperpolarizations, demonstrating functional segregation of IP(3)Rs and RyRs. Finally, IP(3)-induced Ca(2+) release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP(3)-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity.

  1. Inositol 1,4,5-Triphosphate Drives Glutamatergic and Cholinergic Inhibition Selectively in Spiny Projection Neurons in the Striatum

    PubMed Central

    Clements, Michael A.; Swapna, Immani; Morikawa, Hitoshi

    2013-01-01

    The striatum is critically involved in the selection of appropriate actions in a constantly changing environment. The spiking activity of striatal spiny projection neurons (SPNs), driven by extrinsic glutamatergic inputs, is shaped by local GABAergic and cholinergic networks. For example, it is well established that different types of GABAergic interneurons, activated by extrinsic glutamatergic and local cholinergic inputs, mediate powerful feedforward inhibition of SPN activity. In this study, using mouse striatal slices, we show that glutamatergic and cholinergic inputs exert direct inhibitory regulation of SPN activity via activation of metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. While pressure ejection of the group I mGluR (mGluR1/5) agonist DHPG [(S)-3,5-dihydroxyphenylglycine] equally engages both mGluR1 and mGluR5 subtypes, the mGluR-dependent component of IPSCs elicited by intrastriatal electrical stimulation is almost exclusively mediated by the mGluR1 subtype. Ca2+ release from intracellular stores specifically through inositol 1,4,5-triphospahte receptors (IP3Rs) and not ryanodine receptors (RyRs) mediates this form of inhibition by gating two types of Ca2+ -activated K+ channels (i.e., small-conductance SK channels and large-conductance BK channels). Conversely, spike-evoked Ca2+ influx triggers Ca2+ release solely through RyRs to generate SK-dependent slow afterhyperpolarizations, demonstrating functional segregation of IP3Rs and RyRs. Finally, IP3-induced Ca2+ release is uniquely observed in SPNs and not in different types of interneurons in the striatum. These results demonstrate that IP3-mediated activation of SK and BK channels provides a robust mechanism for glutamatergic and cholinergic inputs to selectively suppress striatal output neuron activity. PMID:23392696

  2. Neuronal Dysfunction in iPSC-Derived Medium Spiny Neurons from Chorea-Acanthocytosis Patients Is Reversed by Src Kinase Inhibition and F-Actin Stabilization.

    PubMed

    Stanslowsky, Nancy; Reinhardt, Peter; Glass, Hannes; Kalmbach, Norman; Naujock, Maximilian; Hensel, Niko; Lübben, Verena; Pal, Arun; Venneri, Anna; Lupo, Francesca; De Franceschi, Lucia; Claus, Peter; Sterneckert, Jared; Storch, Alexander; Hermann, Andreas; Wegner, Florian

    2016-11-23

    Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc. Patient-derived MSNs displayed enhanced neurite outgrowth and ramification, whereas synaptic density was similar to controls. Electrophysiological analysis revealed a pathologically elevated synaptic activity in ChAc MSNs. Treatment with the F-actin stabilizer phallacidin or the Src kinase inhibitor PP2 resulted in the significant reduction of disinhibited synaptic currents to healthy control levels, suggesting a Src kinase- and actin-dependent mechanism. This was underlined by increased G/F-actin ratios and elevated Lyn kinase activity in patient-derived MSNs. These data indicate that F-actin stabilization and Src kinase inhibition represent potential therapeutic targets in ChAc that may restore neuronal function.

  3. Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway requires the activation of D1-like receptors and NO/soluble guanylate cyclase/cGMP transmission.

    PubMed

    Arcangeli, Sara; Tozzi, Alessandro; Tantucci, Michela; Spaccatini, Cristiano; de Iure, Antonio; Costa, Cinzia; Di Filippo, Massimiliano; Picconi, Barbara; Giampà, Carmen; Fusco, Francesca Romana; Amoroso, Salvatore; Calabresi, Paolo

    2013-02-01

    Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in striatal NOS-positive interneurons, we hypothesized a relation between NOS-positive interneurons and striatal i-LTP, involving D1R activation and NO production. We investigated the mechanisms involved in i-LTP induced by OGD in corticostriatal slices and found that the D1-like-R antagonist SCH-23390 prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the induction of i-LTP in both substance P-positive, (putative D1R-expressing) and adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i-LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS, guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to prevent i-LTP in the presence of a NO donor or cGMP analog, respectively. Interestingly, the D1-like-R antagonism failed to prevent i-LTP when intracellular cGMP was pharmacologically increased. We propose that NO, produced by striatal NOS-positive interneurons via the stimulation of D1-like-R located on these cells, is critical for i-LTP induction in the entire population of MSNs involving a cGMP-dependent pathway.

  4. Ischemic-LTP in striatal spiny neurons of both direct and indirect pathway requires the activation of D1-like receptors and NO/soluble guanylate cyclase/cGMP transmission

    PubMed Central

    Arcangeli, Sara; Tozzi, Alessandro; Tantucci, Michela; Spaccatini, Cristiano; de Iure, Antonio; Costa, Cinzia; Di Filippo, Massimiliano; Picconi, Barbara; Giampà, Carmen; Fusco, Francesca Romana; Amoroso, Salvatore; Calabresi, Paolo

    2013-01-01

    Striatal medium-sized spiny neurons (MSNs) are highly vulnerable to ischemia. A brief ischemic insult, produced by oxygen and glucose deprivation (OGD), can induce ischemic long-term potentiation (i-LTP) of corticostriatal excitatory postsynaptic response. Since nitric oxide (NO) is involved in the pathophysiology of brain ischemia and the dopamine D1/D5-receptors (D1-like-R) are expressed in striatal NOS-positive interneurons, we hypothesized a relation between NOS-positive interneurons and striatal i-LTP, involving D1R activation and NO production. We investigated the mechanisms involved in i-LTP induced by OGD in corticostriatal slices and found that the D1-like-R antagonist SCH-23390 prevented i-LTP in all recorded MSNs. Immunofluorescence analysis confirmed the induction of i-LTP in both substance P-positive, (putative D1R-expressing) and adenosine A2A-receptor-positive (putative D2R-expressing) MSNs. Furthermore, i-LTP was dependent on a NOS/cGMP pathway since pharmacological blockade of NOS, guanylate-cyclase, or PKG prevented i-LTP. However, these compounds failed to prevent i-LTP in the presence of a NO donor or cGMP analog, respectively. Interestingly, the D1-like-R antagonism failed to prevent i-LTP when intracellular cGMP was pharmacologically increased. We propose that NO, produced by striatal NOS-positive interneurons via the stimulation of D1-like-R located on these cells, is critical for i-LTP induction in the entire population of MSNs involving a cGMP-dependent pathway. PMID:23149555

  5. Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses.

    PubMed

    Lee, Hyun Joo; Weitz, Andrew J; Bernal-Casas, David; Duffy, Ben A; Choy, ManKin; Kravitz, Alexxai V; Kreitzer, Anatol C; Lee, Jin Hyung

    2016-07-20

    A central theory of basal ganglia function is that striatal neurons expressing the D1 and D2 dopamine receptors exert opposing brain-wide influences. However, the causal influence of each population has never been measured at the whole-brain scale. Here, we selectively stimulated D1 or D2 receptor-expressing neurons while visualizing whole-brain activity with fMRI. Excitation of either inhibitory population evoked robust positive BOLD signals within striatum, while downstream regions exhibited significantly different and generally opposing responses consistent with-though not easily predicted from-contemporary models of basal ganglia function. Importantly, positive and negative signals within the striatum, thalamus, GPi, and STN were all associated with increases and decreases in single-unit activity, respectively. These findings provide direct evidence for the opposing influence of D1 and D2 receptor-expressing striatal neurons on brain-wide circuitry and extend the interpretability of fMRI studies by defining cell-type-specific contributions to the BOLD signal. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.

    PubMed

    Kolodziejczyk, Karolina; Raymond, Lynn A

    2016-02-01

    Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input.

  7. ΔFosB Induction in Striatal Medium Spiny Neuron Subtypes in Response to Chronic Pharmacological, Emotional, and Optogenetic Stimuli

    PubMed Central

    Lobo, Mary Kay; Zaman, Samir; Damez-Werno, Diane M.; Koo, Ja Wook; Bagot, Rosemary C.; DiNieri, Jennifer A.; Nugent, Alexandria; Finkel, Eric; Chaudhury, Dipesh; Chandra, Ramesh; Riberio, Efrain; Rabkin, Jacqui; Mouzon, Ezekiell; Cachope, Roger; Cheer, Joseph F.; Han, Ming-Hu; Dietz, David M.; Self, David W.; Hurd, Yasmin L.; Vialou, Vincent

    2013-01-01

    The transcription factor, ΔFosB, is robustly and persistently induced in striatum by several chronic stimuli, such as drugs of abuse, antipsychotic drugs, natural rewards, and stress. However, very few studies have examined the degree of ΔFosB induction in the two striatal medium spiny neuron (MSN) subtypes. We make use of fluorescent reporter BAC transgenic mice to evaluate induction of ΔFosB in dopamine receptor 1 (D1) enriched and dopamine receptor 2 (D2) enriched MSNs in ventral striatum, nucleus accumbens (NAc) shell and core, and in dorsal striatum (dStr) after chronic exposure to several drugs of abuse including cocaine, ethanol, Δ(9)-tetrahydrocannabinol, and opiates; the antipsychotic drug, haloperidol; juvenile enrichment; sucrose drinking; calorie restriction; the serotonin selective reuptake inhibitor antidepressant, fluoxetine; and social defeat stress. Our findings demonstrate that chronic exposure to many stimuli induces ΔFosB in an MSN-subtype selective pattern across all three striatal regions. To explore the circuit-mediated induction of ΔFosB in striatum, we use optogenetics to enhance activity in limbic brain regions that send synaptic inputs to NAc; these regions include the ventral tegmental area and several glutamatergic afferent regions: medial prefrontal cortex, amygdala, and ventral hippocampus. These optogenetic conditions lead to highly distinct patterns of ΔFosB induction in MSN subtypes in NAc core and shell. Together, these findings establish selective patterns of ΔFosB induction in striatal MSN subtypes in response to chronic stimuli and provide novel insight into the circuit-level mechanisms of ΔFosB induction in striatum. PMID:24259563

  8. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward

    PubMed Central

    Calipari, Erin S.; Bagot, Rosemary C.; Purushothaman, Immanuel; Davidson, Thomas J.; Yorgason, Jordan T.; Peña, Catherine J.; Walker, Deena M.; Pirpinias, Stephen T.; Guise, Kevin G.; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J.

    2016-01-01

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context–reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse. PMID:26831103

  9. Type 1 Cannabinoid Receptor Ligands Display Functional Selectivity in a Cell Culture Model of Striatal Medium Spiny Projection Neurons*

    PubMed Central

    Laprairie, Robert B.; Bagher, Amina M.; Kelly, Melanie E. M.; Dupré, Denis J.; Denovan-Wright, Eileen M.

    2014-01-01

    Modulation of type 1 cannabinoid receptor (CB1) activity has been touted as a potential means of treating addiction, anxiety, depression, and neurodegeneration. Different agonists of CB1 are known to evoke varied responses in vivo. Functional selectivity is the ligand-specific activation of certain signal transduction pathways at a receptor that can signal through multiple pathways. To understand cannabinoid-specific functional selectivity, different groups have examined the effect of individual cannabinoids on various signaling pathways in heterologous expression systems. In the current study, we compared the functional selectivity of six cannabinoids, including two endocannabinoids (2-arachidonyl glycerol (2-AG) and anandamide (AEA)), two synthetic cannabinoids (WIN55,212-2 and CP55,940), and two phytocannabinoids (cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC)) on arrestin2-, Gαi/o-, Gβγ-, Gαs-, and Gαq-mediated intracellular signaling in the mouse STHdhQ7/Q7 cell culture model of striatal medium spiny projection neurons that endogenously express CB1. In this system, 2-AG, THC, and CP55,940 were more potent mediators of arrestin2 recruitment than other cannabinoids tested. 2-AG, AEA, and WIN55,212-2, enhanced Gαi/o and Gβγ signaling, with 2-AG and AEA treatment leading to increased total CB1 levels. 2-AG, AEA, THC, and WIN55,212-2 also activated Gαq-dependent pathways. CP55,940 and CBD both signaled through Gαs. CP55,940, but not CBD, activated downstream Gαs pathways via CB1 targets. THC and CP55,940 promoted CB1 internalization and decreased CB1 protein levels over an 18-h period. These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways. To effectively match cannabinoids with therapeutic goals, these compounds must be screened for their signaling bias. PMID:25037227

  10. ΔFosB induction in striatal medium spiny neuron subtypes in response to chronic pharmacological, emotional, and optogenetic stimuli.

    PubMed

    Lobo, Mary Kay; Zaman, Samir; Damez-Werno, Diane M; Koo, Ja Wook; Bagot, Rosemary C; DiNieri, Jennifer A; Nugent, Alexandria; Finkel, Eric; Chaudhury, Dipesh; Chandra, Ramesh; Riberio, Efrain; Rabkin, Jacqui; Mouzon, Ezekiell; Cachope, Roger; Cheer, Joseph F; Han, Ming-Hu; Dietz, David M; Self, David W; Hurd, Yasmin L; Vialou, Vincent; Nestler, Eric J

    2013-11-20

    The transcription factor, ΔFosB, is robustly and persistently induced in striatum by several chronic stimuli, such as drugs of abuse, antipsychotic drugs, natural rewards, and stress. However, very few studies have examined the degree of ΔFosB induction in the two striatal medium spiny neuron (MSN) subtypes. We make use of fluorescent reporter BAC transgenic mice to evaluate induction of ΔFosB in dopamine receptor 1 (D1) enriched and dopamine receptor 2 (D2) enriched MSNs in ventral striatum, nucleus accumbens (NAc) shell and core, and in dorsal striatum (dStr) after chronic exposure to several drugs of abuse including cocaine, ethanol, Δ(9)-tetrahydrocannabinol, and opiates; the antipsychotic drug, haloperidol; juvenile enrichment; sucrose drinking; calorie restriction; the serotonin selective reuptake inhibitor antidepressant, fluoxetine; and social defeat stress. Our findings demonstrate that chronic exposure to many stimuli induces ΔFosB in an MSN-subtype selective pattern across all three striatal regions. To explore the circuit-mediated induction of ΔFosB in striatum, we use optogenetics to enhance activity in limbic brain regions that send synaptic inputs to NAc; these regions include the ventral tegmental area and several glutamatergic afferent regions: medial prefrontal cortex, amygdala, and ventral hippocampus. These optogenetic conditions lead to highly distinct patterns of ΔFosB induction in MSN subtypes in NAc core and shell. Together, these findings establish selective patterns of ΔFosB induction in striatal MSN subtypes in response to chronic stimuli and provide novel insight into the circuit-level mechanisms of ΔFosB induction in striatum.

  11. Involvement of the Striatal Medium Spiny Neurons of the Direct Pathway in the Motor Stimulant Effects of Phencyclidine

    PubMed Central

    Bonito-Oliva, Alessandra; DuPont, Caitlin; Madjid, Nather; Ögren, Sven Ove

    2016-01-01

    Background: The psychotomimetic phencyclidine (PCP) produces behavioral symptoms similar to those observed in schizophrenia, accompanied by increased motor activity. The dopamine and adenosine 3’,5’-cyclic monophosphate-regulated phosphoprotein of 32kDa (DARPP-32) is enriched in the medium spiny neurons (MSNs) of the striatum and has been implicated in the actions of PCP. We examined the effects of deletion of DARPP-32 in distinct populations of striatal MSNs, on the ability of PCP to induce motor activation and memory deficit. Methods: The effects of PCP were examined in mice with conditional knockout of DARPP-32 in the MSNs of the direct, or indirect pathway. DARPP-32 phosphorylation was determined by Western blotting. The motor stimulant effects of PCP were determined by measuring locomotion following acute and chronic administration. Memory deficit was evaluated using the passive avoidance test. Results: Loss of DARPP-32 in direct MSNs prevents PCP-induced phosphorylation and abolishes the motor stimulation effects of PCP. In contrast, lack of DARPP-32 in indirect MSNs does not affect the ability of PCP to promote DARPP-32 phosphorylation and to increase motor activity. The impairment in passive avoidance induced by PCP is independent of the expression of DARPP-32 in direct or indirect MSNs. Conclusions: The increase in DARPP-32 phosphorylation induced by PCP occurs selectively in the MSNs of the direct pathway, which are also specifically involved in the motor stimulant effects of this drug. The memory deficit induced by PCP is not linked to the expression of DARPP-32 in striatal MSNs. PMID:26657176

  12. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward.

    PubMed

    Calipari, Erin S; Bagot, Rosemary C; Purushothaman, Immanuel; Davidson, Thomas J; Yorgason, Jordan T; Peña, Catherine J; Walker, Deena M; Pirpinias, Stephen T; Guise, Kevin G; Ramakrishnan, Charu; Deisseroth, Karl; Nestler, Eric J

    2016-03-08

    The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to extinguish these associations is a key factor contributing to relapse. Dopamine produces these effects by controlling the activity of two subpopulations of NAc medium spiny neurons (MSNs) that are defined by their predominant expression of either dopamine D1 or D2 receptors. Previous work has demonstrated that optogenetically stimulating D1 MSNs promotes reward, whereas stimulating D2 MSNs produces aversion. However, we still lack a clear understanding of how the endogenous activity of these cell types is affected by cocaine and encodes information that drives drug-associated behaviors. Using fiber photometry calcium imaging we define D1 MSNs as the specific population of cells in NAc that encodes information about drug associations and elucidate the temporal profile with which D1 activity is increased to drive drug seeking in response to contextual cues. Chronic cocaine exposure dysregulates these D1 signals to both prevent extinction and facilitate reinstatement of drug seeking to drive relapse. Directly manipulating these D1 signals using designer receptors exclusively activated by designer drugs prevents contextual associations. Together, these data elucidate the responses of D1- and D2-type MSNs in NAc to acute cocaine and during the formation of context-reward associations and define how prior cocaine exposure selectively dysregulates D1 signaling to drive relapse.

  13. The presence of cortical neurons in striatal-cortical co-cultures alters the effects of dopamine and BDNF on medium spiny neuron dendritic development

    PubMed Central

    Penrod, Rachel D.; Campagna, Justin; Panneck, Travis; Preese, Laura; Lanier, Lorene M.

    2015-01-01

    Medium spiny neurons (MSNs) are the major striatal neuron and receive synaptic input from both glutamatergic and dopaminergic afferents. These synapses are made on MSN dendritic spines, which undergo density and morphology changes in association with numerous disease and experience-dependent states. Despite wide interest in the structure and function of mature MSNs, relatively little is known about MSN development. Furthermore, most in vitro studies of MSN development have been done in simple striatal cultures that lack any type of non-autologous synaptic input, leaving open the question of how MSN development is affected by a complex environment that includes other types of neurons, glia, and accompanying secreted and cell-associated cues. Here we characterize the development of MSNs in striatal-cortical co-culture, including quantitative morphological analysis of dendritic arborization and spine development, describing progressive changes in density and morphology of developing spines. Overall, MSN growth is much more robust in the striatal-cortical co-culture compared to striatal mono-culture. Inclusion of dopamine (DA) in the co-culture further enhances MSN dendritic arborization and spine density, but the effects of DA on dendritic branching are only significant at later times in development. In contrast, exogenous Brain Derived Neurotrophic Factor (BDNF) has only a minimal effect on MSN development in the co-culture, but significantly enhances MSN dendritic arborization in striatal mono-culture. Importantly, inhibition of NMDA receptors in the co-culture significantly enhances the effect of exogenous BDNF, suggesting that the efficacy of BDNF depends on the cellular environment. Combined, these studies identify specific periods of MSN development that may be particularly sensitive to perturbation by external factors and demonstrate the importance of studying MSN development in a complex signaling environment. PMID:26257605

  14. Medium spiny neurons of the neostriatal matrix exhibit specific, stereotyped changes in dendritic arborization during a critical developmental period in mice.

    PubMed

    Lee, Hyunchul; Sawatari, Atomu

    2011-11-01

    In mice, the matrix compartment of the striatum (caudate/putamen) undergoes major developmental changes during the second postnatal week, including the establishment of corticostriatal and nigrostriatal afferents, the maturation of parvalbumin-positive interneurons and the appearance of perineuronal nets. It is not known if any of these events influence the dendritic structure of medium spiny neurons, the principal output cells of the striatum. To determine whether any measurable changes in the dendrites of matrix medium spiny neurons occur during this important developmental period, we labeled individual cells at different time points flanking the second postnatal week. These cells exhibit distinct dendritic morphologies from the earliest postnatal time points examined. Furthermore, our data show that the dendritic arbors of these neurons change in length, branch points, diameter and tortuosity, regardless of morphological type. The increase in dendritic length is accompanied by a decrease in the number of branch points that occur in different, but consistent, parts of the dendritic arbor. All of these changes are most pronounced during the second postnatal week, coinciding with a number of developmental events considered important for consolidating circuitry within the striatal matrix. Our results further support the critical importance of this early postnatal period in striatal development.

  15. Multiscale imaging characterization of dopamine transporter knockout mice reveals regional alterations in spine density of medium spiny neurons.

    PubMed

    Berlanga, M L; Price, D L; Phung, B S; Giuly, R; Terada, M; Yamada, N; Cyr, M; Caron, M G; Laakso, A; Martone, M E; Ellisman, M H

    2011-05-16

    The dopamine transporter knockout (DAT KO) mouse is a model of chronic hyperdopaminergia used to study a wide range of neuropsychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), drug abuse, depression, and Parkinson's disease (PD). Early studies characterizing this mouse model revealed a subtle, but significant, decrease in the anterior striatal volume of DAT KO mice accompanied by a decrease in neuronal cell body numbers (Cyr et al., 2005). The present studies were conducted to examine medium spiny neuron (MSN) morphology by extending these earlier reports to include multiscale imaging studies using correlated light microscopy (LM) and electron microscopy (EM) techniques. Specifically, we set out to determine if chronic hyperdopaminergia results in quantifiable or qualitative changes in DAT KO mouse MSNs relative to wild-type (WT) littermates. Using Neurolucida Explorer's morphometric analysis, we measured spine density, dendritic length and synapse number at ages that correspond with the previously reported changes in striatal volume and progressive cell loss. Light microscopic analysis using Neurolucida tracings of photoconverted striatal MSNs revealed a highly localized loss of dendritic spines on the proximal portion of the dendrite (30 μm from the soma) in the DAT KO group. Next, thick sections containing MSN dendritic segments located at a distance of 20-60 μm from the cell soma, a region of the dendrite where spine density is reported to be the highest, were analyzed using electron microscope tomography (EMT). Because of the resolution limits of LM, the EM analysis was an extra measure taken to assure that our analysis included nearly all spines. Spine density measurements collected from the EMT data revealed only a modest decrease in the DAT KO group (n=3 mice) compared to age-matched WT controls (n=3 mice), a trend that supports the LM findings. Finally, a synaptic quantification using unbiased stereology did not

  16. Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons.

    PubMed

    Laprairie, Robert B; Bagher, Amina M; Kelly, Melanie E M; Dupré, Denis J; Denovan-Wright, Eileen M

    2014-09-05

    Modulation of type 1 cannabinoid receptor (CB1) activity has been touted as a potential means of treating addiction, anxiety, depression, and neurodegeneration. Different agonists of CB1 are known to evoke varied responses in vivo. Functional selectivity is the ligand-specific activation of certain signal transduction pathways at a receptor that can signal through multiple pathways. To understand cannabinoid-specific functional selectivity, different groups have examined the effect of individual cannabinoids on various signaling pathways in heterologous expression systems. In the current study, we compared the functional selectivity of six cannabinoids, including two endocannabinoids (2-arachidonyl glycerol (2-AG) and anandamide (AEA)), two synthetic cannabinoids (WIN55,212-2 and CP55,940), and two phytocannabinoids (cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC)) on arrestin2-, Gα(i/o)-, Gβγ-, Gα(s)-, and Gα(q)-mediated intracellular signaling in the mouse STHdh(Q7/Q7) cell culture model of striatal medium spiny projection neurons that endogenously express CB1. In this system, 2-AG, THC, and CP55,940 were more potent mediators of arrestin2 recruitment than other cannabinoids tested. 2-AG, AEA, and WIN55,212-2, enhanced Gα(i/o) and Gβγ signaling, with 2-AG and AEA treatment leading to increased total CB1 levels. 2-AG, AEA, THC, and WIN55,212-2 also activated Gα(q)-dependent pathways. CP55,940 and CBD both signaled through Gα(s). CP55,940, but not CBD, activated downstream Gα(s) pathways via CB1 targets. THC and CP55,940 promoted CB1 internalization and decreased CB1 protein levels over an 18-h period. These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways. To effectively match cannabinoids with therapeutic goals, these compounds must be screened for their signaling bias. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Erbb4 Deletion from Medium Spiny Neurons of the Nucleus Accumbens Core Induces Schizophrenia-Like Behaviors via Elevated GABAA Receptor α1 Subunit Expression.

    PubMed

    Geng, Hong-Yan; Zhang, Jing; Yang, Jian-Ming; Li, Yue; Wang, Ning; Ye, Mao; Chen, Xiao-Juan; Lian, Hong; Li, Xiao-Ming

    2017-08-02

    Medium spiny neurons (MSNs), the major GABAergic projection neurons in the striatum, are implicated in many neuropsychiatric diseases such as schizophrenia, but the underlying mechanisms remain unclear. We found that a deficiency in Erbb4, a schizophrenia risk gene, in MSNs of the nucleus accumbens (NAc) core, but not the dorsomedial striatum, markedly induced schizophrenia-like behaviors such as hyperactivity, abnormal marble-burying behavior, damaged social novelty recognition, and impaired sensorimotor gating function in male mice. Using immunohistochemistry, Western blot, RNA interference, electrophysiology, and behavior test studies, we found that these phenomena were mediated by increased GABAA receptor α1 subunit (GABAAR α1) expression, which enhanced inhibitory synaptic transmission on MSNs. These results suggest that Erbb4 in MSNs of the NAc core may contribute to the pathogenesis of schizophrenia by regulating GABAergic transmission and raise the possibility that GABAAR α1 may therefore serve as a new therapeutic target for schizophrenia.SIGNIFICANCE STATEMENT Although ErbB4 is highly expressed in striatal medium spiny neurons (MSNs), its role in this type of neuron has not been reported previously. The present study demonstrates that Erbb4 deletion in nucleus accumbens (NAc) core MSNs can induce schizophrenia-like behaviors via elevated GABAA receptor α1 subunit (GABAAR α1) expression. To our knowledge, this is the first evidence that ErbB4 signaling in the MSNs is involved in the pathology of schizophrenia. Furthermore, restoration of GABAAR α1 in the NAc core, but not the dorsal medium striatum, alleviated the abnormal behaviors. Here, we highlight the role of the NAc core in the pathogenesis of schizophrenia and suggest that GABAAR α1 may be a potential pharmacological target for its treatment. Copyright © 2017 the authors 0270-6474/17/377450-15$15.00/0.

  18. Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice.

    PubMed

    Schier, Christina J; Marks, William D; Paris, Jason J; Barbour, Aaron J; McLane, Virginia D; Maragos, William F; McQuiston, A Rory; Knapp, Pamela E; Hauser, Kurt F

    2017-06-07

    Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology, with motor impairment a frequent manifestation of chronic infection. However, little is known about the response of individual striatal neuron types to HIV or how this disrupts function. Therefore, we investigated the morphological and electrophysiological effects of HIV-1 trans-activator of transcription (Tat) in dopamine subtype 1 (D1) and dopamine subtype 2 (D2) receptor-expressing striatal medium spiny neurons (MSNs) by breeding transgenic Tat-expressing mice to Drd1a-tdTomato- or Drd2-eGFP-reporter mice. An additional goal was to examine neuronal vulnerability early during the degenerative process to gain insight into key events underlying the neuropathogenesis. In D2 MSNs, exposure to HIV-1 Tat reduced dendritic spine density significantly, increased dendritic damage (characterized by swellings/varicosities), and dysregulated neuronal excitability (decreased firing at 200-300 pA and increased firing rates at 450 pA), whereas insignificant morphologic and electrophysiological consequences were observed in Tat-exposed D1 MSNs. These changes were concomitant with an increased anxiety-like behavioral profile (lower latencies to enter a dark chamber in a light-dark transition task, a greater frequency of light-dark transitions, and reduced rearing time in an open field), whereas locomotor behavior was unaffected by 2 weeks of Tat induction. Our findings suggest that D2 MSNs and a specific subset of neural circuits within the dorsal striatum are preferentially vulnerable to HIV-1.SIGNIFICANCE STATEMENT Despite combination antiretroviral therapy (cART), neurocognitive disorders afflict 30-50% of HIV-infected individuals and synaptodendritic injury

  19. Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of Medium Spiny Neurons in the Nucleus Accumbens Shell

    PubMed Central

    Klenowski, Paul M.; Shariff, Masroor R.; Belmer, Arnauld; Fogarty, Matthew J.; Mu, Erica W. H.; Bellingham, Mark C.; Bartlett, Selena E.

    2016-01-01

    The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc) similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks) and long-term (12 weeks) binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs) from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age-matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology. PMID:27047355

  20. Dopamine-dependent long-term depression is expressed in striatal spiny neurons of both direct and indirect pathways: implications for Parkinson's disease.

    PubMed

    Bagetta, Vincenza; Picconi, Barbara; Marinucci, Silvia; Sgobio, Carmelo; Pendolino, Valentina; Ghiglieri, Veronica; Fusco, Francesca R; Giampà, Carmen; Calabresi, Paolo

    2011-08-31

    Striatal medium spiny neurons (MSNs) are divided into two subpopulations exerting distinct effects on motor behavior. Transgenic mice carrying bacterial artificial chromosome (BAC) able to confer cell type-specific expression of enhanced green fluorescent protein (eGFP) for dopamine (DA) receptors have been developed to characterize differences between these subpopulations. Analysis of these mice, in contrast with original pioneering studies, showed that striatal long-term depression (LTD) was expressed in indirect but not in the direct pathway MSNs. To address this mismatch, we applied a new approach using combined BAC technology and receptor immunohistochemistry. We demonstrate that, in physiological conditions, DA-dependent LTD is expressed in both pathways showing that the lack of synaptic plasticity found in D(1) eGFP mice is associated to behavioral deficits. Our findings suggest caution in the use of this tool and indicate that the "striatal segregation" hypothesis might not explain all synaptic dysfunctions in Parkinson's disease.

  1. Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

    PubMed

    Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

    2015-09-01

    Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically

  2. Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice.

    PubMed

    Naydenov, Alipi V; Sepers, Marja D; Swinney, Katie; Raymond, Lynn A; Palmiter, Richard D; Stella, Nephi

    2014-11-01

    Huntington's disease (HD) is caused by an expanded polyglutamine repeat in huntingtin protein that disrupts synaptic function in specific neuronal populations and results in characteristic motor, cognitive and affective deficits. Histopathological hallmarks observed in both HD patients and genetic mouse models include the reduced expression of synaptic proteins, reduced medium spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2 mice and report that treatment prevents the reduction of excitatory synaptic markers in the striatum (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We conclude that loss of excitatory striatal synapses in HD mice is controlled by CB1(MSN) and can be uncoupled from the motor phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Selective expression of a dominant-negative type Iα PKA regulatory subunit in striatal medium spiny neurons impairs gene expression and leads to reduced feeding and locomotor activity.

    PubMed

    Yang, Linghai; Gilbert, Merle L; Zheng, Ruimao; McKnight, G Stanley

    2014-04-02

    Striatal medium spiny neurons (MSNs) mediate many of the physiological effects of dopamine, including the regulation of feeding and motor behaviors. Dopaminergic inputs from the midbrain modulate MSN excitability through pathways that involve cAMP and protein kinase A (PKA), but the physiological role of specific PKA isoforms in MSN neurons remains poorly understood. One of the major PKA regulatory (R) subunit isoforms expressed in MSNs is RIIβ, which localizes the PKA holoenzyme primarily to dendrites by interaction with AKAP5 and other scaffolding proteins. However, RI (RIα and RIβ) subunits are also expressed in MSNs and the RI holoenzyme has a weaker affinity for most scaffolding proteins and tends to localize in the cell body. We generated mice with selective expression of a dominant-negative RI subunit (RIαB) in striatal MSNs and show that this dominant-negative RIαB localizes to the cytoplasm and specifically inhibits type I PKA activity in the striatum. These mice are normal at birth; however, soon after weaning they exhibit growth retardation and the adult mice are hypophagic, lean, and resistant to high-fat diet-induced hyperphagia and obesity. The RIαB-expressing mice also exhibit decreased locomotor activity and decreased dopamine-regulated CREB phosphorylation and c-fos gene expression in the striatum. Our results demonstrate a critical role for cytoplasmic RI-PKA holoenzyme in gene regulation and the overall physiological function of MSNs.

  4. Multiple actions of a D₃ dopamine receptor agonist, PD128907, on GABAergic inhibitory transmission between medium spiny neurons in mouse nucleus accumbens shell.

    PubMed

    Kohnomi, Shuntaro; Konishi, Shiro

    2015-07-23

    The nucleus accumbens (NAc) plays a crucial role in pathophysiological responses, such as reward-related behaviors, addiction, depression and schizophrenia, through activation of dopaminergic system in the midbrain area. Principal cells in the NAc are medium spiny neurons (MSNs), which constitute the majority (90-95%) of NAc neuron populations in rodents. MSNs are mutually connected to form networks of lateral inhibition. Our previous study showed that activation of D2-like receptors presynaptically inhibited GABAergic transmission between MSN-MSN connections in the NAc. D2-like receptors in MSNs have been reported to consist of D2 and D3 receptors, but their functional roles remain to be elucidated. This study, therefore, aimed at examining the effects of D3 receptor activation on MSN-MSN connections using PD128907, a preferential D3 dopamine receptor agonist, and whole cell recordings from MSNs in acute slices including the NAc. In more than half of cells tested, PD128907 reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner. However, the agonist caused multiple actions, namely, decrease, increase and no significant changes, in the amplitude as well as the frequency of sIPSCs in individual cells. Our data, together with the results from previous studies, show that dopamine could suppress GABAergic transmission, i.e., lateral inhibition between some of MSNs, via activation of both D2 and D3 receptors.

  5. Opposite Effects of mGluR1a and mGluR5 Activation on Nucleus Accumbens Medium Spiny Neuron Dendritic Spine Density

    PubMed Central

    Gross, Kellie S.; Brandner, Dieter D.; Martinez, Luis A.; Olive, M. Foster; Meisel, Robert L.

    2016-01-01

    The group I metabotropic glutamate receptors (mGluR1a and mGluR5) are important modulators of neuronal structure and function. Although these receptors share common signaling pathways, they are capable of having distinct effects on cellular plasticity. We investigated the individual effects of mGluR1a or mGluR5 activation on dendritic spine density in medium spiny neurons in the nucleus accumbens (NAc), which has become relevant with the potential use of group I mGluR based therapeutics in the treatment of drug addiction. We found that systemic administration of mGluR subtype-specific positive allosteric modulators had opposite effects on dendritic spine densities. Specifically, mGluR5 positive modulation decreased dendritic spine densities in the NAc shell and core, but was without effect in the dorsal striatum, whereas increased spine densities in the NAc were observed with mGluR1a positive modulation. Additionally, direct activation of mGluR5 via CHPG administration into the NAc also decreased the density of dendritic spines. These data provide insight on the ability of group I mGluRs to induce structural plasticity in the NAc and demonstrate that the group I mGluRs are capable of producing not just distinct, but opposing, effects on dendritic spine density. PMID:27618534

  6. No Evidence for Sex Differences in the Electrophysiological Properties and Excitatory Synaptic Input onto Nucleus Accumbens Shell Medium Spiny Neurons123

    PubMed Central

    Will, Tyler; Hauser, Caitlin A.; Cao, Jinyan

    2016-01-01

    Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch-clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature EPSCs (mEPSCs). No sex differences were detected; this includes those properties, such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency, that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that, unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions. PMID:27022621

  7. Remodeling of the dendritic structure of the striatal medium spiny neurons accompanies behavioral recovery in a mouse model of Parkinson's disease.

    PubMed

    Kim, Wonju; Im, Mi Jung; Park, Cheol Hyoung; Lee, C Justin; Choi, Sukwoo; Yoon, Bong-June

    2013-12-17

    Medium spiny neurons (MSNs) are the major type of neurons found in the striatum. The dendritic spines on these cells contain glutamatergic synaptic contacts between the cortex (or the thalamus) and the striatum. The complexity of the dendritic structure of MSNs may therefore reflect the functional status of the basal ganglia because the striatum is the major input structure in which signals from different regions are integrated. We examined the structural alterations in the dendrites of striatal MSNs in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). Acute MPTP treatment rapidly damaged dopaminergic neurons and their terminals within the striatum and caused behavioral impairments. However, mice injected with MPTP spontaneously recovered from these behavioral impairments within one week. This recovery was accompanied by the restoration of dendritic structures on MSNs, but the damage to dopaminergic neurons remained extensive. Furthermore, we demonstrated that rasagiline, a monoamine oxidase-B (MAO-B) inhibitor that has been shown to be efficacious for PD, could enhance the dendritic complexity of cultured MSNs. The effect of rasagiline on the spine-like structures of dendrites, however, appears not to require DA availability because the small protrusions of dendrites in cultured MSNs without major source of DA input was similarly changed by rasagiline. Our data suggest that the dendritic structures of striatal MSNs change dynamically, reflecting the progression of motor-related symptoms in PD, and the restoration of functional synapses in the MSNs of PD patients may constitute a clinical target for symptomatic alleviation.

  8. Upregulation and axonal transport of synaptotagmin-IV in the direct-pathway medium spiny neurons in hemi-parkinsonian rats induced by dopamine D1 receptor stimulation.

    PubMed

    Tratnjek, Larisa; Glavan, Gordana; Višnjar, Tanja; Živin, Marko

    2016-04-01

    Synaptotagmin-IV (Syt-IV) may function as a regulator of Ca(2+) -dependent synaptic transmission. In the hemi-parkinsonian rats with unilateral lesions of dopaminergic nigrostriatal neurons Syt-IV and substance-P (SP) mRNAs could be upregulated within the dopaminergically hypersensitive striatum of the lesioned brain hemisphere via the stimulation of striatal dopamine D1 (D1-R), but not D2 receptors. The hypersensitive D1-R-mediated transmission may be the culprit for the undesired expression of levodopa-induced dyskinesia, implying the involvement of Syt-IV and SP in the process. First, striatal cellular phenotypes expressing Syt-IV were determined. It was found to be expressed in all striatal neurons and a small population of astrocytes. Then it was examined, if the D1-R-mediated upregulation of Syt-IV mRNA may result in the upregulation of the translated protein. It was found that, after acute stimulation with a selective D1 agonist, (±)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-82958), Syt-IV was elevated within the SP-expressing striatal neurons of the lesioned side. This was followed by the upregulation of Syt-IV, but not of its mRNA, within the ipsilateral target nuclei of the direct-pathway medium spiny neurons, indicating axonal transport of de novo synthesized protein to their SP-positive synaptic terminals. However, despite the striatal upregulation of SP and Syt-IV following a similar time-course, their subcellular co-localization within the axonal terminals was not found. It was therefore suggested that Syt-IV may regulate the hypersensitive striatal synaptic transmission, although via a SP-independent mechanism. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. gamma-Hydroxybutyrate (GHB) induces GABA(B) receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABA(B) receptors of medium spiny neurons in the nucleus accumbens.

    PubMed

    Molnár, T; Antal, K; Nyitrai, G; Emri, Z

    2009-08-18

    We report on cellular actions of the illicit recreational drug gamma-hydroxybutyrate (GHB) in the brain reward area nucleus accumbens. First, we compared the effects of GHB and the GABA(B) receptor agonist baclofen. Neither of them affected the membrane currents of medium spiny neurons in rat nucleus accumbens slices. GABAergic and glutamatergic synaptic potentials of medium spiny neurons, however, were reduced by baclofen but not GHB. These results indicate the lack of GHB as well as postsynaptic GABA(B) receptors, and the presence of GHB insensitive presynaptic GABA(B) receptors in medium spiny neurons. In astrocytes GHB induced intracellular Ca(2+) transients, preserved in slices from GABA(B) receptor type 1 subunit knockout mice. The effects of tetrodotoxin, zero added Ca(2+) with/without intracellular Ca(2+) store depletor cyclopiazonic acid or vacuolar H-ATPase inhibitor bafilomycin A1 indicate that GHB-evoked Ca(2+) transients depend on external Ca(2+) and intracellular Ca(2+) stores, but not on vesicular transmitter release. GHB-induced astrocytic Ca(2+) transients were not affected by the GHB receptor-specific antagonist NCS-382, suggesting the presence of a novel NCS-382-insensitive target for GHB in astrocytes. The activation of astrocytes by GHB implies their involvement in physiological actions of GHB. Our findings disclose a novel profile of GHB action in the nucleus accumbens. Here, unlike in other brain areas, GHB does not act on GABA(B) receptors, but activates an NCS-382 insensitive GHB-specific target in a subpopulation of astrocytes. The lack of either post- or presynaptic effects on medium spiny neurons in the nucleus accumbens distinguishes GHB from many drugs and natural rewards with addictive properties and might explain why GHB has only a weak reinforcing capacity.

  10. Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column.

    PubMed

    Feldmeyer, Dirk; Lübke, Joachim; Silver, R Angus; Sakmann, Bert

    2002-02-01

    Whole-cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/- 0.13. Both c.v. and percentage of failures decreased with increased average EPSP amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At -60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1-100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame synaptic depression so that the summed EPSP was larger than the first EPSP amplitude in the train. The number of putative synaptic contacts established by the axonal collaterals of the L4 projection neurone with the target neurone in layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs). Synapses were established on basal dendrites of the pyramidal cell. Their mean geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16-196 microm). The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in

  11. Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity.

    PubMed

    Natsubori, Akiyo; Tsutsui-Kimura, Iku; Nishida, Hiroshi; Bouchekioua, Youcef; Sekiya, Hiroshi; Uchigashima, Motokazu; Watanabe, Masahiko; de Kerchove d'Exaerde, Alban; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F

    2017-03-08

    The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca(2+) indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca(2+) elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior.SIGNIFICANCE STATEMENT An opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has

  12. 2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington's disease.

    PubMed

    Wu, Bin; Jiang, Mali; Peng, Qi; Li, Gang; Hou, Zhipeng; Milne, Ginger L; Mori, Susumu; Alonso, Robert; Geisler, John G; Duan, Wenzhen

    2017-03-28

    Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the gene huntingtin. There is no treatment to prevent or delay the disease course of HD currently. Oxidative stress and mitochondrial dysfunction have emerged as key determinants of the disease progression in HD. Therefore, counteracting mutant huntingtin (mHtt)-induced oxidative stress and mitochondrial dysfunction appears as a new approach to treat this devastating disease. Interestingly, mild mitochondrial uncoupling improves neuronal resistance to stress and facilitates neuronal survival. Mild mitochondrial uncoupling can be induced by the proper dose of 2,4-dinitrophenol (DNP), a proton ionophore that was previously used for weight loss. In this study, we evaluated the effects of chronic administration of DNP at three doses (0.5, 1, 5mg/kg/day) on mHtt-induced behavioral deficits and cellular abnormalities in the N171-82Q HD mouse model. DNP at a low dose (1mg/kg/day) significantly improved motor function and preserved medium spiny neuronal marker DARPP32 and postsynaptic protein PSD95 in the striatum of HD mice. Further mechanistic study suggests that DNP at this dose reduced oxidative stress in HD mice, which was indicated by reduced levels of F2-isoprostanes in the brain of HD mice treated with DNP. Our data indicated that DNP provided behavioral benefit and neuroprotective effect at a weight neutral dose in HD mice, suggesting that the potential value of repositioning DNP to HD treatment is warranted in well-controlled clinical trials in HD.

  13. Cortical regulation of striatal medium spiny neuron dendritic remodeling in parkinsonism: modulation of glutamate release reverses dopamine depletion-induced dendritic spine loss.

    PubMed

    Garcia, Bonnie G; Neely, M Diana; Deutch, Ariel Y

    2010-10-01

    Striatal medium spiny neurons (MSNs) receive glutamatergic afferents from the cerebral cortex and dopaminergic inputs from the substantia nigra (SN). Striatal dopamine loss decreases the number of MSN dendritic spines. This loss of spines has been suggested to reflect the removal of tonic dopamine inhibitory control over corticostriatal glutamatergic drive, with increased glutamate release culminating in MSN spine loss. We tested this hypothesis in two ways. We first determined in vivo if decortication reverses or prevents dopamine depletion-induced spine loss by placing motor cortex lesions 4 weeks after, or at the time of, 6-hydroxydopamine lesions of the SN. Animals were sacrificed 4 weeks after cortical lesions. Motor cortex lesions significantly reversed the loss of MSN spines elicited by dopamine denervation; a similar effect was observed in the prevention experiment. We then determined if modulating glutamate release in organotypic cocultures prevented spine loss. Treatment of the cultures with the mGluR2/3 agonist LY379268 to suppress corticostriatal glutamate release completely blocked spine loss in dopamine-denervated cultures. These studies provide the first evidence to show that MSN spine loss associated with parkinsonism can be reversed and point to suppression of corticostriatal glutamate release as a means of slowing progression in Parkinson's disease.

  14. Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus) and a non-vocal learner bird (Colinus virginianus).

    PubMed

    Garcia-Calero, Elena; Bahamonde, Olga; Martinez, Salvador

    2013-01-01

    Striatal projecting neurons, known as medium spiny neurons (MSNs), segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+) MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird): the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+ MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order) and the non-vocal learner bird quail (representative of galliformes order). We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+ MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail), but also between close vocal learner bird families.

  15. The distinct role of medium spiny neurons and cholinergic interneurons in the D₂/A₂A receptor interaction in the striatum: implications for Parkinson's disease.

    PubMed

    Tozzi, Alessandro; de Iure, Antonio; Di Filippo, Massimiliano; Tantucci, Michela; Costa, Cinzia; Borsini, Franco; Ghiglieri, Veronica; Giampà, Carmen; Fusco, Francesca Romana; Picconi, Barbara; Calabresi, Paolo

    2011-02-02

    A(2A) adenosine receptor antagonists are currently under investigation as potential therapeutic agents for Parkinson's disease (PD). However, the molecular mechanisms underlying this therapeutic effect is still unclear. A functional antagonism exists between A(2A) adenosine and D(2) dopamine (DA) receptors that are coexpressed in striatal medium spiny neurons (MSNs) of the indirect pathway. Since this interaction could also occur in other neuronal subtypes, we have analyzed the pharmacological modulation of this relationship in murine MSNs of the direct and indirect pathways as well in striatal cholinergic interneurons. Under physiological conditions, endogenous cannabinoids (eCBs) play a major role in the inhibitory effect on striatal glutamatergic transmission exerted by the concomitant activation of D(2) DA receptors and blockade of A(2A) receptors in both D(2)- and D(1)-expressing striatal MSNs. In experimental models of PD, the inhibition of striatal glutamatergic activity exerted by D(2) receptor activation did not require the concomitant inhibition of A(2A) receptors, while it was still dependent on the activation of CB(1) receptors in both D(2)- and D(1)-expressing MSNs. Interestingly, the antagonism of M1 muscarinic receptors blocked the effects of D(2)/A(2A) receptor modulation on MSNs. Moreover, in cholinergic interneurons we found coexpression of D(2) and A(2A) receptors and a reduction of the firing frequency exerted by the same pharmacological agents that reduced excitatory transmission in MSNs. This evidence supports the hypothesis that striatal cholinergic interneurons, projecting to virtually all MSN subtypes, are involved in the D(2)/A(2A) and endocannabinoid-mediated effects observed on both subpopulations of MSNs in physiological conditions and in experimental PD.

  16. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    PubMed Central

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  17. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not in adolescent rats susceptible to diet-induced obesity.

    PubMed

    Oginsky, Max F; Maust, Joel D; Corthell, John T; Ferrario, Carrie R

    2016-03-01

    Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. We examined differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity and basal differences in striatal neuron function in adult and in adolescent obesity-prone and obesity-resistant rats. Susceptible and resistant outbred rats were identified based on "junk-food" diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine-induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). In rats that became obese after eating junk-food, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ∼60 % at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals, and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats.

  18. Novel fast adapting interneurons mediate cholinergic-induced fast GABAA inhibitory postsynaptic currents in striatal spiny neurons.

    PubMed

    Faust, Thomas W; Assous, Maxime; Shah, Fulva; Tepper, James M; Koós, Tibor

    2015-07-01

    Previous work suggests that neostriatal cholinergic interneurons control the activity of several classes of GABAergic interneurons through fast nicotinic receptor-mediated synaptic inputs. Although indirect evidence has suggested the existence of several classes of interneurons controlled by this mechanism, only one such cell type, the neuropeptide-Y-expressing neurogliaform neuron, has been identified to date. Here we tested the hypothesis that in addition to the neurogliaform neurons that elicit slow GABAergic inhibitory responses, another interneuron type exists in the striatum that receives strong nicotinic cholinergic input and elicits conventional fast GABAergic synaptic responses in projection neurons. We obtained in vitro slice recordings from double transgenic mice in which Channelrhodopsin-2 was natively expressed in cholinergic neurons and a population of serotonin receptor-3a-Cre-expressing GABAergic interneurons were visualized with tdTomato. We show that among the targeted GABAergic interneurons a novel type of interneuron, termed the fast-adapting interneuron, can be identified that is distinct from previously known interneurons based on immunocytochemical and electrophysiological criteria. We show using optogenetic activation of cholinergic inputs that fast-adapting interneurons receive a powerful supra-threshold nicotinic cholinergic input in vitro. Moreover, fast adapting neurons are densely connected to projection neurons and elicit fast, GABAA receptor-mediated inhibitory postsynaptic current responses. The nicotinic receptor-mediated activation of fast-adapting interneurons may constitute an important mechanism through which cholinergic interneurons control the activity of projection neurons and perhaps the plasticity of their synaptic inputs when animals encounter reinforcing or otherwise salient stimuli.

  19. Aneurysms of medium-sized arteries in Marfan syndrome.

    PubMed

    Awais, Mazen; Williams, David M; Deeb, G Michael; Shea, Michael J

    2013-11-01

    Marfan syndrome is a relatively common connective tissue disorder that causes skin, ocular, skeletal, and cardiovascular abnormalities. High morbidity and mortality occur with aortic aneurysm and dissection. Other large-artery aneurysms, including carotid, subclavian, and iliac artery aneurysms, have also been associated with Marfan syndrome. It is not clear whether small- to medium-sized artery aneurysms are associated with Marfan syndrome. This report describes 4 patients with Marfan syndrome who have associated small- to medium-sized artery aneurysms with several complications. Additional investigations are needed to determine whether Marfan syndrome can cause small- to medium-sized artery aneurysms and how patients with these aneurysms should be treated.

  20. Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons

    PubMed Central

    Nair, Anu G.; Eriksson, Olivia; Vincent, Pierre

    2015-01-01

    Transient changes in striatal dopamine (DA) concentration are considered to encode a reward prediction error (RPE) in reinforcement learning tasks. Often, a phasic DA change occurs concomitantly with a dip in striatal acetylcholine (ACh), whereas other neuromodulators, such as adenosine (Adn), change slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs for these neuromodulators in striatal medium spiny neurons (MSNs), which play important roles in plasticity. However, little is known about the interaction between these neuromodulators via GPCRs. The interaction between these transient neuromodulator changes and the effect on cAMP/PKA signaling via Golf- and Gi/o-coupled GPCR are studied here using quantitative kinetic modeling. The simulations suggest that, under basal conditions, cAMP/PKA signaling could be significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an ACh dip is required to gate a subset of D1R/Golf-dependent PKA activation. Furthermore, the interaction between ACh dip and DA peak, via D1R and M4R, is synergistic. In a similar fashion, PKA signaling in D2+ MSNs is under basal inhibition via D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting A2aR/Golf, but D2+ MSNs could also respond to the DA peak via other intracellular pathways. This study highlights the similarity between the two types of MSNs in terms of high basal AC inhibition by Gi/o and the importance of interactions between Gi/o and Golf signaling, but at the same time predicts differences between them with regard to the sign of RPE responsible for PKA activation. SIGNIFICANCE STATEMENT Dopamine transients are considered to carry reward-related signal in reinforcement learning. An increase in dopamine concentration is associated with an unexpected reward or salient stimuli, whereas a decrease is produced by omission of an expected reward. Often dopamine transients are accompanied by other neuromodulatory signals, such as acetylcholine and adenosine. We highlight the

  1. Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex.

    PubMed

    Sun, Qian-Quan; Zhang, Zhi; Sun, June; Nair, Anand S; Petrus, Dan P; Zhang, Chunzhao

    2014-01-01

    Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF's effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF's effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF.

  2. Activation of mGluR5 induces spike afterdepolarization and enhanced excitability in medium spiny neurons of the nucleus accumbens by modulating persistent Na+ currents

    PubMed Central

    D’Ascenzo, Marcello; Podda, Maria Vittoria; Fellin, Tommaso; Azzena, Gian Battista; Haydon, Philip; Grassi, Claudio

    2009-01-01

    The involvement of metabotropic glutamate receptors type 5 (mGluR5) in drug-induced behaviours is well-established but limited information is available on their functional roles in addiction-relevant brain areas like the nucleus accumbens (NAc). This study demonstrates that pharmacological and synaptic activation of mGluR5 increases the spike discharge of medium spiny neurons (MSNs) in the NAc. This effect was associated with the appearance of a slow afterdepolarization (ADP) which, in voltage-clamp experiments, was recorded as a slowly inactivating inward current. Pharmacological studies showed that ADP was elicited by mGluR5 stimulation via G-protein-dependent activation of phospholipase C and elevation of intracellular Ca2+ levels. Both ADP and spike aftercurrents were significantly inhibited by the Na+ channel-blocker, tetrodotoxin (TTX). Moreover, the selective blockade of persistent Na+ currents (INaP), achieved by NAc slice pre-incubation with 20 nm TTX or 10 μm riluzole, significantly reduced the ADP amplitude, indicating that this type of Na+ current is responsible for the mGluR5-dependent ADP. mGluR5 activation also produced significant increases in INaP, and the pharmacological blockade of this current prevented the mGluR5-induced enhancement of spike discharge. Collectively, these data suggest that mGluR5 activation upregulates INaP in MSNs of the NAc, thereby inducing an ADP that results in enhanced MSN excitability. Activation of mGluR5 will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of drug-induced behaviours. PMID:19433572

  3. Long-lasting alterations in membrane properties, k(+) currents, and glutamatergic synaptic currents of nucleus accumbens medium spiny neurons in a rat model of alcohol dependence.

    PubMed

    Marty, Vincent N; Spigelman, Igor

    2012-01-01

    Chronic alcohol exposure causes marked changes in reinforcement mechanisms and motivational state that are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system. Although the NAcc plays an important role in mediating alcohol-seeking behaviors, little is known about the molecular mechanisms underlying alcohol-induced neuroadaptive changes in NAcc function. The aim of this study was to investigate the effects of chronic intermittent ethanol (CIE) treatment, a rat model of alcohol withdrawal and dependence, on intrinsic electrical membrane properties and glutamatergic synaptic transmission of medium spiny neurons (MSNs) in the NAcc core during protracted withdrawal. We show that CIE treatment followed by prolonged withdrawal increased the inward rectification of MSNs observed at hyperpolarized potentials. In addition, MSNs from CIE-treated animals displayed a lower input resistance, faster action potentials (APs), and larger fast afterhyperpolarizations (fAHPs) than MSNs from vehicle-treated animals, all suggestive of increases in K(+)-channel conductances. Significant increases in the Cs(+)-sensitive inwardly rectifying K(+)-current accounted for the increased input resistance, while increases in the A-type K(+)-current accounted for the faster APs and increased fAHPs in MSNs from CIE rats. We also show that the amplitude and the conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated mEPSCs were enhanced in CIE-treated animals due to an increase in a small fraction of functional postsynaptic GluA2-lacking AMPARs. These long-lasting modifications of excitability and excitatory synaptic receptor function of MSNs in the NAcc core could play a critical role in the neuroadaptive changes underlying alcohol withdrawal and dependence.

  4. Long-Lasting Alterations in Membrane Properties, K+ Currents, and Glutamatergic Synaptic Currents of Nucleus Accumbens Medium Spiny Neurons in a Rat Model of Alcohol Dependence

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2012-01-01

    Chronic alcohol exposure causes marked changes in reinforcement mechanisms and motivational state that are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc) is a key structure of the mesolimbic dopaminergic reward system. Although the NAcc plays an important role in mediating alcohol-seeking behaviors, little is known about the molecular mechanisms underlying alcohol-induced neuroadaptive changes in NAcc function. The aim of this study was to investigate the effects of chronic intermittent ethanol (CIE) treatment, a rat model of alcohol withdrawal and dependence, on intrinsic electrical membrane properties and glutamatergic synaptic transmission of medium spiny neurons (MSNs) in the NAcc core during protracted withdrawal. We show that CIE treatment followed by prolonged withdrawal increased the inward rectification of MSNs observed at hyperpolarized potentials. In addition, MSNs from CIE-treated animals displayed a lower input resistance, faster action potentials (APs), and larger fast afterhyperpolarizations (fAHPs) than MSNs from vehicle-treated animals, all suggestive of increases in K+-channel conductances. Significant increases in the Cs+-sensitive inwardly rectifying K+-current accounted for the increased input resistance, while increases in the A-type K+-current accounted for the faster APs and increased fAHPs in MSNs from CIE rats. We also show that the amplitude and the conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated mEPSCs were enhanced in CIE-treated animals due to an increase in a small fraction of functional postsynaptic GluA2-lacking AMPARs. These long-lasting modifications of excitability and excitatory synaptic receptor function of MSNs in the NAcc core could play a critical role in the neuroadaptive changes underlying alcohol withdrawal and dependence. PMID:22701402

  5. Reacquisition of cocaine conditioned place preference and its inhibition by previous social interaction preferentially affect D1-medium spiny neurons in the accumbens corridor

    PubMed Central

    Prast, Janine M.; Schardl, Aurelia; Schwarzer, Christoph; Dechant, Georg; Saria, Alois; Zernig, Gerald

    2014-01-01

    We investigated if counterconditioning with dyadic (i.e., one-to-one) social interaction, a strong inhibitor of the subsequent reacquisition of cocaine conditioned place preference (CPP), differentially modulates the activity of the diverse brain regions oriented along a mediolateral corridor reaching from the interhemispheric sulcus to the anterior commissure, i.e., the nucleus of the vertical limb of the diagonal band, the medial septal nucleus, the major island of Calleja, the intermediate part of the lateral septal nucleus, and the medial accumbens shell and core. We also investigated the involvement of the lateral accumbens core and the dorsal caudate putamen. The anterior cingulate 1 (Cg1) region served as a negative control. Contrary to our expectations, we found that all regions of the accumbens corridor showed increased expression of the early growth response protein 1 (EGR1, Zif268) in rats 2 h after reacquisition of CPP for cocaine after a history of cocaine CPP acquisition and extinction. Previous counterconditioning with dyadic social interaction inhibited both the reacquisition of cocaine CPP and the activation of the whole accumbens corridor. EGR1 activation was predominantly found in dynorphin-labeled cells, i.e., presumably D1 receptor-expressing medium spiny neurons (D1-MSNs), with D2-MSNs (immunolabeled with an anti-DRD2 antibody) being less affected. Cholinergic interneurons or GABAergic interneurons positive for parvalbumin, neuropeptide Y or calretinin were not involved in these CPP-related EGR1 changes. Glial cells did not show any EGR1 expression either. The present findings could be of relevance for the therapy of impaired social interaction in substance use disorders, depression, psychosis, and autism spectrum disorders. PMID:25309368

  6. Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex

    PubMed Central

    Sun, Qian-Quan; Zhang, Zhi; Sun, June; Nair, Anand S.; Petrus, Dan P.; Zhang, Chunzhao

    2014-01-01

    Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF’s effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF’s effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF. PMID:25414642

  7. Segregation and Crosstalk of D1 Receptor-Mediated Activation of ERK in Striatal Medium Spiny Neurons upon Acute Administration of Psychostimulants

    PubMed Central

    Gutierrez-Arenas, Omar; Eriksson, Olivia; Hellgren Kotaleski, Jeanette

    2014-01-01

    The convergence of corticostriatal glutamate and dopamine from the midbrain in the striatal medium spiny neurons (MSN) triggers synaptic plasticity that underlies reinforcement learning and pathological conditions such as psychostimulant addiction. The increase in striatal dopamine produced by the acute administration of psychostimulants has been found to activate not only effectors of the AC5/cAMP/PKA signaling cascade such as GluR1, but also effectors of the NMDAR/Ca2+/RAS cascade such as ERK. The dopamine-triggered effects on both these cascades are mediated by D1R coupled to Golf but while the phosphorylation of GluR1 is affected by reductions in the available amount of Golf but not of D1R, the activation of ERK follows the opposite pattern. This segregation is puzzling considering that D1R-induced Golf activation monotonically increases with DA and that there is crosstalk from the AC5/cAMP/PKA cascade to the NMDAR/Ca2+/RAS cascade via a STEP (a tyrosine phosphatase). In this work, we developed a signaling model which accounts for this segregation based on the assumption that a common pool of D1R and Golf is distributed in two D1R/Golf signaling compartments. This model integrates a relatively large amount of experimental data for neurons in vivo and in vitro. We used it to explore the crosstalk topologies under which the sensitivities of the AC5/cAMP/PKA signaling cascade to reductions in D1R or Golf are transferred or not to the activation of ERK. We found that the sequestration of STEP by its substrate ERK together with the insensitivity of STEP activity on targets upstream of ERK (i.e. Fyn and NR2B) to PKA phosphorylation are able to explain the experimentally observed segregation. This model provides a quantitative framework for simulation based experiments to study signaling required for long term potentiation in MSNs. PMID:24499932

  8. Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2013-01-01

    Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

  9. Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell–derived medium spiny neurons

    PubMed Central

    Straccia, Marco; Garcia-Diaz Barriga, Gerardo; Sanders, Phil; Bombau, Georgina; Carrere, Jordi; Mairal, Pedro Belio; Vinh, Ngoc-Nga; Yung, Sun; Kelly, Claire M; Svendsen, Clive N; Kemp, Paul J; Arjomand, Jamshid; Schoenfeld, Ryan C; Alberch, Jordi; Allen, Nicholas D; Rosser, Anne E; Canals, Josep M

    2015-01-01

    A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE) and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening. PMID:26417608

  10. Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.

    PubMed

    Renteria, Rafael; Maier, Esther Y; Buske, Tavanna R; Morrisett, Richard A

    2017-01-01

    A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The

  11. Workplace Health Promotion within Small and Medium-Sized Enterprises

    ERIC Educational Resources Information Center

    Moore, Ann; Parahoo, Kader; Fleming, Paul

    2010-01-01

    Purpose: The purpose of this study is to explore managers' understanding of workplace health promotion (WHP) and experiences of WHP activity within small and medium-sized enterprises (SMEs) in a Health and Social Care Trust area of Northern Ireland. The paper aims to focus on engagement with activities within the context of prevention of…

  12. Promoting Learning in Small and Medium-Sized Enterprises.

    ERIC Educational Resources Information Center

    Hughes, Maria; Gray, Sue

    1998-01-01

    In 1996, small and medium-sized enterprises constituted 99% of all businesses in the United Kingdom in all but the electricity, gas, and water supply sector, providing 46% of nongovernment employment. SMEs' concern with day-to-day demands leaves them with limited time and resources to consider their training needs. Although providing support and…

  13. Library Webmasters in Medium-Sized Academic Libraries

    ERIC Educational Resources Information Center

    Kneip, Jason

    2007-01-01

    Library webmasters in medium-sized academic libraries were surveyed about their educational backgrounds, job responsibilities, and training and experience levels in Web development. The article summarizes the findings of the survey with recommendations for libraries and library and information science programs. (Contains 7 tables, 5 figures,and 5…

  14. Historical Research and Medium-Sized Public Libraries: The Potential.

    ERIC Educational Resources Information Center

    Piehl, Charles K.

    1982-01-01

    Discusses the special collections and archival materials often found in medium-sized public libraries which should be fully used by historical researchers. It is suggested that public libraries need to advertise their collections which are of historical interest and to be more aware of the needs of the historical researcher. (Author/JL)

  15. Historical Research and Medium-Sized Public Libraries: The Potential.

    ERIC Educational Resources Information Center

    Piehl, Charles K.

    1982-01-01

    Discusses the special collections and archival materials often found in medium-sized public libraries which should be fully used by historical researchers. It is suggested that public libraries need to advertise their collections which are of historical interest and to be more aware of the needs of the historical researcher. (Author/JL)

  16. Workplace Health Promotion within Small and Medium-Sized Enterprises

    ERIC Educational Resources Information Center

    Moore, Ann; Parahoo, Kader; Fleming, Paul

    2010-01-01

    Purpose: The purpose of this study is to explore managers' understanding of workplace health promotion (WHP) and experiences of WHP activity within small and medium-sized enterprises (SMEs) in a Health and Social Care Trust area of Northern Ireland. The paper aims to focus on engagement with activities within the context of prevention of…

  17. Planning-Evaluation in a Medium-Size School District.

    ERIC Educational Resources Information Center

    Giroux, Roger M.

    The rationale, operational framework, and implementation case study of a planning-evaluation model for a medium size school district are discussed. The system defines a management information function in the three components of planning, operations, and evaluation. The relationship among these components is presented in both diagram and narrative…

  18. Systematic Classifier OF Manufacturing Processes For Medium Size Shafts

    NASA Astrophysics Data System (ADS)

    Lychagin, D. V.; Lasukov, A. A.; Walter, A. V.; Arkhipova, D. A.

    2016-04-01

    The article considers some issues of increasing efficiency of manufacturing preparation as a part of manufacturing processes design at a machine building enterprise. A tree of routing manufacturing processes for machining shafts of medium size is described as an example of clustering parts according to their structural and technological characteristics. Processing route for a certain part included into a certain group is developed through choosing machining operations for elementary surfaces of a part from the process route developed for a template representative of the group.

  19. Building medium size telescope structures for the Cherenkov telescope array

    NASA Astrophysics Data System (ADS)

    Schulz, A.; Garczarczyk, M.; Oakes, L.; Schlenstedt, S.; Schwanke, U.

    2017-01-01

    The Cherenkov Telescope Array (CTA) is the future instrument in ground-based gamma-ray astronomy in the energy range from 20 GeV to 300 TeV. Its sensitivity will surpass that of current generation experiments by a factor ˜10, facilitated by telescopes of three sizes. The performance in the core energy regime will be dominated by Medium Size Telescopes (MST) with a reflector of 12 m diameter. A full-size mechanical prototype of the telescope structure has been constructed in Berlin. The performance of the prototype is being evaluated and optimisations, among others, facilitating the assembly procedure and mass production possibilities are being implemented. We present the current status of the developments from prototyping towards pre-production telescopes, which will be deployed at the final site.

  20. Medium-size high-temperature gas-cooled reactor

    SciTech Connect

    Peinado, C.O.; Koutz, S.L.

    1980-08-01

    This report summarizes high-temperature gas-cooled reactor (HTGR) experience for the 40-MW(e) Peach Bottom Nuclear Generating Station of Philadelphia Electric Company and the 330-MW(e) Fort St. Vrain Nuclear Generating Station of the Public Service Company of Colorado. Both reactors are graphite moderated and helium cooled, operating at approx. 760/sup 0/C (1400/sup 0/F) and using the uranium/thorium fuel cycle. The plants have demonstrated the inherent safety characteristics, the low activation of components, and the high efficiency associated with the HTGR concept. This experience has been translated into the conceptual design of a medium-sized 1170-MW(t) HTGR for generation of 450 MW of electric power. The concept incorporates inherent HTGR safety characteristics (a multiply redundant prestressed concrete reactor vessel (PCRV), a graphite core, and an inert single-phase coolant) and engineered safety features (core auxiliary cooling, relief valve, and steam generator dump systems).

  1. Optical properties of medium size noble and transition metal nanoparticles

    NASA Astrophysics Data System (ADS)

    Idrobo, Juan C.; Pantelides, Sokrates T.

    2009-03-01

    Using first-principles methods within time dependent density functional theory and the local density approximation (TDLDA) the absorption spectra of medium size (˜20-80 atoms) silver, gold and copper nanoparticles have been calculated. The nanoparticles are fcc fragments with different aspect ratios. We find that in the case of Ag nanoparticles is well reproduced by classical electrodynamics theory based in Mie's formalism, using the dielectric function of bulk Ag and taking into account the nanoparticle shape. For the case of Cu and Au, there is a similarity in the overall features of the quantum mechanical and classical spectra, but no detailed agreement. We will discuss the role that the d-electrons among all the different elements and the surface states play in controlling the optical properties of the nanoparticles. This work was supported by GOALI NSF grant (DMR-0513048), DOE, the Office of Basic Energy Sciences, Division of Materials Sciences and Engineering, and Alcoa Inc.

  2. Dipole polarizabilities of medium-sized gold clusters

    NASA Astrophysics Data System (ADS)

    Wang, Jinlan; Yang, Mingli; Jellinek, Julius; Wang, Guanghou

    2006-08-01

    The dipole polarizabilities of two families of low-lying structures, cage, and space filling, of the medium-sized AuN (N=32,38,44,50,56) clusters are studied using gradient-corrected density functional theory and finite field method. Both dipole moments and polarizabilities exhibit clear shape-dependent features and the cage structures have systematically smaller dipole moments and larger polarizabilities than the space-filling isomers. The mean polarizability per atom increases with cluster size for the cage structures, but it decreases slowly and tends to approach a constant for the space-filling structures. A linearly correlation between polarizability and cluster volume is noted, complying with the jellium model prediction for spherical metal clusters. The electronic effects including HOMO-LUMO gap and ionization energy on polarizabilities are also explored. The geometric effects play a dominant role on the determination of the polarizability of the cluster over the electronic effects.

  3. In Vivo Profiling Reveals a Competent Heat Shock Response in Adult Neurons: Implications for Neurodegenerative Disorders.

    PubMed

    Carnemolla, Alisia; Lazell, Hayley; Moussaoui, Saliha; Bates, Gillian P

    2015-01-01

    The heat shock response (HSR) is the main pathway used by cells to counteract proteotoxicity. The inability of differentiated neurons to induce an HSR has been documented in primary neuronal cultures and has been proposed to play a critical role in ageing and neurodegeneration. However, this accepted dogma has not been demonstrated in vivo. We used BAC transgenic mice generated by the Gene Expression Nervous System Atlas project to investigate the capacity of striatal medium sized spiny neurons to induce an HSR as compared to that of astrocytes and oligodendrocytes. We found that all cell populations were competent to induce an HSR upon HSP90 inhibition. We also show the presence and relative abundance of heat shock-related genes and proteins in these striatal cell populations. The identification of a competent HSR in adult neurons supports the development of therapeutics that target the HSR pathway as treatments for neurodegenerative disorders.

  4. Climatic Effects of Medium-Sized Asteroid Impacts on Land

    NASA Astrophysics Data System (ADS)

    Bardeen, C.; Garcia, R. R.; Toon, O. B.; Otto-Bliesner, B. L.; Wolf, E. T.

    2015-12-01

    Using the Community Earth System Model (CESM), a three-dimensional coupled climate model with interactive chemistry, we have simulated the climate response to a medium-sized (1 km) asteroid impact on the land. An impact of this size would cause local fires and may also generate submicron dust particles. Dust aerosols are injected into the upper atmosphere where they persist for ~3 years. Soot aerosols from fires are injected into the troposphere and absorb solar radiation heating the air which helps loft the soot into the stratosphere where it persists for ~10 years. Initially, these aerosols cause a heating of over 240 K in the stratosphere and up to a 70% reduction in downwelling solar radiation at the surface. Global average surface temperature cools by as much as -8.5 K, ocean temperature cools by -4.5 K, precipitation is reduced by 50%, and the ozone column is reduced by 55%. The surface UV Index exceeds 20 in the tropics for several years. These changes represent a significant hazard to life on a global scale. These results extend the work of Pierazzo et al. (2010), also using CESM, which found a significant impact on stratospheric ozone, but little change in surface temperature or precipitation, from a 1 km asteroid impact in the ocean.

  5. Overview of the EUROfusion Medium Size Tokamak scientific program

    NASA Astrophysics Data System (ADS)

    Martin, Piero; Coda, Stefano; Eich, Thomas; Hakola, Antti; Meyer, Hendrik; EUROfusion MST1 Team; AUG Team; MAST-U Team; TCV Team

    2016-10-01

    The EUROfusion MST (Medium Size Tokamaks) task force is in charge of the European science programme in the ASDEX Upgrade, TCV and MAST-U tokamaks. This paper will present an overview of the main results obtained in the 2015/16 campaign in AUG and TCV and the future plans. We will discuss, among others, successful disruption and runaway electron control experiments with MGI and 3D fields, the achievement of full ELM suppression with RMP accompanied by the understanding of plasma response and the heat load pattern study, the exploration of regimes with impurity seeding at high P/R with 85% radiation fraction and good confinement, the study of tungsten fuzz, where W samples with pre-formed nanostructures were exposed to H-mode Helium plasmas and the investigation on advanced divertor concepts. A survey of MHD limits and of MHD control in standard and high-beta regimes will be presented. The results from the AUG campaign dedicated to He plasmas in support of ITER initial operation will also be presented, as well as analysis of old MAST data that reveal interesting features in the filamentary transport. See http://www.euro-fusionscipub.org/mst1.

  6. The medium size telescopes of the Cherenkov telescope array

    NASA Astrophysics Data System (ADS)

    Pühlhofer, G.

    2017-01-01

    The Cherenkov Telescope Array (CTA) is the planned next-generation instrument for ground-based gamma-ray astronomy, covering a photon energy range of ˜20 GeV to above 100 TeV. CTA will consist of the order of 100 telescopes of three sizes, installed at two sites in the Northern and Southern Hemisphere. This contribution deals with the 12 meter Medium Size Telescopes (MST) having a single mirror (modified Davies-Cotton, DC) design. In the baseline design of the CTA arrays, 25 MSTs in the South and 15 MSTs in the North provide the necessary sensitivity for CTA in the core energy range of 100 GeV to 10 TeV. DC-MSTs will be equipped with photomultiplier (PMT)-based cameras. Two options are available for these focal plane instruments, that will be provided by the FlashCam and the NectarCAM sub-consortia. In this contribution, a short introduction to the projects and their status is given.

  7. Salary Management System for Small and Medium-sized Enterprises

    NASA Astrophysics Data System (ADS)

    Hao, Zhang; Guangli, Xu; Yuhuan, Zhang; Yilong, Lei

    Small and Medium-sized Enterprises (SMEs) in the process of wage entry, calculation, the total number are needed to be done manually in the past, the data volume is quite large, processing speed is low, and it is easy to make error, which is resulting in low efficiency. The main purpose of writing this paper is to present the basis of salary management system, establish a scientific database, the computer payroll system, using the computer instead of a lot of past manual work in order to reduce duplication of staff labor, it will improve working efficiency.This system combines the actual needs of SMEs, through in-depth study and practice of the C/S mode, PowerBuilder10.0 development tools, databases and SQL language, Completed a payroll system needs analysis, database design, application design and development work. Wages, departments, units and personnel database file are included in this system, and have data management, department management, personnel management and other functions, through the control and management of the database query, add, delete, modify, and other functions can be realized. This system is reasonable design, a more complete function, stable operation has been tested to meet the basic needs of the work.

  8. AAV-dominant negative tumor necrosis factor (DN-TNF) gene transfer to the striatum does not rescue medium spiny neurons in the YAC128 mouse model of Huntington's disease.

    PubMed

    Alto, Laura Taylor; Chen, Xi; Ruhn, Kelly A; Treviño, Isaac; Tansey, Malú G

    2014-01-01

    CNS inflammation is a hallmark of neurodegenerative disease, and recent studies suggest that the inflammatory response may contribute to neuronal demise. In particular, increased tumor necrosis factor (TNF) signaling is implicated in the pathology of both Parkinson's disease (PD) and Alzheimer's disease (AD). We have previously shown that localized gene delivery of dominant negative TNF to the degenerating brain region can limit pathology in animal models of PD and AD. TNF is upregulated in Huntington's disease (HD), like in PD and AD, but it is unknown whether TNF signaling contributes to neuronal degeneration in HD. We used in vivo gene delivery to test whether selective reduction of soluble TNF signaling could attenuate medium spiny neuron (MSN) degeneration in the YAC128 transgenic (TG) mouse model of Huntington's disease (HD). AAV vectors encoding cDNA for dominant-negative tumor necrosis factor (DN-TNF) or GFP (control) were injected into the striatum of young adult wild type WT and YAC128 TG mice and achieved 30-50% target coverage. Expression of dominant negative TNF protein was confirmed immunohistologically and biochemically and was maintained as mice aged to one year, but declined significantly over time. However, the extent of striatal DN-TNF gene transfer achieved in our studies was not sufficient to achieve robust effects on neuroinflammation, rescue degenerating MSNs or improve motor function in treated mice. Our findings suggest that alternative drug delivery strategies should be explored to determine whether greater target coverage by DN-TNF protein might afford some level of neuroprotection against HD-like pathology and/or that soluble TNF signaling may not be the primary driver of striatal neuroinflammation and MSN loss in YAC128 TG mice.

  9. Clinical Spectrum of Medium-Sized Vessel Vasculitis.

    PubMed

    Alibaz-Oner, Fatma; Koster, Matthew J; Crowson, Cynthia S; Makol, Ashima; Ytterberg, Steven R; Salvarani, Carlo; Matteson, Eric L; Warrington, Kenneth J

    2017-06-01

    Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single-organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis. Retrospective cohorts were assembled, consisting of patients with PAN, CA, and GI vasculitis between 1980 and 2014. The demographics, clinical characteristics, treatment, and outcomes of patients were abstracted from medical records. We included 48 patients with PAN, 41 patients with CA, and 19 patients with GI vasculitis. The disease of 1 patient evolved from CA to systemic PAN during the disease course. At diagnosis, 94% of patients with PAN, 93% of patients with CA, and 67% of patients with GI vasculitis were treated with glucocorticoids. Additional immunosuppressive agents were used in 67% of PAN, 37% of GI vasculitis, and 32% of CA cases. The 5-year cumulative relapse rate was 45.2% in CA, and only 9.6% in PAN during a followup of approximately 6 years. No deaths were observed in the CA group. The survival rate at 10 years was 66% in the PAN group and 61% in the GI vasculitis group. Systemic PAN, CA, and GI vasculitis take different clinical courses and therefore may be different diseases, rather than existing on a spectrum of the same disease. Progression of CA to systemic PAN is very rare. Relapse risk is low during followup in PAN. Patients with CA have a higher relapse rate than those with systemic PAN, possibly due to less use of immunosuppressive therapy in CA. © 2016, American College of Rheumatology.

  10. Electrophysiological and Morphological Characteristics and Synaptic Connectivity of Tyrosine Hydroxylase-Expressing Neurons in Adult Mouse Striatum

    PubMed Central

    Ibáñez-Sandoval, Osvaldo; Tecuapetla, Fatuel; Unal, Bengi; Shah, Fulva; Koós, Tibor; Tepper, James M.

    2015-01-01

    Whole-cell recordings were obtained from tyrosine hydroxylase-expressing (TH+) neurons in striatal slices from bacterial artificial chromosome transgenic mice that synthesize enhanced green fluorescent protein (EGFP) selectively in neurons expressing TH transcriptional regulatory sequences. Stereological cell counting indicated that there were ~2700 EGFP–TH+ neurons/striatum. Whole-cell recordings in striatal slices demonstrated that EGFP–TH+ neurons comprise four electrophysiologically distinct neuron types whose electrophysiological properties have not been reported previously in striatum. EGFP–TH+ neurons were identified in retrograde tracing studies as interneurons. Recordings from synaptically connected pairs of EGFP–TH+ interneurons and spiny neurons showed that the interneurons elicited GABAergic IPSPs/IPSCs in spiny neurons powerful enough to significantly delay evoked spiking. EGFP–TH+ interneurons responded to local or cortical stimulation with glutamatergic EPSPs. Local stimulation also elicited GABAA IPSPs, at least some of which arose from identified spiny neurons. Single-cell reverse transcription-PCR showed expression of VMAT1 in EGFP–TH+ interneurons, consistent with previous suggestions that these interneurons may be dopaminergic as well as GABAergic. All four classes of interneurons were medium sized with modestly branching, varicose dendrites, and dense, highly varicose axon collateral fields. These data show for the first time that there exists in the normal rodent striatum a substantial population of TH+/GABAergic interneurons comprising four electrophysiologically distinct subtypes whose electrophysiological properties differ significantly from those of previously described striatal GABAergic interneurons. These interneurons are likely to play an important role in striatal function through fast GABAergic synaptic transmission in addition to, and independent of, their potential role in compensation for dopamine loss in experimental

  11. Dopamine-Induced Changes in Gαolf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of l-DOPA-Induced Dyskinesia in Parkinsonian Mice

    PubMed Central

    Morigaki, Ryoma; Okita, Shinya; Goto, Satoshi

    2017-01-01

    The dopamine precursor, l-3,4-dihydroxyphenylalanine (l-DOPA), exerts powerful therapeutic effects but eventually generates l-DOPA-induced dyskinesia (LID) in patients with Parkinson’s disease (PD). LID has a close link with deregulation of striatal dopamine/cAMP signaling, which is integrated by medium spiny neurons (MSNs). Olfactory type G-protein α subunit (Gαolf), a stimulatory GTP-binding protein encoded by the GNAL gene, is highly concentrated in the striatum, where it positively couples with dopamine D1 (D1R) receptor and adenosine A2A receptor (A2AR) to increase intracellular cAMP levels in MSNs. In the striatum, D1Rs are mainly expressed in the MSNs that form the striatonigral pathway, while D2Rs and A2ARs are expressed in the MSNs that form the striatopallidal pathway. Here, we examined the association between striatal Gαolf protein levels and the development of LID. We used a hemi-parkinsonian mouse model with nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Using quantitative immunohistochemistry (IHC) and a dual-antigen recognition in situ proximity ligation assay (PLA), we here found that in the dopamine-depleted striatum, there appeared increased and decreased levels of Gαolf protein in striatonigral and striatopallidal MSNs, respectively, after a daily pulsatile administration of l-DOPA. This leads to increased responsiveness to dopamine stimulation in both striatonigral and striatopallidal MSNs. Because Gαolf protein levels serve as a determinant of cAMP signal-dependent activity in striatal MSNs, we suggest that l-DOPA-induced changes in striatal Gαolf levels in the dopamine-depleted striatum could be a key event in generating LID. PMID:28239340

  12. Dopamine-Induced Changes in Gαolf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of l-DOPA-Induced Dyskinesia in Parkinsonian Mice.

    PubMed

    Morigaki, Ryoma; Okita, Shinya; Goto, Satoshi

    2017-01-01

    The dopamine precursor, l-3,4-dihydroxyphenylalanine (l-DOPA), exerts powerful therapeutic effects but eventually generates l-DOPA-induced dyskinesia (LID) in patients with Parkinson's disease (PD). LID has a close link with deregulation of striatal dopamine/cAMP signaling, which is integrated by medium spiny neurons (MSNs). Olfactory type G-protein α subunit (Gαolf), a stimulatory GTP-binding protein encoded by the GNAL gene, is highly concentrated in the striatum, where it positively couples with dopamine D1 (D1R) receptor and adenosine A2A receptor (A2AR) to increase intracellular cAMP levels in MSNs. In the striatum, D1Rs are mainly expressed in the MSNs that form the striatonigral pathway, while D2Rs and A2ARs are expressed in the MSNs that form the striatopallidal pathway. Here, we examined the association between striatal Gαolf protein levels and the development of LID. We used a hemi-parkinsonian mouse model with nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Using quantitative immunohistochemistry (IHC) and a dual-antigen recognition in situ proximity ligation assay (PLA), we here found that in the dopamine-depleted striatum, there appeared increased and decreased levels of Gαolf protein in striatonigral and striatopallidal MSNs, respectively, after a daily pulsatile administration of l-DOPA. This leads to increased responsiveness to dopamine stimulation in both striatonigral and striatopallidal MSNs. Because Gαolf protein levels serve as a determinant of cAMP signal-dependent activity in striatal MSNs, we suggest that l-DOPA-induced changes in striatal Gαolf levels in the dopamine-depleted striatum could be a key event in generating LID.

  13. Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.

    PubMed

    Toy, William A; Petzinger, Giselle M; Leyshon, Brian J; Akopian, Garnik K; Walsh, John P; Hoffman, Matilde V; Vučković, Marta G; Jakowec, Michael W

    2014-03-01

    Exercise has been shown to be beneficial for Parkinson's disease (PD). A major interest in our lab has been to investigate how exercise modulates basal ganglia function and modifies disease progression. Dopamine (DA) depletion leads to loss of dendritic spines within the caudate nucleus and putamen (striatum) in PD and its animal models and contributes to motor impairments. Striatal medium spiny neurons (MSNs) can be delineated into two populations, the dopamine D1 receptor (DA-D1R)-containing MSNs of the direct pathway and dopamine D2 receptor (DA-D2R)-containing MSNs of the indirect pathway. There is evidence to suggest that the DA-D2R-indirect pathway MSNs may be preferentially affected after DA-depletion with a predominate loss of dendritic spine density when compared to MSNs of the DA-D1R-direct pathway in rodents; however, others have reported that both pathways may be affected in primates. The purpose of this study was to investigate the effects of intensive exercise on dendritic spine density and arborization in MSNs of these two pathways in the MPTP mouse model of PD. We found that MPTP led to a decrease in dendritic spine density in both DA-D1R- and DA-D2R-containing MSNs and 30 days of intensive treadmill exercise led to increased dendritic spine density and arborization in MSNs of both pathways. In addition, exercise increased the expression of synaptic proteins PSD-95 and synaptophysin. Taken together these findings support the potential effect of exercise in modifying synaptic connectivity within the DA-depleted striatum and in modifying disease progression in individuals with PD.

  14. Design and implementation of web server soft load balancing in small and medium-sized enterprise

    NASA Astrophysics Data System (ADS)

    Yan, Liu

    2011-12-01

    With the expansion of business scale, small and medium-sized enterprises began to use information platform to improve their management and competition ability, the server becomes the core factor which restricts the enterprise's infomationization construction. This paper puts forward a suitable design scheme for small and medium-sized enterprise web server soft load balancing, and proved it effective through experiment.

  15. Managers' Understanding of Workplace Health Promotion within Small and Medium-Sized Enterprises: A Phenomenological Study

    ERIC Educational Resources Information Center

    Moore, Ann; Parahoo, Kader; Fleming, Paul

    2011-01-01

    Objective: This study aimed at exploring managers' understanding of workplace health promotion and experiences of workplace health promotion activity within small and medium-sized enterprises. Design: A Heideggerian interpretive phenomenological methodology was adopted. Setting: This study was undertaken with small and medium-sized enterprise…

  16. Managers' Understanding of Workplace Health Promotion within Small and Medium-Sized Enterprises: A Phenomenological Study

    ERIC Educational Resources Information Center

    Moore, Ann; Parahoo, Kader; Fleming, Paul

    2011-01-01

    Objective: This study aimed at exploring managers' understanding of workplace health promotion and experiences of workplace health promotion activity within small and medium-sized enterprises. Design: A Heideggerian interpretive phenomenological methodology was adopted. Setting: This study was undertaken with small and medium-sized enterprise…

  17. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    PubMed

    Kovalenko, Marina; Dragileva, Ella; St Claire, Jason; Gillis, Tammy; Guide, Jolene R; New, Jaclyn; Dong, Hualing; Kucherlapati, Raju; Kucherlapati, Melanie H; Ehrlich, Michelle E; Lee, Jong-Min; Wheeler, Vanessa C

    2012-01-01

    The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT) exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR) pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111) with mice carrying a conditional (floxed) Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  18. Evaluation research of small and medium-sized enterprise informatization on big data

    NASA Astrophysics Data System (ADS)

    Yang, Na

    2017-09-01

    Under the background of big data, key construction of small and medium-sized enterprise informationization level was needed, but information construction cost was large, while information cost of inputs can bring benefit to small and medium-sized enterprises. This paper established small and medium-sized enterprise informatization evaluation system from hardware and software security level, information organization level, information technology application and the profit level, and information ability level. The rough set theory was used to brief indexes, and then carry out evaluation by support vector machine (SVM) model. At last, examples were used to verify the theory in order to prove the effectiveness of the method.

  19. Spiny plants, mammal browsers, and the origin of African savannas.

    PubMed

    Charles-Dominique, Tristan; Davies, T Jonathan; Hempson, Gareth P; Bezeng, Bezeng S; Daru, Barnabas H; Kabongo, Ronny M; Maurin, Olivier; Muasya, A Muthama; van der Bank, Michelle; Bond, William J

    2016-09-20

    Savannas first began to spread across Africa during the Miocene. A major hypothesis for explaining this vegetation change is the increase in C4 grasses, promoting fire. We investigated whether mammals could also have contributed to savanna expansion by using spinescence as a marker of mammal herbivory. Looking at the present distribution of 1,852 tree species, we established that spinescence is mainly associated with two functional types of mammals: large browsers and medium-sized mixed feeders. Using a dated phylogeny for the same tree species, we found that spinescence evolved at least 55 times. The diversification of spiny plants occurred long after the evolution of Afrotherian proboscideans and hyracoids. However, it is remarkably congruent with diversification of bovids, the lineage including the antelope that predominantly browse these plants today. Our findings suggest that herbivore-adapted savannas evolved several million years before fire-maintained savannas and probably, in different environmental conditions. Spiny savannas with abundant mammal herbivores occur in drier climates and on nutrient-rich soils, whereas fire-maintained savannas occur in wetter climates on nutrient-poor soils.

  20. Spiny plants, mammal browsers, and the origin of African savannas

    PubMed Central

    Charles-Dominique, Tristan; Davies, T. Jonathan; Hempson, Gareth P.; Bezeng, Bezeng S.; Kabongo, Ronny M.; Maurin, Olivier; Muasya, A. Muthama; van der Bank, Michelle; Bond, William J.

    2016-01-01

    Savannas first began to spread across Africa during the Miocene. A major hypothesis for explaining this vegetation change is the increase in C4 grasses, promoting fire. We investigated whether mammals could also have contributed to savanna expansion by using spinescence as a marker of mammal herbivory. Looking at the present distribution of 1,852 tree species, we established that spinescence is mainly associated with two functional types of mammals: large browsers and medium-sized mixed feeders. Using a dated phylogeny for the same tree species, we found that spinescence evolved at least 55 times. The diversification of spiny plants occurred long after the evolution of Afrotherian proboscideans and hyracoids. However, it is remarkably congruent with diversification of bovids, the lineage including the antelope that predominantly browse these plants today. Our findings suggest that herbivore-adapted savannas evolved several million years before fire-maintained savannas and probably, in different environmental conditions. Spiny savannas with abundant mammal herbivores occur in drier climates and on nutrient-rich soils, whereas fire-maintained savannas occur in wetter climates on nutrient-poor soils. PMID:27601649

  1. Dopamine D1-like receptor activation depolarizes medium spiny neurons of the mouse nucleus accumbens by inhibiting inwardly rectifying K+ currents through a cAMP-dependent protein kinase A-independent mechanism.

    PubMed

    Podda, M V; Riccardi, E; D'Ascenzo, M; Azzena, G B; Grassi, C

    2010-05-19

    Dopamine/cAMP signaling has been reported to mediate behavioral responses related to drug addiction. It also modulates the plasticity and firing properties of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), although the effects of cAMP signaling on the resting membrane potential (RMP) of MSNs has not been specifically defined. In this study, activation of dopamine D1-like receptors (D1Rs) by SKF-38393 elicited membrane depolarization and inward currents in MSNs from the NAc core of 14-17 day-old mice. Similar results were obtained following stimulation of adenylyl cyclase (AC) activity with forskolin or application of exogenous cAMP. Forskolin occluded SKF-38393's effects, thus indicating that D1R action is mediated by AC/cAMP signaling. Accordingly, AC blockade by SQ22536 significantly inhibited the responses to SKF-38393. Effects elicited by D1R stimulation or increased cAMP levels were unaffected by protein kinase A (PKA) or protein kinase C (PKC) blockade and were not mimicked by the Epac agonist, 8CPT-2Me-cAMP. Responses to forskolin were also not significantly modified by cyclic nucleotide-gated (CNG) channel blockade. Forskolin-induced membrane depolarization was associated with increased membrane input resistance. Voltage-clamp experiments revealed that forskolin and SKF-38393 effects were due to inhibition of resting K(+) currents exhibiting inward rectification at hyperpolarized potentials and a reversal potential (around -90 mV) that shifted with the extracellular K(+) concentration. Forskolin and D1R agonist effects were abolished by the inward rectifier K(+) (Kir)-channel blocker, BaCl(2). Collectively, these data suggest that stimulation of postsynaptic D1Rs in MSNs of the NAc core causes membrane depolarization by inhibiting Kir currents. This effect is mediated by AC/cAMP signaling but it is independent on PKA, PKC, Epac and CNG channel activation, suggesting that it may stem from cAMP's direct interaction with Kir channels. D1R

  2. 50 CFR 648.232 - Spiny dogfish specifications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish specifications. 648.232... Measures for the Spiny Dogfish Fishery § 648.232 Spiny dogfish specifications. (a) Commercial quota and other specification measures. The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny...

  3. 50 CFR 648.232 - Spiny dogfish specifications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish specifications. 648.232... Measures for the Spiny Dogfish Fishery § 648.232 Spiny dogfish specifications. (a) Commercial quota and other specification measures. The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny...

  4. 50 CFR 648.232 - Spiny dogfish specifications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Spiny dogfish specifications. 648.232... Measures for the Spiny Dogfish Fishery § 648.232 Spiny dogfish specifications. (a) Commercial quota and other specification measures. The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny...

  5. 50 CFR 648.232 - Spiny dogfish specifications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Spiny dogfish specifications. 648.232... Measures for the Spiny Dogfish Fishery § 648.232 Spiny dogfish specifications. (a) Commercial quota and other specification measures. The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny...

  6. 40 CFR 428.60 - Applicability; description of the medium-sized general molded, extruded, and fabricated rubber...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... medium-sized general molded, extruded, and fabricated rubber plants subcategory. 428.60 Section 428.60... (CONTINUED) RUBBER MANUFACTURING POINT SOURCE CATEGORY Medium-Sized General Molded, Extruded, and Fabricated Rubber Plants Subcategory § 428.60 Applicability; description of the medium-sized general...

  7. 40 CFR 428.60 - Applicability; description of the medium-sized general molded, extruded, and fabricated rubber...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... medium-sized general molded, extruded, and fabricated rubber plants subcategory. 428.60 Section 428.60... (CONTINUED) RUBBER MANUFACTURING POINT SOURCE CATEGORY Medium-Sized General Molded, Extruded, and Fabricated Rubber Plants Subcategory § 428.60 Applicability; description of the medium-sized general...

  8. 40 CFR 428.60 - Applicability; description of the medium-sized general molded, extruded, and fabricated rubber...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... medium-sized general molded, extruded, and fabricated rubber plants subcategory. 428.60 Section 428.60... (CONTINUED) RUBBER MANUFACTURING POINT SOURCE CATEGORY Medium-Sized General Molded, Extruded, and Fabricated Rubber Plants Subcategory § 428.60 Applicability; description of the medium-sized general...

  9. 40 CFR 428.60 - Applicability; description of the medium-sized general molded, extruded, and fabricated rubber...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... medium-sized general molded, extruded, and fabricated rubber plants subcategory. 428.60 Section 428.60... RUBBER MANUFACTURING POINT SOURCE CATEGORY Medium-Sized General Molded, Extruded, and Fabricated Rubber Plants Subcategory § 428.60 Applicability; description of the medium-sized general molded, extruded, and...

  10. [Management practices in medium-sized private hospitals in São Paulo, Brazil].

    PubMed

    Brito, Luiz Artur Ledur; Malik, Ana Maria; Brito, Eliane; Bulgacov, Sergio; Andreassi, Tales

    2017-04-03

    Traditional management practices are sometimes considered merely a necessary condition for superior performance. Other resources and competencies with higher barriers to imitation are assumed to be potential sources of competitive advantage. This study describes and analyzes the effect of traditional management practices on the performance of medium-sized hospitals. Medium-sized companies frequently display the greatest differences in management practices, and only recently did the hospital sector seek ways to develop its competitiveness in the administrative arena. The results generally indicate that basic management practices can make differences in performance, offering support for the new practice-based view (PBV). Hospitals with the highest rate of adoption of practices had the highest occupancy rate, hospital-bed admissions, and accreditation. Lack of adoption of management practices by medium-sized hospitals limits their competitive capacity and can be viewed as a component of the so-called Brazil cost, but in this case an internal component.

  11. The cytoarchitectonic and neuronal structure of the red nucleus in guinea pig: Nissl and Golgi studies.

    PubMed

    Robak, A; Szteyn, S; Bogus-Nowakowska, K; Doboszyńska, T; Równiak, M

    2000-01-01

    The present studies were carried out on the brains of adult guinea pigs, Dunkin-Hartley strain. On the basis of preparations, they were stained according to the Nissl and the Klüver-Barrera method's; a short description of the cytoarchitectonics and the characteristics of the rubral cells were written. The red nucleus (RN) of the guinea pig is 1.2 mm in length. Three cellular parts in RN, and three classes (A, B, C) of the rubral cells were distinguished. Taking into consideration the predominant cell size, RN was divided into magnocellular part (RNm), parvocellular part (RNp) and intermediate part (RNi). On the basis of Golgi impregnated preparations four neuronal types (I, II, III, IV) were distinguished. To sum up, in the guinea pig were observed: the large, mainly multipolar (type I) and bipolar (type II) spiny being coarse (class A) in Nissl material; the medium-sized, triangular, aspiny (type III) corresponding to the fine cells (class B); and the small, both spiny and aspiny neurons (type IV), which are the fine or achromatic cells (classes B or C) in Nissl stained slices. The highest degree of dendritic branching was observed in type I, whereas the lowest in cells of types III and IV.

  12. An Agile Methodology for Implementing Service-Oriented Architecture in Small and Medium Sized Organizations

    ERIC Educational Resources Information Center

    Laidlaw, Gregory

    2013-01-01

    The purpose of this study is to evaluate the use of Lean/Agile principles, using action research to develop and deploy new technology for Small and Medium sized enterprises. The research case was conducted at the Lapeer County Sheriff's Department and involves the initial deployment of a Service Oriented Architecture to alleviate the data…

  13. Business Continuity Planning Resources for Small- and Medium-Sized Businesses

    SciTech Connect

    Judd, Kathleen S.; Lesperance, Ann M.

    2010-05-14

    This document/memo summarizes existing resources and guidance on business continuity planning for small- to medium-sized businesses. DTRA will share this information with large commercial businesses who identified the need to help their suppliers and other key collaborators prepare business continuity plans in order to speed recovery from a wide-area bioterrorism incident.

  14. Barriers to Employee Training in Small and Medium Sized Enterprises: Insights and Evidences from Mauritius

    ERIC Educational Resources Information Center

    Padachi, Kesseven; Bhiwajee, Soolakshna Lukea

    2016-01-01

    Purpose: Training is an important component of successful business concerns. However, although there is growing acceptance amongst scholars that small- and medium-sized enterprises (SMEs) are engines that drive economies across nations, through their contribution in terms of job creation and poverty reduction; extant research portray that these…

  15. Barriers to Employee Training in Small and Medium Sized Enterprises: Insights and Evidences from Mauritius

    ERIC Educational Resources Information Center

    Padachi, Kesseven; Bhiwajee, Soolakshna Lukea

    2016-01-01

    Purpose: Training is an important component of successful business concerns. However, although there is growing acceptance amongst scholars that small- and medium-sized enterprises (SMEs) are engines that drive economies across nations, through their contribution in terms of job creation and poverty reduction; extant research portray that these…

  16. Toward a Singleton Undergraduate Computer Graphics Course in Small and Medium-Sized Colleges

    ERIC Educational Resources Information Center

    Shesh, Amit

    2013-01-01

    This article discusses the evolution of a single undergraduate computer graphics course over five semesters, driven by a primary question: if one could offer only one undergraduate course in graphics, what would it include? This constraint is relevant to many small and medium-sized colleges that lack resources, adequate expertise, and enrollment…

  17. Supporting the E-Business Readiness of Small and Medium-Sized Enterprises: Approaches and Metrics.

    ERIC Educational Resources Information Center

    Jutla, Dawn; Bodorik, Peter; Dhaliwal, Jasbir

    2002-01-01

    Presents a conceptual model for governments in creating a climate that facilitates the national adoption of e-business. Focuses on the needs of small and medium-sized enterprises, suggests measures to assess how a country is performing in providing a positive e-business climate, and provides examples from Canada, The Netherlands, Norway, and…

  18. Small and Medium-Sized Information Technology Firms: Assessment of Non-Local Partnership Facilitators

    ERIC Educational Resources Information Center

    Findikoglu, Melike Nur

    2012-01-01

    A two-phased qualitative study was conducted to explore the facilitators of non-local (i.e. domestic or international) partnerships formed by small- and medium-sized firms (SME). Rooted in trust, proximity and dynamic capabilities lenses, the study focused on behaviors of SMEs performing in dynamic, competitive and highly interlinked industry, the…

  19. An Agile Methodology for Implementing Service-Oriented Architecture in Small and Medium Sized Organizations

    ERIC Educational Resources Information Center

    Laidlaw, Gregory

    2013-01-01

    The purpose of this study is to evaluate the use of Lean/Agile principles, using action research to develop and deploy new technology for Small and Medium sized enterprises. The research case was conducted at the Lapeer County Sheriff's Department and involves the initial deployment of a Service Oriented Architecture to alleviate the data…

  20. Key Influencing Factors behind Moodle Adoption in Irish Small to Medium Sized Higher Education Colleges

    ERIC Educational Resources Information Center

    Walker, David; Livadas, Lelia; Miles, Gail

    2011-01-01

    This research investigated Irish Small to Medium Sized Educational Institutions (SMSEs) involved in Higher Education (HE) that adopted Moodle, the OSS (Open Source Software) course management system (CMS). As Moodle has only been adopted in the Irish HE sector in the last 5-7 years, this research crucially studied the attitudes of the SMSEs that…

  1. A Bare Bones Reference Collection for Small and Medium-Sized Public Libraries in Maine.

    ERIC Educational Resources Information Center

    Southern Maine Library District, Portland.

    This reference list was compiled to offer Maine librarians who serve communities with the resources of small- or medium-sized libraries a starting point to assess their reference collections for breadth and depth. Initially based on a list distributed by the Vermont Department of Libraries in 1987, this guide evaluates reference materials on the…

  2. Successful E-Learning in Small and Medium-Sized Enterprises

    ERIC Educational Resources Information Center

    Paulsen, Morten Flate

    2009-01-01

    So far, e-learning has primarily been used when there are many learners involved. The up-front investments related to e-learning are relatively high, and may be perceived as prohibitive for small and medium-sized enterprises (SMEs). Some e-learning is, however, getting less expensive, and some e-learning models are more suited for small-scale…

  3. Marketing Continuing Vocational Education to Small and Medium Sized Enterprises: Key Issues for Higher Education Institutions.

    ERIC Educational Resources Information Center

    Bagwell, Sue

    1998-01-01

    Discusses issues which higher education institutions need to consider when marketing continuing vocational education to small and medium-sized enterprises. Experiences at the University of North London and results from a survey of other institutions and focus group discussions with managers and employees are reviewed. (Author/LRW)

  4. Toward a Singleton Undergraduate Computer Graphics Course in Small and Medium-Sized Colleges

    ERIC Educational Resources Information Center

    Shesh, Amit

    2013-01-01

    This article discusses the evolution of a single undergraduate computer graphics course over five semesters, driven by a primary question: if one could offer only one undergraduate course in graphics, what would it include? This constraint is relevant to many small and medium-sized colleges that lack resources, adequate expertise, and enrollment…

  5. Small and Medium-Sized Information Technology Firms: Assessment of Non-Local Partnership Facilitators

    ERIC Educational Resources Information Center

    Findikoglu, Melike Nur

    2012-01-01

    A two-phased qualitative study was conducted to explore the facilitators of non-local (i.e. domestic or international) partnerships formed by small- and medium-sized firms (SME). Rooted in trust, proximity and dynamic capabilities lenses, the study focused on behaviors of SMEs performing in dynamic, competitive and highly interlinked industry, the…

  6. Supporting the E-Business Readiness of Small and Medium-Sized Enterprises: Approaches and Metrics.

    ERIC Educational Resources Information Center

    Jutla, Dawn; Bodorik, Peter; Dhaliwal, Jasbir

    2002-01-01

    Presents a conceptual model for governments in creating a climate that facilitates the national adoption of e-business. Focuses on the needs of small and medium-sized enterprises, suggests measures to assess how a country is performing in providing a positive e-business climate, and provides examples from Canada, The Netherlands, Norway, and…

  7. Current information technology needs of small to medium sized apparel manufacturers and contractors

    SciTech Connect

    Wipple, C.; Vosti, E.

    1997-11-01

    This report documents recent efforts of the American Textile Partnership (AMTEX) Demand Activated Manufacturing Architecture (DAMA) Project to address needs that are characterized of small to medium sized apparel manufactures and contractors. Background on the AMTEX/DAMA project and objectives for this specific efforts are discussed.

  8. Sustainability and Small to Medium Sized Enterprises--How to Engage Them

    ERIC Educational Resources Information Center

    Condon, Linda

    2004-01-01

    Small and medium sized enterprises (SMEs) have a major advantage over larger organisations in regard to addressing sustainability issues--their size means they are able to react very quickly to changes in the business environment. They are disadvantaged, however, by lack of information on marketplace changes that make sustainability an opportunity…

  9. Planning an Authority Control Project at a Medium-Sized University Library.

    ERIC Educational Resources Information Center

    Zhang, Sha Li

    2001-01-01

    Authority control is a vital part of providing students and faculty with adequate access to collections in university libraries. Small and medium-sized libraries find it challenging to meet rising user expectations and provide adequate access in an online environment through appropriate authority work. A planning process is offered on an authority…

  10. Activin A directs striatal projection neuron differentiation of human pluripotent stem cells

    PubMed Central

    Arber, Charles; Precious, Sophie V.; Cambray, Serafí; Risner-Janiczek, Jessica R.; Kelly, Claire; Noakes, Zoe; Fjodorova, Marija; Heuer, Andreas; Ungless, Mark A.; Rodríguez, Tristan A.; Rosser, Anne E.; Dunnett, Stephen B.; Li, Meng

    2015-01-01

    The efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening and cell therapy for Huntington's disease. GABAergic medium-sized spiny neurons (MSNs) are the principal projection neurons of the striatum and specifically degenerate in the early phase of Huntington's disease. Here we report that activin A induces lateral ganglionic eminence (LGE) characteristics in nascent neural progenitors derived from hESCs and hiPSCs in a sonic hedgehog-independent manner. Correct specification of striatal phenotype was further demonstrated by the induction of the striatal transcription factors CTIP2, GSX2 and FOXP2. Crucially, these human LGE progenitors readily differentiate into postmitotic neurons expressing the striatal projection neuron signature marker DARPP32, both in culture and following transplantation in the adult striatum in a rat model of Huntington's disease. Activin-induced neurons also exhibit appropriate striatal-like electrophysiology in vitro. Together, our findings demonstrate a novel route for efficient differentiation of GABAergic striatal MSNs from human pluripotent stem cells. PMID:25804741

  11. [Types of neurons in the visual cortex of the rat, identified in Nissl- and deimpregnated Golgi preparations].

    PubMed

    Werner, L; Hedlich, A; Winkelmann, E

    1985-01-01

    Neuronal types of the rat's visual cortex were identified in Nissl stained and deimpregnated Golgi sections (rapid Golgi method modified by Fairén et al. 1977, Golgi-Bubenaite, Golgi-Kopsch and modified by Braitenberg; deimpregnation after FAIREN et al. 1977 and Braak and Braak 1982, respectively). Cytoplasm and nucleus become visible in deimpregnated neurons and can then be counter-stained with methylene blue or toluidin blue. Somal and nuclear features of Nissl stained and deimpregnated neurons were compared. Provided that these features as well as the specific localization, the relative size and the shape of the soma agree the neurons are identical. We could find that the following neuronal types are identical in Golgi and Nissl stained sections: pyramidal cells of layers II-VI, pyramid-like neurons of layers VI and VII (VIa, b, c) (type C, Werner et al. 1982), multiangular neurons of layer I (type A, Werner et al. 1982), spiny stellate cells of layer IV, sparsely spined neurons with ascending axons (Martinotti cells) (type H, Werner et al. 1982), large and medium-sized spine-free, multipolar neurons (basket cells) (type B, Werner et al. 1982). Bipolar neurons and chandelier cells are identical with neurons poor in cytoplasm (types E, F, G, Werner et al. 1982). Until today two neuronal types could not be identified: type D of L I (Werner et al. 1982) and small, sparsely-spined neurons of layer IV with variable axons (Hedlich and Winkelmann 1982; Hedlich et al. 1984). Characteristics of somata, dendrites and axons of neurons identified in this paper are summarized in table 1. In most cases, these findings confirm earlier suppositions concerning the identity of neuronal types of the rat's visual cortex in Golgi and Nissl stained sections (Werner et al. 1979) and verify the values of their frequency and distribution pattern (Werner et al. 1982).

  12. 50 CFR 648.233 - Spiny dogfish Accountability Measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish Accountability Measures... Management Measures for the Spiny Dogfish Fishery § 648.233 Spiny dogfish Accountability Measures (AMs). (a... quota described in § 648.232 will be harvested and shall close the EEZ to fishing for spiny dogfish on...

  13. 50 CFR 622.409 - Spiny lobster import prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny lobster import prohibitions. 622... ATLANTIC Spiny Lobster Fishery of the Gulf of Mexico and South Atlantic § 622.409 Spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There are two minimum size limits that...

  14. 50 CFR 622.455 - Landing spiny lobster intact.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Landing spiny lobster intact. 622.455... ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.455 Landing spiny lobster intact. (a) A Caribbean spiny lobster in or from the Caribbean EEZ must be maintained with head...

  15. 50 CFR 622.455 - Landing spiny lobster intact.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Landing spiny lobster intact. 622.455... ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.455 Landing spiny lobster intact. (a) A Caribbean spiny lobster in or from the Caribbean EEZ must be maintained with head...

  16. 50 CFR 622.409 - Spiny lobster import prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny lobster import prohibitions. 622... ATLANTIC Spiny Lobster Fishery of the Gulf of Mexico and South Atlantic § 622.409 Spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There are two minimum size limits that...

  17. 50 CFR 622.458 - Caribbean spiny lobster import prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Caribbean spiny lobster import..., AND SOUTH ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.458 Caribbean spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There...

  18. Teaching Medium-Sized ERP Systems - A Problem-Based Learning Approach

    NASA Astrophysics Data System (ADS)

    Winkelmann, Axel; Matzner, Martin

    In order to increase the diversity in IS education, we discuss an approach for teaching medium-sized ERP systems in master courses. Many of today's IS curricula are biased toward large ERP packages. Nevertheless, these ERP systems are only a part of the ERP market. Hence, this chapter describes a course outline for a course on medium-sized ERP systems. Students had to study, analyze, and compare five different ERP systems during a semester. The chapter introduces a procedure model and scenario for setting up similar courses at other universities. Furthermore, it describes some of the students' outcomes and evaluates the contribution of the course with regard to a practical but also academic IS education.

  19. Services Supporting Knowledge Maturing in Small and Medium-Sized Enterprises

    NASA Astrophysics Data System (ADS)

    Maier, Ronald

    The hype around Web 2.0 has again sparked tremendous interest in IT-supported knowledge management and technology-enhanced learning in organizations. Although there has been abundant evidence of how to benefit from Web 2.0 technologies, information on how to go about deploying these in small and medium-sized enterprises in a coordinated manner are scarce. Based on the findings of an empirical study and an ethnographically informed study on knowledge maturing, this paper suggests a set of knowledge services to support a series of knowledge actions chained with the help of the knowledge maturing model. This set of services can be used by small and medium-sized enterprises for analyzing IT tools and systems which currently support their employees’ knowledge maturing activities, to foster knowledge cooperation with customers, suppliers and partners in their business environment and to find gaps which can be filled particularly by consuming services over the Web.

  20. Analysis of energy-efficiency investment decisions by small and medium-sized manufacturers

    SciTech Connect

    Woodruff, M.G.; Roop, J.M.; Seely, H.E.; Muller, M.R.; Jones, T.W.; Dowd, J.

    1996-05-01

    This report highlights the results of a comprehensive analysis of investment decisions regarding energy-efficiency measures at small and medium-sized manufacturing plants. The analysis is based on the experiences of companies participating in the DOE Industrial Assessment Center (IAC) program. The IAC program is a network of university-based centers that provides energy and waste assessments to small and medium-sized manufacturing plants. The purposes of this report are to do the following: (1) Examine what the data collected reveal about patterns of implementation of recommended energy- efficiency measures, (2) Evaluate how various factors, such as the type of industry, the characteristics of the manufacturing plants, or the cost of the measures, appear to effect implementation rates, (3) Examine reasons why recommended energy-saving measures are accepted or rejected.

  1. Asymmetric Synthesis of Medium-Sized Rings by Intramolecular Au(I)-Catalyzed Cyclopropanation

    PubMed Central

    Watson, Iain D. G.; Ritter, Stefanie; Toste, F. Dean

    2009-01-01

    An efficient method for the asymmetric gold(I)-catalyzed preparation of medium sized rings has been developed. The method provides 7- to 9-membered rings in excellent yield. High enantioselectivities can be achieved for 7- and 8-membered ring products employing chiral gold(I) complexes. The results provide insight into the mechanism, showing the fluxional nature of gold(I)-stabilized vinyl carbenoid intermediates. PMID:19161306

  2. Assessing the effectiveness of safeguards at a medium-sized spent-fuel reprocessing facility

    SciTech Connect

    Higinbotham, W.; Fishbone, L.G.; Suda, S.

    1983-01-01

    In order to evaluate carefully and systematically the effectiveness of safeguards at nuclear-fuel-cycle facilities, the International Atomic Energy Agency has adopted a safeguards effectiveness assessment methodology. The methodology has been applied to a well-characterized, medium-sized, spent-fuel reprocessing plant to understand how explicit safeguards inspection procedures would serve to expose conceivable nuclear materials diversion schemes, should such diversion occur.

  3. Financial and Tax Management in Small and Medium Sized Industrial Enterprises

    NASA Astrophysics Data System (ADS)

    Bestvinová, Viera; Homokyová, Mária; Horváthová, Martina

    2012-12-01

    Target of this paper was to evaluate the importance of small and medium sized enterprises (SMEs) in Slovakia and to determine the application of financial and tax management in this type of enterprises. The results of our findings confirm that SMEs have an important role in Slovakia, and also that especially small businesses have little or no experience with the application of financial and tax management. Therefore the paper contains recommendations for financial and tax management of SMEs.

  4. Consultant-Client Relationship and Knowledge Transfer in Small- and Medium-Sized Enterprises Change Processes.

    PubMed

    Martinez, Luis F; Ferreira, Aristides I; Can, Amina B

    2016-04-01

    Based on Szulanski's knowledge transfer model, this study examined how the communicational, motivational, and sharing of understanding variables influenced knowledge transfer and change processes in small- and medium-sized enterprises, particularly under projects developed by funded programs. The sample comprised 144 entrepreneurs, mostly male (65.3%) and mostly ages 35 to 45 years (40.3%), who filled an online questionnaire measuring the variables of "sharing of understanding," "motivation," "communication encoding competencies," "source credibility," "knowledge transfer," and "organizational change." Data were collected between 2011 and 2012 and measured the relationship between clients and consultants working in a Portuguese small- and medium-sized enterprise-oriented action learning program. To test the hypotheses, structural equation modeling was conducted to identify the antecedents of sharing of understanding, motivational, and communicational variables, which were positively correlated with the knowledge transfer between consultants and clients. This transfer was also positively correlated with organizational change. Overall, the study provides important considerations for practitioners and academicians and establishes new avenues for future studies concerning the issues of consultant-client relationship and the efficacy of Government-funded programs designed to improve performance of small- and medium-sized enterprises.

  5. [Health management in small and medium-sized enterprises: results of a representative survey].

    PubMed

    Zelfel, R C; Alles, T; Weber, A

    2011-08-01

    The prevalence of workplace health promotion in small and medium-sized enterprises (SME) in Germany as well as age management were investigated. Representative data were collected by computer assisted telephone interviews in 1 441 SME (1-250 employees) in 7 regions of Germany. One-third of the SME have a system of health promotion. Disability management is known only in one third of the enterprises, another third of them knew the legal obligations. About half of the enterprises have a system to collect data about health-related absenteeism in business. Effects caused by the demographic change in Germany are feared by nearly 50% of the enterprises, but only 20% have taken action against it. The implementation of work health promotion is higher in enterprises with more employees. The study shows that workplace health promotion (WHP) in German small and medium-sized enterprises is not yet installed to a wide extent. The smaller the enterprises the less WHP is found. The results are verified by similar studies. Small and medium-sized enterprises have a need for consultation in cases of illness or health prevention. But there is not yet an organised structure available for getting advice. The study is the basis for a national project "Gesunde Arbeit", which will establish these consulting structures. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Small- and Medium-Sized Commercial Building Monitoring and Controls Needs: A Scoping Study

    SciTech Connect

    Katipamula, Srinivas; Underhill, Ronald M.; Goddard, James K.; Taasevigen, Danny J.; Piette, M. A.; Granderson, J.; Brown, Rich E.; Lanzisera, Steven M.; Kuruganti, T.

    2012-10-31

    Buildings consume over 40% of the total energy consumption in the U.S. A significant portion of the energy consumed in buildings is wasted because of the lack of controls or the inability to use existing building automation systems (BASs) properly. Much of the waste occurs because of our inability to manage and controls buildings efficiently. Over 90% of the buildings are either small-size (<5,000 sf) or medium-size (between 5,000 sf and 50,000 sf); these buildings currently do not use BASs to monitor and control their building systems from a central location. According to Commercial Building Energy Consumption Survey (CBECS), about 10% of the buildings in the U.S. use BASs or central controls to manage their building system operations. Buildings that use BASs are typically large (>100,000 sf). Lawrence Berkeley National Laboratory (LBNL), Oak Ridge National Laboratory (ORNL) and Pacific Northwest National Laboratory (PNNL) were asked by the U.S. Department of Energy’s (DOE’s) Building Technologies Program (BTP) to identify monitoring and control needs for small- and medium-sized commercial buildings and recommend possible solutions. This study documents the needs and solutions for small- and medium-sized buildings.

  7. 40 CFR 428.60 - Applicability; description of the medium-sized general molded, extruded, and fabricated rubber...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... medium-sized general molded, extruded, and fabricated rubber plants subcategory. 428.60 Section 428.60... RUBBER MANUFACTURING POINT SOURCE CATEGORY Medium-Sized General Molded, Extruded, and Fabricated Rubber... fabricated rubber plants subcategory. The following provisions of this subpart are applicable to...

  8. 75 FR 9431 - Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-02

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities... investigations, investigation No. 332-509, Small and Medium-Sized Enterprises: U.S. and EU Export Activities,...

  9. Preliminary Design Study of Medium Sized Gas Cooled Fast Reactor with Natural Uranium as Fuel Cycle Input

    NASA Astrophysics Data System (ADS)

    Meriyanti, Su'ud, Zaki; Rijal, K.; Zuhair, Ferhat, A.; Sekimoto, H.

    2010-06-01

    In this study a fesibility design study of medium sized (1000 MWt) gas cooled fast reactors which can utilize natural uranium as fuel cycle input has been conducted. Gas Cooled Fast Reactor (GFR) is among six types of Generation IV Nuclear Power Plants. GFR with its hard neuron spectrum is superior for closed fuel cycle, and its ability to be operated in high temperature (850° C) makes various options of utilizations become possible. To obtain the capability of consuming natural uranium as fuel cycle input, modified CANDLE burn-up scheme[1-6] is adopted this GFR system by dividing the core into 10 parts of equal volume axially. Due to the limitation of thermal hydraulic aspects, the average power density of the proposed design is selected about 70 W/cc. As an optimization results, a design of 1000 MWt reactors which can be operated 10 years without refueling and fuel shuffling and just need natural uranium as fuel cycle input is discussed. The average discharge burn-up is about 280 GWd/ton HM. Enough margin for criticallity was obtained for this reactor.

  10. Clinical outcome of medium-sized hepatocellular carcinoma treated with microwave ablation.

    PubMed

    Sun, Ai-Xue; Cheng, Zhi-Li; Wu, Pan-Pan; Sheng, Yue-Hong; Qu, Xiu-Juan; Lu, Wen; Zhao, Cheng-Gong; Qian, Guo-Jun

    2015-03-14

    To evaluate the outcomes of patients with medium-sized hepatocellular carcinoma (HCC) who underwent percutaneous microwave ablation (MWA). We retrospectively reviewed all patients with a single medium-sized HCC who underwent percutaneous MWA from January 2010 to January 2013. Technical success, technical effectiveness and complications were subsequently observed. Survival curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was fitted to each variable. The relative prognostic significance of the variables for predicting overall survival rate, recurrence-free survival rate and local tumor recurrence(s) was assessed using univariate analysis. All variables with a P value < 0.20 were subjected to multivariate analysis. The study included 182 patients (mean age, 58 years; age range: 22-86 years) with a single HCC (mean size, 3.72 ± 0.54 cm; range: 3.02-5.00 cm). The estimated technical effectiveness rate was 93% in 182 patients. The major complication rate was 2.7% (5/182), including liver abscess in 4 cases, and abdominal bleeding at the puncture site in 1 case. Thirty-day mortality rate was 0.5% (1/182). One patient died due to liver abscess-related septicemia. Cumulative recurrence-free survival and overall survival (OS) rates were 51%, 36%, 27% and 89%, 74%, 60% at 1, 2, and 3 years, respectively. Age (P = 0.017) and tumor diameter (P = 0.029) were independent factors associated with local tumor recurrence. None of the factors had a statistically significant impact on recurrence-free survival. Serum albumin level (P = 0.009) and new lesion(s) (P = 0.029) were independently associated with OS. Percutaneous MWA is a relatively safe and effective treatment for patients with medium-sized HCC.

  11. Percutaneous Radiofrequency Ablation with Multiple Electrodes for Medium-Sized Hepatocellular Carcinomas

    PubMed Central

    Lee, Jung; Yoon, Jung-Hwan; Lee, Jae Young; Kim, Se Hyung; Lee, Jeong Eun; Han, Joon Koo; Choi, Byung Ihn

    2012-01-01

    Objective To prospectively evaluate the safety and short-term therapeutic efficacy of switching monopolar radiofrequency ablation (RFA) with multiple electrodes to treat medium-sized (3.1-5.0 cm), hepatocellular carcinomas (HCC). Materials and Methods In this prospective study, 30 patients with single medium-sized HCCs (mean, 3.5 cm; range, 3.1-4.4 cm) were enrolled. The patients were treated under ultrasonographic guidance by percutaneous switching monopolar RFA with a multichannel RF generator and two or three internally cooled electrodes. Contrast-enhanced CT scans were obtained immediately after RFA, and the diameters and volume of the ablation zones were then measured. Follow-up CT scans were performed at the first month after ablation and every three months thereafter. Technical effectiveness, local progression and remote recurrence of HCCs were determined. Results There were no major immediate or periprocedural complications. However, there was one bile duct stricture during the follow-up period. Technical effectiveness was achieved in 29 of 30 patients (97%). The total ablation time of the procedures was 25.4 ± 8.9 minutes. The mean ablation volume was 73.8 ± 56.4 cm3 and the minimum diameter was 4.1 ± 7.3 cm. During the follow-up period (mean, 12.5 months), local tumor progression occurred in three of 29 patients (10%) with technical effectiveness, while new HCCs were detected in six of 29 patients (21%). Conclusion Switching monopolar RFA with multiple electrodes in order to achieve a sufficient ablation volume is safe and efficient. This method also showed relatively successful therapeutic effectiveness on short-term follow up for the treatment of medium-sized HCCs. PMID:22247634

  12. Biotransformation in Egyptian spiny mouse Acomys cahirinus.

    PubMed

    Watkins, J B; LaFollette, J W; Sanders, R A

    1995-01-01

    The activities of several representative biotransformation enzymes were determined in male and female spiny mouse tissues. Cytochrome P450 monooxygenase activity toward benzo(a)pyrene was significantly greater in female spiny mouse intestine than in males. Activity toward benzphetamine in both sexes was high in the liver, with little activity in the kidney and intestine. Sulfotransferase activity was high in kidney and intestine of female spiny mice but undetectable in the same tissues in males. Hepatic glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene in females was significantly higher than in males. UDP-Glucuronosyltransferase activity toward 1-naphthol in both sexes in the kidney was significantly higher than hepatic and intestinal activity. Intestinal N-acetyltransferase activity towards 2-aminofluorene and beta-naphthylamine was significantly greater in females than males. No consistent relation appeared to exist between biotransformation activities in spiny mouse and those in other related rodent species.

  13. Annulation Reactions of Allenyl Esters: An Approach to Bicyclic Diones and Medium-Sized Rings

    PubMed Central

    2015-01-01

    A flexible approach to construct sterically congested bicyclo-alkenedione frameworks is reported. Under the action of potassium carbonate, α-sulphonyl cycloalkanones are added to functionalized allenyl esters, leading to a lactone intermediate that is subsequently reduced to initiate an intramolecular aldol cyclization to [3.2.1], [3.3.1], and [4.3.1] bicycles. Oxidation then affords bicyclic diones in good three-step yields. Under exceptionally mild conditions, these bicycles are converted to highly functionalized medium-sized rings through a Grob-type fragmentation. PMID:25184784

  14. Detection of Medium-Sized Polycyclic Aromatic Hydrocarbons via Fluorescence Energy Transfer

    PubMed Central

    Serio, Nicole; Prignano, Lindsey; Peters, Sean; Levine, Mindy

    2015-01-01

    Reported herein is the use of proximity-induced non-covalent energy transfer for the detection of medium-sized polycyclic aromatic hydrocarbons (PAHs). This energy transfer occurs within the cavity of γ-cyclodextrin in various aqueous environments, including human plasma and coconut water. Highly efficient energy transfer was observed, and the efficiency of the energy transfer is independent of the concentration of γ-cyclodextrin used, demonstrating the importance of hydrophobic binding in facilitating such energy transfer. Low limits of detection were also observed for many of the PAHs investigated, which is promising for the development of fluorescence-based detection schemes. PMID:25821390

  15. Prognostic Factors Affecting Rotator Cuff Healing After Arthroscopic Repair in Small to Medium-sized Tears.

    PubMed

    Park, Ji Soon; Park, Hyung Jun; Kim, Sae Hoon; Oh, Joo Han

    2015-10-01

    Small and medium-sized rotator cuff tears usually have good clinical and anatomic outcomes. However, healing failure still occurs in some cases. To evaluate prognostic factors for rotator cuff healing in patients with only small to medium-sized rotator cuff tears. Case-control study; Level of evidence, 3. Data were prospectively collected from 339 patients with small to medium-sized rotator cuff tears who underwent arthroscopic repair by a single surgeon between March 2004 and August 2012 and who underwent magnetic resonance imaging or computed tomographic arthrography at least 1 year after surgery. The mean age of the patients was 59.8 years (range, 39-80 years), and the mean follow-up time was 20.8 months (range, 12-66 months). The functional evaluation included the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons score, Constant-Murley score, and Simple Shoulder Test. Postoperative VAS for pain and functional scores improved significantly compared with preoperative values (P < .001). Forty-five healing failures occurred (13.3%), and fatty degeneration of the infraspinatus muscle, tear size (anteroposterior dimension), and age were significant factors affecting rotator cuff healing (P < .001, = .018, and = .011, respectively) in multivariate logistic regression analysis. Grade II and higher infraspinatus fatty degeneration correlated with a higher failure rate. The failure rate was also significantly higher in patients with a tear >2 cm in size (34.2%) compared with patients with a tear ≤2 cm (10.6%) (P < .001). A receiver operating characteristic curve was used to determine the predictive cut-off value for the oldest age and the largest tear size for successful healing, which were calculated as 69 years and 2 cm, respectively, with a specificity of 90%. In small to medium-sized rotator cuff tears, grade II fatty degeneration of the infraspinatus muscle according to the Goutallier classification could be a reference point for successful

  16. A 10-step safety management framework for construction small and medium-sized enterprises.

    PubMed

    Gunduz, Murat; Laitinen, Heikki

    2016-07-20

    It is of great importance to develop an occupational health and safety management system (OHS MS) to form a systemized approach to improve health and safety. It is a known fact that thousands of accidents and injuries occur in the construction industry. Most of these accidents occur in small and medium-sized enterprises (SMEs). This article provides a 10-step user-friendly OHS MS for the construction industry. A quantitative OHS MS indexing method is also introduced in the article. The practical application of the system to real SMEs and its promising results are also presented.

  17. Occupational safety and health in small and medium-sized enterprises during social and economic transformation.

    PubMed

    Koradecka, D

    2001-01-01

    Small and medium-sized enterprises (SMEs) in Central and Eastern Europe at the turn of the 1980s and 1990s were characterised by many people exposed to hazardous working conditions. Statistics recorded a considerable increase in the number of occupational diseases. They also showed that it was more dangerous to work for a small company. The transition from planned to market economy has brought about an increase in the number of SMEs in Poland. Data on them are provided. The role of the Central Institute for Labour Protection in studying SMEs is presented. A pilot study of employers and employees is discussed.

  18. Bank Size and Small- and Medium-sized Enterprise (SME) Lending: Evidence from China.

    PubMed

    Shen, Yan; Shen, Minggao; Xu, Zhong; Bai, Ying

    2009-04-01

    Using panel data collected in 2005, we evaluate how bank size, discretion over credit, incentive schemes, competition, and the institutional environment affect lending to small- and medium-sized enterprises in China. We deal with the endogeneity problem using instrumental variables, and a reduced-form approach is also applied to allow for weak instruments in estimation. We find that total bank asset is an insignificant factor for banks' decision on small- and medium-enterprise (SME) lending, but more local lending authority, more competition, carefully designed incentive schemes, and stronger law enforcement encourage commercial banks to lend to SMEs.

  19. Bank Size and Small- and Medium-sized Enterprise (SME) Lending: Evidence from China

    PubMed Central

    SHEN, YAN; SHEN, MINGGAO; XU, ZHONG; BAI, YING

    2014-01-01

    Summary Using panel data collected in 2005, we evaluate how bank size, discretion over credit, incentive schemes, competition, and the institutional environment affect lending to small- and medium-sized enterprises in China. We deal with the endogeneity problem using instrumental variables, and a reduced-form approach is also applied to allow for weak instruments in estimation. We find that total bank asset is an insignificant factor for banks’ decision on small- and medium-enterprise (SME) lending, but more local lending authority, more competition, carefully designed incentive schemes, and stronger law enforcement encourage commercial banks to lend to SMEs. PMID:26052179

  20. Promising practices in promotion of healthy weight at small and medium-sized US worksites.

    PubMed

    Hersey, James; Williams-Piehota, Pamela; Sparling, Phillip B; Alexander, Jennifer; Hill, Mary D; Isenberg, Karen Bandel; Rooks, Adrienne; Dunet, Diane O

    2008-10-01

    We developed a new evaluation method to identify promising practices for promoting healthy weight among employees at small and medium-sized worksites. We used a structured rating and selection process to select 9 worksites with approximately 100 to 3,000 employees from a pool of worksites with health promotion programs reputed to be exemplary. A site visit over 2 sequential half-days at each site included interviews with senior management, program staff, vendors, and wellness committees; observation guided by a written environmental assessment; and structured review of program data on health outcomes of wellness program participants. The team corroborated findings from interviews, observations, and reviews of aggregate data on health outcomes of participants. Using the site visit reports, the project team and a separate panel of experts identified worksite health promotion practices that were promising, innovative, feasible to implement in a variety of settings, sustainable, and relevant for public health. Innovative practices included peer coaching, wellness screening coupled with motivational interviewing and follow-up, free access to fitness facilities, and incentives such as days of paid leave for participation in wellness programs. Introduction of incentives was associated with higher participation rates. To build the business case for their programs, staff at several worksites used aggregate data on decreases in high blood pressure, serum cholesterol concentrations, and body weight in longitudinal samples of program participants. The evaluation method identified promising practices implemented at small and medium-sized worksites to promote healthy weight and related favorable health outcomes.

  1. Increase of chronic low back pain prevalence in a medium-sized city of southern Brazil

    PubMed Central

    2013-01-01

    Background Chronic low back pain (CLBP) is a highly disabling morbidity with high social, economic and individual effects. Demographic, occupational and behavioral changes that took place in Brazil over the last decade are related with an increasing burden of chronic conditions. Despite these changes, comparison studies on CLBP prevalence and associated factors, over time are scarce in the literature in general, and unknown in Brazil. The present study compared the CLBP prevalence in a medium sized city in Brazil between the years 2002 and 2010 and examined factors associated with prevalence in 2010. Methods Two cross-sectional studies with similar methodology were conducted in a medium-sized city in southern Brazil, in 2002 and 2010. 3182 individuals were interviewed in the first study and 2732 in the second one, all adults aged twenty years or more. Those who reported pain for seven weeks or more in the last three months in the lumbar region where considered cases of CLBP. Results The CLBP prevalence increased from 4.2% to 9.6% in 8 years. In most of the studied subgroups the CLBP prevalence has at least doubled and the increase was even larger among younger individuals with more years of education and higher economic status. Conclusions Increase in CLBP prevalence is worrisome because it is a condition responsible for substantial social impact, besides being an important source of demand for health services. PMID:23634830

  2. Identification of Medium-Sized Copy Number Alterations in Whole-Genome Sequencing

    PubMed Central

    Ozer, Hatice Gulcin; Usubalieva, Aisulu; Dorrance, Adrienne; Yilmaz, Ayse Selen; Caligiuri, Michael; Marcucci, Guido; Huang, Kun

    2014-01-01

    The genome-wide discoveries such as detection of copy number alterations (CNA) from high-throughput whole-genome sequencing data enabled new developments in personalized medicine. The CNAs have been reported to be associated with various diseases and cancers including acute myeloid leukemia. However, there are multiple challenges to the use of current CNA detection tools that lead to high false-positive rates and thus impede widespread use of such tools in cancer research. In this paper, we discuss these issues and propose possible solutions. First, since the entire genome cannot be mapped due to some regions lacking sequence uniqueness, current methods cannot be appropriately adjusted to handle these regions in the analyses. Thus, detection of medium-sized CNAs is also being directly affected by these mappability problems. The requirement for matching control samples is also an important limitation because acquiring matching controls might not be possible or might not be cost efficient. Here we present an approach that addresses these issues and detects medium-sized CNAs in cancer genomes by (1) masking unmappable regions during the initial CNA detection phase, (2) using pool of a few normal samples as control, and (3) employing median filtering to adjust CNA ratios to its surrounding coverage and eliminate false positives. PMID:25788829

  3. Performance of a Medium-Size Area nGEM Detector for Neutron Beam Diagnostics

    NASA Astrophysics Data System (ADS)

    Croci, G.; Cazzaniga, C.; Albani, G.; Muraro, A.; Claps, G.; Cavenago, M.; Grosso, G.; Murtas, F.; Pasqualotto, R.; Cippo, E. Perelli; Rebai, M.; Tardocchi, M.; Gorini, G.

    Fast neutron detectors with a sub-centimetric space resolution are required in order to qualify neutron beams in applications related to magnetically-controlled nuclear fusion plasmas and to spallation sources. Based on the results obtained with small area prototypes, the first medium-size (20 x 35.2 cm2 active area) nGEM detector has been realized for both the CNESM diagnostic system of the SPIDER NBI prototype for ITER and as a beam monitor for fast neutrons beam lines at spallation sources, too. The nGEM is a Triple GEM gaseous detector equipped with polyethylene layers used to convert fast neutrons into recoil protons through the elastic scattering process. This paper describes the performance of the medium-size nGEM detector tested at the VESUVIO beam line of the ISIS spallation source. Being this detector the actual largest area fast neutron detector based on the GEM technology, particular attention was paid in the study of detector response in different points over the active area. Measurements of GEM counting rate (both as a function of VGEM and of time) and of the capability of the detector to reconstruct the beam in different positions are presented. This detector serves as a basis for the realization of an even larger area detector that will be used in the MITICA NBI prototype for ITER that represents the evolution of SPIDER.

  4. Infrahyoid myocutaneous flap for medium-sized head and neck defects: surgical outcome and technique modification.

    PubMed

    Peng, Hanwei; Wang, Steven J; Yang, Xihong; Guo, Haipeng; Liu, Muyuan

    2013-01-01

    To evaluate the surgical outcomes associated with infrahyoid myocutaneous flaps used in the reconstruction of medium-sized defects following head and neck cancer resection, as well as to discuss a novel technique modification. Case series with chart review. University cancer hospital. A total of 20 patients with oral or hypopharyngeal carcinoma who underwent infrahyoid myocutaneous flap reconstruction between June 2005 and December 2011 were retrospectively studied. A novel technical modification of flap harvest, preservation of the cranial portion of the anterior jugular vein, was attempted in 15 flaps and was successful in 13 flaps. Functional evaluation was performed in all patients 3 to 6 months after the operation or postoperative radiation. Total flap necrosis, marginal skin paddle necrosis, and total skin paddle loss were observed in 1, 2, and 1 patient(s), respectively. Pharyngocutaneous fistula without flap problem occurred in 1 patient. No flap complications occurred in 13 cases where the cranial portion of the anterior jugular vein was successfully preserved. Functional results were excellent in 16 patients, good in 3 patients, and fair in 1 patient. The infrahyoid myocutaneous flap is a reliable and convenient technique that can serve as an alternative to free flaps in the reconstruction of medium-sized defects of the oral cavity or hypopharynx. Preservation of the cranial portion of the anterior jugular vein is a novel technical modification of harvesting this flap, which may result in better venous return of the skin paddle and reduce skin paddle necrosis.

  5. Innovation Gateways for SMEs: Finding the Formula for Successful Interaction between Universities and Small and Medium-Size Firms.

    ERIC Educational Resources Information Center

    Davies, Peter T.

    1995-01-01

    The University of Warwick's Breakthrough Technologies program links with small and medium-sized businesses to stimulate awareness of innovations. The Manufacturing Excellence Initiative provides postgraduate training for company staff that focuses on best practices and change management. (SK)

  6. Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors

    PubMed Central

    Lambot, Laurie; Chaves Rodriguez, Elena; Houtteman, Delphine; Li, Yuquing; Schiffmann, Serge N.; Gall, David

    2016-01-01

    The basal ganglia (BG) control action selection, motor programs, habits, and goal-directed learning. The striatum, the principal input structure of BG, is predominantly composed of medium-sized spiny neurons (MSNs). Arising from these spatially intermixed MSNs, two inhibitory outputs form two main efferent pathways, the direct and indirect pathways. Striatonigral MSNs give rise to the activating, direct pathway MSNs and striatopallidal MSNs to the inhibitory, indirect pathway (iMSNs). BG output nuclei integrate information from both pathways to fine-tune motor procedures and to acquire complex habits and skills. Therefore, balanced activity between both pathways is crucial for harmonious functions of the BG. Despite the increase in knowledge concerning the role of glutamate NMDA receptors (NMDA-Rs) in the striatum, understanding of the specific functions of NMDA-R iMSNs is still lacking. For this purpose, we generated a conditional knock-out mouse to address the functions of the NMDA-R in the indirect pathway. At the cellular level, deletion of GluN1 in iMSNs leads to a reduction in the number and strength of the excitatory corticostriatopallidal synapses. The subsequent scaling down in input integration leads to dysfunctional changes in BG output, which is seen as reduced habituation, delay in goal-directed learning, lack of associative behavior, and impairment in action selection or skill learning. The NMDA-R deletion in iMSNs causes a decrease in the synaptic strength of striatopallidal neurons, which in turn might lead to a imbalanced integration between direct and indirect MSN pathways, making mice less sensitive to environmental change. Therefore, their ability to learn and adapt to the environment-based experience was significantly affected. SIGNIFICANCE STATEMENT The striatum controls habits, locomotion, and goal-directed behaviors by coordinated activation of two antagonistic pathways. Insofar as NMDA receptors (NMDA-Rs) play a key role in synaptic

  7. Glass formability in medium-sized molecular systems/pharmaceuticals. I. Thermodynamics vs. kinetics

    NASA Astrophysics Data System (ADS)

    Tu, Wenkang; Li, Xiangqian; Chen, Zeming; Liu, Ying Dan; Labardi, Massimiliano; Capaccioli, Simone; Paluch, M.; Wang, Li-Min

    2016-05-01

    Scrutinizing critical thermodynamic and kinetic factors for glass formation and the glass stability of materials would benefit the screening of the glass formers for the industry of glassy materials. The present work aims at elucidating the factors that contribute to the glass formation by investigating medium-sized molecules of pharmaceuticals. Glass transition related thermodynamics and kinetics are performed on the pharmaceuticals using calorimetric, dielectric, and viscosity measurements. The characteristic thermodynamic and kinetic parameters of glass transition are found to reproduce the relations established for small-molecule glass formers. The systematic comparison of the thermodynamic and kinetic contributions to glass formation reveals that the melting-point viscosity is the crucial quantity for the glass formation. Of more interest is the finding of a rough correlation between the melting-point viscosity and the entropy of fusion normalized by the number of beads of the pharmaceuticals, suggesting the thermodynamics can partly manifest its contribution to glass formation via kinetics.

  8. Networked Virtual Organizations: A Chance for Small and Medium Sized Enterprises on Global Markets

    NASA Astrophysics Data System (ADS)

    Cellary, Wojciech

    Networked Virtual Organizations (NVOs) are a right answer to challenges of globalized, diversified, and dynamic contemporary economy. NVOs need more than e-trade and outsourcing, namely, they need out-tasking and e-collaboration. To out-task, but retain control on the way a task is performed by an external partner, two integrations are required: (1) integration of computer management systems of enterprises cooperating within an NVO; and (2) integration of cooperating representatives of NVO member enterprises into a virtual team. NVOs provide a particular chance to Small and Medium size Enterprises (SMEs) to find their place on global markets and to play a significant role on them. Requirements for SMEs to be able to successfully join an NVO are analyzed in the paper.

  9. Actuator development at IAAT for the Cherenkov telescope array medium size telescopes

    NASA Astrophysics Data System (ADS)

    Diebold, S.; Dick, J.; Pühlhofer, G.; Renner, S.; Santangelo, A.; Schanz, T.; Tenzer, C.

    2017-01-01

    The Cherenkov Telescope Array (CTA) will be the future observatory for TeV gamma-ray astronomy. In order to increase the sensitivity and to extend the energy coverage beyond the capabilities of current facilities, its design concept features telescopes of three diffierent size classes. Based on the experience from H.E.S.S. phase II, the Institute for Astronomy and Astrophysics Tübingen (IAAT) develops actuators for the mirror control system of the CTA Medium Size Telescopes (MSTs). The goals of this effiort are durability, high precision, and mechanical stability under all environmental conditions. Up to now, several revisions were developed and the corresponding prototypes were extensively tested. In this contribution our latest design revision proposed for the CTA MSTs are presented.

  10. Software-Defined Solutions for Managing Energy Use in Small to Medium Sized Commercial Buildings

    SciTech Connect

    Peffer, Therese; Blumstein, Carl; Culler, David; Modera, Mark; Meier, Alan

    2015-09-10

    The Project uses state-of-the-art computer science to extend the benefits of Building Automation Systems (BAS) typically found in large buildings (>100,000 square foot) to medium-sized commercial buildings (<50,000 sq ft). The BAS developed in this project, termed OpenBAS, uses an open-source and open software architecture platform, user interface, and plug-and-play control devices to facilitate adoption of energy efficiency strategies in the commercial building sector throughout the United States. At the heart of this “turn key” BAS is the platform with three types of controllers—thermostat, lighting controller, and general controller—that are easily “discovered” by the platform in a plug-and-play fashion. The user interface showcases the platform and provides the control system set-up, system status display and means of automatically mapping the control points in the system.

  11. Melting Properties of Medium-Sized Silicon Nanoclusters: A Molecular Dynamics Study

    NASA Astrophysics Data System (ADS)

    Li, Haipeng; Xu, Runfeng; Bi, Zetong; Shen, Xiaopeng; Han, Kui

    2017-07-01

    The structures and melting properties of the medium-sized silicon nanoclusters have been comparatively studied using the molecular dynamics method. Structural and thermodynamic parameters are used to characterize the melting properties of the clusters. The size dependence of the melting temperature of silicon nanoclusters is determined using the computation results. Different from the homogeneous melting of bulk silicon, melting of silicon nanoparticles proceeds over a finite temperature range due to surface effects, which shows the heterogeneous melting of nanoclusters. We found that the melting starts at the cluster surface and progressively shifts into the core region. This study provides a fundamental perspective on the melting behaviors of semiconductor silicon nanoclusters at the atomistic level.

  12. Toward the construction of a medium size prototype Schwarzschild-Couder telescope for CTA

    NASA Astrophysics Data System (ADS)

    Rousselle, J.; Byrum, K.; Cameron, R.; Connaughton, V.; Errando, M.; Griffiths, S.; Guarino, V.; Humensky, T. B.; Jenke, P.; Kaaret, P.; Kieda, D.; Limon, M.; Mognet, I.; Mukherjee, R.; Nieto, D.; Okumura, A.; Peck, A.; Petrashyk, A.; Ribeiro, D.; Stevenson, B.; Vassiliev, V.; Yu, P.

    2015-09-01

    The construction of a prototype Schwarzschild-Couder telescope (pSCT) started in early June 2015 at the Fred Lawrence Whipple Observatory in Southern Arizona, as a candidate medium-sized telescope for the Cherenkov Telescope Array (CTA). Compared to current Davies-Cotton telescopes, this novel instrument with an aplanatic two-mirror optical system will offer a wider field-of-view and improved angular resolution. In addition, the reduced plate scale of the camera allows the use of highly-integrated photon detectors such as silicon photo multipliers. As part of CTA, this design has the potential to greatly improve the performance of the next generation ground-based observatory for very high-energy (E>60 GeV) gamma-ray astronomy. In this contribution we present the design and performance of both optical and alignment systems of the pSCT.

  13. IT Governance Practices in Small and Medium-Sized Enterprises: Recommendations from an Empirical Study

    NASA Astrophysics Data System (ADS)

    Huang, Rui; Zmud, Robert W.; Price, R. Leon

    Much has been learned through IT governance research about the nature of IT-related decisions, the location of decision rights for these decisions, and governance mechanisms applied to facilitate associated decision processes in large organisations. Our knowledge about IT governance structures in small and medium-sized enterprises (SME), on the other hand, is quite limited. Adopting a qualitative and inductive approach, this study examines the nature and influence of IT governance in SMEs through interviews with executives from three SMEs. Our results demonstrate that IT decision authority was centralized in all three SMEs but that senior management involvement in governance procedures and communication practices about governance policies were observed to explain differences in these organisations’ IT use. We propose recommendations based on the findings of this study.

  14. Melting Properties of Medium-Sized Silicon Nanoclusters: A Molecular Dynamics Study

    NASA Astrophysics Data System (ADS)

    Li, Haipeng; Xu, Runfeng; Bi, Zetong; Shen, Xiaopeng; Han, Kui

    2016-11-01

    The structures and melting properties of the medium-sized silicon nanoclusters have been comparatively studied using the molecular dynamics method. Structural and thermodynamic parameters are used to characterize the melting properties of the clusters. The size dependence of the melting temperature of silicon nanoclusters is determined using the computation results. Different from the homogeneous melting of bulk silicon, melting of silicon nanoparticles proceeds over a finite temperature range due to surface effects, which shows the heterogeneous melting of nanoclusters. We found that the melting starts at the cluster surface and progressively shifts into the core region. This study provides a fundamental perspective on the melting behaviors of semiconductor silicon nanoclusters at the atomistic level.

  15. Current information technology needs of small to medium sized apparel manufacturers and contractors

    SciTech Connect

    Wimple, C., LLNL

    1998-04-01

    This report documents recent efforts of the American Textile Partnership (AMTEX{sup TM}) Demand Activated Manufacturing Architecture (DAMA) Project to identify opportunities for cost effective enhanced information technology use by small to medium sized apparel manufacturers and contractors. Background on the AMTEX/DAMA project and objectives for the specific DAMA Small and Medium Enterprise (SME) effort are discussed in this section. The approach used to gather information about current opportunities or needs is outlined in Section 2 Approach, and relevant findings are identified and a brief analysis of the information gathered is presented in Section 3 Findings. Recommendations based on the analysis, are offered in Section 4 Recommendations, and plans are suggested for DAMA follow-on in Section 5 Future Plans. Trip reports for each of the companies visited are contained in Appendix E - Company Trip Reports. These individual reports contain the data upon which the analysis presented in Section 3 Findings is based.

  16. Development of engineering model of medium-sized aperture camera system

    NASA Astrophysics Data System (ADS)

    Kim, Ee-Eul; Choi, Young-Wan; Soon Yang, Ho; Kang, Myung-Seok; Jeong, Seong-Keun; Yang, Seung-Uk; Kim, Jong-Un; Rasheed, Ad. Aziz Ad.; Nasir, Hafizah Md.; Rosdi, Md. Rushdan Md.; Hai, Asma Hani Ad.; Ismail, Ismahadi; Sabirin Arshad, Ahmad

    2005-01-01

    SaTReC i and ATSB are developing medium-sized aperture camera (MAC) system for earth observation. Following the first model, the development of the engineering model (EM) was completed. The optical subsystem incorporates a conventional approach of using low-expansion optical and structural materials. It is a 300-mm on-axis system with two aspheric mirrors and two field correction lenses. It has five linear detectors aligned on its focal plane together with proximity electronics. The electronics subsystem consists of five modules; two for management and control in cold redundancy, two for image data storage and one for power supply. EM was developed to have a storage capacity of 16 Gbits, which can be easily increased to 32 Gbits by adding memory packs for following models. EM weighs about 41.9 kg and consumes about 45.4 W of peak power.

  17. Ticks (Acari: Ixodidae) collected from small and medium-sized Kansas mammals.

    PubMed

    Brillhart, D B; Fox, L B; Upton, S J

    1994-05-01

    Seven species of hard-bodied ticks were collected from 20 species of small and medium-sized mammals in Kansas; Amblyomma americanum L., Dermacentor variabilis (Say), Haemaphysalis leporispalustris (Packard), Ixodes cookei Packard, I. kingi Bishopp, I. sculptus Neumann, and I. texanus Banks. Dermacentor variabilis was found statewide, A. americanum only in the eastern one-third of the state, and the Ixodes spp. and H. leporispalustris were widely scattered. The most common tick found was D. variabilis, both by itself and in association with other ticks. Mammals that ticks were collected from included Canis latrans Say, Cynomys ludovicianus ludovicianus (Ord), Didelphis virginianus Kerr, Geomys bursarius (Shaw), Lynx rufus (Schreber), Marmota monax bunkeri Black, Mephitis mephitis (Schreber), Microtus ochrogaster (Wagner), Mus musculus L., Peromyscus leucopus (Rafinesque), P. maniculatus (Wagner), Procyon lotor hirtus Nelson and Goldman, Reithrodontomys megalotis (Baird), Sciurus niger rufiventer Geoffroy, Sigmodon hispidus texianus (Audubon and Bachman), Sylvilagus floridanus (J. A. Allen), Taxidea taxus taxus (Schreber), and Vulpes velox velox (Say).

  18. The natural selection of organizational and safety culture within a small to medium sized enterprise (SME).

    PubMed

    Brooks, Benjamin

    2008-01-01

    Small to Medium Sized Enterprises (SMEs) form the majority of Australian businesses. This study uses ethnographic research methods to describe the organizational culture of a small furniture-manufacturing business in southern Australia. Results show a range of cultural assumptions variously 'embedded' within the enterprise. In line with memetics - Richard Dawkin's cultural application of Charles Darwin's theory of Evolution by Natural Selection, the author suggests that these assumptions compete to be replicated and retained within the organization. The author suggests that dominant assumptions are naturally selected, and that the selection can be better understood by considering the cultural assumptions in reference to Darwin's original principles and Frederik Barth's anthropological framework of knowledge. The results are discussed with reference to safety systems, negative cultural elements called Cultural Safety Viruses, and how our understanding of this particular organizational culture might be used to build resistance to these viruses.

  19. In-beam evaluation of a medium-size Resistive-Plate WELL gaseous particle detector

    NASA Astrophysics Data System (ADS)

    Moleri, L.; Amaro, F. D.; Arazi, L.; Azevedo, C. D. R.; Breskin, A.; Coimbra, A. E. C.; Oliveri, E.; Pereira, F. A.; Shaked Renous, D.; Schaarschmidt, J.; dos Santos, J. M. F.; Veloso, J. F. C. A.; Bressler, S.

    2016-09-01

    In-beam evaluation of a fully-equipped medium-size 30 × 30 cm2 Resistive Plate WELL (RPWELL) detector is presented. It consists here of a single element gas-avalanche multiplier with Semitron ESD225 resistive plate, 1 cm2 readout pads and APV25/SRS electronics. Similarly to previous results with small detector prototypes, stable operation at high detection efficiency (> 98%) and low average pad multiplicity (~ 1.2) were recorded with 150 GeV muon and high-rate pion beams, in Ne/(5%CH4), Ar/(5%CH4) and Ar/(7%CO2). This is an important step towards the realization of robust detectors suitable for applications requiring large-area coverage; among them Digital Hadron Calorimetry.

  20. Glass formability in medium-sized molecular systems/pharmaceuticals. I. Thermodynamics vs. kinetics.

    PubMed

    Tu, Wenkang; Li, Xiangqian; Chen, Zeming; Liu, Ying Dan; Labardi, Massimiliano; Capaccioli, Simone; Paluch, M; Wang, Li-Min

    2016-05-07

    Scrutinizing critical thermodynamic and kinetic factors for glass formation and the glass stability of materials would benefit the screening of the glass formers for the industry of glassy materials. The present work aims at elucidating the factors that contribute to the glass formation by investigating medium-sized molecules of pharmaceuticals. Glass transition related thermodynamics and kinetics are performed on the pharmaceuticals using calorimetric, dielectric, and viscosity measurements. The characteristic thermodynamic and kinetic parameters of glass transition are found to reproduce the relations established for small-molecule glass formers. The systematic comparison of the thermodynamic and kinetic contributions to glass formation reveals that the melting-point viscosity is the crucial quantity for the glass formation. Of more interest is the finding of a rough correlation between the melting-point viscosity and the entropy of fusion normalized by the number of beads of the pharmaceuticals, suggesting the thermodynamics can partly manifest its contribution to glass formation via kinetics.

  1. Energy performance of medium-sized healthcare buildings in Victoria, Australia- a case study.

    PubMed

    Rajagopalan, Priyadarsini; Elkadi, Hisham

    2014-01-01

    This paper investigates the energy performance of three medium-sized healthcare buildings in Victoria, Australia, that operate only during the daytime. The aim is to provide preliminary understanding of energy consumption in this particular typology in Australia in relation to the available benchmarks. This paper also identifies the differences of energy consumption between different functional areas within medium health facilities. Building features and operational characteristics contributing to the variations in healthcare energy performance are discussed. The total annual energy consumption data ranging from 167-306 kWh/m(2) or 42-72 kWh/m(3) were compared against international data from various climatic zones. Some of the drivers of energy consumption were determined and potentials for energy and water conservation were identified. Comparison with international standards shows a possibility to achieve lower energy consumption in Victorian healthcare buildings.

  2. Selecting Sustainability Indicators for Small to Medium Sized Urban Water Systems Using Fuzzy-ELECTRE.

    PubMed

    Chhipi-Shrestha, Gyan; Hewage, Kasun; Sadiq, Rehan

    2017-03-01

      Urban water systems (UWSs) are challenged by the sustainability perspective. Certain limitations of the sustainability of centralized UWSs and decentralized household level wastewater treatments can be overcome by managing UWSs at an intermediate scale, referred to as small to medium sized UWSs (SMUWSs). SMUWSs are different from large UWSs, mainly in terms of smaller infrastructure, data limitation, smaller service area, and institutional limitations. Moreover, sustainability assessment systems to evaluate the sustainability of an entire UWS are very limited and confined only to large UWSs. This research addressed the gap and has developed a set of 38 applied sustainability performance indicators (SPIs) by using fuzzy-Elimination and Choice Translating Reality (ELECTRE) I outranking method to assess the sustainability of SMUWSs. The developed set of SPIs can be applied to existing and new SMUWSs and also provides a flexibility to include additional SPIs in the future based on the same selection criteria.

  3. Larval assemblages of large and medium-sized pelagic species in the Straits of Florida

    NASA Astrophysics Data System (ADS)

    Richardson, David E.; Llopiz, Joel K.; Guigand, Cedric M.; Cowen, Robert K.

    2010-07-01

    Critical gaps in our understanding of the distributions, interactions, life histories and preferred habitats of large and medium-size pelagic fishes severely constrain the implementation of ecosystem-based, spatially structured fisheries management approaches. In particular, spawning distributions and the environmental characteristics associated with the early life stages are poorly documented. In this study, we consider the diversity, assemblages, and associated habitat of the larvae of large and medium-sized pelagic species collected during 2 years of monthly surveys across the Straits of Florida. In total, 36 taxa and 14,295 individuals were collected, with the highest diversity occurring during the summer and in the western, frontal region of the Florida Current. Only a few species (e.g. Thunnus obesus, T. alalunga, Tetrapturus pfluegeri) considered for this study were absent. Small scombrids (e.g. T. atlanticus, Katsuwonus pelamis, Auxis spp.) and gempylids dominated the catch and were orders of magnitude more abundant than many of the rare species (e.g. Thunnus thynnus,Kajikia albida). Both constrained (CCA) and unconstrained (NMDS) multivariate analyses revealed a number of species groupings including: (1) a summer Florida edge assemblage (e.g. Auxis spp., Euthynnus alleterattus, Istiophorus platypterus); (2) a summer offshore assemblage (e.g. Makaira nigricans, T. atlanticus, Ruvettus pretiosus, Lampris guttatus); (3) an ubiquitous assemblage (e.g. K. pelamis, Coryphaena hippurus, Xiphias gladius); and (4) a spring/winter assemblage that was widely dispersed in space (e.g. trachipterids). The primary environmental factors associated with these assemblages were sea-surface temperature (highest in summer-early fall), day length (highest in early summer), thermocline depth (shallowest on the Florida side) and fluorescence (highest on the Florida side). Overall, the results of this study provide insights into how a remarkable diversity of pelagic species

  4. Healthy lifestyle behavior of employees in small and medium-sized enterprises in Aydin, Turkey

    PubMed Central

    Ozvurmaz, Safiye; Mandiracioglu, Aliye

    2017-01-01

    Objective: To determine healthy lifestyle behavior and affecting risk factors in workers at small and medium-sized enterprises from four different sectors in Aydin, Turkey. Methods: This cross-sectional study was conducted at four different small and medium-sized enterprises in Aydin, Turkey and 264 employees participated in the study. A questionnaire was used for data collection. It consisted of questions about socio-demographic features (age, gender, marital status, education, perceived income, occupation and having children), health status, and medical history, medication use, having occupational accidents and occupational health and safety. Healthy Lifestyle Behavior Scale, which was developed by Walker et al. in 1996, was used to evaluate healthy lifestyle behaviors of the workers. Results: The mean score for Healthy Lifestyle Behavior Scale was 135.46±22.49. Gender, marital status, perceived income, sector of workplace, title, presence of a chronic disease, finding oneself healthy in the previous year and having an occupational accident in the previous year did not significantly affect any subscales of Healthy Lifestyle Behavior Scale. The workers aged over 50 years had significantly higher scores for health responsibility than those aged 20-29 years (p<0.05). The workers living in a village got significantly higher scores for Healthy Lifestyle Behavior Scale and its subscales health responsibility, physical activity, nutrition and spiritual development than those living in a city (p<0.05). Conclusion: Although workers have good spiritual development, they may not adopt physical activity as a healthy lifestyle and that workers benefiting from occupational health and safety services can display healthy lifestyle behavior. PMID:28523046

  5. Healthy lifestyle behavior of employees in small and medium-sized enterprises in Aydin, Turkey.

    PubMed

    Ozvurmaz, Safiye; Mandiracioglu, Aliye

    2017-01-01

    To determine healthy lifestyle behavior and affecting risk factors in workers at small and medium-sized enterprises from four different sectors in Aydin, Turkey. This cross-sectional study was conducted at four different small and medium-sized enterprises in Aydin, Turkey and 264 employees participated in the study. A questionnaire was used for data collection. It consisted of questions about socio-demographic features (age, gender, marital status, education, perceived income, occupation and having children), health status, and medical history, medication use, having occupational accidents and occupational health and safety. Healthy Lifestyle Behavior Scale, which was developed by Walker et al. in 1996, was used to evaluate healthy lifestyle behaviors of the workers. The mean score for Healthy Lifestyle Behavior Scale was 135.46±22.49. Gender, marital status, perceived income, sector of workplace, title, presence of a chronic disease, finding oneself healthy in the previous year and having an occupational accident in the previous year did not significantly affect any subscales of Healthy Lifestyle Behavior Scale. The workers aged over 50 years had significantly higher scores for health responsibility than those aged 20-29 years (p<0.05). The workers living in a village got significantly higher scores for Healthy Lifestyle Behavior Scale and its subscales health responsibility, physical activity, nutrition and spiritual development than those living in a city (p<0.05). Although workers have good spiritual development, they may not adopt physical activity as a healthy lifestyle and that workers benefiting from occupational health and safety services can display healthy lifestyle behavior.

  6. Survey of food safety practices on small to medium-sized farms and in farmers markets.

    PubMed

    Harrison, Judy A; Gaskin, Julia W; Harrison, Mark A; Cannon, Jennifer L; Boyer, Renee R; Zehnder, Geoffrey W

    2013-11-01

    As produce consumption has increased, so have foodborne disease outbreaks associated with fresh produce. Little research has addressed food safety practices used on small to medium-sized farms selling locally or in farmers markets. This study evaluated current food safety practices used by farmers on small to medium-sized farms and managers of farmers markets in Georgia, Virginia, and South Carolina based on responses to surveys. Surveys were developed, pretested, and revised before implementation with target audiences and were implemented via mail and the Web to maximize participation, with reminders sent to nonrespondents. Data were collected from 226 farmers and 45 market managers. Frequencies and percentages were calculated for all response variables. Responses from farmers indicated that more than 56% of them use manures. Of those who use manures, 34% use raw or mixtures of raw and composted manure, and over 26% wait fewer than 90 days between application of raw manure and harvest. Over 27% use water sources that have not been tested for safety for irrigation, and 16% use such water sources for washing produce. Over 43% do not sanitize surfaces that touch produce at the farm. Only 33% of farmers always clean transport containers between uses. Responses from market managers indicated that over 42% have no food safety standards in place for the market. Only 2 to 11% ask farmers specific questions about conditions on the farm that could affect product safety. Less than 25% of managers sanitize market surfaces. Only 11% always clean market containers between uses. Over 75% of markets offer no sanitation training to workers or vendors. While farmers and market managers are using many good practices, the results indicate that some practices being used may put consumers at risk of foodborne illness. Consequently, there is a need for training for both farmers and market managers.

  7. 50 CFR 648.233 - Spiny dogfish Accountability Measures (AMs).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Spiny dogfish Accountability Measures... Management Measures for the Spiny Dogfish Fishery § 648.233 Spiny dogfish Accountability Measures (AMs). (a... dogfish on that date for the remainder of that semi-annual period by publishing notification in the...

  8. 50 CFR 648.233 - Spiny dogfish Accountability Measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish Accountability Measures... Management Measures for the Spiny Dogfish Fishery § 648.233 Spiny dogfish Accountability Measures (AMs). (a... dogfish on that date for the remainder of that semi-annual period by publishing notification in the...

  9. 50 CFR 640.27 - Spiny lobster import prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Spiny lobster import prohibitions. 640.27... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management Measures § 640.27 Spiny lobster import prohibitions. (a) Minimum size limits...

  10. 50 CFR 622.50 - Caribbean spiny lobster import prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Caribbean spiny lobster import... ATLANTIC Management Measures § 622.50 Caribbean spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There are two minimum size limits that apply to importation of...

  11. 50 CFR 622.50 - Caribbean spiny lobster import prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Caribbean spiny lobster import... ATLANTIC Management Measures § 622.50 Caribbean spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There are two minimum size limits that apply to importation of...

  12. 50 CFR 640.27 - Spiny lobster import prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Spiny lobster import prohibitions. 640.27... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management Measures § 640.27 Spiny lobster import prohibitions. (a) Minimum size limits...

  13. 50 CFR 622.50 - Caribbean spiny lobster import prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Caribbean spiny lobster import... ATLANTIC Management Measures § 622.50 Caribbean spiny lobster import prohibitions. (a) Minimum size limits for imported spiny lobster. There are two minimum size limits that apply to importation of...

  14. 50 CFR 640.27 - Spiny lobster import prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Spiny lobster import prohibitions. 640.27... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Management Measures § 640.27 Spiny lobster import prohibitions. (a) Minimum size limits...

  15. Morphology, topography and cytoarchitectonics of the pterygopalatine ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest).

    PubMed

    Szczurkowski, Aleksander; Kuder, Tadeusz; Nowak, Elzbieta; Kuchinka, Jacek

    2002-01-01

    Using the thiocholine method of Koelle and Friedenwald and histological techniques the pterygopalatine ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest) was studied. The ganglion was found to be a single irregular cluster of neurocytes, situated on the medial surface of the maxillary nerve. The ganglion is composed of oval, elliptical and sometimes fusiform ganglionic neurones in compact arrangement without a thick connective-tissue capsule.

  16. Morphology, topography and cytoarchitectonics of the otic ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest).

    PubMed

    Szczurkowski, A; Kuder, T; Nowak, E; Kuchinka, J

    2001-01-01

    Using the thiocholine method of Koelle and Friedenwald and histological techniques, the otic ganglion in Egyptian spiny mouse (Acomys cahirinus, Desmarest) was studied. The ganglion was found to be a single oval cluster of neurocytes, situated at the medial and posterior surface of the mandibular nerve just above the maxillary artery. The ganglion is composed of typical ganglionic neurons in compact arrangement without a thick connective-tissue capsule.

  17. Understanding the structural transformation, stability of medium-sized neutral and charged silicon clusters.

    PubMed

    Ding, Li Ping; Zhang, Fang Hui; Zhu, Yong Sheng; Lu, Cheng; Kuang, Xiao Yu; Lv, Jian; Shao, Peng

    2015-11-03

    The structural and electronic properties for the global minimum structures of medium-sized neutral, anionic and cationic Sin(μ) (n = 20-30, μ = 0, -1 and +1) clusters have been studied using an unbiased CALYPSO structure searching method in conjunction with first-principles calculations. A large number of low-lying isomers are optimized at the B3PW91/6-311 + G* level of theory. Harmonic vibrational analysis has been performed to assure that the optimized geometries are stable. The growth behaviors clearly indicate that a structural transition from the prolate to spherical-like geometries occurs at n = 26 for neutral silicon clusters, n = 27 for anions and n = 25 for cations. These results are in good agreement with the available experimental and theoretical predicted findings. In addition, no significant structural differences are observed between the neutral and cation charged silicon clusters with n = 20-24, both of them favor prolate structures. The HOMO-LUMO gaps and vertical ionization potential patterns indicate that Si22 is the most chemical stable cluster, and its dynamical stability is deeply discussed by the vibrational spectra calculations.

  18. Gastrointestinal nematodes in grazing dairy cattle from small and medium-sized farms in southern Poland.

    PubMed

    Piekarska, J; Płoneczka-Janeczko, K; Kantyka, M; Kuczaj, M; Gorczykowski, M; Janeczko, K

    2013-11-15

    This study aimed to estimate the prevalence of gastrointestinal nematodes and the intensity of infection in grazing dairy cattle from small and medium-sized farms in southern Poland. The level of antibodies against Ostertagia ostertagi in the bulk tank milk (BTM) from the animals was also assessed. Rectal fecal samples collected from 361 cows on 20 farms were examined using Willis-Schlaaf flotation and the McMaster method. BTM samples were tested for the presence of O. ostertagi antibodies using ELISA. Multiplex PCR was used to identify the third-stage larvae (L3) of gastrointestinal nematodes derived from the culture of pooled fecal samples from sampled farms. Gastrointestinal nematode eggs were found in the samples from 18 of the 20 herds with a prevalence range from 20.4 to 94.5%. The average number of eggs excreted in the feces of the herds was 200 eggs per gram (EPG). Antibodies to O. ostertagi were found in 20 of the examined herds (100%), of which 6 had optical density ratios (ODR) greater than 0.5. PCR results showed the presence of three nematode species: Ostertagia ostertagi, Cooperia oncophora and Oesophagostomum radiatum.

  19. Expedient total synthesis of small to medium-sized membrane proteins via Fmoc chemistry.

    PubMed

    Zheng, Ji-Shen; Yu, Mu; Qi, Yun-Kun; Tang, Shan; Shen, Fei; Wang, Zhi-Peng; Xiao, Liang; Zhang, Longhua; Tian, Chang-Lin; Liu, Lei

    2014-03-05

    Total chemical synthesis provides a unique approach for the access to uncontaminated, monodisperse, and more importantly, post-translationally modified membrane proteins. In the present study we report a practical procedure for expedient and cost-effective synthesis of small to medium-sized membrane proteins in multimilligram scale through the use of automated Fmoc chemistry. The key finding of our study is that after the attachment of a removable arginine-tagged backbone modification group, the membrane protein segments behave almost the same as ordinary water-soluble peptides in terms of Fmoc solid-phase synthesis, ligation, purification, and mass spectrometry characterization. The efficiency and practicality of the new method is demonstrated by the successful preparation of Ser64-phosphorylated M2 proton channel from influenza A virus and the membrane-embedded domain of an inward rectifier K(+) channel protein Kir5.1. Functional characterizations of these chemically synthesized membrane proteins indicate that they provide useful and otherwise-difficult-to-access materials for biochemistry and biophysics studies.

  20. Quantitative evaluation of waste prevention on the level of small and medium sized enterprises (SMEs).

    PubMed

    Laner, David; Rechberger, Helmut

    2009-02-01

    Waste prevention is a principle means of achieving the goals of waste management and a key element for developing sustainable economies. Small and medium sized enterprises (SMEs) contribute substantially to environmental degradation, often not even being aware of their environmental effects. Therefore, several initiatives have been launched in Austria aimed at supporting waste prevention measures on the level of SMEs. To promote the most efficient projects, they have to be evaluated with respect to their contribution to the goals of waste management. It is the aim of this paper to develop a methodology for evaluating waste prevention measures in SMEs based on their goal orientation. At first, conceptual problems of defining and delineating waste prevention activities are briefly discussed. Then an approach to evaluate waste prevention activities with respect to their environmental performance is presented and benchmarks which allow for an efficient use of the available funds are developed. Finally the evaluation method is applied to a number of former projects and the calculated results are analysed with respect to shortcomings and limitations of the model. It is found that the developed methodology can provide a tool for a more objective and comprehensible evaluation of waste prevention measures.

  1. Use of anthropogenic linear features by two medium-sized carnivores in reserved and agricultural landscapes.

    PubMed

    Andersen, Georgina E; Johnson, Christopher N; Barmuta, Leon A; Jones, Menna E

    2017-09-14

    Many carnivores are threatened by habitat loss and fragmentation. These changes create linear features and habitat edges that can facilitate foraging and/or travel. To understand the significance of anthropogenic linear features in the ecology of carnivores, fine-scaled studies are needed. We studied two medium-sized carnivores: the endangered Tasmanian devil (Sarcophilus harrisii) and the near threatened spotted-tailed quoll (Dasyurus maculatus), in a mixed landscape of conservation and agricultural land. Using GPS tracking, we investigated their use of intact habitat versus linear features such as roads, fences and the pasture/cover interface. Both species showed a positive selection for anthropogenic linear features, using the pasture/cover interface for foraging and roads for movement and foraging. Devils travelled along fence lines, while quolls showed little preference for them. Otherwise, both species foraged in forest and travelled through pasture. While devils and quolls can utilise anthropogenic linear features, we suggest that their continued survival in these habitats may depend on the intensity of other threats, e.g. persecution, and providing that sufficient intact habitat remains to sustain their ecological needs. We suggest that the management of both species and probably many other species of carnivores should focus on controlling mortality factors associated with human use of landscapes.

  2. Energy conserved and costs saved by small and medium-size manufacturers, 1988--1989

    SciTech Connect

    Kirsch, F.W.

    1991-05-01

    Energy Analysis and Diagnostic Centers (EADCs) provided energy-conserving and cost saving assistance in 339 small and medium-size manufacturing plants nationwide during 1988-89. This report presents the results of what was recommended to those manufacturers, the record of what was implemented by them, and an analysis of the financial rewards gained by them. It also includes an accounting of the financial returns to the federal government, derived from taxes upon the cost savings, or incremental income, of the manufacturers who implement the EADCs` recommendations. EADCs collect implementation data within a year of the energy audit, and for these results that time period extended through 1990. The EADCs are located at accredited engineering departments of universities and staffed by faculty and students. At present there are 18 EADCs serving manufacturers in 37 states; of these, two were established as a result of the 1989 competition, and five more were chosen competitively in 1990. Most of the results in this report were generated by 11 EADCs (named in the Appendix); two others withdrew voluntarily after completing only 10 energy audits during 1988-89. Primary responsibility for selecting, training, evaluating, and managing the EADCs belongs to the Industrial Technology and Energy Management (ITEM) division of University City Science Center (UCSC). The Department of Energy`s Office of Industrial Technologies sponsors the EADC program through an agreement with UCSC.

  3. Understanding the structural transformation, stability of medium-sized neutral and charged silicon clusters

    PubMed Central

    Ding, Li Ping; Zhang, Fang Hui; Zhu, Yong Sheng; Lu, Cheng; Kuang, Xiao Yu; Lv, Jian; Shao, Peng

    2015-01-01

    The structural and electronic properties for the global minimum structures of medium-sized neutral, anionic and cationic Sinμ (n = 20–30, μ = 0, −1 and +1) clusters have been studied using an unbiased CALYPSO structure searching method in conjunction with first-principles calculations. A large number of low-lying isomers are optimized at the B3PW91/6-311 + G* level of theory. Harmonic vibrational analysis has been performed to assure that the optimized geometries are stable. The growth behaviors clearly indicate that a structural transition from the prolate to spherical-like geometries occurs at n = 26 for neutral silicon clusters, n = 27 for anions and n = 25 for cations. These results are in good agreement with the available experimental and theoretical predicted findings. In addition, no significant structural differences are observed between the neutral and cation charged silicon clusters with n = 20–24, both of them favor prolate structures. The HOMO-LUMO gaps and vertical ionization potential patterns indicate that Si22 is the most chemical stable cluster, and its dynamical stability is deeply discussed by the vibrational spectra calculations. PMID:26526519

  4. Hybrid neural intelligent system to predict business failure in small-to-medium-size enterprises.

    PubMed

    Borrajo, M Lourdes; Baruque, Bruno; Corchado, Emilio; Bajo, Javier; Corchado, Juan M

    2011-08-01

    During the last years there has been a growing need of developing innovative tools that can help small to medium sized enterprises to predict business failure as well as financial crisis. In this study we present a novel hybrid intelligent system aimed at monitoring the modus operandi of the companies and predicting possible failures. This system is implemented by means of a neural-based multi-agent system that models the different actors of the companies as agents. The core of the multi-agent system is a type of agent that incorporates a case-based reasoning system and automates the business control process and failure prediction. The stages of the case-based reasoning system are implemented by means of web services: the retrieval stage uses an innovative weighted voting summarization of self-organizing maps ensembles-based method and the reuse stage is implemented by means of a radial basis function neural network. An initial prototype was developed and the results obtained related to small and medium enterprises in a real scenario are presented.

  5. A radiophotoluminescent glass plate system for medium-sized field dosimetry

    SciTech Connect

    Nakagawa, Keiichi; Koyanagi, Hiroki; Shiraki, Takashi; Saegusa, Shigeki; Sasaki, Katsutake; Oritate, Takashi; Mima, Kazuo; Miyazawa, Masanori; Ishidoya, Tatsuyo; Ohtomo, Kuni; Yoda, Kiyoshi

    2005-10-15

    A two-dimensional radiophotoluminescent system for medium-sized field dosimetry has been developed using a silver-activated phosphate glass plate with a dimension of 120 mmx120 mmx1 mm and a readout unit comprising a UV excitation lamp and a CCD imager. A dose ranging from 0 to 400 cGy, provided by a 6 MV x-ray beam, was delivered to the glass plate oriented perpendicularly to the beam and positioned in a water phantom at a depth of 10 cm, where the center of the glass plate coincided with the linac isocenter. After the dose delivery, the glass plate was placed in the readout system. The CCD output intensity increased linearly with the applied dose. The angular dependence of response on the direction of radiation incidence was measured by rotating the glass plate in the water phantom, indicating that the output remained constant up to 75 deg. from perpendicular incident direction, followed by a steep reduction down to 85% at an angle of 90 deg. A lateral dose distribution resulting from a 60 mmx60 mm irradiation was compared between the glass plate and an x-ray film having had the same exposure, showing that the glass plate and the x-ray film led to identical dose distributions. The dose reproducibility for a glass plate and the sensitivity variation among different glass plates were also evaluated.

  6. Resource efficiency and culture--workplace training for small and medium-sized enterprises.

    PubMed

    Bliesner, Anna; Liedtke, Christa; Rohn, Holger

    2014-05-15

    Although there are already some qualification offers available for enterprises to support resource efficiency innovations, the high potentials that can be identified especially for small and medium sized enterprises (SMEs) have not been activated until now. As successful change lies in the hands of humans, the main aim of vocational education has to be the promotion of organisational and cultural changes in the enterprises. As there is already a small but increasing number of enterprises that perform very well in resource efficiency innovations one question arises: What are typical characteristics of those enterprises? Leaning on a good-practice approach, the project "ResourceCulture" is going to prove or falsify the hypothesis that enterprises being successful with resource efficiency innovations have a specific culture of trust, which substantially contributes to innovation processes, or even initially enables them. Detailed empirical field research will light up which correlations between resource efficiency, innovation and cultures of trust can be found and will offer important aspects for the improvement of management instruments and qualification concepts for workplace training. The project seizes qualification needs that were likewise mentioned by enterprises and consultants, regarding the implementation of resource efficiency. This article - based on first empirical field research results - derives preliminary indications for the design of the qualification module for the target groups resource efficiency consultants and managers. On this basis and in order to implement "ResourceCulture" conceptual and methodological starting points for workplace training are outlined. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand

    PubMed Central

    DeLuca, Samuel; Khar, Karen; Meiler, Jens

    2015-01-01

    RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand) making it unfeasible for use in virtual High Throughput Screening (vHTS). To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial ‘low-resolution’ docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10–15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the ‘high-resolution’ full atom refinement step. PMID:26207742

  8. Modeling, simulation, and concept design for hybrid-electric medium-size military trucks

    NASA Astrophysics Data System (ADS)

    Rizzoni, Giorgio; Josephson, John R.; Soliman, Ahmed; Hubert, Christopher; Cantemir, Codrin-Gruie; Dembski, Nicholas; Pisu, Pierluigi; Mikesell, David; Serrao, Lorenzo; Russell, James; Carroll, Mark

    2005-05-01

    A large scale design space exploration can provide valuable insight into vehicle design tradeoffs being considered for the U.S. Army"s FMTV (Family of Medium Tactical Vehicles). Through a grant from TACOM (Tank-automotive and Armaments Command), researchers have generated detailed road, surface, and grade conditions representative of the performance criteria of this medium-sized truck and constructed a virtual powertrain simulator for both conventional and hybrid variants. The simulator incorporates the latest technology among vehicle design options, including scalable ultracapacitor and NiMH battery packs as well as a variety of generator and traction motor configurations. An energy management control strategy has also been developed to provide efficiency and performance. A design space exploration for the family of vehicles involves running a large number of simulations with systematically varied vehicle design parameters, where each variant is paced through several different mission profiles and multiple attributes of performance are measured. The resulting designs are filtered to remove dominated designs, exposing the multi-criterial surface of optimality (Pareto optimal designs), and revealing the design tradeoffs as they impact vehicle performance and economy. The results are not yet definitive because ride and drivability measures were not included, and work is not finished on fine-tuning the modeled dynamics of some powertrain components. However, the work so far completed demonstrates the effectiveness of the approach to design space exploration, and the results to date suggest the powertrain configuration best suited to the FMTV mission.

  9. Sustainability indices as a tool for urban managers, evidence from four medium-sized Chinese cities

    SciTech Connect

    Dijk, Meine Pieter van . E-mail: mpvandijk@few.eur.nl; Zhang Mingshun . E-mail: z.mingshun@ihs.nl

    2005-08-15

    This research in four medium-sized Chinese cities aims at measuring urban sustainability in China and focuses on three issues. First, the situation in these four cities with regard to urban sustainability is evaluated. Secondly, a number of relations between different aspects of urban sustainability is explored. Finally, it is indicated how urban managers can improve with sustainability indices as tools currently ineffective urban management practices. Although all four cities are moving towards sustainable development, the current situation shows still weak sustainability in three, and even non-sustainability in one city. The social and, in particular, the economic dimensions of urban sustainability make significant positive contributions to overall urban sustainability. However, the decline of natural resources and environmental degradation are influencing it negatively. It is therefore suggested that more priority should be assigned to urban environmental protection and management in China. The fundamental reason for environmental degradation is believed to be inefficient urban management. To implement effective urban management in China, there is an urgent need to redefine the role of local government, reform local organizational structure, enhance local participatory institutional capacity, properly distribute the urban welfare, and thus integrate economic, social and environmental objectives local strategic and action plans.

  10. Diode laser anastemoses of medium-size arteries with indocyanine green dye-enhanced albumine

    NASA Astrophysics Data System (ADS)

    Weng, Guo-Xing; Williamson, Warren; Aretz, H. Thomas

    1998-11-01

    In order to achieve a better long-term patency result and solve the problem of tensile strength in laser artery anastomoses, diode laser and Indocyanine Green (ICG) enhanced albumin were applied to medium-size artery anastomoses with three different methods, that is, direct laser vascular anastomoses, direct method enforced with ICG albumin, and laser welding with ICG albumin as 'solder'. Internal mammary artery (IMA) harvested from patients undergoing coronary bypass procedures, in vivo rat abdominal artery, and in vitro swine heart and IMA were chosen as the experimental materials. The results revealed that only 3.15 +/- 0.36 minutes were required for each anastomosis; the bursting pressure and tensile strength were greater in the groups enforced with ICG albumin and laser welding than that with direct laser anastomoses. In the laser soldering group, the thermal damage was limited in the adventitial layer, only at a depth of 200 micrometers . There was also a satisfied result in the in vivo laser welding rat's abdominal adventitial layer, only at a depth of 200 micrometers . There was also a satisfied result in the in vivo laser welding rat's abdominal arteries. However, end-to-side laser welding of IMA soronary artery with ICG albumin needs further investigation about its tensile strength in an in vivo model.

  11. Generation of antitumor active neutral medium-sized alpha-glycan in apple vinegar fermentation.

    PubMed

    Abe, Kaoru; Kushibiki, Toshisada; Matsue, Hajime; Furukawa, Ken-Ichi; Motomura, Shigeru

    2007-09-01

    The physiologically active substances in apple vinegar have not yet been chemically characterized. We studied the biological functions of apple vinegar produced from crushed apples, and found that the constituent neutral medium-sized alpha-glycan (NMalphaG) acts as an antitumor agent against experimental mouse tumors. NMalphaG is a homoglycan composed of glucose having a molecular weight of about 10,000 and a branched structure bearing alpha (1-4,6) linkages. In this study, we clarified the origin of NMalphaG in apple vinegar by examination of its content in alcohol and acetic acid fermentation products sequentially. We found that NMalphaG appeared in acetic acid fermentation, but not in alcohol fermentation. Furthermore we investigated NMalphaG origin using acetic acid fermentation from alcohol fortifiied apple without alcohol fermentation and from raw material with varying amounts of pomace. The results indicate that NMalphaG originated in the apple fruit body and that its production requires both fermentation processes.

  12. Evaluating the control software for CTA in a medium size telescope prototype

    NASA Astrophysics Data System (ADS)

    Oya, I.; Behera, B.; Birsin, E.; Koeppel, H.; Melkumyan, D.; Schmidt, T.; Schwanke, U.; Wegner, P.; Wiesand, S.; Winde, M.; Consortium, CTA

    2012-12-01

    CTA (Cherenkov Telescope Array) is one of the largest ground-based astronomy projects being pursued and will be the largest facility for ground-based γ-ray observations ever built. CTA will consist of two arrays (one in the Northern hemisphere and one in the Southern hemisphere) composed of telescopes of several sizes. A prototype for the Medium Size Telescope (MST) of a diameter of 12 m will be installed in Berlin by the end of 2012. This MST prototype will be composed of the mechanical structure, drive system and mirror facets mounted with powered actuators to enable active control. Five Charge-Coupled Device (CCD) cameras and a weather station will allow the measurement of the performance of the instrument. The Atacama Large Millimeter/submillimeter Array (ALMA) Common Software (ACS) distributed control framework is currently being considered by the CTA consortium to serve as the array control middleware. In order to evaluate the ACS software, it has been decided to implement an ACS-based readout and control system for the MST prototype. The design of the control software is following the concepts and tools under evaluation within the CTA consortium, like the use of a Unified Modeling Language (UML) based code generation framework for ACS component modeling, and the use of OPen Connectivity-Unified Architecture (OPC UA) for hardware access. In this contribution, the progress in the implementation of the control system for this CTA prototype telescope is described.

  13. Experimental testing of centrifugal pump: small and medium sized enterprise product

    NASA Astrophysics Data System (ADS)

    Ismail, R.; Paddiyatu, F.; Khafidh, M.; Nugroho, S.; Sugiyanto, S.; Jamari, J.

    2014-06-01

    This paper reports the experimental testing for centrifugal pump for fisherman ship, manufactured by small and medium sized enterprises in Central Java Province, Indonesia. The research covers material analysis, component observation, endurance and vibration test. Six centrifugal pumps are tested and three main pump components are discussed: shaft, bearings and seals. The results show that the material of the shaft is predicted to support and transmit the load from the engine to impeller. The problem found in the tolerance and geometry accuracy of the shaft which causes difficulties during assembling process, excessive wear and leakage during testing. From the endurance and vibration test, the ball bearings fail and lock the shaft due to the fatigue on the rolling elements and raceways. The oil seal and water seal also fail in maintaining the oil and water in the chamber and induce the unlubricated system for the ball bearings. Some suggestions are delivered to improve the product quality of the centrifugal pump. A good quality of the centrifugal pump for fishermen ship and long life span is expected to be produced by local SMEs to win the free trade competition in the Indonesian market.

  14. Computational fluid dynamic modeling of a medium-sized surface mine blasthole drill shroud

    PubMed Central

    Zheng, Y.; Reed, W.R.; Zhou, L.; Rider, J.P.

    2016-01-01

    The Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health (NIOSH) recently developed a series of models using computational fluid dynamics (CFD) to study airflows and respirable dust distribution associated with a medium-sized surface blasthole drill shroud with a dry dust collector system. Previously run experiments conducted in NIOSH’s full-scale drill shroud laboratory were used to validate the models. The setup values in the CFD models were calculated from experimental data obtained from the drill shroud laboratory and measurements of test material particle size. Subsequent simulation results were compared with the experimental data for several test scenarios, including 0.14 m3/s (300 cfm) and 0.24 m3/s (500 cfm) bailing airflow with 2:1, 3:1 and 4:1 dust collector-to-bailing airflow ratios. For the 2:1 and 3:1 ratios, the calculated dust concentrations from the CFD models were within the 95 percent confidence intervals of the experimental data. This paper describes the methodology used to develop the CFD models, to calculate the model input and to validate the models based on the experimental data. Problem regions were identified and revealed by the study. The simulation results could be used for future development of dust control methods for a surface mine blasthole drill shroud. PMID:27932851

  15. Respirable quartz exposure on two medium-sized farms in southern Mozambique.

    PubMed

    Franque Mirembo, José C; Swanepoel, Andrew J; Rees, David

    2013-01-01

    Little is known about the potential for overexposure to respirable quartz in farming, in most parts of the world. To measure respirable dust and quartz exposure of tractor operators on two medium-sized dry climate farms. This is a descriptive cross-sectional study of dust exposure of four tractor operators. Farms were selected by convenience sampling. The MDHS 14/3 and FTIR MDHS 101 HSE methods were used to measure dust and to analyze the mass of quartz in dust, respectively. Seventy respirable dust measurements were done. Respirable dust and quartz ranged from 0·01 to 2·88 and 0·001 to 0·30 mg/m(3), respectively. All operators had at least one respirable quartz exposure above 0·1 mg/m(3). Only 17% of respirable quartz concentrations were lower than the ACGIH TLV of 0·025 mg/m(3). The potential for overexposure to respirable quartz was demonstrated. There was a great deal of exposure variability on these farms which has implications for sampling strategies for dust in farming.

  16. NectarCAM : a camera for the medium size telescopes of the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Glicenstein, J. F.; Abril, O.; Barrio, J.-A.; Blanch Bigas, O.; Bolmont, J.; Bouyjou, F.; Brun, P.; Chabanne, E.; Champion, C.; Colonges, S.; Corona, P.; Delagnes, E.; Delgado, C.; Diaz Ginzo, C.; Durand, D.; Ernenwein, J.-P.; Fegan, S.; Ferreira, O.; Fesquet, M.; Fiasson, A.; Fontaine, G.; Fouque, N.; Gascon, D.; Giebels, B.; Henault, F.; Hermel, R.; Hoffmann, D.; Horan, D.; Houles, J.; Jean, P.; Jocou, L.; Karkar, S.; Knödlseder, J.; Kossakowski, R.; Lamanna, G.; Le Flour, T.; Lenain, J.-P.; Leveque, A.; Louis, F.; Martinez, G.; Moudden, Y.; Moulin, E.; Nayman, P.; Nunio, F.; Olive, J.-F.; Panazol, J.-L.; Pavy, S.; Petrucci, P.-O.; Pierre, E.; Prast, J.; Punch, M.; Ramon, P.; Rateau, S.; Ravel, T.; Rosier-Lees, S.; Sanuy, A.; Shayduk, M.; Sizun, P.-Y.; Sulanke, K.-H.; Tavernet, J.-P.; Tejedor Alvarez, L.-A.; Toussenel, F.; Vasileiadis, G.; Voisin, V.; Waegebert, V.; Wischnewski, R.; Consortium, CTA

    2015-07-01

    NectarCAM is a camera proposed for the medium-sized telescopes of the Cherenkov Telescope Array (CTA) covering the central energy range of ~100 GeV to ~30 TeV. It has a modular design and is based on the NECTAr chip, at the heart of which is a GHz sampling Switched Capacitor Array and a 12-bit Analog to Digital converter. The camera will be equipped with 265 7-photomultiplier modules, covering a field of view of 8 degrees. Each module includes the photomultiplier bases, high voltage supply, pre-amplifier, trigger, readout and Ethernet transceiver. The recorded events last between a few nanoseconds and tens of nanoseconds. The camera trigger will be flexible so as to minimize the read-out dead-time of the NECTAr chips. NectarCAM is designed to sustain a data rate of more than 4 kHz with less than 5\\% dead time. The camera concept, the design and tests of the various subcomponents and results of thermal and electrical prototypes are presented. The design includes the mechanical structure, cooling of the electronics, read-out, clock distribution, slow control, data-acquisition, triggering, monitoring and services.

  17. Feasibility of a medium-size central cogenerated energy facility, energy management memorandum

    NASA Astrophysics Data System (ADS)

    Porter, R. W.

    1982-09-01

    The thermal-economic feasibility was studied of a medium-size central cogenerated energy facility designed to serve five varied industries. Generation options included one dual-fuel diesel and one gas turbine, both with waste heat boilers, and five fired boilers. Fuels included natural gas, and for the fired-boiler cases, also low-sulphur coal and municipal refuse. The fired-boiler cogeneration systems employed back-pressure steam turbines. For coal and refuse, the option of steam only without cogeneration was also assessed. The refuse-fired cases utilized modular incinerators. The options provided for a wide range of steam and electrical capacities. Deficient steam was assumed generated independently in existing equipment. Excess electrical power over that which could be displaced was assumed sold to Commonwealth Edison Company under PURPA (Public Utility Regulator Policies Act). The facility was assumed operated by a mutually owned corporation formed by the cogenerated power users. The economic analysis was predicted on currently applicable energy-investment tax credits and accelerated depreciation for a January 1985 startup date. Based on 100% equity financing, the results indicated that the best alternative was the modular-incinerator cogeneration system.

  18. Drivers for OSH interventions in small and medium-sized enterprises.

    PubMed

    Cagno, Enrico; Masi, Donato; Leão, Celina Pinto

    2016-01-01

    The debate concerning occupational safety and health (OSH) interventions has recently focused on the need of improving the evaluation of interventions, and in particular on the need for providing information about why the intervention worked or not, under what circumstances and in which context. Key concepts in the analysis of the context are the drivers, i.e., those factors enabling, fostering or facilitating OSH interventions. However, the concept of driver for an OSH intervention is both confused and contested. Although the term is widely used, there is little consensus on how drivers should be understood, how important they are in different contexts and how they can facilitate interventions. This exploratory study based on interviews with the owner-managers and the safety officers of small and medium-sized enterprises (SMEs) gives an overview of the most characteristic drivers for OSH interventions. The results will be used to make an initial evaluation of SMEs' needs, and will help orient interventions and future research.

  19. An effective physical fitness program for small and medium-sized enterprises.

    PubMed

    Tsai, Han Hui; Peng, Shu Mei; Yeh, Ching Ying; Chen, Chiou Jong; Chen, Ruey Yu

    2011-01-01

    The aim of this study is to develop a practicable worksite physical fitness program for small and medium-sized enterprises (SMEs). Community-based intervention consisting of a three-month exercise course was conducted, and its benefits evaluated. A self-administrated structured questionnaire and physical fitness examination were designed to compare the difference between pre and post intervention. A total of 133 SME workers completed the lifestyle/exercise course and filled out the questionnaire, but 16 were excluded from the exercise group due to health reasons. After the intervention, health indicators such as weight, blood pressure, resting heart rate, waistline, BMI, front and back trunk flexibility, abdominal muscle durability and back muscle strength were significantly improved, and improvements in musculoskeletal disorders were seen in reduced neck pain (18.8%), wrist pain (17.4%), and upper/lower back pain (8.7% and 21.7%, respectively). Cardiovascular risk factors (BMI and resting heart rate) showed a significant improvement related to frequent participation in the program (p=0.02), and the exercise group reported a significant difference in overall health (p=0.02). This study has demonstrated an effective approach to community-based fitness intervention through SMEs.

  20. Mousso structure: A deeply eroded, medium-sized, complex impact crater in northern Chad?

    NASA Astrophysics Data System (ADS)

    Buchner, Elmar; Schmieder, Martin

    2007-10-01

    The Mousso structure, a complex, ˜3.8 km circular structure centred on 17°58' N/19°53' E and located near the Mousso oasis, Borkou-Ennedi-Tibesti, northern Chad, displays structural features typical for complex impact structures: a circular rim with concentric faults, an annular basin, and a central peak. Remote sensing investigations based on Landsat-7 Enhanced Thematic Mapper Plus (ETM+) and Shuttle Radar Topographic Mission (SRTM) data reveal a specific morphological-structural resemblance of the complex central peak of the Mousso structure to the central uplift of the Spider impact structure, Western Australia, and, to some degree, to the central uplifts of the Upheaval Dome, Sierra Madera, and Gosses Bluff impact structures. This is consistent with the layered sedimentary rocks associated with all of these structures. No endogenic geological processes such as magmatism, diapirism, karst dissolution, and glacial or fluvial erosion can conclusively explain the formation of the Mousso structure within a large area of flat-lying early Paleozoic sandstones. Thus, this paper proposes that the Mousso structure might represent a deeply eroded, medium-sized, complex impact structure. As field investigations are currently impossible due to the civil war in Chad, the search for shock-metamorphic effects in rocks of the Mousso structure remains outstanding.

  1. TELICS—A Telescope Instrument Control System for Small/Medium Sized Astronomical Observatories

    NASA Astrophysics Data System (ADS)

    Srivastava, Mudit K.; Ramaprakash, A. N.; Burse, Mahesh P.; Chordia, Pravin A.; Chillal, Kalpesh S.; Mestry, Vilas B.; Das, Hillol K.; Kohok, Abhay A.

    2009-10-01

    For any modern astronomical observatory, it is essential to have an efficient interface between the telescope and its back-end instruments. However, for small and medium-sized observatories, this requirement is often limited by tight financial constraints. Therefore a simple yet versatile and low-cost control system is required for such observatories to minimize cost and effort. Here we report the development of a modern, multipurpose instrument control system TELICS (Telescope Instrument Control System) to integrate the controls of various instruments and devices mounted on the telescope. TELICS consists of an embedded hardware unit known as a common control unit (CCU) in combination with Linux-based data acquisition and user interface. The hardware of the CCU is built around the ATmega 128 microcontroller (Atmel Corp.) and is designed with a backplane, master-slave architecture. A Qt-based graphical user interface (GUI) has been developed and the back-end application software is based on C/C++. TELICS provides feedback mechanisms that give the operator good visibility and a quick-look display of the status and modes of instruments as well as data. TELICS has been used for regular science observations since 2008 March on the 2 m, f/10 IUCAA Telescope located at Girawali in Pune, India.

  2. Spiny hopsage fruit and seed morphology

    Treesearch

    Nancy L. Shaw; Emerenciana G. Hurd; Marshall R. Haferkamp

    1996-01-01

    Rangeland seedings of spiny hopsage (Gruyia spinosa [Hook.] Moq.) may be made with either bracted utricles or seeds. Problems have resulted from inconsistent use of terminology describing these 2 structures and the fact their germination and seedling emergence is not the same with similar environmental conditions and seeding techniques. We examined...

  3. Acitretin-induced spiny follicular hyperkeratosis.

    PubMed

    Yanik, Mehmet Emin; Erfan, Gamze; Albayrak, Hulya; Tasolar, Kaan; Albayrak, Sule; Gelincik, Ibrahim; Kulac, Mustafa

    2015-08-12

    Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin.

  4. Acitretin-induced spiny follicular hyperkeratosis.

    PubMed

    Yanik, Mehmet Emin; Erfan, Gamze; Albayrak, Hulya; Tasolar, Kaan; Albayrak, Sule; Gelincik, Ibrahim; Kulac, Mustafa

    2016-01-01

    Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin.

  5. Cholinergic neuronal defect without cell loss in Huntington's disease.

    PubMed

    Smith, Ruben; Chung, Hinfan; Rundquist, Sara; Maat-Schieman, Marion L C; Colgan, Lesley; Englund, Elisabet; Liu, Yong-Jian; Roos, Raymund A C; Faull, Richard L M; Brundin, Patrik; Li, Jia-Yi

    2006-11-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.

  6. 50 CFR 648.230 - Spiny dogfish Annual Catch Limits (ACLs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish Annual Catch Limits (ACLs... Management Measures for the Spiny Dogfish Fishery § 648.230 Spiny dogfish Annual Catch Limits (ACLs). (a) The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny Dogfish Committee, an ACL for the...

  7. 50 CFR 648.230 - Spiny dogfish Annual Catch Limits (ACLs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish Annual Catch Limits (ACLs... Management Measures for the Spiny Dogfish Fishery § 648.230 Spiny dogfish Annual Catch Limits (ACLs). (a) The Spiny Dogfish Monitoring Committee shall recommend to the Joint Spiny Dogfish Committee, an ACL for the...

  8. 76 FR 17788 - Fisheries of the Northeastern United States; Spiny Dogfish Fishery; Annual Quota Harvested

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... Northeastern United States; Spiny Dogfish Fishery; Annual Quota Harvested AGENCY: National Marine Fisheries...; closure of spiny dogfish fishery. SUMMARY: NMFS announces that the spiny dogfish commercial quota... spiny dogfish vessels may not fish for, possess, transfer, or land spiny dogfish until May 1, 2011, when...

  9. 75 FR 4004 - Fisheries of the Northeastern United States; Spiny Dogfish Fishery; Commercial Period 2 Quota...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-26

    ... United States; Spiny Dogfish Fishery; Commercial Period 2 Quota Harvested AGENCY: National Marine...: Temporary rule; Closure of spiny dogfish fishery. SUMMARY: NMFS announces that the spiny dogfish commercial..., federally permitted spiny dogfish vessels may not fish for, possess, transfer, or land spiny dogfish until...

  10. 76 FR 52286 - Fisheries of the Northeastern United States; Spiny Dogfish Fishery; Commercial Period 1 Quota...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-22

    ... Northeastern United States; Spiny Dogfish Fishery; Commercial Period 1 Quota Harvested AGENCY: National Marine...: Temporary rule; closure of spiny dogfish fishery. SUMMARY: NMFS announces that the spiny dogfish commercial..., federally permitted spiny dogfish vessels may not fish for, possess, transfer, or land spiny dogfish until...

  11. 75 FR 52650 - Fisheries of the Northeastern United States; Spiny Dogfish Fishery; Commercial Period 1 Quota...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... United States; Spiny Dogfish Fishery; Commercial Period 1 Quota Harvested AGENCY: National Marine...: Temporary rule; closure of spiny dogfish fishery. SUMMARY: NMFS announces that the spiny dogfish commercial..., federally permitted spiny dogfish vessels may not fish for, possess, transfer, or land spiny dogfish until...

  12. High-Resolution Spectroscopic Studies of Complexes Formed by Medium-Size Organic Molecules.

    PubMed

    Becucci, Maurizio; Melandri, Sonia

    2016-05-11

    A wealth of structural and dynamical information has been obtained in the last 30 years from the study of high-resolution spectra of molecular clusters generated in a cold supersonic expansion by means of highly resolved spectroscopic methods. The data obtained, generally lead to determination of the structures of stable conformations. In addition, in the case of weakly bound molecular complexes, it is usual to observe the effects of internal motions due to the shallowness of the potential energy surfaces involved and the flexibility of the systems. In the case of electronic excitation experiments, also the effect of electronic distribution changes on both equilibrium structures and internal motions becomes accessible. The structural and dynamical information that can be obtained by applying suitable theoretical models to the analysis of these unusually complex spectra allows the determination and understanding of the driving forces involved in formation of the molecular complex. In this way, many types of non-covalent interactions have been characterized, from pure van der Waals interactions in complexes of rare gases to moderate-strength and weak hydrogen bonds and to the most recent halogen bonds and n-π interactions. The aim of this review is to underline how the different experimental and theoretical methods converge in giving a detailed picture of weak interactions in small molecular adducts involving medium-size molecules. The conclusions regarding geometries and energies can contribute to understanding of the different driving forces involved in the dynamics of the processes and can be exploited in all fields of chemistry and biochemistry, from design of new materials with novel properties to rational design of drugs.

  13. Urbanization alters communities of flying arthropods in parks and gardens of a medium-sized city.

    PubMed

    Lagucki, Edward; Burdine, Justin D; McCluney, Kevin E

    2017-01-01

    Urbanization transforms undeveloped landscapes into built environments, causing changes in communities and ecological processes. Flying arthropods play important roles in these processes as pollinators, decomposers, and predators, and can be important in structuring food webs. The goal of this study was to identify associations between urbanization and the composition of communities of flying (and floating) arthropods within gardens and parks in a medium-sized mesic city. We predicted that flying arthropod abundance and diversity would respond strongly to percent impervious surface and distance to city center, measurements of urbanization. Flying arthropods were sampled from 30 gardens and parks along an urbanization gradient in Toledo, Ohio, during July and August 2016, using elevated pan traps. A variety of potential predictor variables were also recorded at each site. We collected a total of 2,369 individuals representing nine orders. We found that flying arthropod community composition was associated with percent impervious surface and canopy cover. Overall flying arthropod abundance was negatively associated with percent impervious surface and positively associated with distance to city center. Hymenoptera (bees, wasps, ants), Lepidoptera (moths, butterflies), and Araneae (spiders) were positively associated with distance to city center. Hemiptera (true bugs), Diptera (flies), and Araneae were negatively associated with percent impervious surface. Both distance to city center and percent impervious surface are metrics of urbanization, and this study shows how these factors influence flying arthropod communities in urban gardens and city parks, including significant reductions in taxa that contain pollinators and predators important to urban agriculture and forestry. A variety of environmental factors also showed significant associations with responses (e.g. canopy cover and soil moisture), suggesting these factors may underlie or modulate the urbanization

  14. Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution

    NASA Astrophysics Data System (ADS)

    Meyer, H.; Eich, T.; Beurskens, M.; Coda, S.; Hakola, A.; Martin, P.; Adamek, J.; Agostini, M.; Aguiam, D.; Ahn, J.; Aho-Mantila, L.; Akers, R.; Albanese, R.; Aledda, R.; Alessi, E.; Allan, S.; Alves, D.; Ambrosino, R.; Amicucci, L.; Anand, H.; Anastassiou, G.; Andrèbe, Y.; Angioni, C.; Apruzzese, G.; Ariola, M.; Arnichand, H.; Arter, W.; Baciero, A.; Barnes, M.; Barrera, L.; Behn, R.; Bencze, A.; Bernardo, J.; Bernert, M.; Bettini, P.; Bilková, P.; Bin, W.; Birkenmeier, G.; Bizarro, J. P. S.; Blanchard, P.; Blanken, T.; Bluteau, M.; Bobkov, V.; Bogar, O.; Böhm, P.; Bolzonella, T.; Boncagni, L.; Botrugno, A.; Bottereau, C.; Bouquey, F.; Bourdelle, C.; Brémond, S.; Brezinsek, S.; Brida, D.; Brochard, F.; Buchanan, J.; Bufferand, H.; Buratti, P.; Cahyna, P.; Calabrò, G.; Camenen, Y.; Caniello, R.; Cannas, B.; Canton, A.; Cardinali, A.; Carnevale, D.; Carr, M.; Carralero, D.; Carvalho, P.; Casali, L.; Castaldo, C.; Castejón, F.; Castro, R.; Causa, F.; Cavazzana, R.; Cavedon, M.; Cecconello, M.; Ceccuzzi, S.; Cesario, R.; Challis, C. D.; Chapman, I. T.; Chapman, S.; Chernyshova, M.; Choi, D.; Cianfarani, C.; Ciraolo, G.; Citrin, J.; Clairet, F.; Classen, I.; Coelho, R.; Coenen, J. W.; Colas, L.; Conway, G.; Corre, Y.; Costea, S.; Crisanti, F.; Cruz, N.; Cseh, G.; Czarnecka, A.; D'Arcangelo, O.; De Angeli, M.; De Masi, G.; De Temmerman, G.; De Tommasi, G.; Decker, J.; Delogu, R. S.; Dendy, R.; Denner, P.; Di Troia, C.; Dimitrova, M.; D'Inca, R.; Dorić, V.; Douai, D.; Drenik, A.; Dudson, B.; Dunai, D.; Dunne, M.; Duval, B. P.; Easy, L.; Elmore, S.; Erdös, B.; Esposito, B.; Fable, E.; Faitsch, M.; Fanni, A.; Fedorczak, N.; Felici, F.; Ferreira, J.; Février, O.; Ficker, O.; Fietz, S.; Figini, L.; Figueiredo, A.; Fil, A.; Fishpool, G.; Fitzgerald, M.; Fontana, M.; Ford, O.; Frassinetti, L.; Fridström, R.; Frigione, D.; Fuchert, G.; Fuchs, C.; Furno Palumbo, M.; Futatani, S.; Gabellieri, L.; Gałązka, K.; Galdon-Quiroga, J.; Galeani, S.; Gallart, D.; Gallo, A.; Galperti, C.; Gao, Y.; Garavaglia, S.; Garcia, J.; Garcia-Carrasco, A.; Garcia-Lopez, J.; Garcia-Munoz, M.; Gardarein, J.-L.; Garzotti, L.; Gaspar, J.; Gauthier, E.; Geelen, P.; Geiger, B.; Ghendrih, P.; Ghezzi, F.; Giacomelli, L.; Giannone, L.; Giovannozzi, E.; Giroud, C.; Gleason González, C.; Gobbin, M.; Goodman, T. P.; Gorini, G.; Gospodarczyk, M.; Granucci, G.; Gruber, M.; Gude, A.; Guimarais, L.; Guirlet, R.; Gunn, J.; Hacek, P.; Hacquin, S.; Hall, S.; Ham, C.; Happel, T.; Harrison, J.; Harting, D.; Hauer, V.; Havlickova, E.; Hellsten, T.; Helou, W.; Henderson, S.; Hennequin, P.; Heyn, M.; Hnat, B.; Hölzl, M.; Hogeweij, D.; Honoré, C.; Hopf, C.; Horáček, J.; Hornung, G.; Horváth, L.; Huang, Z.; Huber, A.; Igitkhanov, J.; Igochine, V.; Imrisek, M.; Innocente, P.; Ionita-Schrittwieser, C.; Isliker, H.; Ivanova-Stanik, I.; Jacobsen, A. S.; Jacquet, P.; Jakubowski, M.; Jardin, A.; Jaulmes, F.; Jenko, F.; Jensen, T.; Jeppe Miki Busk, O.; Jessen, M.; Joffrin, E.; Jones, O.; Jonsson, T.; Kallenbach, A.; Kallinikos, N.; Kálvin, S.; Kappatou, A.; Karhunen, J.; Karpushov, A.; Kasilov, S.; Kasprowicz, G.; Kendl, A.; Kernbichler, W.; Kim, D.; Kirk, A.; Kjer, S.; Klimek, I.; Kocsis, G.; Kogut, D.; Komm, M.; Korsholm, S. B.; Koslowski, H. R.; Koubiti, M.; Kovacic, J.; Kovarik, K.; Krawczyk, N.; Krbec, J.; Krieger, K.; Krivska, A.; Kube, R.; Kudlacek, O.; Kurki-Suonio, T.; Labit, B.; Laggner, F. M.; Laguardia, L.; Lahtinen, A.; Lalousis, P.; Lang, P.; Lauber, P.; Lazányi, N.; Lazaros, A.; Le, H. B.; Lebschy, A.; Leddy, J.; Lefévre, L.; Lehnen, M.; Leipold, F.; Lessig, A.; Leyland, M.; Li, L.; Liang, Y.; Lipschultz, B.; Liu, Y. Q.; Loarer, T.; Loarte, A.; Loewenhoff, T.; Lomanowski, B.; Loschiavo, V. P.; Lunt, T.; Lupelli, I.; Lux, H.; Lyssoivan, A.; Madsen, J.; Maget, P.; Maggi, C.; Maggiora, R.; Magnussen, M. L.; Mailloux, J.; Maljaars, B.; Malygin, A.; Mantica, P.; Mantsinen, M.; Maraschek, M.; Marchand, B.; Marconato, N.; Marini, C.; Marinucci, M.; Markovic, T.; Marocco, D.; Marrelli, L.; Martin, Y.; Solis, J. R. Martin; Martitsch, A.; Mastrostefano, S.; Mattei, M.; Matthews, G.; Mavridis, M.; Mayoral, M.-L.; Mazon, D.; McCarthy, P.; McAdams, R.; McArdle, G.; McCarthy, P.; McClements, K.; McDermott, R.; McMillan, B.; Meisl, G.; Merle, A.; Meyer, O.; Milanesio, D.; Militello, F.; Miron, I. G.; Mitosinkova, K.; Mlynar, J.; Mlynek, A.; Molina, D.; Molina, P.; Monakhov, I.; Morales, J.; Moreau, D.; Morel, P.; Moret, J.-M.; Moro, A.; Moulton, D.; Müller, H. W.; Nabais, F.; Nardon, E.; Naulin, V.; Nemes-Czopf, A.; Nespoli, F.; Neu, R.; Nielsen, A. H.; Nielsen, S. K.; Nikolaeva, V.; Nimb, S.; Nocente, M.; Nouailletas, R.; Nowak, S.; Oberkofler, M.; Oberparleiter, M.; Ochoukov, R.; Odstrčil, T.; Olsen, J.; Omotani, J.; O'Mullane, M. G.; Orain, F.; Osterman, N.; Paccagnella, R.; Pamela, S.; Pangione, L.; Panjan, M.; Papp, G.; Papřok, R.; Parail, V.; Parra, F. I.; Pau, A.; Pautasso, G.; Pehkonen, S.-P.; Pereira, A.; Perelli Cippo, E.; Pericoli Ridolfini, V.; Peterka, M.; Petersson, P.; Petrzilka, V.; Piovesan, P.; Piron, C.; Pironti, A.; Pisano, F.; Pisokas, T.; Pitts, R.; Ploumistakis, I.; Plyusnin, V.; Pokol, G.; Poljak, D.; Pölöskei, P.; Popovic, Z.; Pór, G.; Porte, L.; Potzel, S.; Predebon, I.; Preynas, M.; Primc, G.; Pucella, G.; Puiatti, M. E.; Pütterich, T.; Rack, M.; Ramogida, G.; Rapson, C.; Rasmussen, J. Juul; Rasmussen, J.; Rattá, G. A.; Ratynskaia, S.; Ravera, G.; Réfy, D.; Reich, M.; Reimerdes, H.; Reimold, F.; Reinke, M.; Reiser, D.; Resnik, M.; Reux, C.; Ripamonti, D.; Rittich, D.; Riva, G.; Rodriguez-Ramos, M.; Rohde, V.; Rosato, J.; Ryter, F.; Saarelma, S.; Sabot, R.; Saint-Laurent, F.; Salewski, M.; Salmi, A.; Samaddar, D.; Sanchis-Sanchez, L.; Santos, J.; Sauter, O.; Scannell, R.; Scheffer, M.; Schneider, M.; Schneider, B.; Schneider, P.; Schneller, M.; Schrittwieser, R.; Schubert, M.; Schweinzer, J.; Seidl, J.; Sertoli, M.; Šesnić, S.; Shabbir, A.; Shalpegin, A.; Shanahan, B.; Sharapov, S.; Sheikh, U.; Sias, G.; Sieglin, B.; Silva, C.; Silva, A.; Silva Fuglister, M.; Simpson, J.; Snicker, A.; Sommariva, C.; Sozzi, C.; Spagnolo, S.; Spizzo, G.; Spolaore, M.; Stange, T.; Stejner Pedersen, M.; Stepanov, I.; Stober, J.; Strand, P.; Šušnjara, A.; Suttrop, W.; Szepesi, T.; Tál, B.; Tala, T.; Tamain, P.; Tardini, G.; Tardocchi, M.; Teplukhina, A.; Terranova, D.; Testa, D.; Theiler, C.; Thornton, A.; Tolias, P.; Tophøj, L.; Treutterer, W.; Trevisan, G. L.; Tripsky, M.; Tsironis, C.; Tsui, C.; Tudisco, O.; Uccello, A.; Urban, J.; Valisa, M.; Vallejos, P.; Valovic, M.; Van den Brand, H.; Vanovac, B.; Varoutis, S.; Vartanian, S.; Vega, J.; Verdoolaege, G.; Verhaegh, K.; Vermare, L.; Vianello, N.; Vicente, J.; Viezzer, E.; Vignitchouk, L.; Vijvers, W. A. J.; Villone, F.; Viola, B.; Vlahos, L.; Voitsekhovitch, I.; Vondráček, P.; Vu, N. M. T.; Wagner, D.; Walkden, N.; Wang, N.; Wauters, T.; Weiland, M.; Weinzettl, V.; Westerhof, E.; Wiesenberger, M.; Willensdorfer, M.; Wischmeier, M.; Wodniak, I.; Wolfrum, E.; Yadykin, D.; Zagórski, R.; Zammuto, I.; Zanca, P.; Zaplotnik, R.; Zestanakis, P.; Zhang, W.; Zoletnik, S.; Zuin, M.; ASDEX Upgrade, the; MAST; TCV Teams

    2017-10-01

    Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n  =  2 RMP maintaining good confinement {{H}\\text{H≤ft(98,\\text{y}2\\right)}}≈ 0.95 . Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes. In the future we will refer to the author list of the paper as the EUROfusion MST1 Team.

  15. Microbiological tap water profile of a medium-sized building and effect of water stagnation.

    PubMed

    Lipphaus, Patrick; Hammes, Frederik; Kötzsch, Stefan; Green, James; Gillespie, Simon; Nocker, Andreas

    2014-01-01

    Whereas microbiological quality of drinking water in water distribution systems is routinely monitored for reasons of legal compliance, microbial numbers in tap water are grossly understudied. Motivated by gross differences in water from private households, we applied in this study flow cytometry as a rapid analytical method to quantify microbial concentrations in water sampled at diverse taps in a medium size research building receiving chlorinated water. Taps differed considerably in frequency of usage and were located in laboratories, bathrooms, and a coffee kitchen. Substantial differences were observed between taps with concentrations (per mL) in the range from 6.29 x 10(3) to 7.74 x 10(5) for total cells and from 1.66 x 10(3) to 4.31 x 10(5) for intact cells. The percentage of intact cells varied between 7% and 96%. Water from taps with very infrequent use showed the highest bacterial numbers and the highest proportions of intact cells. Stagnation tended to increase microbial numbers in water from those taps which were otherwise frequently used. Microbial numbers in other taps that were rarely opened were not affected by stagnation as their water is probably mostly stagnant. For cold water taps, microbial numbers and the percentage of intact cells tended to decline with flushing with the greatest decline for taps used least frequently whereas microbial concentrations in water from hot water taps tended to be somewhat more stable. We conclude that microbiological water quality is mainly determined by building-specific parameters. Tap water profiling can provide valuable insight into plumbing system hygiene and maintenance.

  16. Morbidity of asylum seekers in a medium-sized German city.

    PubMed

    Führer, Amand; Eichner, Friederike; Stang, Andreas

    2016-07-01

    Asylum seekers constitute a particularly vulnerable group. Not only is their physical and mental health exposed to multiple stresses, but also their access to health care in Germany is legally restricted. Up to now, there is very limited scientific literature investigating the health-outcomes of asylum seekers in Germany. The aim of this study was to provide prevalence data on the morbidity and vaccination status of asylum seekers in a medium-sized German city. We used a structured questionnaire in a cross-sectional study on 214 adult asylum seekers (182 males, 24 females, 8 unknown) in Halle, Germany, 2015. The questionnaire inquired about the respondent's self-reported physical health and vaccination status and assessed their mental health using the Hopkins-Symptom-Checklist-25 and the Harvard Trauma Questionnaire. Pain (37.9 %) and psychological illness (depression: 54.7 %, anxiety disorder: 40.2 %; post-traumatic stress disorder: 18.2 %) were the most prevalent complaints. Among asylum seekers with psychological complaints, co-morbidity was high (64.2 % had more than one psychological disease). 5.6 % of the respondents mentioned suicidal thoughts. The prevalence of chronic diseases was low. We suggest interventions to improve asylum seekers' health on two levels: first, the obligatory initial medical examination after the refugees' arrival at the reception centre should be complemented with questions related to the vaccination status and the most common complaints including pain and psychological diseases. Second, medical infrastructure should be expanded to better serve the needs of culturally and linguistically diverse patient populations, so that those screened positive can be referred for early diagnosis and treatment.

  17. Clinical audit of multidisciplinary care at a medium-sized hospital in Spain

    PubMed Central

    2014-01-01

    Background Multidisciplinary care is a key enabler in the provision of high quality care for cancer patients. Despite compelling evidence supporting their benefit to patients and for providers, multidisciplinary cancer conferences (MCC) are not universally occurring. Team composition of MCC reflects the multidisciplinary nature of the body. Lack of nursing input can have a negative impact on team decision making. The objective of this study was to evaluate multidisciplinary care and adherence to national recommendations at a medium-sized hospital through a clinical audit of cancer conferences and clinical records. Methods A total of 77 multidisciplinary cancer conferences were visited and 496 electronic health records were reviewed. The regularity of meetings and multidisciplinary attendance were evaluated. Each electronic health record was checked to verify documented prospective discussion before any treatment was started. Results Nine multidisciplinary teams meet on a weekly or biweekly basis at the hospital with an average number of ten people and six different specialties represented. Average duration of meetings was 46.8 min. Though most patients (64.5%) were discussed at some point at the relevant cancer conference, only 40% had a documented multidisciplinary team discussion prior to the first treatment. Pathological stage (pTNM) was documented in 53.6% of clinical records. Conclusions Nursing representatives should be included as usual attendees at cancer conferences. Prospective discussion of all cancer cases should be encouraged. Use of checklists and systematic collection of key information, specifically cancer staging, could improve clinical documentation in the electronic clinical record. PMID:24597686

  18. [Problems of implementing integration management at company level in small and medium-sized enterprises].

    PubMed

    Hetzel, C; Flach, T; Weber, A; Schian, H-M

    2006-05-01

    At company level responsibility increases for the employment of workers with health-related problems or disabilities, but realisation in small and medium-sized enterprises (SME) is lacking. Therefore a model is developed based on theory and a survey. Minimum requirements for "betriebliches Eingliederungsmanagement" (integration management at company level) according to section 84 (2) SGB IX Book 9 of the German Social Code, the main products of the international movement "disability management", a description of roles for realisation and the main sources of employers' support are described. Although external supporting of SMEs is unquestioned, it is expensive and retards own initiative and own activity counting solely on this. Only by developing a minimum of SME's awareness, acceptance and competence, this will open up to (currently suboptimal) external support. Goal is identifying SME managers' attitudes, activities, proposals and expectations referring integration management at company level to derive concepts of SME's support. 13 interviews are analysed by qualitative content analysis identifying the following barriers: information deficit, absence of priority, limited possibilities for transitional work, cost, partially limited workers' self-responsibility, illness as a "tabes" subject. Possibilities overcoming these barriers are delineated. On that basis a model is presented: pragmatically for realisation, a company contact person with minimum competence, uniform external support, institutional partners' integration and quality assurance according to disability management. Interlocking SME world and social insurance world means first to support SME's awareness, acceptance and competence, second to create for SME a central contact in the "rehabilitation jungle" and third to develop SME-suitable premiums according to section 84 (3) SGB IX, Book 9 of the German social code.

  19. A structured strategy for assessing chemical risks, suitable for small and medium-sized enterprises.

    PubMed

    Balsat, A; de Graeve, J; Mairiaux, P

    2003-10-01

    A previous study carried out in 20 Belgian companies, especially small and medium-sized enterprises (SMEs), showed that prevention advisors did not use any structured approaches to assess chemical risk. They used their personal judgement and the information contained in manufacturers' Safety Data Sheets to assess the risk. The purpose of the Regetox network is to provide companies with a global approach for assessing chemical health risks. The structured approach proposed consists of two successive steps of increasing complexity. For the first step, we chose a method developed by the INRS (France), the 'ranking of potential risk', which allows the safety officer or staff member to identify hazards and to set priorities among all the supplied products used in the workplace. For the second step, we applied the COSHH method and EASE model established by the UK Health & Safety Executive for assessing 'chemical risk by reference to occupational exposure limits'. The INRS and COSHH Essentials methods were chosen because they define hazards using R-phrases of the European classification system and assess the exposure by using simple information that is easy to collect in the workplace and toxicological databases. A feasibility study conducted in two enterprises shows the usefulness of this approach. In addition to the intrinsic limitations of the methods, the approach showed some limitations related to the inaccuracy of the manufactured safety data sheets and to the collection of the basic information needed for ranking potential risks. The use of the Regetox approach needs training of prevention advisors and a strategy involving employers, staff members and workers in collecting basic information and managing chemical risks. Under these conditions, Regetox seems to be a useful tool for chemical risk assessment in SMEs.

  20. Provision and perception of occupational health in small and medium-sized enterprises in Sheffield, UK.

    PubMed

    Bradshaw, L M; Curran, A D; Eskin, F; Fishwick, D

    2001-02-01

    A random sample of managers of small and medium-sized enterprises (SMEs) was selected from a database of businesses in Sheffield, UK. They were invited to take part in a study to evaluate the provision and perception of occupational health in SMEs in Sheffield. The study used an interviewer-led questionnaire, which collected quantitative and qualitative data; each interview took approximately 40 min to complete. Several approaches to recruitment were adopted during the study. Twenty-eight managers were interviewed over the 6 month study period. All of the SMEs employed <250 people; 43.2% did not have or had never reviewed a written health and safety policy. Only 18% had a written occupational health policy; 14.4% employed the services of a part-time occupational health physician; 7.2% employed a health and safety advisor; and 10.8% employed a part-time occupational health nurse. Twenty-five per cent had a nominated person responsible for occupational health and 67% thought that a doctor or nurse would be the best person to provide an occupational health service. Twenty-eight per cent of the companies carried out some form of pre-employment screening and 14.2% carried out health promotion. Fifteen (53.5%) collected some form of health related absence data. Eight companies (28.6%) organized a formal induction programme for all new employees. Further work should be undertaken in an attempt to improve access to local industry and particularly to SMEs. This study has clearly shown that access is possible, but different strategies of approach were required before a workable strategy could be found. Undoubtedly, this access can be improved by better understanding of the interaction between researchers, occupational health providers and local managers of SMEs.

  1. Place and type of meals consumed by adults in medium sized cities

    PubMed Central

    Carús, Juliana Pires; França, Giovanny V A; Barros, Aluísio J D

    2014-01-01

    OBJECTIVE To describe the meals consumed by adults living in a midsize city in the South of Brazil, according to the place and preparation. METHODS A population-based cross-sectional study was conducted in Pelotas, Southern Brazil, in 2012. The two-stage sampling design used the 2010 census tracts as primary sampling units. Data were collected on the place of meals (at home or out) and on the kind of preparations consumed at home (homemade, snacks, take away food) covering the two days prior to the interview, using a standardized questionnaire. RESULTS The study included 2,927 adults, of which 59.0% were female, 60.0% were below 50 years of age and 58.0% were in work. Data were collected on 11,581 meals consumed on the two days preceding the interview, 25.0% were consumed outside of the home at lunchtime, and 10.0% at dinnertime. Considering home meals, most participants reported eating food prepared at home at both lunch and dinner. The majority of out-of-home meals (64.0% for lunch and 61.0% for dinner) were consumed in the work place, mostly based on food prepared at home. Individuals eating out of home were mostly male, young and highly educated. The occupational categories that ate at restaurants more often were trade workers, businessmen, teachers and graduate professionals. CONCLUSIONS Despite the changes in eating patterns described in Brazil in recent years, residents of medium-sized towns still mostly eat at home, consuming homemade food. PMID:24789639

  2. Are fragment-based quantum chemistry methods applicable to medium-sized water clusters?

    PubMed

    Yuan, Dandan; Shen, Xiaoling; Li, Wei; Li, Shuhua

    2016-06-28

    Fragment-based quantum chemistry methods are either based on the many-body expansion or the inclusion-exclusion principle. To compare the applicability of these two categories of methods, we have systematically evaluated the performance of the generalized energy based fragmentation (GEBF) method (J. Phys. Chem. A, 2007, 111, 2193) and the electrostatically embedded many-body (EE-MB) method (J. Chem. Theory Comput., 2007, 3, 46) for medium-sized water clusters (H2O)n (n = 10, 20, 30). Our calculations demonstrate that the GEBF method provides uniformly accurate ground-state energies for 10 low-energy isomers of three water clusters under study at a series of theory levels, while the EE-MB method (with one water molecule as a fragment and without using the cutoff distance) shows a poor convergence for (H2O)20 and (H2O)30 when the basis set contains diffuse functions. Our analysis shows that the neglect of the basis set superposition error for each subsystem has little effect on the accuracy of the GEBF method, but leads to much less accurate results for the EE-MB method. The accuracy of the EE-MB method can be dramatically improved by using an appropriate cutoff distance and using two water molecules as a fragment. For (H2O)30, the average deviation of the EE-MB method truncated up to the three-body level calculated using this strategy (relative to the conventional energies) is about 0.003 hartree at the M06-2X/6-311++G** level, while the deviation of the GEBF method with a similar computational cost is less than 0.001 hartree. The GEBF method is demonstrated to be applicable for electronic structure calculations of water clusters at any basis set.

  3. The Impact of the Public Library on Business Success: An Analysis Based on Medium-Sized Businesses in Ontario.

    ERIC Educational Resources Information Center

    Vaughan, Liwen Qiu

    1997-01-01

    Describes a survey of Ontario (Canada) medium-sized businesses that was conducted to investigate the impact of the public library on business success and discusses results that found a significant relationship between public library use and business success. A copy of the questionnaire used is appended. (Author/LRW)

  4. 40 CFR 141.81 - Applicability of corrosion control treatment steps to small, medium-size and large water systems.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... treatment steps to small, medium-size and large water systems. 141.81 Section 141.81 Protection of... WATER REGULATIONS Control of Lead and Copper § 141.81 Applicability of corrosion control treatment steps... review and approve the addition of a new source or long-term change in water treatment before it...

  5. 40 CFR 141.81 - Applicability of corrosion control treatment steps to small, medium-size and large water systems.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... treatment steps to small, medium-size and large water systems. 141.81 Section 141.81 Protection of... WATER REGULATIONS Control of Lead and Copper § 141.81 Applicability of corrosion control treatment steps... review and approve the addition of a new source or long-term change in water treatment before it...

  6. 40 CFR 141.81 - Applicability of corrosion control treatment steps to small, medium-size and large water systems.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... treatment steps to small, medium-size and large water systems. 141.81 Section 141.81 Protection of... WATER REGULATIONS Control of Lead and Copper § 141.81 Applicability of corrosion control treatment steps... review and approve the addition of a new source or long-term change in water treatment before it...

  7. 78 FR 22801 - Request for Comments on Developing a Program To Provide Loan Guarantees to Small- or Medium-Sized...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... structure loan guarantees for small- and medium-sized manufacturers through its authority under the... manufacture of innovative products, processes, or ideas developed by research funded in whole or in part by... listed below, on ways to structure this program, in order to assess the level of demand for such a...

  8. 40 CFR 141.81 - Applicability of corrosion control treatment steps to small, medium-size and large water systems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Applicability of corrosion control... WATER REGULATIONS Control of Lead and Copper § 141.81 Applicability of corrosion control treatment steps to small, medium-size and large water systems. (a) Systems shall complete the applicable...

  9. 40 CFR 141.81 - Applicability of corrosion control treatment steps to small, medium-size and large water systems.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Applicability of corrosion control... WATER REGULATIONS Control of Lead and Copper § 141.81 Applicability of corrosion control treatment steps to small, medium-size and large water systems. (a) Systems shall complete the applicable...

  10. A Bayesian Approach to International Distributor Selection for Small and Medium-Sized Enterprises in the Software Industry

    ERIC Educational Resources Information Center

    Lui, Joseph P.

    2013-01-01

    Identifying appropriate international distributors for small and medium-sized enterprises (SMEs) in the software industry for overseas markets can determine a firm's future endeavors in international expansion. SMEs lack the complex skills in market research and decision analysis to identify suitable partners to engage in global market entry.…

  11. Using the Critical Incident Technique to Research Decision Making regarding Access to Training and Development in Medium-Sized Enterprises

    ERIC Educational Resources Information Center

    Coetzer, Alan; Redmond, Janice; Sharafizad, Jalleh

    2012-01-01

    Employees in small and medium-sized enterprises (SMEs) form part of a "disadvantaged" group within the workforce that receives less access to training and development (T&D) than employees in large firms. Prior research into reasons for the relatively low levels of employee participation in training and development has typically…

  12. Using the Critical Incident Technique to Research Decision Making regarding Access to Training and Development in Medium-Sized Enterprises

    ERIC Educational Resources Information Center

    Coetzer, Alan; Redmond, Janice; Sharafizad, Jalleh

    2012-01-01

    Employees in small and medium-sized enterprises (SMEs) form part of a "disadvantaged" group within the workforce that receives less access to training and development (T&D) than employees in large firms. Prior research into reasons for the relatively low levels of employee participation in training and development has typically…

  13. A Bayesian Approach to International Distributor Selection for Small and Medium-Sized Enterprises in the Software Industry

    ERIC Educational Resources Information Center

    Lui, Joseph P.

    2013-01-01

    Identifying appropriate international distributors for small and medium-sized enterprises (SMEs) in the software industry for overseas markets can determine a firm's future endeavors in international expansion. SMEs lack the complex skills in market research and decision analysis to identify suitable partners to engage in global market entry.…

  14. Revenue-Based Financial Modeling: A Sustainable Model for Medium-Size, Private, Mission-Based Schools of Education

    ERIC Educational Resources Information Center

    Harbouk, Joseph

    2011-01-01

    This study examined the implementation and assessment of revenue-based budgeting at a medium-size, private, mission-based graduate school of education (SOE), under the pseudonym Peter Claver University (PCU). Additionally, two other similar schools were included in the study because they used revenue-based budgeting for a period of 10 years or…

  15. The Anonymity of Catalan and the Authenticity of Estonian: Two Paths for the Development of Medium-Sized Languages

    ERIC Educational Resources Information Center

    Soler, Josep

    2013-01-01

    Catalan and Estonian can be considered "medium-sized" languages with some key common features that allow us to analyze the evolution of the two cases comparatively. Firstly, other formerly hegemonic languages (Spanish and Russian, respectively) have historically minoritized them. Secondly, the political equilibrium has now changed in…

  16. Virtual Class: Distance Learning for Small and Medium Sized Enterprises in the Spanish Region of Castilla y Leon.

    ERIC Educational Resources Information Center

    Rodriguez, Blanca; Perez, Maria Angeles; Verdu, Maria Jesus; Navazo, Maria Agustina; Lopez, Ricardo; Mompo, Rafael; Garcia, Joaquin

    Lifelong learning is becoming a necessity in the new Information Society where everyone, particularly small and medium sized enterprises (SMEs), must keep up with new technologies. Education and training are of the most importance in this updating. An interdisciplinary and inter-university work group called "Canalejas" (Spain) has…

  17. Graduate Transition into Work: The Bridging Role of Graduate Placement Programmes in the Small- and Medium-Sized Enterprise Workplace

    ERIC Educational Resources Information Center

    Gallagher, Pádraig

    2015-01-01

    This research looks at the role of graduate placement programmes in bridging the gap between higher education and the small- and medium-sized enterprise (SME) sector. The research design and methodology used in this study was exploratory, in-depth and qualitative in nature. The research took the form of a multiple case study and focused on seven…

  18. Entrepreneurial Training for the Growth of Small and Medium-Sized Enterprises: Lessons from Central and Eastern Europe. Report.

    ERIC Educational Resources Information Center

    European Training Foundation, Turin (Italy).

    This report brings together a number of principles as to best practice in supporting, through training, growth of small and medium-sized enterprises (SMEs) in Central and Eastern Europe. Chapter 2 identifies key principles to be drawn from the West through a literature review. Chapter 3 reviews the "practice" of entrepreneurial training…

  19. Is Small Finally Becoming Beautiful? Small and Medium-Size Enterprises in the New Economy. IES Report.

    ERIC Educational Resources Information Center

    Dejonckheere, J.; Ramioul, M.; Van Hootegem, G.

    This report addresses small and medium-sized enterprises' (SMEs') role in the changing international division of labor and trade in information service activities. Chapter 2 describes the EMERGENCE project to map and measure eWork. Chapter 3 reviews literature that shows SMEs account for the overwhelming majority of companies and make a crucial…

  20. Using Computer-Based Continuing Professional Education of Training Staff to Develop Small- and Medium-Sized Enterprises in Thailand

    ERIC Educational Resources Information Center

    Sooraksa, Nanta

    2012-01-01

    This paper describes a career development program for staff involved in providing training for small- and medium-sized enterprises (SMEs) in Thailand. Most of these staff were professional vocational teachers in schools. The program uses information communication technology (ICT), and its main objective is to teach Moodle software as a tool for…

  1. Attitudes about OCLC in Small and Medium-Sized Libraries. Illinois Valley Library System OCLC Experimental Project. Report No. 4.

    ERIC Educational Resources Information Center

    Bills, Linda G.; Wilford, Valerie

    A project was conducted from 1980 to 1982 to determine the costs and benefits of OCLC use in 29 small and medium-sized member libraries of the Illinois Valley Library System (IVLS). Academic, school, public, and special libraries participated in the project. Based on written attitude surveys of and interviews with library directors, staff,…

  2. Workplace Education Programs in Small and Medium-Sized Michigan Firms. Staff Working Paper 92-13.

    ERIC Educational Resources Information Center

    Hollenbeck, Kevin; Anderson, William

    A project collected data from small and medium-sized firms (employing fewer than 500) in Michigan concerning workplace education programs. It addressed why firms were or were not offering programs, program characteristics, and program impacts on firms and employees. Case studies of 28 businesses were undertaken from May 1991-July 1992 and a…

  3. Organoselenium and DMAP co-catalysis: regioselective synthesis of medium-sized halolactones and bromooxepanes from unactivated alkenes.

    PubMed

    Verma, Ajay; Jana, Sadhan; Prasad, Ch Durga; Yadav, Abhimanyu; Kumar, Sangit

    2016-03-18

    A catalytic system consisting of bis(4-methoxyphenyl)selenide and 4-(dimethylamino)pyridine (DMAP) has been developed for the regioselective synthesis of medium-sized bromo/iodo lactones and bromooxepanes possessing high transannular strain. (77)Se NMR, mass spectrometry and theoretical studies reveal that the reaction proceeds via a quaternary selenium intermediate.

  4. Workplace Education Programs in Small and Medium-Sized Michigan Firms. Staff Working Paper 92-13.

    ERIC Educational Resources Information Center

    Hollenbeck, Kevin; Anderson, William

    A project collected data from small and medium-sized firms (employing fewer than 500) in Michigan concerning workplace education programs. It addressed why firms were or were not offering programs, program characteristics, and program impacts on firms and employees. Case studies of 28 businesses were undertaken from May 1991-July 1992 and a…

  5. Graduate Transition into Work: The Bridging Role of Graduate Placement Programmes in the Small- and Medium-Sized Enterprise Workplace

    ERIC Educational Resources Information Center

    Gallagher, Pádraig

    2015-01-01

    This research looks at the role of graduate placement programmes in bridging the gap between higher education and the small- and medium-sized enterprise (SME) sector. The research design and methodology used in this study was exploratory, in-depth and qualitative in nature. The research took the form of a multiple case study and focused on seven…

  6. Signaling in striatal neurons: the phosphoproteins of reward, addiction, and dyskinesia.

    PubMed

    Girault, Jean-Antoine

    2012-01-01

    The striatum is a deep region of the forebrain involved in action selection, control of movement, and motivation. It receives a convergent excitatory glutamate input from the cerebral cortex and the thalamus, controlled by dopamine (DA) released in response to unexpected rewards and other salient stimuli. Striatal function and its dysfunction in drug addiction or Parkinson's disease depend on the interplay between these neurotransmitters. Signaling cascades in striatal medium-sized spiny neurons (MSNs) involve multiple kinases, phosphatases, and phosphoproteins, some of which are highly enriched in these neurons. They control the properties of ion channels and the plasticity of MSNs, in part through their effects on gene transcription. This chapter summarizes signaling in MSNs and focuses on the regulation of multiple protein phosphatases through DA and glutamate receptors and the role of ERK. It is hypothesized that these pathways are particularly adapted to the specific computing properties of MSNs and the function of the basal ganglia circuits in which they participate. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Think locally, act locally: Detection of small, medium-sized, and large communities in large networks

    NASA Astrophysics Data System (ADS)

    Jeub, Lucas G. S.; Balachandran, Prakash; Porter, Mason A.; Mucha, Peter J.; Mahoney, Michael W.

    2015-01-01

    It is common in the study of networks to investigate intermediate-sized (or "meso-scale") features to try to gain an understanding of network structure and function. For example, numerous algorithms have been developed to try to identify "communities," which are typically construed as sets of nodes with denser connections internally than with the remainder of a network. In this paper, we adopt a complementary perspective that communities are associated with bottlenecks of locally biased dynamical processes that begin at seed sets of nodes, and we employ several different community-identification procedures (using diffusion-based and geodesic-based dynamics) to investigate community quality as a function of community size. Using several empirical and synthetic networks, we identify several distinct scenarios for "size-resolved community structure" that can arise in real (and realistic) networks: (1) the best small groups of nodes can be better than the best large groups (for a given formulation of the idea of a good community); (2) the best small groups can have a quality that is comparable to the best medium-sized and large groups; and (3) the best small groups of nodes can be worse than the best large groups. As we discuss in detail, which of these three cases holds for a given network can make an enormous difference when investigating and making claims about network community structure, and it is important to take this into account to obtain reliable downstream conclusions. Depending on which scenario holds, one may or may not be able to successfully identify "good" communities in a given network (and good communities might not even exist for a given community quality measure), the manner in which different small communities fit together to form meso-scale network structures can be very different, and processes such as viral propagation and information diffusion can exhibit very different dynamics. In addition, our results suggest that, for many large realistic

  8. Karyotypes of some medium-sized Dytiscidae (Agabinae and Colymbetinae) (Coleoptera)

    PubMed Central

    Angus, Robert B.; Clery, Molly J.; Carter, Jodie C.; Wenczek, Daniel E.

    2013-01-01

    Abstract An account is given of the karyotypes of 29 species of medium sized Dytiscidae (Coleoptera). Of the 20 species of Agabus Leach, 1817, 18 have karyotypes comprising 21 pairs of autosomes and sex chromosomes which are either X0(♂) or XX (♀). These species are Agabus serricornis (Paykull, 1799), Agabus labiatus (Brahm, 1791), Agabus congener (Thunberg, 1794), Agabus lapponicus (Thomson, 1867), Agabus thomsoni (J. Sahlberg, 1871), Agabus confinis (Gyllenhal, 1808), Agabus sturmii (Gyllenhal, 1808), Agabus bipustulatus (Linnaeus, 1767), Agabus nevadensis Håkan Lindberg, 1939, Agabus wollastoni Sharp, 1882, Agabus melanarius Aubé, 1837, Agabus biguttatus (Olivier, 1795), Agabus binotatus Aubé, 1837, Agabus affinis (Paykull, 1798), Agabus unguicularis (Thomson, 1867), Agabus ramblae Millan & Ribera, 2001, Agabus conspersus (Marsham, 1802) and Agabus nebulosus (Forster, 1771). However two species, Agabus infuscatus Aubé, 1838 and Agabus adpressus Aubé, 1837, have developed a neo-XY system, with karyotypes comprising 21 pairs of autosomes and XY sex chromosomes (♂). No chromosomal differences have been detected between typical Agabus bipustulatus and Agabus bipustulatus var. solieri Aubé, 1837, nor have any been found between the three species of the Agabus bipustulatus complex (Agabus bipustulatus, Agabus nevadensis and Agabus wollastoni). The four species of Colymbetes Clairville, 1806, Colymbetes fuscus (Linnaeus, 1758), Colymbetes paykulli Erichson, 1837, Colymbetes piceus Klug, 1834 and Colymbetes striatus (Linnaeus, 1758) have karyotypes comprising 20 pairs of autosomes and sex chromosomes which are X0 (♂), XX (♀). Two of the species of Rhantus Dejean, 1833, Rhantus exsoletus (Forster, 1771) and Rhantus suturellus (Harris, 1828) have karyotypes comprising 20 pairs of autosomes and X0/XX sex chromosomes, but the other three species, Rhantus grapii (Gyllenhal, 1808), Rhantus frontalis (Marsham, 1802) and Rhantus suturalis (Macleay, 1825) have 22

  9. Arthroscopic repair of small and medium-sized bony Bankart lesions.

    PubMed

    Kim, Young-Kyu; Cho, Seung-Hyun; Son, Won-Su; Moon, Sung-Hoon

    2014-01-01

    postoperative Rowe scores increased from 60 to 95 in cases of anatomic reduction compared with an increase from 56 to 76 in cases of nonanatomic reduction. The Rowe score was statistically correlated with anatomic reduction of medium-sized bony fragments (P = .046). In small Bankart lesions, restoration of capsulolabral soft tissue tension alone may be enough, whereas in medium lesions, the osseous architecture of the glenoid should be reconstructed for more functional improvement and less pain.

  10. Development and Evaluation of Algorithms to Improve Small- and Medium-Size Commercial Building Operations

    SciTech Connect

    Kim, Woohyun; Katipamula, Srinivas; Lutes, Robert G.; Underhill, Ronald M.

    2016-10-31

    Small- and medium-sized (<100,000 sf) commercial buildings (SMBs) represent over 95% of the U.S. commercial building stock and consume over 60% of total site energy consumption. Many of these buildings use rudimentary controls that are mostly manual, with limited scheduling capability, no monitoring or failure management. Therefore, many of these buildings are operated inefficiently and consume excess energy. SMBs typically utilize packaged rooftop units (RTUs) that are controlled by an individual thermostat. There is increased urgency to improve the operating efficiency of existing commercial building stock in the U.S. for many reasons, chief among them is to mitigate the climate change impacts. Studies have shown that managing set points and schedules of the RTUs will result in up to 20% energy and cost savings. Another problem associated with RTUs is short-cycling, where an RTU goes through ON and OFF cycles too frequently. Excessive cycling can lead to excessive wear and lead to premature failure of the compressor or its components. The short cycling can result in a significantly decreased average efficiency (up to 10%), even if there are no physical failures in the equipment. Also, SMBs use a time-of-day scheduling is to start the RTUs before the building will be occupied and shut it off when unoccupied. Ensuring correct use of the zone set points and eliminating frequent cycling of RTUs thereby leading to persistent building operations can significantly increase the operational efficiency of the SMBs. A growing trend is to use low-cost control infrastructure that can enable scalable and cost-effective intelligent building operations. The work reported in this report describes three algorithms for detecting the zone set point temperature, RTU cycling rate and occupancy schedule detection that can be deployed on the low-cost infrastructure. These algorithms only require the zone temperature data for detection. The algorithms have been tested and validated using

  11. Karyotypes of some medium-sized Dytiscidae (Agabinae and Colymbetinae) (Coleoptera).

    PubMed

    Angus, Robert B; Clery, Molly J; Carter, Jodie C; Wenczek, Daniel E

    2013-01-01

    An account is given of the karyotypes of 29 species of medium sized Dytiscidae (Coleoptera). Of the 20 species of Agabus Leach, 1817, 18 have karyotypes comprising 21 pairs of autosomes and sex chromosomes which are either X0(♂) or XX (♀). These species are Agabus serricornis (Paykull, 1799), Agabus labiatus (Brahm, 1791), Agabus congener (Thunberg, 1794), Agabus lapponicus (Thomson, 1867), Agabus thomsoni (J. Sahlberg, 1871), Agabus confinis (Gyllenhal, 1808), Agabus sturmii (Gyllenhal, 1808), Agabus bipustulatus (Linnaeus, 1767), Agabus nevadensis Håkan Lindberg, 1939, Agabus wollastoni Sharp, 1882, Agabus melanarius Aubé, 1837, Agabus biguttatus (Olivier, 1795), Agabus binotatus Aubé, 1837, Agabus affinis (Paykull, 1798), Agabus unguicularis (Thomson, 1867), Agabus ramblae Millan & Ribera, 2001, Agabus conspersus (Marsham, 1802) and Agabus nebulosus (Forster, 1771). However two species, Agabus infuscatus Aubé, 1838 and Agabus adpressus Aubé, 1837, have developed a neo-XY system, with karyotypes comprising 21 pairs of autosomes and XY sex chromosomes (♂). No chromosomal differences have been detected between typical Agabus bipustulatus and Agabus bipustulatus var. solieri Aubé, 1837, nor have any been found between the three species of the Agabus bipustulatus complex (Agabus bipustulatus, Agabus nevadensis and Agabus wollastoni). The four species of Colymbetes Clairville, 1806, Colymbetes fuscus (Linnaeus, 1758), Colymbetes paykulli Erichson, 1837, Colymbetes piceus Klug, 1834 and Colymbetes striatus (Linnaeus, 1758) have karyotypes comprising 20 pairs of autosomes and sex chromosomes which are X0 (♂), XX (♀). Two of the species of Rhantus Dejean, 1833, Rhantus exsoletus (Forster, 1771) and Rhantus suturellus (Harris, 1828) have karyotypes comprising 20 pairs of autosomes and X0/XX sex chromosomes, but the other three species, Rhantus grapii (Gyllenhal, 1808), Rhantus frontalis (Marsham, 1802) and Rhantus suturalis (Macleay, 1825) have 22 pairs of

  12. The Small- and Medium-sized Enterprises Office (SME Office) at the European Medicines Agency.

    PubMed

    Carr, M

    2010-01-01

    On 15 December 2005, the European Medicines Agency (EMEA) launched an "SME Office" to provide financial and administrative assistance to micro-, small- and medium-sized enterprises (SMEs), with the aim of promoting innovation and the development of new human and veterinary medicinal products by SMEs. According to current EU definition of an SME, companies with fewer than 250 employees, and an annual turnover of not more than 50 million euro or an annual balance sheet total of not more than 43 million euro, are eligible for assistance from the SME Office. Incentives available from the EMEA for SMEs, include: Administrative and procedural assistance from SME Office within the Agency; Fee reductions (90%) for scientific advice and inspections; Fee exemptions for certain administrative services (excluding parallel distribution); Deferral of the fee payable for an application for marketing authorisation or related inspection until after the grant of the marketing authorisation; Conditional fee exemption where scientific advice followed and marketing application is unsuccessful; Assistance with translations of the product information documents. At the end of May 2009, more than 380 companies from 21 countries across the European Economic Area (EEA) had SME status assigned by the EMEA. The large majority of companies are developing medicinal products for human use, 16 are veterinary companies, 15 companies are developing products for both human and veterinary use and 38 are regulatory consultants. Since the SME initiative started the Agency has processed more than 130 requests for scientific advice with fee reductions totalling of 6.9 million euro. Regulatory assistance has been provided to more than 170 companies and 12 companies have benefited from the SME translation service. Stakeholders have acknowledged the significant role the SME Office now plays as a service provider. In the period between January 2006 and June 2009, 34 applications for marketing authorization

  13. Grayia spinosa (Hook.) Moq.: spiny hopsage

    Treesearch

    Nancy L. Shaw; Marshall R. Haferkamp; Emerenciana G. Hurd

    2008-01-01

    The genus Grayia Hook. & Arn., named for the American botanist Asa Gray, contains a single species - spiny hopsage (table 1). Plants are erect to rounded, summer-deciduous shrubs 0.3 to 1.2 (1.5) m tall. Branches are divergent and thorn-tipped, with whitish gray to brownish bark that exfoliates in long strips. Leaves are gray-green, alternate, entire, and fleshy,...

  14. Job Stress in the United Kingdom: Are Small and Medium-Sized Enterprises and Large Enterprises Different?

    PubMed

    Lai, Yanqing; Saridakis, George; Blackburn, Robert

    2015-08-01

    This paper examines the relationships between firm size and employees' experience of work stress. We used a matched employer-employee dataset (Workplace Employment Relations Survey 2011) that comprises of 7182 employees from 1210 private organizations in the United Kingdom. Initially, we find that employees in small and medium-sized enterprises experience lower level of overall job stress than those in large enterprises, although the effect disappears when we control for individual and organizational characteristics in the model. We also find that quantitative work overload, job insecurity and poor promotion opportunities, good work relationships and poor communication are strongly associated with job stress in the small and medium-sized enterprises, whereas qualitative work overload, poor job autonomy and employee engagements are more related with larger enterprises. Hence, our estimates show that the association and magnitude of estimated effects differ significantly by enterprise size.

  15. [Uncertainty in estimating short-term health effects of air pollution in small- and medium-size cities].

    PubMed

    Giannini, Simone; Zauli Sajani, Stefano; De Girolamo, Gianfranco; Goldoni, Carlo Alberto; Lauriola, Paolo

    2016-01-01

    Over the years, a growing number of small- and medium-size cities have been included in meta-analytic studies on short-term health effects of air pollution in order to increase the statistical power of these studies. This has produced an increase in the precision of meta-analytic estimates, but also a growing interest in city-specific results. As a consequence, relevant differences in the estimates have been frequently found, even for nearby cities with similar environmental and sociodemographic characteristics. This article aims at showing the variability of effect estimates for small- to medium-size cities in relation to the extent of the considered time frame, highlighting quantitatively the caution that must be taken in interpreting and communicating the results derived from short time series of data. The study was based on the analysis of the data from two cities in Emilia-Romagna Region (Northern Italy): Ravenna and Reggio Emilia.

  16. The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth.

    PubMed

    Dickinson, Hayley; Walker, David W; Cullen-McEwen, Luise; Wintour, E Marelyn; Moritz, Karen

    2005-08-01

    The spiny mouse is relatively mature at birth. We hypothesized that like other organs, the kidney may be more developed in the spiny mouse at birth, than in other rodents. If nephrogenesis is complete before birth, the spiny mouse may provide an excellent model with which to study the effects of an altered intrauterine environment on renal development. Due to its desert adaptation, the spiny mouse may have a reduced cortex-to-medulla ratio but an equivalent total nephron number to the C57/BL mouse. Kidneys were collected from fetal and neonatal spiny mice and sectioned for gross examination of metanephric development. Kidneys were collected from adult spiny mice (10 wk of age), and glomerular number, volume, and cortex-to-medulla ratios were determined using unbiased stereology. Nephrogenesis is complete in spiny mouse kidneys before birth. Metanephrogenesis begins at approximately day 18, and by day 38 of a 40-day gestation, the nephrogenic zone is no longer present. Spiny mice have a significantly (P < 0.001) lower total nephron number compared with C57/BL mice, although the total glomerular volume is similar. The cortex-to-medulla ratio of the spiny mouse is significantly (P < 0.01) smaller. The spiny mouse is the first rodent species shown to complete nephrogenesis before birth. This makes it an attractive candidate for the study of fetal and neonatal kidney development and function. The reduced total nephron number and cortex-to-medulla ratio in the spiny mouse may contribute to its ability to highly concentrate its urine under stressful conditions (i.e., dehydration).

  17. Environmental education for small- and medium-sized enterprises: methodology and e-learning experience in the Valencian region.

    PubMed

    Cloquell-Ballester, Vicente-Agustín; Monterde-Díaz, Rafael; Cloquell-Ballester, Víctor-Andrés; Torres-Sibille, Ana Del Carmen

    2008-05-01

    The last decades have shown an increasing social demand for environmental awareness, which firms are inevitably required to adapt to. More and more, small- and medium-sized enterprises (SMEs) are finding it necessary to train their staff in environmental issues if they wish to survive in a market where it is no longer sufficient to excel in price competitiveness exclusively, but where quality, service and environmental standards also play an important role.

  18. VOLTTRON™: Tech-to-Market Best-Practices Guide for Small- and Medium-Sized Commercial Buildings

    SciTech Connect

    Cort, Katherine A.; Haack, Jereme N.; Katipamula, Srinivas; Nicholls, Andrew K.

    2016-07-11

    VOLTTRON™ is an open-source distributed control and sensing platform developed by Pacific Northwest National Laboratory for the U.S. Department of Energy. It was developed to be used by the Office of Energy Efficiency and Renewable Energy to support transactive controls research and deployment activities. VOLTTRON is designed to be an overarching integration platform that could be used to bring together vendors, users, and developers and enable rapid application development and testing. The platform is designed to support modern control strategies, including the use of agent- and transaction-based controls. It also is designed to support the management of a wide range of applications, including heating, ventilation, and air-conditioning systems; electric vehicles; and distributed-energy and whole-building loads. This report was completed as part of the Building Technologies Office’s Technology-to-Market Initiative for VOLTTRON’s Market Validation and Business Case Development efforts. The report provides technology-to-market guidance and best practices related to VOLTTRON platform deployments and commercialization activities for use by entities serving small- and medium-sized commercial buildings. The report characterizes the platform ecosystem within the small- and medium-sized commercial building market and articulates the value proposition of VOLTTRON for three core participants in this ecosystem: 1) platform owners/adopters, 2) app developers, and 3) end-users. The report also identifies key market drivers and opportunities for open platform deployments in the small- and medium-sized commercial building market. Possible pathways to the market are described—laboratory testing to market adoption to commercialization. We also identify and address various technical and market barriers that could hinder deployment of VOLTTRON. Finally, we provide “best practice” tech-to-market guidance for building energy-related deployment efforts serving small- and

  19. Added value of online satellite data transmission for flood forecasting: warning systems in medium-size catchments.

    PubMed

    Ruch, C; Stadler, H

    2009-01-01

    The present paper deals with the implementation of online data transferred via LEO satellite communication in a flood forecasting system. Although the project is ongoing, it is already recognised that the information chain: "measurement-transmission-forecast-alert" can be shortened, i.e., the flood danger can be more rapidly communicated to the population at risk. This gain is particularly valuable for medium size catchments where the concentration time (basin time of response to rainfall) is short.

  20. Energy conserved and costs saved by small and medium-size manufacturers. 1983-84 EADC Program period

    SciTech Connect

    Kirsch, F.W.; Perrotti, G.M.

    1986-02-01

    Almost 300 small and medium-size manufacturers were able to benefit during 1983-84 from the services provided in their plants by 12 Energy Analysis and diagnostic Centers (EADCs) managed by University City Science Center under an agreement with the US Department of Energy, Office of Industrial Programs. This report describes and analyzes what the EADCs recommended, reviews and assesses what the manufacturers implemented, and evaluates how cost-effective the manufacturers found the EADCs' recommendations to be.

  1. Assessment of metal exposure, ecological status and required water quality monitoring strategies in small- to medium-size temperate rivers.

    PubMed

    Marijić, Vlatka Filipović; Perić, Mirela Sertić; Kepčija, Renata Matoničkin; Dragun, Zrinka; Kovarik, Ivana; Gulin, Vesna; Erk, Marijana

    2016-01-01

    The present study was undertaken to obtain a better understanding of the seasonal variability of total dissolved metal/metalloid levels and physicochemical parameters within small- to medium-size freshwater ecosystems in temperate climate region. The research was conducted in four seasons in the Sutla River, medium-size polluted, and the Črnomerec Stream, small-size unpolluted watercourse in Croatia. In the Sutla River, characterized by the rural/industrial catchment, physicochemical parameters and total dissolved metal concentrations of 21 trace and 4 macro elements were analysed downstream of the point source of pollution, the glass production facility, indicating for the first time their variability across four seasons. Based on dissolved oxygen, total dissolved solids, nutrient concentrations, conductivity and total chemical oxygen demand, quality status of the Sutla River was good, but moderate to poor during summer, what was additionally confirmed by the highest levels of the most of 25 measured metals/metalloids in summer. Comparison with the reference small-size watercourse, the Črnomerec Stream, indicated significant anthropogenic impact on the Sutla River, most evident for Fe, Mn, Mo, Ni, Pb, Rb and Tl levels (3-70-fold higher in the Sutla River across all seasons). Generally, presented results indicated significant decrease of the water quality in the anthropogenically impacted small- to medium-size watercourses in summer, regarding physicochemical water parameters and total dissolved metal/metalloid concentrations, and pointed to significant seasonality of these parameters. Confirmed seasonality of river ecological status indicates that seasonal assessment represents a prerequisite for proper classification of the water quality in small- to medium-size temperate rivers.

  2. Neurolymphomatosis in Primary Cutaneous CD4+ Pleomorphic Small/Medium-sized T-cell Lymphoma Mimicking Hansen's Disease.

    PubMed

    Khader, Anza; Vineetha, Mary; George, Mamatha; Manakkad, Shiny Padinjarayil; Balakrishnan, Sunitha; Rajan, Uma

    2017-01-01

    Neurolymphomatosis (NL) refers to nerve infiltration by neurotropic neoplastic cells in the setting of a known or an unknown hematological malignancy. It typically presents as painful or painless peripheral mononeuropathy, mononeuritis multiplex, polyneuropathy, polyradiculopathy, or cranial neuropathy. A 32-year-old male presented with a hyperpigmented hypoesthetic plaque over the anterolateral aspect of the right leg with thickening of the right common peroneal nerve and foot drop clinically diagnosed as Hansen's disease. Biopsy taken from skin showed infiltrates of pleomorphic small and medium sized lymphocytes in the dermis and subcutis. On immunohistochemistry, the cells were positive for CD3, CD4 and negative for CD8, CD20, and CD30. Ultrasonography-guided fine-needle aspiration of the thickened nerve showed infiltrates of atypical lymphoid cells. Based on these findings, a diagnosis of NL in primary cutaneous CD4+ pleomorphic small/medium-sized T-cell lymphoma was made. The disease responded to systemic chemotherapy and localized radiotherapy with no evidence of relapse during 3 years follow-up. NL in primary cutaneous CD4+ pleomorphic small/medium-sized T-cell lymphoma presenting with manifestations redolent of Hansen's disease is not described in available literature. This case also demonstrates the utility of fine needle aspiration of nerve, a minimally invasive procedure in the diagnosis of NL.

  3. Differential foraging preferences on seed size by rodents result in higher dispersal success of medium-sized seeds.

    PubMed

    Cao, Lin; Wang, Zhenyu; Yan, Chuan; Chen, Jin; Guo, Cong; Zhang, Zhibin

    2016-11-01

    Rodent preference for scatter-hoarding large seeds has been widely considered to favor the evolution of large seeds. Previous studies supporting this conclusion were primarily based on observations at earlier stages of seed dispersal, or on a limited sample of successfully established seedlings. Because seed dispersal comprises multiple dispersal stages, we hypothesized that differential foraging preference on seed size by animal dispersers at different dispersal stages would ultimately result in medium-sized seeds having the highest dispersal success rates. In this study, by tracking a large number of seeds for 5 yr, we investigated the effects of seed size on seed fates from seed removal to seedling establishment of a dominant plant Pittosporopsis kerrii (Icacinaceae) dispersed by scatter-hoarding rodents in tropical forest in southwest China. We found that small seeds had a lower survival rate at the early dispersal stage where more small seeds were predated at seed stations and after removal; large seeds had a lower survival rate at the late dispersal stage, more large seeds were recovered, predated after being cached, or larder-hoarded. Medium-sized seeds experienced the highest dispersal success. Our study suggests that differential foraging preferences by scatter-hoarding rodents at different stages of seed dispersal could result in conflicting selective pressures on seed size and higher dispersal success of medium-sized seeds. © 2016 by the Ecological Society of America.

  4. Comparison of endoscopic transcanal myringoplasty and endoscopic type I tympanoplasty in repairing medium-sized tympanic perforations.

    PubMed

    Tseng, Chih-Chieh; Lai, Ming-Tang; Wu, Chia-Che; Yuan, Sheng-Po; Ding, Yi-Fang

    2017-12-01

    The tympanomeatal flap elevation technique has been used in tympanoplasty for decades; however, this procedure has disadvantages. In recent years, endoscopic transcanal myringoplasty (ETM) has been increasingly practiced and has yielded positive results.This study compares the efficacy of ETM and endoscopic type I tympanoplasty (ETT) in repairing medium-sized perforations of the tympanic membrane. This retrospective medical record review included patients undergoing surgery for medium-sized perforations of the tympanic membrane from January 1, 2013 to August 1, 2015. We divided our patients into 2 groups: the ETM group and ETT group. The main outcome measure was comparison of the graft take rates and hearing results between ETM and ETT. A total of 113 patients were enrolled in this study; of these patients, 64 underwent ETM and 49 received ETT. The overall graft take rates and improvement of air-bone gaps were comparable between the groups. However, the patients in the ETM group had shorter operative times and fewer follow-up visits over 3 months than those in the ETT group did. We recommend that ETM (instead of ETT) be used for repairing medium-sized perforations of the tympanic membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Distinguishing between the bone fragments of medium-sized mammals and children. A histological identification method for archaeology.

    PubMed

    Cuijpers, Saddha A G F M

    2009-06-01

    In archaeology, it is not always possible to identify bone fragments. A novel approach was chosen to assess the potential of histology as an identification tool. Instead of studying a few bones of different categories from many species, this study concentrated on the diaphyses of long bones in four species of comparable size which are relevant to archaeology; young humans, pigs, sheep and goats, to broaden the insight into variations in diaphyseal bone structure within and between these species. A general difference in the primary bone structure was found between children older than one year and the three medium-sized mammals, namely lamellar vs. fibro-lamellar primary bone. Although, the diaphyseal bone structure of children below the age of one year also showed (developing) fibro-lamellar bone, its composition was distinctive from the medium-sized mammals. A difference in the secondary bone structure was also observed. Connecting (Volkmann's) canals, giving the secondary bone a reticular aspect, were seen in the medium-sized mammals but not in the young human long bones. To confirm the validity and applicability of these observed histological differences, a blind test was conducted on 14 diaphyseal fragments of identified long bones from archaeological sites. The results were very promising. All the bone fragments were correctly attributed using the difference in primary bone structure, even when the bone was severely degraded.

  6. [Company integration management in small and medium-sized companies. Legal requirements and prerequisites for successful implementation].

    PubMed

    Ramm, D; Mahnke, C; Tauscher, A; Welti, F; Seider, H; Shafaei, R

    2012-01-01

    The article is based on the results of the project “Company integration management in small and medium-sized companies. Legal requirements and prerequisites for a successful implementation” (01 January 2009-31 August 2010). Since 2004 all employers have been legally bound to offer company integration management (BEM, Betriebliches Eingliederungsmanagement) for all employees who have been incapacitated for work for more than 6 weeks within a year (Section 84 SGB IX, Book 9 of the German Social Code). Objective of this law is to ensure ongoing employment. The aim of the study was to investigate the requirements companies, rehabilitation centres and services as well as social insurance institutions are faced with according to Section 84 SGB IX. Prerequisites for an effective implementation of BEM in small and medium-sized enterprises were analyzed. Protocol-based interviews with experts were adopted. A total of 38 interviews with experts were carried out. The experts interviewed were either willing to give information by interest (concernment) or were named by law as an initiator or co-operator in the process of integration. A substantial literature research was performed in advance of the interviews. The awareness level of BEM is still very low even 7 years after its introduction. Small and medium-sized enterprises do not have any significant experiential knowledge of long-term incapacity for work and, hence, about BEM. Due to a lack of workers representation in many small and medium companies, management does not receive initiatives or support in implementation of BEM from employees' side. Employers prefer a central contact point providing them with the information and help needed, the common service units, however, being widely unknown in this context. Cost comparisons suggest that a company integration management might be more cost-effective than dismissing employees who are incapacitated for some fields of work. These findings might even hold true for small

  7. 78 FR 51746 - Trade Barriers That U.S. Small and Medium-sized Enterprises Perceive as Affecting Exports to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Trade Barriers That U.S. Small and Medium-sized Enterprises Perceive as Affecting Exports to the... prepare a report that catalogs trade barriers that U.S. small and medium-sized enterprises (SMEs) perceive...

  8. 50 CFR 648.235 - Spiny dogfish possession and landing restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish possession and landing... Management Measures for the Spiny Dogfish Fishery § 648.235 Spiny dogfish possession and landing restrictions. (a) Quota period 1. From May 1 through October 31, vessels issued a valid Federal spiny dogfish...

  9. 50 CFR 648.239 - Spiny dogfish framework adjustments to management measures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Spiny dogfish framework adjustments to... UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.239 Spiny dogfish framework... consistent with the goals and objectives of the Spiny Dogfish FMP. (1) Adjustment process. After the Councils...

  10. 50 CFR 648.239 - Spiny dogfish framework adjustments to management measures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish framework adjustments to... UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.239 Spiny dogfish framework... consistent with the goals and objectives of the Spiny Dogfish FMP. (1) Adjustment process. After the Councils...

  11. 50 CFR 648.235 - Spiny dogfish possession and landing restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish possession and landing... Management Measures for the Spiny Dogfish Fishery § 648.235 Spiny dogfish possession and landing restrictions. (a) Possession limit. Vessels issued a valid Federal spiny dogfish permit under § 648.4(a)(11) may...

  12. 50 CFR 648.235 - Spiny dogfish possession and landing restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Spiny dogfish possession and landing... Management Measures for the Spiny Dogfish Fishery § 648.235 Spiny dogfish possession and landing restrictions. (a) Quota Period 1. From May 1 through October 31, vessels issued a valid Federal spiny dogfish...

  13. 50 CFR 648.239 - Spiny dogfish framework adjustments to management measures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish framework adjustments to... UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.239 Spiny dogfish framework... consistent with the goals and objectives of the Spiny Dogfish FMP. (1) Adjustment process. After the...

  14. 50 CFR 648.239 - Spiny dogfish framework adjustments to management measures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Spiny dogfish framework adjustments to... UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.239 Spiny dogfish framework... consistent with the goals and objectives of the Spiny Dogfish FMP. (1) Adjustment process. After the...

  15. Early serial Q-switched ruby laser therapy for medium-sized to giant congenital melanocytic naevi.

    PubMed

    Kishi, K; Okabe, K; Ninomiya, R; Konno, E; Hattori, N; Katsube, K; Imanish, N; Nakajima, H; Nakajima, T

    2009-08-01

    Medium-sized to giant congenital melanocytic naevi (CMN) are difficult to treat, especially if the lesions appear on the face or extremities where treated areas are visible and cosmesis is important. In infants, nests of pigmented naevus reside more superficially and the skin is more transparent than in adults, so we treated medium-sized to giant CMN with early serial Q-switched ruby laser therapy from infancy. We treated nine patients with medium-sized to giant CMN on the face or upper limbs from 1 month of age with early serial Q-switched ruby laser therapy. The laser power was initially 5 J cm(-2) and increased in 0.5 J cm(-2) steps to a maximum of 10 J cm(-2). There were three treatment sites on the forehead, one on the temple, one on the cheek and four on the upper arm. It took 8-15 treatments for the CMN to become a colour similar to the surrounding skin. The mean number of treatments was 9.6. The colour was reduced to 0-20% of the colour of the baseline lesion in all nine patients. Partial slight repigmentation occurred in eight of these patients. These naevi were treated with an additional one or two Q-switched ruby laser irradiations and successfully lightened for at least 1 year. In the remaining patient, pigmentation returned to a level similar to the original lesion within 1 month of the last treatment. Therefore, the lesion was excised for cosmetic reasons. After the treatment series, the skin texture was fine and no patients had hypertrophic scarring. Although treatment of one patient with the Q-switched ruby laser therapy failed, the remaining patients responded well and had good to excellent skin texture without hypertrophic scarring. Early serial Q-switched ruby laser treatment, starting from infancy, is a promising treatment method for this condition.

  16. Characteristics of small to medium-sized rotator cuff tears with and without disruption of the anterior supraspinatus tendon.

    PubMed

    Namdari, Surena; Donegan, Ryan P; Dahiya, Nirvikar; Galatz, Leesa M; Yamaguchi, Ken; Keener, Jay D

    2014-01-01

    The purpose of this study was to examine the baseline function and results of arthroscopic cuff repair in shoulders with small and medium-sized full-thickness cuff tears with complete supraspinatus disruption compared with those with an intact anterior supraspinatus tendon. The study evaluated 112 subjects with small and medium-sized cuff tears. Subjects were grouped according to anterior supraspinatus integrity (83 shoulders intact, group 1; and 29 shoulders with anterior supraspinatus tendon disruption, group 2). Functional assessments included visual analogue scale for pain, American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test score, and Constant score. Repair integrity was assessed by ultrasound examination. Group 2 shoulders had greater mean tear width, length, and area (P < .0001) and greater supraspinatus muscle degenerative changes (P < .0001) compared with shoulders with an intact anterior supraspinatus tendon. There were no differences in demographics or baseline function (ASES score: 45 group 1 vs 46 group 2, P = .79; Constant score: 56 group 1 vs 52 group 2, P = .29) before surgery. There were no differences in any functional parameter (ASES score: 92 group 1 vs 93 group 2, P = .71; Constant score: 84 group 1 vs 85 group 2, P = .84) after surgery. There was no difference in tendon healing rates (93% group 1 vs 86% group 2; P = .26). In the setting of painful small and medium-sized rotator cuff tears, disruption of the anterior supraspinatus tendon was associated with greater tear size and more advanced supraspinatus muscle degeneration. However, anterior supraspinatus tendon integrity had no influence on the clinical presentation or the functional and structural results of cuff repair surgery. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  17. Discriminating between Medium-Sized Tridactyl Trackmakers: Tracking Ornithopod Tracks in the Base of the Cretaceous (Berriasian, Spain)

    PubMed Central

    Castanera, Diego; Pascual, Carlos; Razzolini, Novella L.; Vila, Bernat; Barco, José L.; Canudo, José I.

    2013-01-01

    Background Recent work on the Jurassic-Cretaceous transition of the Iberian Range (Spain) has opened a new window onto the interpretation of the trackmakers of some medium-sized tridactyl tracks. The ichnotaxon Therangospodus oncalensis has been described in the Huérteles Formation (Berriasian) and is one of the classical tracks from the area assigned to medium-sized theropods. Methodology/Principal Findings A review of the type locality of Therangospodus oncalensis (Fuentesalvo tracksite) and other tracksites from the Huérteles Formation (Berriasian) has yielded new information on the morphology, gait and trackmaker identity of the aforementioned ichnospecies. The new data suggest that the trackmaker is an ornithopod rather than a theropod on the basis of the length/width ratio, the anterior triangle length-width ratio, the short steps, the round to quadrangular heel pad impression and the probable manus impressions. Conclusions/Significance T. oncalensis shows similarities with various tracks from the Berriasian of Europe assigned to Iguanodontipus. The ichnotaxonomical status of this ichnospecies is here considered as Iguanodontipus? oncalensis due to the current state of knowledge of the ichnotaxonomy of medium-sized ornithopod tracks. This reassessment of I? oncalensis also has two significant implications for the palaeoecology of the faunas during the deposition of the Huérteles Formation: 1- the high number and percentage of theropod tracks would be lower than previous papers have suggested. 2- the gregarious behaviour described in the type locality (Fuentesalvo) would be among ornithopods instead of theropods. PMID:24303075

  18. Mechanization of Library Procedures in the Medium-sized Medical Library: X. Uniqueness of Compression Codes for Bibliographic Retrieval *

    PubMed Central

    Coe, Mary Jordan

    1970-01-01

    Two-word compression techniques, the University of Chicago experimental search code and a phonetic code similar to the SOUNDEX coding system, were tested as search codes on a data base of 7,464 bibliographic records. These codes were automatically generated and tested for uniqueness. A modified version of the University of Chicago search code produced the best results with a uniqueness factor of 98.83 percent. The algorithms for generating these codes are explained, and implication of the findings for medium-sized libraries are discussed. PMID:4924789

  19. Intra-Arterial Angiolymphoid Hyperplasia with Eosinophilia: A Rare Case Report of Peripheral Medium Sized Muscular Artery Involvement.

    PubMed

    Amin, Ashima; Umashankar, T; Dsouza, Chryselle Olive

    2015-08-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vasoproliferative disease with distinct clinical and histopathological features. The most common clinical presentation is dermal and subcutaneous painless nodules in the head and neck region. The involvement of medium sized peripheral muscular artery is uncommon. It predominantly affects Caucasian adults during the third and fourth decades, but is also known to occur in Asians and it very rarely occurs in children. We here by present a case of intravascular ALHE in a 46-year-old female presenting with subcutaneous forearm nodule clinically diagnosed as ulnar artery thrombosis.

  20. Betaherpesvirus sequences in eastern spiny mice and Wagner's dipodils.

    PubMed

    Tarlinton, Rachael E; Tate, Hannah F J; Mohallal, Eman M E; Daly, Janet M; Behnke, Jerzy M

    2011-10-01

    Eastern spiny mice (Acomys dimidiatus; also known as Sinai spiny mice) have been extensively studied in terms of the influence of parasite load on population size and reproductive fitness. The physical isolation of these rodent populations makes them interesting models for disease interactions in a real-life population as opposed to a laboratory. We identify betaherpesvirus sequences in eastern spiny mice and Wagner's dipodils (Dipodillus dasyurus), species that inhabit dry montane wadis (dry creek valleys) of the Sinai, highlighting the need for a comprehensive analysis of the full pathogen repertoire of these rodents in long-term studies.

  1. Antennular projections to the midbrain of the spiny lobster. II. Sensory innervation of the olfactory lobe.

    PubMed

    Schmidt, M; Ache, B W

    1992-04-15

    The projection pattern of antennular sensory afferents in the olfactory lobe (OL) of the spiny lobster, Panulirus argus, was examined by backfilling axons in the antennular nerve (AN) with biocytin. Thin, presumptive olfactory afferents from the lateral division of the AN form a tract in the brain that diverges into a dense plexus that completely envelops the glomerular cortex of the OL. Most of the thin (diameter less than or equal to 0.3-1 microns) afferents project to single glomeruli. About 10% of the thin afferents, however, branch in the plexus and project to multiple glomeruli. A smaller number of medium-sized to thick (diameter 2-10 microns), presumably mechanosensory, afferents also innervate the OL and co-project to multiple glomeruli with the thin afferents. Afferents arborize profusely within the columnar glomeruli into very fine processes that penetrate to the base of the columns, but selectively terminate in either the cap/subcap region or in the innermost part of the base of the columns, often with conspicuous terminal boutons, forming two distinct regions of presumptive synaptic output. These results suggest that 1) The majority of the OL innervation is provided by olfactory sensilla (aesthetascs), but that other types of sensilla provide additional, likely mechanosensory, input to the OL. 2) The projection of olfactory afferents is not strictly uniglomerular. 3) The columnar organization of crustacean olfactory glomeruli is functionally significant and may provide an evolutionary correlate of the recently proposed subdivision of the vertebrate olfactory bulb into "functional columns."

  2. Estimated performance of an adaptive trailing-edge device aimed at reducing fuel consumption on a medium-size aircraft

    NASA Astrophysics Data System (ADS)

    Diodati, Gianluca; Concilio, Antonio; Ricci, Sergio; De Gaspari, Alessandro; Huvelin, Fabien; Dumont, Antoine; Godard, Jean-Luc

    2013-03-01

    This paper deals with the estimation of the performance of a medium-size aircraft (3-hour flight range) equipped with an adaptive trailing edge device (ATED) that runs span-wise from the wing root in the flap zone and extends chord-wise for a limited percentage of the MAC. Computations are calculated referring to the full wing and do not refer to the complete aircraft configuration. Aerodynamic computations, taking into account ideal shapes, have been performed by using both Euler and Navier- Stokes method in order to extract the wing polars for the reference and the optimal wing, implementing an ATED, deflected upwards and downwards. A comparison of the achieved results is discussed. Considering the shape domain, a suitable interpolation procedure has been set up to obtain the wing polar envelop of the adaptive wing, intended as the set of "best" values, picked by each different polar. At the end, the performances of the complete reference and adaptive wing are computed and compared for a symmetric, centered, leveled and steady cruise flight for a medium size aircraft. A significant fuel burn reduction estimate or, alternatively, an increased range capability is demonstrated, with margins of further improvements. The research leading to these results has gratefully received funding from the European Union Seventh Framework Programme (FP7/2007- 2013) under Grant Agreement n° 284562.

  3. A biological and chemical characterization strategy for small and medium-sized industries connected to municipal sewage treatment plants

    SciTech Connect

    Tarkpea, M.; Eklund, B.; Andren, C.; Gravenfors, E.; Kukulska, Z.

    1998-02-01

    A cost-effective strategy for the characterization of wastewater from small and medium-sized industries is described. A mobile laboratory, equipped for performing on-site biological tests, was established near wastewater treatment facilities in two cities in Sweden for 1 week each in November 1992 and November 1993. The biological and chemical characterization was done on 24-h samples from 29 industries representing 12 types of activity with a bias toward the surface treatment and graphics industries. The biological testing program included a modified nitrification test, the Microtox test, and a modified growth inhibition test using Selenastrum capricornutum (an alga test). A Ceriodaphnia dubia (crustacean) test was also used for some industries. Different chemical assessments, aimed at indicating toxic, persistent, and bioaccumulating substances, were chosen for each industry on the basis of information they provided. Results show that sampling period and time are important factors to consider when designing a characterization strategy. Twenty-four-hour sampling is preferred to weekly sampling because highly toxic emissions of short duration that are detrimental to the biological treatment plant may occur. Variability in emissions was shown in this study but would not have been detected by a study based on weekly sampling. The strategy developed in this study was shown to be both a cost-effective and efficient tool for characterizing effluents from small and medium-sized industries.

  4. A qualitative study of pandemic influenza preparedness among small and medium-sized businesses in New York City.

    PubMed

    Burton, Deron C; Confield, Evan; Gasner, Mary Rose; Weisfuse, Isaac

    2011-10-01

    Small businesses need to engage in continuity planning to assure delivery of goods and services and to sustain the economy during an influenza pandemic. This is especially true in New York City, where 98 per cent of businesses have fewer than 100 employees. It was an objective therefore, to determine pandemic influenza business continuity practices and strategies suitable for small and medium-sized NYC businesses. The study design used focus groups, and the participants were owners and managers of businesses with fewer than 500 employees in New York City. The main outcome measures looked for were the degree of pandemic preparedness, and the feasibility of currently proposed business continuity strategies. Most participants reported that their businesses had no pandemic influenza plan. Agreement with feasibility of specific business continuity strategies was influenced by the type of business represented, cost of the strategy, and business size. It was concluded that recommendations for pandemic-related business continuity plans for small and medium-sized businesses should be tailored to the type and size of business and should highlight the broad utility of the proposed strategies to address a range of business stressors.

  5. The role of fcc tetrahedral subunits in the phase behavior of medium sized Lennard-Jones clusters.

    PubMed

    Saika-Voivod, Ivan; Poon, Louis; Bowles, Richard K

    2010-08-21

    The free energy of a 600-atom Lennard-Jones cluster is calculated as a function of surface and bulk crystallinity in order to study the structural transformations that occur in the core of medium sized clusters. Within the order parameter range studied, we find the existence of two free energy minima at temperatures near freezing. One minimum, at low values of both bulk and surface order, belongs to the liquid phase. The second minimum exhibits a highly ordered core with a disordered surface and is related to structures containing a single fcc-tetrahedral subunit, with an edge length of seven atoms (l=7), located in the particle core. At lower temperatures, a third minimum appears at intermediate values of the bulk order parameter which is shown to be related to the formation of multiple l=6 tetrahedra in the core of the cluster. We also use molecular dynamics simulations to follow a series of nucleation events and find that the clusters freeze to structures containing l=5, 6, 7, and 8 sized tetrahedra as well as those containing no tetrahedral units. The structural correlations between bulk and surface order with the size of the tetrahedral units in the cluster core are examined. Finally, the relationships between the formation of fcc tetrahedral subunits in the core, the phase behavior of medium sized clusters and the nucleation of noncrystalline global structures such as icosahedra and decahedra are discussed.

  6. Communicating Hydrocephalus Associated with Small- to Medium-Sized Vestibular Schwannomas: Clinical Significance of the Tumor Apparent Diffusion Coefficient Map.

    PubMed

    Taniguchi, Masaaki; Nakai, Tomoaki; Kohta, Masaaki; Kimura, Hidehito; Kohmura, Eiji

    2016-10-01

    The etiology of hydrocephalus associated with the small- to medium-sized vestibular schwannomas is still controversial. We investigated tumor-specific factors related to the association of hydrocephalus with small- to medium-sized vestibular schwannomas. Among the 77 patients with vestibular schwannoma smaller than 30 mm, 9 patients demonstrated associated communicating hydrocephalus. Patient medical records, radiologic data, and histopathologic specimens were reviewed retrospectively. The age of the patients, and size, mean apparent diffusion coefficient (ADC) value, and histologic features of the tumors were compared with those of patients without hydrocephalus. The symptoms related to hydrocephalus improved in all patients after tumor removal. Both the mean size and ADC values exhibited a statistically significant difference between the tumors with and without hydrocephalus (P < 0.01). The size and ADC value of the tumor were significantly related to the association with hydrocephalus. The increased tumor ADC value was considered to be the result of degenerative change and suggested the involvement of protein sloughing in the etiology of the associated hydrocephalus. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Calculation of Iron Loss of Medium-sized High Voltage Motor which Have Axial Ventilation Holes in Rotor

    NASA Astrophysics Data System (ADS)

    Meng, Da-wei; Li, Jin-xiao

    2017-05-01

    When optimizing the ventilation and cooling system of medium-sized high power density asynchronous motor, it is found that the temperature rise of the motor can be greatly reduced after punching the axial ventilation holes in the rotor yoke, but the traditional method based on the magnetic circuit method cannot accurately calculate the motor iron loss of this new structure. In this paper combined with the finite element field-circuit-motion coupled analysis method, taking YXKK355-4, 355kW and YKK400-4, 400kW medium-sized high voltage asynchronous motor for example, a two-dimensional geometric model and mathematical model of the motor are established, then the iron loss calculation method is improved. Using this method not only the iron loss value of the whole motor can be obtained, but also the specific distribution of iron loss in different areas of the motor can be known, and the correctness of the simulation results is proved by experiments.

  8. Müllerian mimicry in aposematic spiny plants

    PubMed Central

    2009-01-01

    Müllerian mimicry is common in aposematic animals but till recently, like other aspects of plant aposematism was almost unknown. Many thorny, spiny and prickly plants are considered aposematic because their sharp defensive structures are colorful and conspicuous. Many of these spiny plant species (e.g., cacti and Agave in North American deserts; Aloe, Euphorbia and acacias with white thorns in Africa; spiny plants in Ohio; and spiny members of the Asteraceae in the Mediterranean basin) have overlapping territories, and also similar patterns of conspicuous coloration, and suffer from the evolutionary pressure of grazing by the same large herbivores. I propose that many of these species form Müllerian mimicry rings. PMID:19816137

  9. Müllerian mimicry in aposematic spiny plants.

    PubMed

    Lev-Yadun, Simcha

    2009-06-01

    Müllerian mimicry is common in aposematic animals but till recently, like other aspects of plant aposematism was almost unknown. Many thorny, spiny and prickly plants are considered aposematic because their sharp defensive structures are colorful and conspicuous. Many of these spiny plant species (e.g., cacti and Agave in North American deserts; Aloe, Euphorbia and acacias with white thorns in Africa; spiny plants in Ohio; and spiny members of the Asteraceae in the Mediterranean basin) have overlapping territories, and also similar patterns of conspicuous coloration, and suffer from the evolutionary pressure of grazing by the same large herbivores. I propose that many of these species form Müllerian mimicry rings.

  10. Masking and temporal niche switches in spiny mice.

    PubMed

    Cohen, Rotem; Smale, Laura; Kronfeld-Schor, Noga

    2010-02-01

    Activity patterns are the product of interactions between an internal circadian clock and direct responses to photic and nonphotic features of the environment that are said to "mask" the influence of that clock. Evolutionary transitions between nocturnality and diurnality involve changes in mechanisms underlying both of these processes. Here, the authors examined how masking influences activity patterns of golden spiny mice ( Acomys russatus), which can be either nocturnal or diurnal, and common spiny mice (Acomys cahirinus), which are strictly nocturnal. Animals kept on a 12:12 LD cycle were exposed to 3-h dark pulses starting at ZT 2, light pulses of varying intensities (50, 100, 700, or 1500 lux) at ZT 14, and a 3.5:3.5-h LD cycle. In common spiny mice, activity increased by 379% during the dark pulse and decreased during light pulses to 23% of baseline levels. Golden spiny mice also increased their activity in response to the dark pulse (by 345%), but there was extreme inter-and intraindividual variability and no significant response to light pulses at night. In the 3.5:3.5 LD cycle, common spiny mice showed a preference for the dark phase with 86% +/- 0.01% of activity occurring then, whereas golden spiny mice showed a pronounced circadian rhythm but no evidence of masking. Masking responses to light and dark were thus unsurprising in common spiny mice but were highly unusual in golden spiny mice. Patterns seen in the latter species may reflect mechanisms enabling these animals to occupy either a diurnal or a nocturnal niche in their natural habitat.

  11. Non-Markovian Model for Transport and Reactions of Particles in Spiny Dendrites

    NASA Astrophysics Data System (ADS)

    Fedotov, Sergei; Méndez, Vicenç

    2008-11-01

    Motivated by the experiments [Santamaria , Neuron 52, 635 (2006)NERNET0896-627310.1016/j.neuron.2006.10.025] that indicated the possibility of subdiffusive transport of molecules along dendrites of cerebellar Purkinje cells, we develop a mesoscopic model for transport and chemical reactions of particles in spiny dendrites. The communication between spines and a parent dendrite is described by a non-Markovian random process and, as a result, the overall movement of particles can be subdiffusive. A system of integrodifferential equations is derived for the particles densities in dendrites and spines. This system involves the spine-dendrite interaction term which describes the memory effects and nonlocality in space. We consider the impact of power-law waiting time distributions on the transport of biochemical signals and mechanism of the accumulation of plasticity-inducing signals inside spines.

  12. Coordination of planar cell polarity pathways through Spiny-legs

    PubMed Central

    Ambegaonkar, Abhijit A; Irvine, Kenneth D

    2015-01-01

    Morphogenesis and physiology of tissues and organs requires planar cell polarity (PCP) systems that orient and coordinate cells and their behaviors, but the relationship between PCP systems has been controversial. We have characterized how the Frizzled and Dachsous-Fat PCP systems are connected through the Spiny-legs isoform of the Prickle-Spiny-legs locus. Two different components of the Dachsous-Fat system, Dachsous and Dachs, can each independently interact with Spiny-legs and direct its localization in vivo. Through characterization of the contributions of Prickle, Spiny-legs, Dachsous, Fat, and Dachs to PCP in the Drosophila wing, eye, and abdomen, we define where Dachs-Spiny-legs and Dachsous-Spiny-legs interactions contribute to PCP, and provide a new understanding of the orientation of polarity and the basis of PCP phenotypes. Our results support the direct linkage of PCP systems through Sple in specific locales, while emphasizing that cells can be subject to and must ultimately resolve distinct, competing PCP signals. DOI: http://dx.doi.org/10.7554/eLife.09946.001 PMID:26505959

  13. Understanding the behavioural phenotype of the precocial spiny mouse.

    PubMed

    Ratnayake, Udani; Quinn, Tracey; Daruwalla, Kerman; Dickinson, Hayley; Walker, David W

    2014-12-15

    The use of the spiny mouse (Acomys cahirinus) in experimental research is steadily increasing, due to the precocial nature of this species and the similarities in endocrinology to the human. The characterisation of normal behavioural traits throughout development has not been comprehensively measured in the spiny mouse. Therefore the aim of this study was to behaviourally phenotype the spiny mouse, with the use of behavioural paradigms commonly used to assess behaviour in rat and mouse models of human behavioural disorders such as autism, attention-deficit disorder, and schizophrenia. Male and female spiny mice were assessed at 1-5, 10-15, 20-25, 40-45 and 80-85 days of age using the open field test, novel object recognition test, rotarod, elevated plus maze, a social interaction test, and prepulse inhibition. Exploratory activity, motor coordination, fear, anxiety and social behaviours could be accurately measured from 1 day of age. Open field exploration and motor coordination on a modified rotarod were precociously developed by 10-15 and 20-25 days of age, respectively, when they were equivalent to the performance of conventional adult mice. Learning and memory (assessed by the novel object recognition test), and sensory gating (prepulse inhibition) could be reliably determined only after 20-25 days of age, and performance on these tests differed significantly between male and female spiny mice, particularly in adulthood. This study characterises the behavioural traits of spiny mice and provides important information about critical periods of behavioural development throughout postnatal life.

  14. Development of Proof-of-Concept Units for the Advanced Medium-Sized Mobile Power Sources (AMMPS) Program

    SciTech Connect

    Andriulli, JB

    2002-04-03

    The purpose of this report is to document the development of the proof-of-concept units within the Advanced Medium-sized Mobile Power Sources (AMMPS) program. The design used a small, lightweight diesel engine, a permanent magnet alternator, power electronics and digital controls as outlined in the philosophy detailed previously. One small proof-of-concept unit was completed and delivered to the military. The unit functioned well but was not optimized at the time of delivery to the military. A tremendous amount of experience was gained during this phase that can be used in the development of any follow-on AMMPS production systems. Lessons learned and recommendations for follow-on specifications are provided. The unit demonstrated that significant benefits are possible with the new design philosophy. Trade-offs will have to be made but many of the advantages appear to be within the technical grasp of the market.

  15. Social participation among older adults living in medium-sized cities in Belgium: the role of neighbourhood perceptions.

    PubMed

    Buffel, Tine; De Donder, Liesbeth; Phillipson, Chris; Dury, Sarah; De Witte, Nico; Verté, Dominique

    2014-12-01

    This study examines the associations between neighbourhood perceptions and social participation in a sample of older adults living in medium-sized cities in Flanders, Belgium. Strong evidence of the influence of place on older people's physical and mental health exists. However, the question of how neighbourhoods promote or hinder social participation remains under-explored in social gerontology. Using data generated from the Belgian Ageing Studies, a multivariate regression model (n = 1877) is tested, with personal characteristics, subjective neighbourhood assessments and objective city-level measures as independent variables, and two indicators of social participation as dependent variables: social activity and formal participation. Positive predictors included neighbourhood involvement, frequent contact with neighbours and availability of activities for older people. However, the predictive role of neighbourhood perceptions is stronger for formal participation than for social activity, which is explained more by individual characteristics. The article concludes by discussing the implications of the findings for research and practice pertaining to health promotion interventions.

  16. Environmental Management in Small and Medium-Sized Companies: An Analysis from the Perspective of the Theory of Planned Behavior

    PubMed Central

    Sánchez-Medina, Agustín J.; Romero-Quintero, Leonardo; Sosa-Cabrera, Silvia

    2014-01-01

    In the business context, concern for the environment began to develop when pressure from the public administration and environmental awareness groups raised the specific requirements for companies. The Theory of Planned Behavior considers that people's conduct is determined by the intention of carrying out a certain behavior. Thus, the individual's intent is determined by three factors related to the desired outcome of the behavior: the Personal Attitude toward the Results, the Perceived Social Norms, and the Perceived Behavioral Control over the action. Therefore, the objectives of this paper are to clarify the attitudes of the managers of Canarian small and medium-sized companies about taking environmental measures, and try to demonstrate whether there is a relationship between the proposed factors and the intention to take these measures. PMID:24533094

  17. Aggregate Production Planning, Casestudy in a Medium-sized Industry of the Rubber Production Line in Ecuador.

    NASA Astrophysics Data System (ADS)

    Rosero-Mantilla, César; Sánchez-Sailema, Mayra; Sánchez-Rosero, Carlos; Galleguillos-Pozo, Rosa

    2017-06-01

    This research aims to improve the productivity in the rubber line of a medium-sized industry by increasing the production capacities through the use of the Aggregate Production Planning model. For this purpose an analysis of the production processes of the line was made and the aggregate plan was defined evaluating two strategies: Exact Production Plan (Zero Inventory) and Constant Workforce Plan (Vary Inventory) by studying the costs of both inventory maintenance and workforce. It was also determined how the installed capacity was used with the standards of the rubber line and measures for decreasing production costs were proposed. It was proven that only 70% of the plant capacity was being used so it could be possible to produce more units and to obtain a bigger market for the products of this line.+

  18. Occupational Safety and Health Conditions Aboard Small- and Medium-Size Fishing Vessels: Differences among Age Groups

    PubMed Central

    Zytoon, Mohamed A.; Basahel, Abdulrahman M.

    2017-01-01

    Although marine fishing is one of the most hazardous occupations, research on the occupational safety and health (OSH) conditions aboard marine fishing vessels is scarce. For instance, little is known about the working conditions of vulnerable groups such as young and aging fishermen. The objective of the current paper is to study the OSH conditions of young and aging fishermen compared to middle-aged fishermen in the small- and medium-size (SM) marine fishing sector. A cross-sectional study was designed, and 686 fishermen working aboard SM fishing vessels were interviewed to collect information about their safety and health. The associations of physical and psychosocial work conditions with safety and health outcomes, e.g., injuries, illnesses and job satisfaction, are presented. The results of the current study can be utilized in the design of effective accident prevention and OSH training programs for the three age groups and in the regulation of working conditions aboard fishing vessels. PMID:28245578

  19. Energy conserved and costs saved by small and medium-size manufacturers: 1986-1987 EADC program period

    SciTech Connect

    Kirsch, F.W.

    1989-03-01

    The Energy Analysis and Diagnostic Center (EADC) program provides energy-conserving and cost-saving assistance to small and medium-size manufacturers in 36 states. Engineering faculty from 13 universities, assisted by graduate and undergraduate students, analyze energy usage and manufacturing operations in each plant and then prepare an individualized report that recommends specific actions and estimates their costs and their benefits. Manufacturing plants are eligible if they meet the size criteria and are not more than 150 miles from an EADC. The US Department of Energy, Office of Industrial Programs, sponsors the EADC program, which is managed by University City Science Center, through its Industrial Technology and Energy Management (ITEM) Division. This and similar reports are prepared from data which ITEM staff members extract as they review every energy audit report prepared by the EADCs. Eventually these data also include the results of manufacturers' implementation of EADCs' recommendations, together with costs and savings. 14 tabs.

  20. Quantum chemical study of the electronic properties of an Iridium-based photosensitizer bound to medium-sized silver clusters

    NASA Astrophysics Data System (ADS)

    Bokareva, Olga S.; Kühn, Oliver

    2015-08-01

    The equilibrium structures and electronic excitation spectra of the Ir(III) photosensitizer [Ir(ppy)2(bpy)]+ bound to medium-sized silver clusters Agn (n = 19, 20) are investigated using time-dependent density functional theory. The long-range corrected LC-BLYP approach is used with a system-specific range separation parameter. The weak physisorption of the hybrid complexes yields only small changes in the broadened absorption spectra of the hybrid system as compared with its constituents. However, the density of states as well as the fine structure of the spectra is strongly modified upon complexation. It is shown that the standard range separation parameter (0.47 bohr-1) cannot predict these properties correctly and the optimized value of 0.16 bohr-1 should be used instead.

  1. [Cultivation strategy and path analysis on big brand Chinese medicine for small and medium-sized enterprises].

    PubMed

    Wang, Yong-Yan; Yang, Hong-Jun

    2014-03-01

    Small and medium-sized enterprises (SMEs) are important components in Chinese medicine industry. However, the lack of big brand is becoming an urgent problem which is critical to the survival of SMEs. This article discusses the concept and traits of Chinese medicine of big brand, from clinical, scientific and market value three aspects. Guided by market value, highlighting clinical value, aiming at the scientific value improvement of big brand cultivation, we put forward the key points in cultivation, aiming at obtaining branded Chinese medicine with widely recognized efficacy, good quality control system and mechanism well explained and meanwhile which can bring innovation improvement to theory of Chinese medicine. According to the characters of SMEs, we hold a view that to build multidisciplinary research union could be considered as basic path, and then, from top-level design, skill upgrading and application three stages to probe the implementation strategy.

  2. Occupational Safety and Health Conditions Aboard Small- and Medium-Size Fishing Vessels: Differences among Age Groups.

    PubMed

    Zytoon, Mohamed A; Basahel, Abdulrahman M

    2017-02-24

    Although marine fishing is one of the most hazardous occupations, research on the occupational safety and health (OSH) conditions aboard marine fishing vessels is scarce. For instance, little is known about the working conditions of vulnerable groups such as young and aging fishermen. The objective of the current paper is to study the OSH conditions of young and aging fishermen compared to middle-aged fishermen in the small- and medium-size (SM) marine fishing sector. A cross-sectional study was designed, and 686 fishermen working aboard SM fishing vessels were interviewed to collect information about their safety and health. The associations of physical and psychosocial work conditions with safety and health outcomes, e.g., injuries, illnesses and job satisfaction, are presented. The results of the current study can be utilized in the design of effective accident prevention and OSH training programs for the three age groups and in the regulation of working conditions aboard fishing vessels.

  3. Environmental management in small and medium-sized companies: an analysis from the perspective of the theory of planned behavior.

    PubMed

    Sánchez-Medina, Agustín J; Romero-Quintero, Leonardo; Sosa-Cabrera, Silvia

    2014-01-01

    In the business context, concern for the environment began to develop when pressure from the public administration and environmental awareness groups raised the specific requirements for companies. The Theory of Planned Behavior considers that people's conduct is determined by the intention of carrying out a certain behavior. Thus, the individual's intent is determined by three factors related to the desired outcome of the behavior: the Personal Attitude toward the Results, the Perceived Social Norms, and the Perceived Behavioral Control over the action. Therefore, the objectives of this paper are to clarify the attitudes of the managers of Canarian small and medium-sized companies about taking environmental measures, and try to demonstrate whether there is a relationship between the proposed factors and the intention to take these measures.

  4. Molecular (global) and atom-in-cluster (local) polarizabilities of medium-size gold nanoclusters: isomer structure effects

    NASA Astrophysics Data System (ADS)

    Rodríguez, Juan I.; Baltazar-Méndez, Maria I.; Autschbach, Jochen; Castillo-Alvarado, F. L.

    2013-06-01

    In this work, we extend our recent study [J.I. Rodríguez, J. Autschbach, F.L. Castillo-Alvarado, M.I. Baltazar-Méndez, J. Chem. Phys. 135, 034109 (2011)] to quantify the isomer structure effects on the atom-in-cluster polarizabilities of medium size gold clusters Au ( n = 6, 12, 20, 34, 54). For three isomers for each cluster size, a density functional perturbation theory calculation was performed to compute the cluster polarizability and the polarizability of each atom in the cluster using Bader's "quantum theory of atoms in molecules" formalism. The cluster polarizability tensor is expressed as a sum of the atom-in-cluster atomic tensors. We found that the strong quadratic correlation ( R 2 = 0.98) in the isotropic polarizability of atoms in the cluster and their distance to the cluster center of mass reported before holds independently of the cluster structure.

  5. The Alignment System for a Medium-Sized Schwarzschild-Couder Telescope Prototype for the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Ribeiro, Deivid; Humensky, Brian; Nieto, Daniel; V Vassiliev Group in UCLA division of Astronomy and Astrophysics, P Kaaret Group at Iowa University Department of Physics and Astronomy, CTA Consortium

    2016-01-01

    The Cherenkov Telescope Array (CTA) is an international project for a next-generation ground-based gamma-ray observatory. CTA, conceived as an array of tens of imaging atmospheric Cherenkov telescopes, comprising small, medium and large-size telescopes, is aiming to improve on the sensitivity of current-generation experiments by an order of magnitude and provide energy coverage from 20 GeV to more than 300 TeV. The Schwarzschild-Couder design is a candidate 9-m diameter medium-sized telescope featuring a novel aplanatic two-mirror optical design capable of a wide field of view with significantly improved imaging resolution as compared to the traditional Davies-Cotton optical design. Achieving this imaging resolution imposes strict mirror alignment requirements that necessitate a sophisticated alignment system. This system uses a collection of position sensors between panels to determine the relative position of adjacent panels; each panel is mounted on a Stewart platform to allow motion control with six degrees of freedom, facilitating the alignment of the optical surface for the segmented primary and secondary mirrors. Alignments of the primary and secondary mirrors and the camera focal plane with respect to each other are performed utilizing a set of CCD cameras which image LEDs placed on the mirror panels to measure relative translation, and custom-built auto-collimators to measure relative tilt between the primary and secondary mirrors along the optical axis of the telescope. In this contribution we present the status of the development of the SC optical alignment system, soon to be materialized in a full-scale prototype SC medium-size telescope (pSCT) at the Fred Lawrence Whipple Observatory in southern Arizona.

  6. Comparison of the reservoir competence of medium-sized mammals and Peromyscus leucopus for Anaplasma phagocytophilum in Connecticut.

    PubMed

    Levin, Michael L; Nicholson, William L; Massung, Robert F; Sumner, John W; Fish, Durland

    2002-01-01

    In the northeastern United States, Anaplasma phagocytophilum, the agent of human granulocytic ehrlichiosis (HGE), is transmitted by the tick vector Ixodes scapularis. The white-footed mouse Peromyscus leucopus is a competent reservoir for this agent, but the reservoir competence of non-Peromyscus hosts of I. scapularis has not been studied. Here, we report data confirming reservoir competence of medium-sized mammals for A. phagocytophilum. Raccoons, Virginia opossums, gray squirrels, and striped skunks were live-trapped in June-August of 1998-1999 at two locations in Connecticut. Captured animals were kept for several days at the laboratory in wire-mesh cages over water to allow naturally attached ticks to drop off. Samples of blood and serum were taken from each animal prior to its release at the site of capture. Engorged ticks collected from each animal were allowed to molt. Resulting I. scapularis nymphs and adults were tested for the presence of A. phagocytophilum DNA by polymerase chain reaction, as were the blood samples from the animals. A. phagocytophilum DNA was detected in the blood of >10% of the raccoons tested. Raccoons, opossums, squirrels, and skunks produced adult I. scapularis infected with the agent of HGE. Prevalence of infection was the highest in adult ticks fed as nymphs upon raccoons (23%) and the lowest in those fed upon skunks and opossums (5-7%). The agent was present in nymphal I. scapularis fed as larvae upon raccoons and squirrels, but not in ticks fed upon skunks or opossums. We also tested the ability of I. scapularis to transmit A. phagocytophilum to laboratory-reared white-footed mice after acquiring it from medium-sized mammals. Ticks that acquired the agent from raccoons and squirrels successfully transmitted it to mice. Thus, raccoons and gray squirrels are reservoir-competent for the agent of HGE-they become naturally infected, and are capable of transmitting the infection to feeding ticks.

  7. Impact of land use on urban mobility patterns, emissions and air quality in a Portuguese medium-sized city.

    PubMed

    Bandeira, Jorge M; Coelho, Margarida C; Sá, Maria Elisa; Tavares, Richard; Borrego, Carlos

    2011-02-15

    The main objective of this work was to evaluate the impact of urban development trends in mobility patterns of a medium sized Portuguese city and air quality consequences, using a sequential modeling process, comprising i) land use and transportation, TRANUS model; ii) road traffic air pollutants emissions, TREM model and; iii) air quality, TAPM model. This integrated methodology was applied to a medium sized Portuguese city. In order to evaluate the implementation of the methodology, a preliminary study was performed, which consisted on the comparison of modeled mobility patterns and CO and PM(10) concentrations with measured data used in the definition of the current scenario. The comparison between modeled and monitored mobility patterns at the morning peak hour for a weekday showed an RMSE of 31%. Regarding CO concentrations, an underestimation of the modeled results was observed. Nevertheless, the modeled PM(10) concentrations were consistent with the monitored data. Overall, the results showed a reasonable consistency of the modeled data, which allowed the use of the integrated modeling system for the study scenarios. The future scenarios consisted on the definition of different mobility patterns and vehicle technology characteristics, according to two main developing trends: (1) "car pooling" scenario, which imposes a mean occupancy rate of 3 passengers by vehicle and (2) the "Euro 6" scenario, which establishes that all vehicles accomplish at least the Euro 6 standard technology. Reductions of 54% and 83% for CO, 44% and 95% for PM(10), 44% and 87% for VOC and 44% and 79% for NO(x) emissions were observed in scenarios 1 and 2, respectively. Concerning air quality, a reduction of about 100 μg m(-3) of CO annual average concentration was observed in both scenarios. The results of PM(10) annual concentrations showed a reduction of 1.35 μg m(-3) and 2.7 μg m(-3) for scenarios 1 and 2 respectively. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Enhancing work motivation for Japanese female nurses in small to medium-sized private hospitals by analyzing job satisfaction.

    PubMed

    Kudo, Yasushi; Kido, Shigeri; Shahzad, Machiko Taruzuka; Shida, Kyoko; Satoh, Toshihiko; Aizawa, Yoshiharu

    2010-03-01

    Proper work environments are important for nurses to feel motivated. We examined the associations between work motivation and job satisfaction among Japanese nurses to improve their motivation. In Japan, relatively small and medium-sized private hospitals play a central role in the healthcare industry. In the present study, the subjects were nurses working in 23 small and medium-sized private hospitals that had 65 to 326 beds. We analyzed 1,116 registered and licensed practical female nurses (average age, 38.3 years; standard deviation, 11.3 years). Many nurses with their specialized nursing skills dedicate themselves to patient care. However, many of these nurses may not be interested in contributing to their hospitals. Nurses may have different opinions regarding dedication to patient care and contribution to their hospitals. Therefore, concerning work motivation, we produced these two different items, "Nurses' dedication to patients" and "Nurses' contribution to their hospitals." We also produced our own original new job satisfaction questionnaire. We found 7 facets of job satisfaction: "Work as specialists," "Workplace safety," "Relationships with superiors," "Work-life balance," "Relationships among nurses," "Communications with physicians," and "Salary." Multiple linear regression analyses show that both "Nurses' dedication to patients" and "Nurses' contribution to their hospitals" were significantly associated with "Work as specialists." Nurses feel their jobs of protecting people's lives and health are valuable. They do not feel motivated only by money. They value the intrinsic nature of their jobs. Creating proper work environments is important for nurses to be able to work as specialists.

  9. Patterns and Pathways of Evolving Catchment Response in a Medium-Sized Mediterranean Catchment on a Millennium Scale

    NASA Astrophysics Data System (ADS)

    van Beek, L. P. H.; Bierkens, M. F. P.

    2012-04-01

    The meso-scale landscape dynamics model, CALEROS, has been developed to simulate the interactions between climate, soil production and erosion, vegetation and land use on geomorphological to human time scales in Mediterranean environments. Starting from an initial landscape consisting of a DTM, soil distribution and underlying lithology, the landscape is free to develop in response to the imposed climate variability and seismicity. In addition to changes in soil distribution and bedrock lowering, this includes the establishment of vegetation as conditioned by a selection of plant functional types and, optionally, population and land use dynamics as conditioned by land use scenarios specifying technological and dietary constraints for different periods. As such CALEROS is well-suited to investigate the relative impacts of climate, land cover and human activities on the hydrological catchment response and the associated sediment fluxes due to soil erosion and mass movements. Here we use CALEROS to i) investigate the redistribution of water and sediment across the landscape in a medium-sized Mediterranean catchment (Contrada Maddalena; ~14km2, Calabria, Italy) and ii) to establish patterns of co-evolution in soil properties and vegetation under pristine and anthropogenically impacted conditions on a millennium-scale. Using summary statistics to describe the emergent properties and to verify them against observations, we then delineate areas of uniform morphology and describe the various pathways of development. This information allows us to identify elements of consistent hydrological response and the associated transfer of material across different scales. It also provides essential information on essential feedbacks and the resulting convergence or divergence in landscape development under the impact of climatic or seismic events or human intervention. Although the results are evidently conditioned by the physiographic setting of the study area and by the

  10. Impact of Platelet-Rich Plasma on Arthroscopic Repair of Small- to Medium-Sized Rotator Cuff Tears

    PubMed Central

    Holtby, Richard; Christakis, Monique; Maman, Eran; MacDermid, Joy C.; Dwyer, Tim; Athwal, George S.; Faber, Kenneth; Theodoropoulos, John; Woodhouse, Linda J.; Razmjou, Helen

    2016-01-01

    Background: Increased interest in using platelet-rich plasma (PRP) as an augment to rotator cuff repair warrants further investigation, particularly in smaller rotator cuff tears. Purpose: To examine the effectiveness of PRP application in improving perioperative pain and function and promoting healing at 6 months after arthroscopic repair of small- or medium-sized rotator cuff tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a double-blinded randomized controlled trial of patients undergoing arthroscopic repair of partial- or full-thickness rotator cuff tears of up to 3 cm who were observed for 6 months. Patients were randomized to either repair and PRP application (study group) or repair only (control group) groups. The patient-oriented outcome measures utilized were the visual analog scale (VAS), the Short Western Ontario Rotator Cuff Index (ShortWORC), the American Shoulder and Elbow Surgeons (ASES) form, and the Constant-Murley Score (CMS). Range of motion (ROM) and inflammatory and coagulation markers were measured before and after surgery. Magnetic resonance imaging was used at 6 months to assess retear and fatty infiltration rate. Results: Eighty-two patients (41 males) with a mean age of 59 ± 8 years were enrolled; 41 patients were included in each group. Both the PRP and control groups showed a significant improvement in their pain level based on the VAS within the first 30 days (P < .0001), with the PRP group reporting less pain than the control group (P = .012), which was clinically significantly different from days 8 through 11. The PRP group reported taking less painkillers (P = .026) than the control group within the first 30 days. All outcome measure scores and ROM improved significantly after surgery (P < .0001), with no between-group differences. No differences were observed between groups in inflammatory or coagulation marker test results (P > .05), retear (14% vs 18% full retear; P = .44), or fatty

  11. 75 FR 26920 - Mid-Atlantic Fishery Management Council; Spiny Dogfish Amendment 3 Scoping Process

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ...; Spiny Dogfish Amendment 3 Scoping Process AGENCY: National Marine Fisheries Service (NMFS), National... not noted in the initial Notice of Intent (NOI) for Amendment 3 to the Spiny Dogfish Fishery.... The scoping comment period for issues previously announced for Amendment 3 to the Spiny Dogfish...

  12. 77 FR 30224 - Fisheries of the Northeastern United States; Final 2012 Spiny Dogfish Fishery Specifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... reflect recent increases in spiny dogfish biomass. The action is expected to result in positive economic.... The commenter suggested that spiny dogfish biomass has been underestimated, and that catch limits for... argued that the high biomass of male dogfish contributes to predation on spiny dogfish pups and more...

  13. 50 CFR 622.453 - Prohibition on harvest of egg-bearing spiny lobster.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Prohibition on harvest of egg-bearing... Prohibition on harvest of egg-bearing spiny lobster. (a) Egg-bearing spiny lobster in the Caribbean EEZ must be returned to the water unharmed. An egg-bearing spiny lobster may be retained in a trap,...

  14. 50 CFR 622.453 - Prohibition on harvest of egg-bearing spiny lobster.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Prohibition on harvest of egg-bearing... Prohibition on harvest of egg-bearing spiny lobster. (a) Egg-bearing spiny lobster in the Caribbean EEZ must be returned to the water unharmed. An egg-bearing spiny lobster may be retained in a trap,...

  15. Conducting Creativity Brainstorming Sessions in Small and Medium-Sized Enterprises Using Computer-Mediated Communication Tools

    NASA Astrophysics Data System (ADS)

    Murthy, Uday S.

    A variety of Web-based low cost computer-mediated communication (CMC) tools are now available for use by small and medium-sized enterprises (SME). These tools invariably incorporate chat systems that facilitate simultaneous input in synchronous electronic meeting environments, allowing what is referred to as “electronic brainstorming.” Although prior research in information systems (IS) has established that electronic brainstorming can be superior to face-to-face brainstorming, there is a lack of detailed guidance regarding how CMC tools should be optimally configured to foster creativity in SMEs. This paper discusses factors to be considered in using CMC tools for creativity brainstorming and proposes recommendations for optimally configuring CMC tools to enhance creativity in SMEs. The recommendations are based on lessons learned from several recent experimental studies on the use of CMC tools for rich brainstorming tasks that require participants to invoke domain-specific knowledge. Based on a consideration of the advantages and disadvantages of the various configuration options, the recommendations provided can form the basis for selecting a CMC tool for creativity brainstorming or for creating an in-house CMC tool for the purpose.

  16. Development of the ACS+OPC UA based control system for a CTA medium size telescope prototype

    NASA Astrophysics Data System (ADS)

    Behera, Bagmeet; Oya, Igor; Birsin, Emrah; Köppel, Hendryk; Melkumyan, David; Schlenstedt, Stefan; Schmidt, Torsten; Schwanke, Ullrich; Wegner, Peter; Wiesand, Stephan; Winde, Michael

    2012-09-01

    The Cherenkov Telescope Array (CTA) is the next generation Very High Energy (VHE, defined as > 50GeV to several 100TeV) telescope facility, currently in the design and prototyping phase, and expected to come on-line around 2016. The array would have both a Northern and Southern hemisphere site, together delivering nearly complete sky coverage. The CTA array is planned to have ~100 telescopes of several different sizes to fulfill the sensitivity and energy coverage needs. Each telescope has a number of subsystems with varied hardware and control mechanisms; a drive system that gets commands and inputs via OPC UA (OPC Unified Architecture), mirror alignment systems based on XBee/ZigBee protocol and/or CAN bus, weather monitor accessed via serial/Ethernet ports, CCD cameras for calibration, Cherenkov camera, and the data read out electronics, etc. Integrating the control and data-acquisitions of such a distributed heterogeneous system calls for a framework that can handle such a multi-platform, multi-protocol scenario. The CORBA based ALMA Common software satisfies these needs very well and is currently being evaluated as the base software for developing the control system for CTA. A prototype for a Medium Size Telescope (MST, ~12m) is being developed and will be deployed in Berlin, by end of 2012. We present the development being carried out to integrate and control the various hardware subsystems of this MST prototype using ACS.

  17. The use of bipolar cautery, laparosonic coagulating shears, and vascular clips for hemostasis of small and medium-sized vessels.

    PubMed

    Spivak, H; Richardson, W S; Hunter, J G

    1998-02-01

    Advanced laparoscopic surgery requires a reliable method of hemostasis. In order to determine the efficacy of common hemostatic devices, we tested bipolar electrosurgery (BPES), laparosonic coagulating shears (LCS), and vascular clips (VC) on arteries of various sizes to compare the strength of hemostasis against elevated intraarterial pressure. The procedures were performed on a porcine model through a laparotomy. Segments of visceral arteries were isolated and cannulated with an angiocatheter that was linked to a pressure monitor. After hemostasis with the tested instrument and division of the vessel, the intraarterial pressure was elevated by infusion of saline solution through the angiocatheter. The pressure was recorded when bleeding occurred through the cut end of the vessel or when the pressure reached 300 mm Hg. All three devices were effective in maintaining hemostasis on small (diameter, 0.25-0.5 mm) and medium-sized arteries (diameter, 2-3.5 mm) with a success rate ranging between 75% and 100% (p = n.s.). Practice and technical finesse were required with the use of the LCS and BPES before excellent results could be obtained. The LCS has an advantage over BPES because it allows the surgeon to perform hemostasis and division simultaneously, thus keeping the operating field clean and avoiding instrument adhesion to the tissue.

  18. FIRST-based survey of Compact Steep Spectrum sources. II. MERLIN and VLA observations of medium-sized symmetric objects

    NASA Astrophysics Data System (ADS)

    Kunert-Bajraszewska, M.; Marecki, A.; Thomasson, P.; Spencer, R. E.

    2005-09-01

    A new sample of candidate Compact Steep Spectrum (CSS) sources that are much weaker than the CSS source prototypes has been selected from the VLA FIRST catalogue. MERLIN "snapshot" observations of the sources at 5 GHz indicate that six of them have an FR II-like morphology, but are not edge-brightened as is normal for Medium-sized Symmetric Objects (MSOs) and FR IIs. Further observations of these six sources with the VLA at 4.9 GHz and MERLIN at 1.7 GHz, as well as subsequent full-track observations with MERLIN at 5 GHz of what appeared to be the two sources of greatest interest are presented. The results are discussed with reference to the established evolutionary model of CSS sources being young but in which not all of them evolve to become old objects with extended radio structures. A lack of stable fuelling in some of them may result in an early transition to a so-called coasting phase so that they fade away instead of growing to become large-scale objects. It is possible that one of the six sources (1542+323) could be labelled as a prematurely "dying" MSO or a "fader".

  19. Impact of local urban design and traffic restrictions on air quality in a medium-sized town.

    PubMed

    Acero, J A; Simon, A; Padro, A; Santa Coloma, O

    2012-01-01

    Traffic is the major air pollution source in most urban areas. Nowadays, most of the strategies carried out to improve urban air quality are focused on reducing traffic emissions. Nevertheless, acting locally on urban design can also reduce levels of air pollutants. In this paper, both strategies are studied in several scenarios for a medium-sized town of the Basque Country (Spain). Two main actions are analysed in order to reduce traffic emissions: (1) minor extension ofa pre-existing low emission zone (LEZ); (2) substitution of 10% of passenger cars that are older than 5 years by hybrid and electric vehicles. Regarding local urban design, three alternatives for the development of one side of a street canyon are considered: (1) a park with trees; (2) an open space without obstacles; (3) a building. Two different urban traffic dispersion models are used to calculate the air quality scenarios: PROKAS (Gaussian&box) to analyse the reduction of traffic emissions in the whole urban area and WinMISKAM (CFD) to evaluate specific urban designs. The results show the effectiveness of the analysed actions. On one hand, the definition of a small LEZ, as well as the introduction in 2015 of vehicles with new technology (hybrid and electric), results in minor impacts on PM10 and NO2 ambient concentrations. On the other hand, local urban design can cause significant variation in spatial distribution ofpollutant concentrations emitted inside street canyons. Consequently, urban planners should consider all these aspects when dealing with urban air pollution control.

  20. Study on recent execution of overall evaluation bidding method in small and medium-sized regional local governments

    NASA Astrophysics Data System (ADS)

    Fujishima, Hirohide; Yanase, Norihiko

    About 70% of local governments in Japan, endeavored to introduce overall evaluation bidding method for their public works in 2011 and each authority ordered one or some projects in according to the new bidding process. That is, their enforcement was an only trial level and they say that the reason why is long-term procedure and heavily administrative load of the system. The author think that such burden has relationship of human affairs of local govern ments, practical problems on kinds and price of constructions and the officers' experience on the new bidding method. The aim of this study is to analyze such problems among the officers' profession, posts and experience of administrative matter by statistical data, questionnaire and hearing to the officers. The result could indicate that a group of small local governments uses the method appropriately and that another group of medium-sized rejects to increase more contracts in according to the new bidding system because of unbalance between the stuffs' ability and order quantity of public works.

  1. Boys who pee the farthest have a large hollow head, a thin skin, and medium-size manhood

    NASA Astrophysics Data System (ADS)

    Attinger, Daniel; Lee, Vincent

    2016-11-01

    Following a recent trend of scientific studies on artwork, we study here the thermodynamics of a jetting thermometer made of ceramic, related to the Chinese tea culture. The thermometer represents a boy who "urinates" shortly after hot water is poured onto his head. Long jetting distance indicates if the water temperature is hot enough to brew tea. Here, a thermofluid model describes the jetting phenomenon of that pee-pee boy. The study demonstrates how thermal expansion of an interior air pocket causes jetting. The validity of assumptions underlying the Hagen-Poiseuille flow is discussed for urethra of finite length. A thermodynamic potential is shown to define maximum jetting velocity. Seven optimization criteria to maximize jetting distance are provided, including two dimensionless numbers. The dimensionless numbers are obtained by comparing the time scales of the internal pressure buildup due to heating, with that of pressure relief due to jetting. Optimization results show that longer jets are produced by large individuals, with low body mass index, with a boyhood of medium size inclined at an angle π/4. Analogies are drawn with pissing contests among humans and lobsters. The study ends by noting similitudes of working principle between that politically incorrect thermometer and Galileo Galilei's thermoscope.

  2. On the variational computation of a large number of vibrational energy levels and wave functions for medium-sized molecules

    NASA Astrophysics Data System (ADS)

    Mátyus, Edit; Šimunek, Ján; Császár, Attila G.

    2009-08-01

    In a recent publication [J. Chem. Phys. 127, 084102 (2007)], the nearly variational DEWE approach (DEWE denotes Discrete variable representation of the Watson Hamiltonian using the Eckart frame and an Exact inclusion of a potential energy surface expressed in arbitrarily chosen coordinates) was developed to compute a large number of (ro)vibrational eigenpairs for medium-sized semirigid molecules having a single well-defined minimum. In this publication, memory, CPU, and hard disk usage requirements of DEWE, and thus of any DEWE-type approach, are carefully considered, analyzed, and optimized. Particular attention is paid to the sparse matrix-vector multiplication, the most expensive part of the computation, and to rate-determining steps in the iterative Lanczos eigensolver, including spectral transformation, reorthogonalization, and restart of the iteration. Algorithmic improvements are discussed in considerable detail. Numerical results are presented for the vibrational band origins of the C12H4 and C12H2D2 isotopologues of the methane molecule. The largest matrix handled on a personal computer during these computations is of the size of (4•108)×(4•108). The best strategy for determining vibrational eigenpairs depends largely on the actual details of the required computation. Nevertheless, for a usual scenario requiring a large number of the lowest eigenpairs of the Hamiltonian matrix the combination of the thick-restart Lanczos method, shift-fold filtering, and periodic reorthogonalization appears to result in the computationally most feasible approach.

  3. Analyzing the efficiency of small and medium-sized enterprises of a national technology innovation research and development program.

    PubMed

    Park, Sungmin

    2014-01-01

    This study analyzes the efficiency of small and medium-sized enterprises (SMEs) of a national technology innovation research and development (R&D) program. In particular, an empirical analysis is presented that aims to answer the following question: "Is there a difference in the efficiency between R&D collaboration types and between government R&D subsidy sizes?" Methodologically, the efficiency of a government-sponsored R&D project (i.e., GSP) is measured by Data Envelopment Analysis (DEA), and a nonparametric analysis of variance method, the Kruskal-Wallis (KW) test is adopted to see if the efficiency differences between R&D collaboration types and between government R&D subsidy sizes are statistically significant. This study's major findings are as follows. First, contrary to our hypothesis, when we controlled the influence of government R&D subsidy size, there was no statistically significant difference in the efficiency between R&D collaboration types. However, the R&D collaboration type, "SME-University-Laboratory" Joint-Venture was superior to the others, achieving the largest median and the smallest interquartile range of DEA efficiency scores. Second, the differences in the efficiency were statistically significant between government R&D subsidy sizes, and the phenomenon of diseconomies of scale was identified on the whole. As the government R&D subsidy size increases, the central measures of DEA efficiency scores were reduced, but the dispersion measures rather tended to get larger.

  4. [The certification of advanced therapy medicinal products. A quality label for product development in small and medium-sized enterprises].

    PubMed

    Berger, A; Schüle, S; Flory, E

    2011-07-01

    Advanced therapy medicinal products (ATMPs) are gene therapy, cell therapy, and tissue engineered products. To gain access to the market within the European Union, ATMPs must be authorized by the European Commission (EC). Especially for small and medium-sized enterprises (SMEs), the European centralized procedure of marketing authorization that is conducted by the European Medicines Agency (EMA) constitutes a major challenge, because SMEs often have little experience with regulatory procedures and many have limited financial possibilities. To tackle these challenges, a certification procedure exclusively for SMEs and their ATMP development was introduced by the EC. Independently from a marketing authorization application, development and/or production processes can be certified. An issued certificate demonstrates that the respective process meets the current regulatory and scientific requirements of the EMA, representing a valuable milestone for putative investors and licensees. This article highlights the background, the detailed procedure, the minimum requirements, as well as the costs of certification, while giving further noteworthy guidance for interested parties.

  5. Deriving default dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises.

    PubMed

    Warren, N; Goede, H A; Tijssen, S C H A; Oppl, R; Schipper, H J; van Hemmen, J J

    2003-11-01

    This paper describes the derivation of default task-based dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises (SMEs). A set of separately determined dermal exposure modifiers have been applied to published studies of dermal exposure to obtain 'normalized' dermal exposure data sets. These data sets are grouped according to task and then further subdivided by making a distinction between processes involving solid and liquid products. For each of the resulting 12 groups, two default exposure rates are required: potential exposure rate to the hands and potential exposure rate to the body. Default values for risk assessment are then derived by taking a weighted average of the 75th percentiles of these normalized exposure distributions. In addition, a measure of peak surface concentration is required to take into account the risk of local skin effects. The higher of the (modified) hand and body exposure rates after applying the relevant penetration factors for clothing and gloves is used. Usually this will be the hand exposure rate. These default values serve as robust initial exposure estimates in a risk assessment toolkit for SMEs.

  6. Risk determinants of small and medium-sized manufacturing enterprises (SMEs) - an exploratory study in New Zealand

    NASA Astrophysics Data System (ADS)

    Islam, Ariful; Tedford, Des

    2012-08-01

    The smooth running of small and medium-sized manufacturing enterprises (SMEs) presents a significant challenge irrespective of the technological and human resources they may have at their disposal. SMEs continuously encounter daily internal and external undesirable events and unwanted setbacks to their operations that detract from their business performance. These are referred to as `disturbances' in our research study. Among the disturbances, some are likely to create risks to the enterprises in terms of loss of production, manufacturing capability, human resource, market share, and, of course, economic losses. These are finally referred to as `risk determinant' on the basis of their correlation with some risk indicators, which are linked to operational, occupational, and economic risks. To deal with these risk determinants effectively, SMEs need a systematic method of approach to identify and treat their potential effects along with an appropriate set of tools. However, initially, a strategic approach is required to identify typical risk determinants and their linkage with potential business risks. In this connection, we conducted this study to explore the answer to the research question: what are the typical risk determinants encountered by SMEs? We carried out an empirical investigation with a multi-method research approach (a combination of a questionnaire-based mail survey involving 212 SMEs and five in-depth case studies) in New Zealand. This paper presents a set of typical internal and external risk determinants, which need special attention to be dealt with to minimize operational risks of an SME.

  7. Pediatric Oncology Clinic Care Model: Achieving Better Continuity of Care for Patients in a Medium-sized Program.

    PubMed

    Johnston, Donna L; Halton, Jacqueline; Bassal, Mylène; Klaassen, Robert J; Mandel, Karen; Ramphal, Raveena; Simpson, Ewurabena; Peckan, Li

    2016-10-25

    Providing the best care in both the inpatient and outpatient settings to pediatric oncology patients is all programs goal. Using continuous improvement methodologies, we changed from a solely team-based physician care model to a hybrid model. All patients were assigned a dedicated oncologist. There would then be 2 types of weeks of outpatient clinical service. A "Doc of the Day" week where each oncologist would have a specific day in clinic when their assigned patients would be scheduled, and then a "Doc of the Week" week where one physician would cover clinic for the week. Patient satisfaction surveys done before and 14 months after changing the model of care showed that patients were very satisfied with the care they received in both models. A questionnaire to staff 14 months after changing showed that the biggest effect was increased continuity of care, followed by more efficient clinic workflow and increased consistency of care. Staff felt it provided better planning and delivery of care. A hybrid model of care with a primary physician for each patient and assigned clinic days, alternating with weeks of single physician coverage is a feasible model of care for a medium-sized pediatric oncology program.

  8. Effectiveness of a Comprehensive Stress Management Program to Reduce Work-Related Stress in a Medium-Sized Enterprise

    PubMed Central

    2014-01-01

    Objectives To assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management. Methods A comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker’s Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011. Results Most of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved. Conclusions In light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan. PMID:24524591

  9. Infectious vasculopathy of intracranial large- and medium-sized vessels in neurological intensive care unit: a clinico-radiological study.

    PubMed

    Katchanov, J; Siebert, E; Klingebiel, R; Endres, M

    2010-06-01

    Infections are a well-known cause of cerebral vasculopathy and vasculitis. We aimed to analyze the frequency of intracranial vasculopathy attributable to infection, the spectrum of causative microorganisms, imaging, and cerebrospinal fluid (CSF) characteristics as well as clinical course and outcome. We used our institution's medical record system to identify all patients diagnosed with nonatherosclerotic central nervous system vasculopathy from January 1, 1999 through February 28, 2009. We reviewed their clinical charts, imaging data, and results of CSF studies. Twenty-five adult patients with nonatherosclerotic cerebral vasculopathy of large- and medium-sized intracranial vessels were identified. Eight patients had vasculopathy attributable to infection (32%). The underlying pathologies were acute bacterial meningitis (n = 4), varicella zoster virus (VZV) infection (n = 2), borreliosis (n = 1), and syphilis (n = 1). In six patients, magnetic resonance angiography was performed and showed vasculopathic changes in all patients examined (100%). In both patients with VZV-associated vasculopathy, the arterial wall enhanced on magnetic resonance imaging. The CSF examination of the patients with infectious vasculopathy showed a significantly higher white blood cell count. The outcome of the infectious cohort was unfavorable with one death, two patients with locked-in syndrome, and five patients discharged from intensive care with severe neurological deficits. In this cohort, one-third of all cases of nonatherosclerotic vasculopathy were due to infectious vasculopathy of large and medium intracranial vessels.

  10. African swine fever outbreak on a medium-sized farm in Uganda: biosecurity breaches and within-farm virus contamination.

    PubMed

    Chenais, Erika; Sternberg-Lewerin, Susanna; Boqvist, Sofia; Liu, Lihong; LeBlanc, Neil; Aliro, Tonny; Masembe, Charles; Ståhl, Karl

    2017-02-01

    In Uganda, a low-income country in east Africa, African swine fever (ASF) is endemic with yearly outbreaks. In the prevailing smallholder subsistence farming systems, farm biosecurity is largely non-existent. Outbreaks of ASF, particularly in smallholder farms, often go unreported, creating significant epidemiological knowledge gaps. The continuous circulation of ASF in smallholder settings also creates biosecurity challenges for larger farms. In this study, an on-going outbreak of ASF in an endemic area was investigated on farm level, including analyses of on-farm environmental virus contamination. The study was carried out on a medium-sized pig farm with 35 adult pigs and 103 piglets or growers at the onset of the outbreak. Within 3 months, all pigs had died or were slaughtered. The study included interviews with farm representatives as well as biological and environmental sampling. ASF was confirmed by the presence of ASF virus (ASFV) genomic material in biological (blood, serum) and environmental (soil, water, feed, manure) samples by real-time PCR. The ASFV-positive biological samples confirmed the clinical assessment and were consistent with known virus characteristics. Most environmental samples were found to be positive. Assessment of farm biosecurity, interviews, and the results from the biological and environmental samples revealed that breaches and non-compliance with biosecurity protocols most likely led to the introduction and within-farm spread of the virus. The information derived from this study provides valuable insight regarding the implementation of biosecurity measures, particularly in endemic areas.

  11. 78 FR 25862 - Fisheries of the Northeastern United States; Final 2013-2015 Spiny Dogfish Fishery Specifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-03

    ... United States; Final 2013-2015 Spiny Dogfish Fishery Specifications AGENCY: National Marine Fisheries.... SUMMARY: This rule implements specifications and management measures for the spiny dogfish fishery for the... spiny dogfish fishery while maintaining the conservation objectives of the Spiny Dogfish Fishery...

  12. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Spiny dogfish Annual Catch Target (ACT... OF THE NORTHEASTERN UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.231 Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL). (a) The Spiny Dogfish...

  13. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Spiny dogfish Annual Catch Target (ACT... OF THE NORTHEASTERN UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.231 Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL). (a) The Spiny Dogfish...

  14. 50 CFR 648.231 - Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Spiny dogfish Annual Catch Target (ACT... OF THE NORTHEASTERN UNITED STATES Management Measures for the Spiny Dogfish Fishery § 648.231 Spiny dogfish Annual Catch Target (ACT) and Total Allowable Level of Landings (TAL). (a) The Spiny Dogfish...

  15. Paternal behavior in the spiny mouse (Acomys cahirinus).

    PubMed

    Makin, J W; Porter, R H

    1984-07-01

    The responsiveness of adult male spiny mice (Acomys cahirinus) to both their own and alien precocial young was investigated. Paternal behavior was manifested primarily by the males huddling with their offspring and the coordination of pup attendance between adult males and females. With less than 2 days exposure to their own neonates, males were found to discriminate between their own and alien young. Experience plays an important role in the development of paternal behavior in spiny mice. Males who have never had pups of their own sniff and attack unfamiliar neonates more than males who have fathered pups. The adaptive significance of paternal investment in this uniquely precocial murid rodent was discussed.

  16. Circadian activity rhythms in the spiny mouse, Acomys cahirinus.

    PubMed

    Weber, E T; Hohn, V M

    2005-11-15

    Circadian locomotor rhythms were examined in adult common spiny mice, Acomys cahirinus. Spiny mice demonstrated nocturnal activity, with onset of activity coinciding promptly with onset of darkness. Re-entrainment to 6-h delays of the light-dark cycle was accomplished faster than to 6-h advances. Access to running wheels yielded significant changes in period and duration of daily activity. Novelty-induced wheel running had no effect on phase of activity rhythms. Circadian responses to light at various times of the circadian cycle were temporally similar to those observed in other nocturnal rodent species. No gender differences were observed in any of the parameters measured.

  17. Inferred Variable FeO Content in Medium-sized Lunar Pyroclastic Deposits from LRO Diviner Data

    NASA Technical Reports Server (NTRS)

    Bennett, K. A.; Horgan, B.; Greenhagen, B.; Allen, C.; Bell, J. F., III

    2014-01-01

    Lunar pyroclastic deposits (LPDs) are low albedo features that mantle underlying terrain (Gaddis et al. 1985). They are high priority targets for science and exploration as they are believed to originate from and therefore reflect the composition of the deep lunar interior (NRC, 2011). They are also the best potential resource of oxygen out of any Apollo samples (Allen et al. 1996). Historically, LPDs have been divided into regional versus local categories (Gaddis et al. 2003). The large (>1000 km2 area) regional deposits are deeply sourced (>400 km deep) and result from fire fountaining. Small (<1000 km2) local deposits are thought to result from Vulcanian eruptions in which magma is slowly emplaced beneath the surface until enough volatiles exsolve and the high pressure causes an explosion. Bennett et al. (2013) identified a local deposit (674 km2 area) that may have resulted from both Vulcanian activity and fire fountaining. This deposit potentially represents a new intermediate class of LPDs that straddles the interface between the two formation mechanisms. The deposit also exhibits the highest inferred FeO wt.% of any known lunar glass. In this work we investigate the inferred FeO abundances of other medium-sized deposits to characterize this potential new class of deposits and understand the magnitude of variations in inferred FeO among pyroclastic deposits. We use the method of Greenhagen et al. (2010) to calculate the wavelength of the Christiansen Feature (CF) from Lunar Reconnaissance Orbiter Diviner Lunar Radiometer instrument thermal-infrared observations for four medium-sized deposits. From the CF values, we estimate each deposit's FeO abundance using the method of Allen et al. (2012). The four LPDs that we examined (Oppenheimer South, Beer, Cleomedes, and J. Herschel) all have average CF values from 8.22-8.28 microns, corresponding to FeO abundances of approx. 10-15 wt.%. All of these values are within the range and uncertainties of FeO abundances

  18. Examinations on the Meteorologic Factors of Urban Heat Island Development in Small and Medium-sized Towns of Hungary

    NASA Astrophysics Data System (ADS)

    Szegedi, S.; Gyarmati, R.; Kapocska, L.; Toth, T.

    2010-09-01

    EXAMINATIONS ON THE METEOROLOGICAL FACTORS OF URBAN HEAT ISLAND DEVELOPMENT IN SMALL AND MEDIUM-SIZED TOWNS OF HUNGARY Sandor Szegedi, Renata Gyarmati, Laszlo Kapocska and Tamas Toth University of Debrecen Department of Meteorology, 4032 Debrecen Egyetem tér 1. The thermal difference between the settlements and their environment is called urban heat island (UHI). Potential UHI intensities are mainly determined by the size, population and built-up structure of settlements. Meteorological conditions have a determinant impact on the development of the heat island at a certain moment. International and Hungarian studies usually deal with metropolises and big cities; much less attention is paid to medium-sized and small towns. Consequently this study has been focused on the development of UHI in such Hungarian urbanized areas as mentioned above. Settlements, located near the city of Debrecen (ca. 220,000 inhabitants) in East Hungary, with population of about 30000, 20000 10000 and 1000 were chosen for the research. Car-mounted digital thermometers with data loggers were used. Twenty four measurements were carried out during a one-year-long campaign in 2003-2004. Synoptic conditions, especially cloudiness, wind direction and wind speed were taken to consideration as determinant factors. Spatial characteristics of UHI have been described. Results have proved the existence of UHI even in the smallest settlement under suitable weather conditions. The non-heating season proved to be more advantageous for the development of UHI due to stronger irradiance and frequent anticyclonic synoptic conditions. Effects of cloudiness and wind speed have been revealed as well. St type clouds have proved to be most effective in preventing the formation of UHI. A 90-100% St cover could completely eliminate the thermal differences between natural and artificial surfaces. Ci type clouds had the weakest impact, they could prevent the formation of the heat island only in the smallest

  19. Synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates: formal total synthesis of (+)-calystegine b(2).

    PubMed

    Marco-Contelles, José; de Opazo, Elsa

    2002-05-31

    The free radical cyclization (FR) and the ring-closing metathesis (RCM) reaction have been analyzed in order to develop new and original synthetic protocols for the synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates. As a result, we report here for the first time examples of the 7-exo FR cyclization of acyclic radical precursors derived from sugars. This process appears to be extremely sensitive to the conformational mobility of the radical species in the transition state. The use of two isopropylidene groups blocking four of the total present hydroxyl groups and a good radical acceptor (as an alpha,beta-unsaturated ester) are mandatory conditions for a successful ring closure protocol. The RCM reaction by using Grubbs' catalyst on selected carbohydrate-derived precursors has afforded variable yields of the expected unsaturated cycloheptane or cycloctane derivatives. The synthesis of the cycloheptitols has been carried out in good yields, regardless of the absolute configuration at the different stereocenters and the nature of the O-functional groups bound in allylic positions to one of the double bonds implicated in the metathesis reaction. Conversely, in the cyclooctane synthesis, we have observed that the success of the reaction depends not only on the absolute configuration at the different stereocenters close to the double bonds but also on the nature of the O-protecting groups on these stereocenters. Finally, the RCM strategy has been used in an attempt to prepare natural (+)-calystegine B(2) from D-glucose. The synthesis of compound 92 from D-glucose constitutes a formal total synthesis of (+)-calystegine B(2), showing the importance of the steric hindrance in allylic positions for a successful RCM reaction.

  20. Contamination and risk assessment of metals in road-deposited sediments in a medium-sized city of China.

    PubMed

    Bian, Bo; Lin, Cheng; Wu, Hai suo

    2015-02-01

    Road-deposited sediment (RDS) is a valuable environmental medium for characterizing contamination of metals in urban areas and the associated risks to human health. A total of 62 RDS samples were collected for metal test in four urban areas in a medium size city in eastern China. The areas that represented different land uses consisted of intense traffic area (ITA), commercial area (CA), residential area (RA), and riverside park area (RPA). The effects of particle size and different land uses on metal contamination and health risk were the major focus in this study. The test results showed that RDS in ITA appeared to have higher metal content, enrichment factor (EF), ecological risk index (RI), and the non-cancer and cancer risks than in the other areas. The metal contamination and health risk increased inversely with particle size. The particles less than 63 μm were found to be most critical in development of metal contamination and health risk. The EF was measured to be greater than 2.0 in the four areas, indicating a moderate enrichment. The measured RI ranged between 50 and 200, indicating considerable to moderate risks. The non-cancer risk for children was high in the four areas but was low for adults in all test areas except in ITA. The cancer risk of Cr for children was high in all test areas. Based on the test results, the contamination control and management for metals in RDS shall focus on the effects from such factors as particles (<63 μm) and the land use for intense traffic (ITA).

  1. Concentration, sources and light absorption characteristics of dissolved organic carbon on a medium-sized valley glacier, northern Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Yan, Fangping; Kang, Shichang; Li, Chaoliu; Zhang, Yulan; Qin, Xiang; Li, Yang; Zhang, Xiaopeng; Hu, Zhaofu; Chen, Pengfei; Li, Xiaofei; Qu, Bin; Sillanpää, Mika

    2016-11-01

    Light-absorbing dissolved organic carbon (DOC) constitutes a major part of the organic carbon in glacierized regions, and has important influences on the carbon cycle and radiative forcing of glaciers. However, few DOC data are currently available from the glacierized regions of the Tibetan Plateau (TP). In this study, DOC characteristics of a medium-sized valley glacier (Laohugou Glacier No. 12, LHG) on the northern TP were investigated. Generally, DOC concentrations on LHG were comparable to those in other regions around the world. DOC concentrations in snow pits, surface snow and surface ice (superimposed ice) were 332 ± 132, 229 ± 104 and 426 ± 270 µg L-1, respectively. The average discharge-weighted DOC of proglacial stream water was 238 ± 96 µg L-1, and the annual DOC flux released from this glacier was estimated to be 6949 kg C yr-1, of which 46.2 % of DOC was bioavailable and could be decomposed into CO2 within 1 month of its release. The mass absorption cross section (MAC) of DOC at 365 nm was 1.4 ± 0.4 m2 g-1 in snow and 1.3 ± 0.7 m2 g-1 in ice, similar to the values for dust transported from adjacent deserts. Moreover, there was a significant relationship between DOC and Ca2+; therefore, mineral dust transported from adjacent arid regions likely made important contributions to DOC of the glacierized regions, although contributions from autochthonous carbon and autochthonous/heterotrophic microbial activity cannot be ruled out. The radiative forcing of snow pit DOC was calculated to be 0.43 W m-2, demonstrating that DOC in snow needs to be taken into consideration in accelerating melt of glaciers on the TP.

  2. A passive DOAS instrument for trace gas measurements on medium sized UAS: Instrumental design and first measurements.

    NASA Astrophysics Data System (ADS)

    Horbanski, Martin; Pöhler, Denis; Mahr, Tobias; Wagner, Thomas; Keleshis, Christos; Ioannou, Stelios; Lange, Manfred A.; Lelieveld, Jos; Platt, Ulrich

    2013-04-01

    Unmanned Aerial Systems (UAS) are a new powerful tool for observations in the atmospheric boundary layer. Recent developments in measuring technology allow the construction of compact and sensitive active and passive DOAS instruments which can fit the space and weight constraints on UAS. This opens new possibilities for trace gas measurements in the lower troposphere, especially in areas which are not accessible to manned aviation e.g. volcanic plumes or which should be monitored regularly (e.g. industrial emissions of a stack). We present a new developed passive DOAS instrument for the APAESO Platform of the Cyprus Institute, a medium size UAS. It is equipped with two telescopes for observations in downward (nadir) and horizontal (limb) viewing direction, respectively. Thus it allows determining height profiles and the horizontal distribution of trace gases. This is accomplished by analyzing the radiation collected by the telescopes with compact spectrometers, which cover the UV-blue spectral range allowing to measure a broad variety of atmospheric trace gases (e.g. NO2, SO2, BrO, IO, H2O ...) as well as aerosol properties via O4 absorption. Additionally, the nadir direction is equipped with a VIS-NIR spectrometer. It is used to measure reflection spectra of different types of vegetation. These will serve as references for satellite measurements to create global maps. First measurements on the APAESO platform were performed in October 2012 on Cyprus in a rural area south of Nicosia. The instrument is shown to work reliably and was able to detect NO2, H2O and O4 at atmospheric column densities. The instrumental design and first measurements will be presented and discussed.

  3. The Role of Remote Sensing for Sustainable Elephant Management in South Africa. Four Medium Sized Game Reserves as Case Studies

    NASA Astrophysics Data System (ADS)

    Jordaan, M.

    2012-07-01

    Loxodonta africana (African Elephant) are running out of living space so the protection of what space they have is essential. Existing areas of suitable elephant habitat need to be protected not only from human development but from the elephants themselves. As most elephant populations in South Africa are enclosed and multiplying, there is some increasing cause for concern as the damage caused will escalate and could reach unsustainable proportions. This study examined the utilization of satellite images for the detection of elephant induced ecosystem modification. A pilot study was conducted on four medium sized Game Reserves (each ±30 000 ha) in South Africa. The aim was to ascertain the feasibility of using image analysis as instrument by which Game Reserve managers could assess biodiversity richness, habitat loss, and population-habitat viability. NDVI as indicator of primary production in vegetation is one of the instruments used to evaluate whether the carrying capacity for elephants of each Game Reserve has been reached and to compare the current biomass with those of previous years. The study also looked at the use of the woody canopy cover as target for change detection analysis. Spectral characteristics of specific trees species which are known for being preferred by elephants were used to conduct a temporal analysis on satellite images starting from the period when the elephants were re-introduced into each Game Reserve, thus attempting to identify possible impact on the biodiversity of the respective Game Reserves. Images from satellites such as Landsat, SPOT, Quickbird and SumbandilaSAT provided the needed data and maps.

  4. Impact of psychosocial job stress on non-fatal occupational injuries in small and medium-sized manufacturing enterprises.

    PubMed

    Nakata, Akinori; Ikeda, Tomoko; Takahashi, Masaya; Haratani, Takashi; Hojou, Minoru; Fujioka, Yosei; Swanson, Naomi G; Araki, Shunichi

    2006-08-01

    Workers involved in manufacturing are known to comprise a high-risk population for occupational injury, and this risk is greater in small and medium-sized enterprises (SMEs). The purpose of this study was to examine the association between psychosocial job stress and occupational injuries among workers in SMEs. One thousand forty-nine men and 721 women from 244 SMEs participated in this study. Perceived job stress was evaluated with the Japanese version of the generic job stress questionnaire, which covered 14 job stress variables. Occupational injury was assessed by self-report during the last 1-year period. Workers with high quantitative workload (odds ratio [OR] = 1.55 for men, 1.62 for women), high cognitive demands (OR = 1.70 for men, 1.53 for women), and low job satisfaction (OR = 1.33 for men, 1.93 for women) had a significantly increased risk of occupational injury in the multivariate model. High variance in workload (OR = 1.70) and high job future ambiguity (OR = 1.35) in men, and low job control (OR = 2.04) and high intragroup conflict (OR = 1.66) in women were significantly associated with occupational injury. In manufacturing/production workers, high quantitative workload (OR = 1.91), high variance in workload (OR = 2.02), and high depressive symptoms (OR = 1.55) were significantly associated with injury in men, while low social support from colleagues (OR = 2.36) or family (OR = 2.51) was related to injury in women. These data point to an independent relationship between psychosocial job stress and self-reported occupational injury in SMEs. Copyright 2006 Wiley-Liss, Inc

  5. Self-reported illnesses and service utilisation among migrants working in small-to medium sized enterprises in Guangdong, China.

    PubMed

    Zou, G; Zeng, Z; Chen, W; Ling, L

    2015-07-01

    As one of the most vulnerable populations in China, many migrants work in the small-to-medium-sized enterprises (SMEs). This study aims to describe the self-reported illnesses and service utilization of the migrants working in the SMEs in Pearl River Delta Areas (PRDA) of Guangdong province, China. Cross-sectional survey. We interviewed 856 migrants working in the SMEs of different manufacturing industries in 2012. Descriptive analysis was employed to report self-reported illnesses and service utilisation among migrants in the last two weeks and in the last year. Statistical tests such as χ2 test were used to explore factors influencing their service utilisation. In the last two weeks, 91(11%) of the respondents reported having any illness. The most reported illness was respiratory problem (69%), while 9.9%, 7.7% and 13% reported having digestive, skin and other problems respectively. The most important symptom was cough (39%). Thirty-seven percent of the respondents who reported any illness had visited health facilities. The lower income group were more likely to visit health facilities than the higher income group (P = 0.006). The most reported reason for not visiting health facilities was 'feeling not serious' (65%). In the last year, 13% reported having respiratory problems and 7.8% reported accidental injuries. Less than 3% received hospitalization care. The proportion of those without hospitalization to those who should have been hospitalized was 31%. Underuse of the health service among migrants working in the SMEs could be associated with the 'healthy migrant' effect. However, when assessed among the ill migrants in the SMEs, the utilisation rate was still low mainly due to their poor health awareness. Improving their risk perception and integration of occupational and general health service is crucial to improve the health conditions and utilisation of service among migrants in the SMES. Copyright © 2015 The Royal Society for Public Health. Published

  6. 78 FR 45969 - Trade Barriers That U.S. Small and Medium-Sized Enterprises Perceive as Affecting Exports to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-30

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Trade Barriers That U.S. Small and Medium-Sized Enterprises Perceive as Affecting Exports to the... Trade Commission. ACTION: Institution of investigation and scheduling of public hearing. SUMMARY...

  7. Funding Continuing Training in Small and Medium-Sized Enterprises: Discussion and Case Studies from across the EU. CEDEFOP Panorama Series.

    ERIC Educational Resources Information Center

    Pukkinen, Tommi; Romijn, Clemens; Elson-Rogers, Sarah

    There are three main parts to this report of a study that used case studies to showcase the different approaches used to encourage more continuing training within small and medium-sized enterprises (SMEs) across the European Union (EU). Section 1 discusses the importance of funding training in SMEs and highlights the various types of funding…

  8. The Soviet Union and Eastern Europe: A Bibliographic Guide to Recommended Books for Small and Medium-Sized Libraries and School Media Centers.

    ERIC Educational Resources Information Center

    Horak, Stephan M.

    Intended to aid librarians in small- and medium-sized libraries and media centers, this annotated bibliography lists 1,555 books focusing on the Soviet Union and Eastern Europe. The book is divided into four parts: (1) "General and Interrelated Themes--Union of the Soviet Socialist Republics and Eastern European Countries"; (2)…

  9. Towards a Service-Oriented Enterprise: The Design of a Cloud Business Integration Platform in a Medium-Sized Manufacturing Enterprise

    ERIC Educational Resources Information Center

    Stamas, Paul J.

    2013-01-01

    This case study research followed the two-year transition of a medium-sized manufacturing firm towards a service-oriented enterprise. A service-oriented enterprise is an emerging architecture of the firm that leverages the paradigm of services computing to integrate the capabilities of the firm with the complementary competencies of business…

  10. Knowledge Management as a Service: Co-operation between Small and Medium-Sized Enterprises (SMEs) and Training, Consulting and Research Institutions.

    ERIC Educational Resources Information Center

    Scheff, Josef; Kailer, Norbert

    1999-01-01

    A study of 372 companies examined the cooperation between small-to-medium-sized businesses and external providers of training in Austria. New forms of cooperation such as integrated training and consulting programs, process consultation of in-house projects, and support of cooperation are needed. (JOW)

  11. The Soviet Union and Eastern Europe: A Bibliographic Guide to Recommended Books for Small and Medium-Sized Libraries and School Media Centers.

    ERIC Educational Resources Information Center

    Horak, Stephan M.

    Intended to aid librarians in small- and medium-sized libraries and media centers, this annotated bibliography lists 1,555 books focusing on the Soviet Union and Eastern Europe. The book is divided into four parts: (1) "General and Interrelated Themes--Union of the Soviet Socialist Republics and Eastern European Countries"; (2)…

  12. Towards a Service-Oriented Enterprise: The Design of a Cloud Business Integration Platform in a Medium-Sized Manufacturing Enterprise

    ERIC Educational Resources Information Center

    Stamas, Paul J.

    2013-01-01

    This case study research followed the two-year transition of a medium-sized manufacturing firm towards a service-oriented enterprise. A service-oriented enterprise is an emerging architecture of the firm that leverages the paradigm of services computing to integrate the capabilities of the firm with the complementary competencies of business…

  13. Impact of Top Management Team on Firm Performance in Small and Medium-Sized Enterprises Adopting Commercial Open-Source Enterprise Resource Planning

    ERIC Educational Resources Information Center

    Cereola, Sandra J.; Wier, Benson; Norman, Carolyn Strand

    2012-01-01

    Based on the large number of small and medium-sized enterprises (SMEs) in the United States, their increasing interest in enterprise-wide software systems and their impact on the US economy, it is important to understand the determinants that can facilitate the successful implementation and assimilation of such technology into these firms' daily…

  14. A Cost-Benefit Analysis of a Collections Inventory Project: A Statistical Analysis of Inventory Data from a Medium-Sized Academic Library

    ERIC Educational Resources Information Center

    Sung, Jan S.; Whisler, John A.; Sung, Nackil

    2009-01-01

    Using an electronic shelf-reading system a cost-benefit analysis was conducted of an inventory/shelf-reading project in a medium-sized academic library. Analyses include time spent, cataloging discrepancies, books found with active statuses, mis-shelving rate and distance, and subsequent use of found books. Correctly re-shelving "missing"…

  15. Energy efficiency in the US economy technical report four: Analysis of energy-efficiency investment decisions by small and medium-sized manufacturers

    SciTech Connect

    1996-03-01

    This report highlights the results of a comprehensive analysis of investment decisions regarding energy-efficiency measures at small and medium-sized manufacturing plants. The analysis is based primarily on the experiences of companies participating in the US Department of Energy`s Industrial Assessment Center (IAC) program.

  16. Report on the 2nd European conference on computer-aided design (CAD) in small- and medium-size industries (MICAD 82)

    SciTech Connect

    Magnuson, W.G. Jr.

    1982-10-01

    A summary is presented of the 2nd European conference on computer aided design (CAD) in small- and medium-size industries (MICAD82) held in Paris, France, September 21-23, 1982. The conference emphasized applications of CAD in industries with limited investment resources and which are forced to innovate in order to sustain competition.

  17. Impact of Top Management Team on Firm Performance in Small and Medium-Sized Enterprises Adopting Commercial Open-Source Enterprise Resource Planning

    ERIC Educational Resources Information Center

    Cereola, Sandra J.; Wier, Benson; Norman, Carolyn Strand

    2012-01-01

    Based on the large number of small and medium-sized enterprises (SMEs) in the United States, their increasing interest in enterprise-wide software systems and their impact on the US economy, it is important to understand the determinants that can facilitate the successful implementation and assimilation of such technology into these firms' daily…

  18. 50 CFR 622.458 - Caribbean spiny lobster import prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., AND SOUTH ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.458.... Virgin Islands, and a more restrictive minimum size limit that applies to Puerto Rico and the U.S. Virgin... weight into Puerto Rico or the U.S. Virgin Islands. For the purposes of paragraph (a) of this section, a...

  19. A superovulation protocol for the spiny mouse (Acomys cahirinus).

    PubMed

    Pasco, Rachael; Gardner, David K; Walker, David W; Dickinson, Hayley

    2012-01-01

    This study aimed to develop a superovulation protocol for the spiny mouse (Acomys cahirinus). The spiny mouse is a desert-adapted rodent species, with a long oestrus cycle (11 days) compared with rat and mouse, and gives birth to few (mean litter size is 3) precocial offspring after a relatively long gestation (39 days). We successfully optimised a superovulation protocol that elicited a 5-fold increase in the normal ovulation rate of this species. To induce superovulation in the spiny mouse 2 injections of equine chorionic gonadotrophin (eCG, 10 IU each), 9h apart, were required, followed by 20 IU of human chorionic gonadotrophin (hCG). This protocol was successful in 100% of females trialed and at 33 h post-hCG an average of 14.7 ± 1.5, 1-2 cell embryos were recovered. Histological analysis of ovaries following superovulation revealed large corpus lutea and post-ovulatory follicles occupying a large part of the ovary. Ovulation commenced 6-12 h after the hCG injection and continued until 24-33 h post-hCG as indicated by both histological analysis of ovaries and the presence of oocytes/embryos in the oviduct. This superovulation protocol will facilitate the development of an in vitro culture system for spiny mouse embryos.

  20. Development of a Low NOx Medium sized Industrial Gas Turbine Operating on Hydrogen-Rich Renewable and Opportunity Fuels

    SciTech Connect

    Srinivasan, Ram

    2013-07-31

    This report presents the accomplishments at the completion of the DOE sponsored project (Contract # DE-FC26-09NT05873) undertaken by Solar Turbines Incorporated. The objective of this 54-month project was to develop a low NOx combustion system for a medium sized industrial gas turbine engine operating on Hydrogen-rich renewable and opportunity Fuels. The work in this project was focused on development of a combustion system sized for 15MW Titan 130 gas turbine engine based on design analysis and rig test results. Although detailed engine evaluation of the complete system is required prior to commercial application, those tasks were beyond the scope of this DOE sponsored project. The project tasks were organized in three stages, Stages 2 through 4. In Stage 2 of this project, Solar Turbines Incorporated characterized the low emission capability of current Titan 130 SoLoNOx fuel injector while operating on a matrix of fuel blends with varying Hydrogen concentration. The mapping in this phase was performed on a fuel injector designed for natural gas operation. Favorable test results were obtained in this phase on emissions and operability. However, the resulting fuel supply pressure needed to operate the engine with the lower Wobbe Index opportunity fuels would require additional gas compression, resulting in parasitic load and reduced thermal efficiency. In Stage 3, Solar characterized the pressure loss in the fuel injector and developed modifications to the fuel injection system through detailed network analysis. In this modification, only the fuel delivery flowpath was modified and the air-side of the injector and the premixing passages were not altered. The modified injector was fabricated and tested and verified to produce similar operability and emissions as the Stage 2 results. In parallel, Solar also fabricated a dual fuel capable injector with the same air-side flowpath to improve commercialization potential. This injector was also test verified to produce 15

  1. Think Locally, Act Locally: The Detection of Small, Medium-Sized, and Large Communities in Large Networks

    PubMed Central

    Jeub, Lucas G. S.; Balachandran, Prakash; Porter, Mason A.; Mucha, Peter J.; Mahoney, Michael W.

    2016-01-01

    It is common in the study of networks to investigate intermediate-sized (or “meso-scale”) features to try to gain an understanding of network structure and function. For example, numerous algorithms have been developed to try to identify “communities,” which are typically construed as sets of nodes with denser connections internally than with the remainder of a network. In this paper, we adopt a complementary perspective that “communities” are associated with bottlenecks of locally-biased dynamical processes that begin at seed sets of nodes, and we employ several different community-identification procedures (using diffusion-based and geodesic-based dynamics) to investigate community quality as a function of community size. Using several empirical and synthetic networks, we identify several distinct scenarios for “size-resolved community structure” that can arise in real (and realistic) networks: (i) the best small groups of nodes can be better than the best large groups (for a given formulation of the idea of a good community); (ii) the best small groups can have a quality that is comparable to the best medium-sized and large groups; and (iii) the best small groups of nodes can be worse than the best large groups. As we discuss in detail, which of these three cases holds for a given network can make an enormous difference when investigating and making claims about network community structure, and it is important to take this into account to obtain reliable downstream conclusions. Depending on which scenario holds, one may or may not be able to successfully identify “good” communities in a given network (and good communities might not even exist for a given community quality measure), the manner in which different small communities fit together to form meso-scale network structures can be very different, and processes such as viral propagation and information diffusion can exhibit very different dynamics. In addition, our results suggest that

  2. Use of High Spatial Resolution Remote Sensing for Hydro-Geomorphologic Analysis of Medium-sized Arid Basins

    NASA Astrophysics Data System (ADS)

    Sadeh, Yuval; Blumberg, Dan G.; Cohen, Hai; Morin, Efrat; Maman, Shimrit

    2016-04-01

    Arid environments are often remote, expansive, difficult to access and especially vulnerable to flash flood hazards due to the poor understanding of the phenomenon and the lack of meteorological, geomorphological, and hydrological data. For many years, catchment characteristics have been observed using point-based measurements such as rain gauges and soil sample analysis; on the other hand, use of remote sensing technologies can provide spatially continuous hydrological parameters and variables. The advances in remote sensing technologies can provide new geo-spatial data using high spatial and temporal resolution for basin-scale geomorphological analysis and hydrological models. This study used high spatial resolution remote sensing for hydro-geomorphologic analysis of the arid medium size Rahaf watershed (76 km2), located in the Judean Desert, Israel. During the research a high resolution geomorphological map of Rahaf basin was created using WorldView-2 multispectral satellite imageries; surface roughness was estimated using SIR-C and COSMO-SkyMed Synthetic Aperture Radar (SAR) spaceborne sensors; and rainstorm characteristics were extracted using ground-based meteorological radar. The geomorphological mapping of Rahaf into 17 classes with good accuracy. The surface roughness extraction using SAR over the basin showed that the correlation between the COSMO-SkyMed backscatter coefficient and the surface roughness was very strong with an R2 of 0.97. This study showed that using x-band spaceborne sensors with high spatial resolution, such as COSMO-SkyMed, are more suitable for surface roughness evaluation in flat arid environments and should be in favor with longer wavelength operating sensors such as the SIR-C. The current study presents an innovative method to evaluate Manning's hydraulic roughness coefficient (n) in arid environments using radar backscattering. The weather radar rainfall data was calibrated using rain gauges located in the watershed. The

  3. Evaluation of the COSHH Essentials model with a mixture of organic chemicals at a medium-sized paint producer.

    PubMed

    Lee, Eun Gyung; Slaven, James; Bowen, Russell B; Harper, Martin

    2011-01-01

    The Control of Substances Hazardous to Health (COSHH) Essentials model was evaluated using full-shift exposure measurements of five chemical components in a mixture [acetone, ethylbenzene, methyl ethyl ketone, toluene, and xylenes] at a medium-sized plant producing paint materials. Two tasks, batch-making and bucket-washing, were examined. Varying levels of control were already established in both tasks and the average exposures of individual chemicals were considerably lower than the regulatory and advisory 8-h standards. The average exposure fractions using the additive mixture formula were also less than unity (batch-making: 0.25, bucket-washing: 0.56) indicating the mixture of chemicals did not exceed the combined occupational exposure limit (OEL). The paper version of the COSHH Essentials model was used to calculate a predicted exposure range (PER) for each chemical according to different levels of control. The estimated PERs of the tested chemicals for both tasks did not show consistent agreement with exposure measurements when the comparison was made for each control method and this is believed to be because of the considerably different volatilities of the chemicals. Given the combination of health hazard and exposure potential components, the COSHH Essentials model recommended a control approach 'special advice' for both tasks, based on the potential reproductive hazard ascribed to toluene. This would not have been the same conclusion if some other chemical had been substituted (for example styrene, which has the same threshold limit value as toluene). Nevertheless, it was special advice, which had led to the combination of hygienic procedures in place at this plant. The probability of the combined exposure fractions exceeding unity was 0.0002 for the batch-making task indicating that the employees performing this task were most likely well protected below the OELs. Although the employees involved in the bucket-washing task had greater potential to exceed

  4. Moving to business - changes in physical activity and sedentary behavior after multilevel intervention in small and medium-size workplaces.

    PubMed

    Aittasalo, Minna; Livson, Matleena; Lusa, Sirpa; Romo, Ahti; Vähä-Ypyä, Henri; Tokola, Kari; Sievänen, Harri; Mänttäri, Ari; Vasankari, Tommi

    2017-04-17

    Regular physical activity (PA) promotes and excessive sedentary behavior (SB) deteriorates health. Yet the Finnish working-aged population spends most of the day sitting. A 1-year Moving To Business (MTB) -intervention supported small and medium-size workplaces to combat sedentariness. This paper reports the changes in employees' PA and SB from before MTB (baseline) to 1 year after baseline (follow-up). Twelve workplaces with a total of 396 employees participated. Each workplace nominated a team to promote PA and reduce SB at organizational, working unit and employee level. The teams were mentored regionally through meetings, workshop and tools. Changes in PA and SB were assessed with a questionnaire and an accelerometer. Wald Confidence Interval (Cl) for a difference of proportions with matched pairs was used in the questionnaire data (%-points with 95% CI) and linear mixed model in the accelerometer data (minutes and % of wear-time with 95% CI). The mean age of the respondents to the questionnaire (N = 296; 75%) was 42.6 (SD 10.9), 64% were women, 95% had some education after high school, 74% worked in the day shift, 71% did sedentary work and 51% were overweight. The mean number of actions implemented in the workplaces was 6.8 and the multilevel approach was fully applied in 6 workplaces. Based on the questionnaire the time spent in SB decreased from baseline to follow-up 16% (95% CI -29 to -3) in total and 22% (-41 to -3) at work. The accelerometer showed daily increases of 33.7 min (15.3 to 52.1) and 6.8% (3.1 to 10.4) in total PA, 30.9 min (15.3 to 46.5) and 6.1% (2.9 to 9.2) in light PA and 673 (209 to 1139) more steps at work. Daily SB at work decreased 44.9 min (-68.0 to -21.8) and 7.6% (-11.9 to -3.2). Daily leisure PA declined 11.0 min (-24.9 to 2.9) and 3.2% (-6.2 to -0.2). Number of levels or actions had no effect on changes. Employees' PA increased and SB reduced at work during the intervention. At the same time leisure PA decreased slightly

  5. Lunar Gravity Studies from the Lunar Prospector Line-of-Sight Acceleration Data: Isostatic Compensation of Medium Sized Craters

    NASA Astrophysics Data System (ADS)

    Sugano, T.; Heki, K.

    2002-12-01

    Direct estimation of mass distribution on the lunar nearside surface using the Lunar Prospector (LP) line-of-sight (LOS) acceleration data has several merits over conventional methods to estimate Stokes' coefficients of the lunar gravity field, such as (1) high resolution gravity anomaly recovery without introducing Kaula's constraint, (2) fast inversion calculation by stepwise estimation of parameter sets enabled by small correlation between parameters sets. Resolution of the lunar free-air gravity anomaly map obtained here, is as high as a gravity model complete to degree/order 225, and yet less noisy than the recent models. Next we performed terrain correction for the raw LOS acceleration data using lunar topography model from the Clementine laser altimetry data and the average crustal density of 2.9 g/cm3. By conducting the same inversion for the data after the correction, we obtained the map of Bouguer gravity anomaly that mainly reflects the MOHO topography. By comparing maps we notice that signatures of medium-sized (80-300 km in diameter) craters visible as topographic depression and negative free air anomaly, disappear in the Bouguer anomaly. The absence of mass deficits in the Bouguer anomaly suggests that the MOHO beneath them is flat. Generally speaking, longer wavelength topographic features have to be supported by MOHO topography (Airy isostatic compensation) while small scale topographic features are supported by lithospheric strength. The boundary between these two modes constrains the lithosphere thickness, and hence thermal structure near the surface. Larger craters are known to have become Mascons; mantle plugs and high-density mare basalts cause positive gravity anomalies there. The smallest Mascon has diameters a little larger than 300 km (e.g. Schiller-Zuccius), and the boundary between the two compensation status seems to lie around 300 km. Thermal evolution history of the Moon suggests temporally increasing thickness of lithosphere over its

  6. Structural alterations of spiny stellate cells in the somatosensory cortex in ephrin-A5-deficient mice.

    PubMed

    Guellmar, André; Rudolph, Judith; Bolz, Jürgen

    2009-12-10

    Previous studies demonstrated that in ephrin-A5-deficient mice corticothalamic arbors are reduced by more than 50% in layer 4 of the somatosensory cortex (S1), where ephrin-A5 is normally expressed. Here we examined possible consequences of the reduced thalamic input on spiny stellate cells, the target neurons of thalamocortical afferents. Using ballistic delivery of particles coated with lipophilic dyes in fixed slices and confocal laser-microscopy, we could quantitatively analyze the morphology of these neurons. Cells were examined in S1 at postnatal day 8 (P8), when thalamic afferents establish synaptic contacts and the dendrites of their target cells are covered with filopodia, and at P23, after synapse formation and replacement of filopodia by spines. Our results indicate that at P8 the dendrites of cells in mutant animals exhibit more filopodia and are more branched than dendrites of wildtype cells. In contrast, there is no difference in the extent of the dendritic tree between knockout and control animals. At P23, dendrites of neurons in ephrin-A5-deficient mice are still more branched, but possess fewer spines than wildtype cells. Thus, at early stages layer 4 neurons appear to compensate the reduced thalamic input by increasing dendritic branching and the density of filopodia. However, while at later stages the dendrites of layer 4 neurons in mutants are still more branched, their spine density is now lower than in wildtype cells. Taken together, these data demonstrate that the structure of spiny stellate cells is shaped by thalamic input and Eph receptor signaling.

  7. Morphology of VIP/nNOS-immunoreactive myenteric neurons in the human gut.

    PubMed

    Brehmer, A; Schrödl, F; Neuhuber, W

    2006-05-01

    In this study, we characterized human myenteric neurons co-immunoreactive for neuronal nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP) by their morphology and their proportion as related to the putative entire myenteric neuronal population. Nine wholemounts (small and large intestinal samples) from nine patients were triple-stained for VIP, neurofilaments (NF) and nNOS. Most neurons immunoreactive for all three markers displayed radially emanating, partly branching dendrites with spiny endings. These neurons were called spiny neurons. The spiny character of their dendrites was more pronounced in the small intestinal specimens and differed markedly from enkephalinergic stubby neurons described earlier. Exclusively in the duodenum, some neurons displayed prominent main dendrites with spiny side branches. Of the axons which could be followed from the ganglion of origin within primary strands of the myenteric plexus beyond the next ganglion (70 out of 140 traced neurons), 94.3% run anally and 5.7% orally. Very few neurons reactive for both VIP and nNOS could not be morphologically classified due to weak or absent NF-immunoreactivity. Another six wholemounts were triple-stained for VIP, nNOS and Hu proteins (HU). The proportion of VIP/nNOS-coreactive neurons in relation to the number of HU-reactive neurons was between 5.8 and 11.5% in the small and between 10.6 and 17.5% in the large intestinal specimens. We conclude that human myenteric spiny neurons co-immunoreactive for VIP and nNOS represent either inhibitory motor or descending interneurons.

  8. Co-localization of the D1 dopamine receptor in a subset of DARPP-32-containing neurons in rat caudate-putamen.

    PubMed

    Langley, K C; Bergson, C; Greengard, P; Ouimet, C C

    1997-06-01

    DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, apparent molecular weight of 32,000) is part of the D1 dopamine receptor signal transduction cascade. Both the D1 receptor and DARPP-32 are found in the caudate putamen, but it is not known if they co-localize in the medium-sized spiny neurons. In the present study, double-labelling immunocytochemistry was used to simultaneously localize the D1 receptor and DARPP-32 in the rat caudate-putamen. The neuropil was heavily and uniformly immunoreactive for both the D1 receptor and DARPP-32. All cell bodies immunopositive for the D1 receptor were immunopositive for DARPP-32. The D1 receptor was not detectable, however, in nearly half of the DARPP-32-containing cell bodies. DARPP-32 is present in striatopallidal and striatonigral projections. The D1 receptor co-localized with DARPP-32 in fibres of the entopeduncular nucleus and the pars reticulata of the substantia nigra. In the globus pallidus, however, D1 receptor immunoreactivity was barely detectable, while DARPP-32 immunolabelling of axons and axon terminals was intense. These data suggest that the striatal somata containing both the D1 receptor and DARPP-32 project to the entopeduncular nucleus and substantia nigra, whereas somata containing only DARPP-32 immunoreactivity project to the globus pallidus. Thus, the differences in expression of the D1 receptor and of DARPP-32 within striatal cell bodies are likely reflected in their projections. The co-localization of the D1 receptor and DARPP-32 is consistent with the known regulation of DARPP-32 phosphorylation by D1 receptor activation. The demonstration of a large population of striatal neurons that contain DARPP-32 but apparently do not contain D1 receptors substantiates the premise that these cells have an alternative signal transduction pathway. Subsequent studies are needed to search for a signal transduction pathway for these neurons analogous to the dopamine D1 receptor pathway.

  9. Evaluation of the COSHH Essentials Model with a Mixture of Organic Chemicals at a Medium-Sized Paint Producer

    PubMed Central

    Lee, Eun Gyung; Slaven, James; Bowen, Russell B.; Harper, Martin

    2011-01-01

    The Control of Substances Hazardous to Health (COSHH) Essentials model was evaluated using full-shift exposure measurements of five chemical components in a mixture [acetone, ethylbenzene, methyl ethyl ketone, toluene, and xylenes] at a medium-sized plant producing paint materials. Two tasks, batch-making and bucket-washing, were examined. Varying levels of control were already established in both tasks and the average exposures of individual chemicals were considerably lower than the regulatory and advisory 8-h standards. The average exposure fractions using the additive mixture formula were also less than unity (batch-making: 0.25, bucket-washing: 0.56) indicating the mixture of chemicals did not exceed the combined occupational exposure limit (OEL). The paper version of the COSHH Essentials model was used to calculate a predicted exposure range (PER) for each chemical according to different levels of control. The estimated PERs of the tested chemicals for both tasks did not show consistent agreement with exposure measurements when the comparison was made for each control method and this is believed to be because of the considerably different volatilities of the chemicals. Given the combination of health hazard and exposure potential components, the COSHH Essentials model recommended a control approach ‘special advice’ for both tasks, based on the potential reproductive hazard ascribed to toluene. This would not have been the same conclusion if some other chemical had been substituted (for example styrene, which has the same threshold limit value as toluene). Nevertheless, it was special advice, which had led to the combination of hygienic procedures in place at this plant. The probability of the combined exposure fractions exceeding unity was 0.0002 for the batch-making task indicating that the employees performing this task were most likely well protected below the OELs. Although the employees involved in the bucket-washing task had greater potential to

  10. The substructure of the suprachiasmatic nucleus: Similarities between nocturnal and diurnal spiny mice.

    PubMed

    Cohen, Rotem; Kronfeld-Schor, Noga; Ramanathan, Chidambaram; Baumgras, Anna; Smale, Laura

    2010-01-01

    Evolutionary transitions between nocturnal and diurnal patterns of adaptation to the day-night cycle must have involved fundamental changes in the neural mechanisms that coordinate the daily patterning of activity, but little is known about how these mechanisms differ. One reason is that information on these systems in very closely related diurnal and nocturnal species is lacking. In this study, we characterize the suprachiasmatic nucleus (SCN), the primary brain structure involved in the generation and coordination of circadian rhythms, in two members of the genus Acomys with very different activity patterns, Acomys russatus (the golden spiny mouse, diurnal) and Acomys cahirinus (the common spiny mouse, nocturnal). Immunohistochemical techniques were used to label cell bodies containing vasoactive intestinal polypeptide (VIP), vasopressin (VP), gastrin-releasing peptide (GRP) and calbindin (CalB) in the SCN, as well as two sets of inputs to it, those containing serotonin (5-HT) and neuropeptide Y (NPY), respectively. All were present in the SCN of both species and no differences between them were seen. On the basis of neuronal phenotype, the SCN was organized into three basic regions that contained VIP-immunoreactive (-ir), CalB-ir and VP-ir cells, in the ventral, middle and dorsal SCN, respectively. In the rostral SCN, GRP-ir cells were in both the VIP and the CalB cell regions, and in the caudal area they were distributed across a portion of each of the other three regions. Fibers containing NPY-ir and serotonin (5-HT)-ir were most concentrated in the areas containing VIP-ir and CalB-ir cells, respectively. The details of the spatial relationships among the labeled cells and fibers seen here are discussed in relation to different approaches investigators have taken to characterize the SCN more generally.

  11. Energy conserved and costs saved by small and medium-size manufacturers: 1985-1986 EADC (Energy Analysis and Diagnostic Center) program period

    SciTech Connect

    Kirsch, F.W.

    1988-03-01

    The Energy Analysis and Diagnostic Center (EADC) program continues to provide energy-conserving and cost-saving assistance in the plants of small and medium-size manufacturers. This report presents the results of energy audits in 300 such plants carried out by ten EADCs during the 1985-86 program period. Also included are the results obtained during 1987 from manufacturers who implemented 1267 of the EADCs' recommendations from the preceding year.

  12. Energy conserved and costs saved by small and medium-size manufacturers: (Final and annual report), 1985-86 EADC (Energy Analysis and Diagnostic Center) program period

    SciTech Connect

    Kirsch, F.W.

    1988-03-01

    The Energy Analysis and Diagnostic Center (EADC) program continues to provide energy-conserving and cost-saving assistance in the plants of small and medium-size manufacturers. This report presents the results of energy audits in 300 such plants carried out by ten EADCs during the 1985-1986 program period. Also included are the results obtained during 1987 from manufacturers who implemented 1,267 of the EADCs' recommendations from the preceding year.

  13. The coupling law of the interaction between economic development and eco-environment in medium-sized city: a case from Lianyungang city in China

    NASA Astrophysics Data System (ADS)

    Li, Tingyou; Lin, Zhenshan; Xie, Biao

    2008-10-01

    City plays a strong role in the development of national economy and society. But its high economic development speed results in big resource depletion and environmental pressure. The coupling law between economic development and eco-environment refers to the collection of all interaction non-linear relations among economic, social and eco-environmental system during the economic development course. Many large cities have been in the medium or later stage of industrialization while medium-sized cities are just in the beginning for the industrialization. For this special development period of industrialization of medium-sized city, it is a great practical significance for analyzing the coupling law of the interaction between economic development and eco-environment. In this paper, Lianyungang City was selected as the study demonstration area. 6 mathematics models for describing the quantitative relations between environment and economic development were achieved through the analysis of the relativity and quadratic and cubic equation fit and regression based on the data of environmental quality, pollutant discharge and economic development in the period of the years 1983-2006. The results showed that there exists the coupling law of the Interaction between Economic Development and Eco-environment. Through the establishment of conceptual model, the coupling law of the interaction between economic development and eco-environment in Lianyungang City was quantitatively analyzed and studied, which is helpful for the comprehensive policy-making and sustainable development in medium-sized city.

  14. Use of Care Management Practices in Small- and Medium-Sized Physician Groups: Do Public Reporting of Physician Quality and Financial Incentives Matter?

    PubMed Central

    Alexander, Jeffrey A; Maeng, Daniel; Casalino, Lawrence P; Rittenhouse, Diane

    2013-01-01

    Objective To examine the effect of public reporting (PR) and financial incentives tied to quality performance on the use of care management practices (CMPs) among small- and medium-sized physician groups. Data Survey data from The National Study of Small and Medium-sized Physician Practices were used. Primary data collection was also conducted to assess community-level PR activities. The final sample included 643 practices engaged in quality reporting; about half of these practices were subject to PR. Study Design We used a treatment effects model. The instrumental variables were the community-level variables that capture the level of PR activity in each community in which the practices operate. Findings (1) PR is associated with increased use of CMPs, but the estimate is not statistically significant; (2) financial incentives are associated with greater use of CMPs; (3) practices' awareness/sensitivity to quality reports is positively related to their use of CMPs; and (4) combined PR and financial incentives jointly affect CMP use to a greater degree than either of these factors alone. Conclusion Small- to medium-sized practices appear to respond to PR and financial incentives by greater use of CMPs. Future research needs to investigate the appropriate mix and type of incentive arrangements and quality reporting. PMID:22880957

  15. Axial levodopa-induced dyskinesias and neuronal activity in the dorsal striatum.

    PubMed

    Alberico, Stephanie L; Kim, Young-Cho; Lence, Tomas; Narayanan, Nandakumar S

    2017-02-20

    Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias. We developed an automated 3-dimensional motion tracking system to capture the development of axial dyskinesias at ∼10ms resolution, and correlated these movements with neuronal activity of striatal medium spiny neurons and fast-spiking interneurons. The average firing rate of medium spiny neurons increased as axial dyskinesias developed, and both medium spiny neurons and fast-spiking interneurons were modulated around axial dyskinesias. We also found that delta field potential power increased in the striatum with dyskinesia, and that this increased delta power coupled with striatal neurons. Our findings provide insight into how striatal networks change as levodopa-induced dyskinesias develop, and suggest that increased medium spiny neuron firing, increased delta field potential power, and abnormal delta-coupling may be neurophysiological signatures of dyskinesias. These data could be helpful in understanding the role of the striatum in the pathogenesis of dyskinesias in Parkinson's disease.

  16. Fezf2 directs the differentiation of corticofugal neurons from striatal progenitors in vivo.

    PubMed

    Rouaux, Caroline; Arlotta, Paola

    2010-11-01

    In the developing cerebral cortex, cell-extrinsic and cell-intrinsic signals govern the establishment of neuron subtype-specific identity. Here we show that, within the niche of the striatum, the expression of a single transcription factor, Fezf2, is sufficient to generate corticofugal neurons from progenitors fated to become medium spiny neurons. This demonstrates that a specific population of cortical projection neurons can be directed to differentiate outside of the cortex by cell-autonomous signaling.

  17. Prenatally administered dexamethasone impairs folliculogenesis in spiny mouse offspring.

    PubMed

    Hułas-Stasiak, Monika; Dobrowolski, Piotr; Tomaszewska, Ewa

    2015-01-07

    This study was designed to determine whether prenatal dexamethasone treatment has an effect on follicular development and atresia in the ovary of spiny mouse (Acomys cahirinus) offspring. Dexamethasone (125µg kg-1 bodyweight per day) was administered to pregnant spiny mice from Day 20 of gestation to parturition. The processes of follicle loss were analysed using classical markers of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling reaction, active caspase-3) and autophagy (Lamp1). The present study indicated that dexamethasone reduced the pool of healthy primordial follicles. Moreover, the oocytes from these follicles showed intensive caspase-3 and Lamp1 staining. Surprisingly, dexamethasone caused an increase in the number of secondary follicles; however, most of these follicles were characterised by extensive degeneration of the oocyte and caspase-3 and Lamp1 labelling. Western-blot analysis indicated that the glucocorticoid receptor as well as apoptosis and autophagy markers were more strongly expressed in the DEX-treated group than in the control. On the basis of these findings, we have concluded that dexamethasone impairs spiny mouse folliculogenesis and enhances follicular atresia through induction of autophagy or combined autophagy and apoptosis.

  18. Relative impact of on-road vehicular and point-source industrial emissions of air pollutants in a medium-sized Andean city

    NASA Astrophysics Data System (ADS)

    González, C. M.; Gómez, C. D.; Rojas, N. Y.; Acevedo, H.; Aristizábal, B. H.

    2017-03-01

    Cities in emerging countries are facing a fast growth and urbanization; however, the study of air pollutant emissions and its dynamics is scarce, making their populations vulnerable to potential effects of air pollution. This situation is critical in medium-sized urban areas built along the tropical Andean mountains. This work assesses the contribution of on-road vehicular and point-source industrial activities in the medium-sized Andean city of Manizales, Colombia. Annual fluxes of criteria pollutants, NMVOC, and greenhouse gases were estimated. Emissions were dominated by vehicular activity, with more than 90% of total estimated releases for the majority of air pollutants. On-road vehicular emissions for CO (43.4 Gg/yr) and NMVOC (9.6 Gg/yr) were mainly associated with the use of motorcycles (50% and 81% of total CO and NMVOC emissions respectively). Public transit buses were the main source of PM10 (47%) and NOx (48%). The per-capita emission index was significantly higher in Manizales than in other medium-sized cities, especially for NMVOC, CO, NOx and CO2. The unique mountainous terrain of Andean cities suggest that a methodology based on VSP model could give more realistic emission estimates, with additional model components that include slope and acceleration. Food and beverage facilities were the main contributors of point-source industrial emissions for PM10 (63%), SOx (55%) and NOx (45%), whereas scrap metal recycling had high emissions of CO (73%) and NMVOC (47%). Results provide the baseline for ongoing research in atmospheric modeling and urban air quality, in order to improve the understanding of air pollutant fluxes, transport and transformation in the atmosphere. In addition, this emission inventory could be used as a tool to identify areas of public health exposure and provide information for future decision makers.

  19. Effects of birth asphyxia on neonatal hippocampal structure and function in the spiny mouse.

    PubMed

    Fleiss, B; Coleman, H A; Castillo-Melendez, M; Ireland, Z; Walker, D W; Parkington, H C

    2011-11-01

    Studies of human neonates, and in animal experiments, suggest that birth asphyxia results in functional compromise of the hippocampus, even when structural damage is not observable or resolves in early postnatal life. The aim of this study was to determine if changes in hippocampal function occur in a model of birth asphyxia in the precocial spiny mouse where it is reported there is no major lesion or infarct. Further, to assess if, as in human infants, this functional deficit has a sex-dependent component. At 37 days gestation (term=39 days) spiny mice fetuses were either delivered immediately by caesarean section (control group) or exposed to 7.5min of in utero asphyxia causing systemic acidosis and hypoxia. At 5 days of age hippocampal function was assessed ex vivo in brain slices, or brains were collected for examination of structure or protein expression. This model of birth asphyxia did not cause infarct or cystic lesion in the postnatal day 5 (P5) hippocampus, and the number of proliferating or pyknotic cells in the hippocampus was unchanged, although neuronal density in the CA1 and CA3 was increased. Protein expression of synaptophysin, brain-derived neurotrophic factor (BDNF), and the inositol trisphosphate receptor 1 (IP(3)R1) were all significantly increased after birth asphyxia, while long-term potentiation (LTP), paired pulse facilitation (PPF), and post-tetanic potentiation (PTP) were all reduced at P5 by birth asphyxia. In control P5 pups, PPF and synaptic fatigue were greater in female compared to male pups, and after birth asphyxia PPF and synaptic fatigue were reduced to a greater extent in female vs. male pups. In contrast, the asphyxia-induced increase in synaptophysin expression and neuronal density were greater in male pups. Thus, birth asphyxia in this precocial species causes functional deficits without major structural damage, and there is a sex-dependent effect on the hippocampus. This may be a clinically relevant model for assessing

  20. 77 FR 76458 - Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Spiny Lobster Fishery of Puerto...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-28

    ... determine spiny lobster growth and movement patterns, and an attempt will be made to estimate the spiny lobster population size in the U.S. Virgin Islands. Currently, data on U.S. Caribbean spiny lobster life history are limited, particularly growth rates and abundance patterns. Additional life history information...

  1. 76 FR 75488 - Fisheries of the Caribbean, Gulf of Mexico, and South Atlantic; Spiny Lobster Fishery of the Gulf...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ...) Poisons and explosives may not be used to take a spiny lobster in the EEZ as defined in Sec. 640.1(b). For... flush a spiny lobster out of rocks or coral, are poisons. A vessel in the spiny lobster fishery may...

  2. What affects the innovation performance of small and medium-sized enterprises (SMEs) in the biotechnology industry? An empirical study on Korean biotech SMEs.

    PubMed

    Kang, Kyung-Nam; Lee, Yoon-Sik

    2008-10-01

    Research-intensive small and medium-sized enterprises (SMEs) play a crucial role in the advancement of the biotechnology industry. This paper explored the impacts of internal and contextual variables on innovative activity in Korea and compared the results of this analysis with previous studies of other countries. Our analysis of 149 Korean biotech SMEs showed that the ratio of R&D expenditure to sales, the ratio of R&D employees to total employees, CEO characteristics, governmental support and international networking are positively correlated with a firm's innovation performance. The results may help decision makers to better foster SMEs in the Korean biotechnology industry.

  3. Eruptive activity of enigmatic medium-sized volcanoes in the Michoacán-Guanajuato Volcanic Field (MGVF), Central Mexico: The case of El Metate

    NASA Astrophysics Data System (ADS)

    Chevrel, M.; Siebe, C.; Guilbaud, M. N.

    2014-12-01

    The MGVF has a total area of ca. 40,000 km2 and is well known for being the host of the only two monogenetic volcanoes in Mexico that were born in historical times: Jorullo (1759-1774) and Paricutin (1943-1952). Another particularity of the MGVF is its high number of eruptive vents with over 1000 small monogenetic cones and associated lava flows (average vol. of 0.021 km3) and ca. 400 medium-sized volcanoes (average vol. from 0.5 to 50 km3). Most of these medium-sized volcanoes may be characterized as shields that were produced dominantly by effusive activity as opposed to the small cones formed also by explosive phases of activity. The products of the small cones range from olivine basalts to andesites whereas the medium-sized volcanoes are restricted to a smaller compositional range in the andesitic domain. Although the medium-sized volcanoes are more sparsely distributed in time and space and less abundant than the small cones, the risks associated with renewal of this type of activity should not be neglected. This study focuses on El Metate which is probably the youngest shield of the MGVF (< 3,700 y. BP). Unlike a typical shield volcano composed of a succession of thin fluid basaltic flows, El Metate consists of well-preserved >60 m thick andesite flows distributed radially around a summit dome. Detailed mapping and sampling allowed us to reconstruct its eruptive activity and the time sequence of lava flow emplacement. We have identified 13 individual lava flows with lengths ranging between 3 and 15 km covering 103 km2 and average thicknesses between 60 and 150 m. Individual volumes range between 0.5 and 3.5 km3 for a total of 11 to 15 km3. Estimates of flow emplacement parameters indicate maximum average effusion rates ranging between 15 and 100 m3.s-1 and a cumulative duration from 15 to 30 years. Such a short emplacement time is comparable to the historical monogenetic eruption of nearby Paricutin volcano (9 years) but the erupted volume of lava is

  4. 77 FR 15991 - Fisheries of the Northeastern United States; Proposed 2012 Spiny Dogfish Fishery Specifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... available scientific information and reflect recent increases in spiny dogfish biomass. The proposed action... (Center) updated spiny dogfish stock status, using the most recent catch data and biomass estimates from the 2011 spring trawl survey. Updated estimates indicate that the female spawning stock biomass (SSB...

  5. 75 FR 11129 - Mid-Atlantic Fishery Management Council; Atlantic Mackerel, Butterfish, Atlantic Bluefish, Spiny...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ...; Atlantic Mackerel, Butterfish, Atlantic Bluefish, Spiny Dogfish, Summer Flounder, Scup, Black Sea Bass... Atlantic mackerel, butterfish, Atlantic bluefish, spiny dogfish, summer flounder, scup, black sea bass... Council has been in the process of developing an Omnibus Amendment to the FMPs for Atlantic...

  6. Distribution and function of splash, an achaete-scute homolog in the adult olfactory organ of the Caribbean spiny lobster Panulirus argus

    PubMed Central

    Tadesse, Tizeta; Schmidt, Manfred; Walthall, William W.; Tai, Phang C.; Derby, Charles D.

    2011-01-01

    achaete-scute complex (ASC) genes, which encode basic helix-loop-helix transcription factors, regulate embryonic and adult neurogenesis in many animals. In adult arthropods, including crustaceans, ASC homologs have been identified but rarely functionally characterized. We took advantage of the recently identified crustacean homolog, splash (spiny lobster achaete scute homolog), in the olfactory organ of the Caribbean spiny lobster Panulirus argus to examine its role in adult neurogenesis. We tested the hypothesis that splash is associated with but not restricted to sensory neuron formation in the olfactory organ, the antennular lateral flagellum (LF), of adult spiny lobsters. We demonstrated splash labeling in epithelial cells across LF developmental zones (i.e., proliferation and mature zones), in auxiliary cells surrounding dendrites of olfactory receptor neurons (ORNs), and in immature and mature ORNs, but not in granulocytes or chromatophores. Since ORN proliferation varies with molt stage, we examined splash expression across molt stages and found that molt stage affected splash expression in the ORN mature zone but not in the proliferation zone. In vivo incorporation of bromodeoxyuridine (BrdU) showed no correlation in the cellular pattern of splash expression and BrdU labeling. The intensity of splash labeling was dramatically enhanced in the proliferation zones following LF damage, suggesting enhanced splash expression during repair and/or regeneration. We conclude that splash is not closely associated with the formation of sensory neurons under normal physiological conditions, and we propose that splash is involved in repair and regeneration. We also propose that splash has additional roles other than neurogenesis in adult crustaceans. PMID:21394934

  7. The Cairo spiny mouse Acomys cahirinus shows a strong affinity to the Mongolian gerbil Meriones unguiculatus.

    PubMed

    Agulnik, S I; Silver, L M

    1996-01-01

    The classification of the African spiny mice (genus Acomys) within the Muridae family of rodents has been fraught with controversy. Morphological data suggest a close affinity between this group and true old world mice of the genus Mus. However, the combined results of immunological, biochemical, and DNA melting studies suggest that spiny mice should not even be considered as members of the Murinae subfamily. To further elucidate the position of the spiny mice within the rodent phylogenetic tree, we performed a direct sequence comparison of a 583-nucleotide homologous region from the spiny mouse type species Acomys cahirinus and five other representative rodent species. Our results provide incontrovertible evidence to support the contention that the spiny mouse is more closely related to the Mongolian gerbil Meriones unguiculatus than it is to Mus musculus.

  8. Selective Effects of PDE10A Inhibitors on Striatopallidal Neurons Require Phosphatase Inhibition by DARPP-321,2,3

    PubMed Central

    Polito, Marina; Guiot, Elvire; Gangarossa, Giuseppe; Longueville, Sophie; Doulazmi, Mohamed; Valjent, Emmanuel; Hervé, Denis; Girault, Jean-Antoine; Paupardin-Tritsch, Danièle; Castro, Liliana R. V.

    2015-01-01

    Abstract Type 10A phosphodiesterase (PDE10A) is highly expressed in the striatum, in striatonigral and striatopallidal medium-sized spiny neurons (MSNs), which express D1 and D2 dopamine receptors, respectively. PDE10A inhibitors have pharmacological and behavioral effects suggesting an antipsychotic profile, but the cellular bases of these effects are unclear. We analyzed the effects of PDE10A inhibition in vivo by immunohistochemistry, and imaged cAMP, cAMP-dependent protein kinase A (PKA), and cGMP signals with biosensors in mouse brain slices. PDE10A inhibition in mouse striatal slices produced a steady-state increase in intracellular cAMP concentration in D1 and D2 MSNs, demonstrating that PDE10A regulates basal cAMP levels. Surprisingly, the PKA-dependent AKAR3 phosphorylation signal was strong in D2 MSNs, whereas D1 MSNs remained unresponsive. This effect was also observed in adult mice in vivo since PDE10A inhibition increased phospho-histone H3 immunoreactivity selectively in D2 MSNs in the dorsomedial striatum. The PKA-dependent effects in D2 MSNs were prevented in brain slices and in vivo by mutation of the PKA-regulated phosphorylation site of 32 kDa dopamine- and cAMP-regulated phosphoprotein (DARPP-32), which is required for protein phosphatase-1 inhibition. These data highlight differences in the integration of the cAMP signal in D1 and D2 MSNs, resulting from stronger inhibition of protein phosphatase-1 by DARPP-32 in D2 MSNs than in D1 MSNs. This study shows that PDE10A inhibitors share with antipsychotic medications the property of activating preferentially PKA-dependent signaling in D2 MSNs. PMID:26465004

  9. Interspecific competition and torpor in golden spiny mice: two sides of the energy-acquisition coin.

    PubMed

    Levy, Ofir; Dayan, Tamar; Kronfeld-Schor, Noga

    2011-09-01

    We studied the occurrence of torpor in golden spiny mice in a hot rocky desert near the Dead Sea. In this rodent assemblage, a congener, the nocturnal common spiny mouse, competitively excluded the golden spiny mouse from the nocturnal part of the diel cycle and forced it into diurnal activity; this temporal partitioning allows the two species to partition their prey populations, particularly in summer when the diet of the two species is comprised mainly of arthropods, and largely overlap. We studied the effect of the presence of the common spiny mice at two resource levels (natural food availability and food added ad libitum) on populations of golden spiny mice in four large outdoor enclosures: two with common spiny mice removed and two enclosures with populations of both species. We hypothesized that with interspecific competition and/or reduced resources, golden spiny mice will increase their use of torpor. As we expected, supplemented food reduced the total time spent torpid. In summer, when the different activity periods of the two species results in prey species partitioning, removal of the congener did not affect torpor in the golden spiny mouse. However, in winter, when insect populations are low and the two species of mice overlap in a largely vegetarian diet, removal of the common spiny mouse reduced torpor in golden spiny mice, whether food was supplemented or not. This result suggests that torpor, a mechanism that allows small mammals to sustain periods of low availability of resources or high energetic requirements, may also help them to tolerate periods of enhanced interspecific competition. This may be a significant short-term mechanism that reduces competition and hence increases fitness, in particular of individuals of the subordinate species whose accessibility to resources may be limited.

  10. Post-operative complications associated with the Arthrex Canine Cranial Cruciate Ligament Repair Anchor System in small- to medium-sized dogs: A retrospective analysis (2009–2012)

    PubMed Central

    Rappa, Nick S.; Radasch, Robert M.

    2016-01-01

    This study classified and determined the post-operative complication rate associated with stabilization of cranial (CCL) ligament deficient stifles in small- to medium-sized dogs with the Arthrex Canine Cranial Cruciate Ligament Repair Anchor System (CCLRAS). Eighty-five medical records from 2009 to 2012 from 1 institution were evaluated. Complications were classified according to previously proposed definitions for orthopedic studies in veterinary medicine. Fifty-two owners were contacted by telephone at least 6 months after surgery and given a questionnaire to classify complications related to the implant. A visual analog scale was used to assess functionality and degree of pain. The overall complication rate was 30.3% with an inflammation-infection rate of 5.4% and a documented infection rate requiring implant removal of 1.8%. Owners reported full or acceptable function in 96% of cases with an average functional score of 86.5. Stabilization of CCL-deficient stifles in small- to medium-sized dogs with the Arthrex Canine CCLRAS is reliable with acceptable complication rates. PMID:27493284

  11. A signet-ring cell melanoma arising from a medium-sized congenital melanocytic nevus in an adult: A case report and literature review.

    PubMed

    Tajima, Shogo; Koda, Kenji

    2015-07-01

    Patients with congenital nevus, especially giant congenital melanocytic nevus (CMN) measuring >20 cm, are known to be at elevated risk of developing melanomas, especially during the first and second decades of life. Melanomas rarely develop in patients with small and medium-sized CMNs, but if they do, they occur during the fourth and fifth decades of life. We present a case of a rapidly enlarging signet-ring cell melanoma (over 3 months) that arose from a medium-sized CMN in a 57-year-old Japanese man. Only 11 other cases of signet-ring cell melanomas at the primary site have been reported. On the basis of morphology alone, it is difficult to diagnose a nodule appearing in a CMN as a signet-ring cell melanoma, because even a benign melanocytic nevus can appear as signet-ring cell morphology. Moreover, a rapidly growing proliferative nodule (PN) more often develops in a CMN than melanoma; PNs may at times exhibit enough atypia to be comparable to melanomas. In our case, loss of p16 expression in the melanoma distinguished it from the nevus cells and was helpful in making the correct diagnosis. Clinical information, such as the patient's age, was also useful in establishing the diagnosis.

  12. Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies.

    PubMed

    Hwang, Thomas J; Kesselheim, Aaron S

    2016-02-01

    Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats.

  13. Impact of the Local Public Hospital Reform on the Efficiency of Medium-Sized Hospitals in Japan: An Improved Slacks-Based Measure Data Envelopment Analysis Approach.

    PubMed

    Zhang, Xing; Tone, Kaoru; Lu, Yingzhe

    2017-03-06

    To assess the change in efficiency and total factor productivity (TFP) of the local public hospitals in Japan after the local public hospital reform launched in late 2007, which was aimed at improving the financial capability and operational efficiency of hospitals. Secondary data were collected from the Ministry of Internal Affairs and Communications on 213 eligible medium-sized hospitals, each operating 100-400 beds from FY2006 to FY2011. The improved slacks-based measure nonoriented data envelopment analysis models (Quasi-Max SBM nonoriented DEA models) were used to estimate dynamic efficiency score and Malmquist Index. The dynamic efficiency measure indicated an efficiency gain in the first several years of the reform and then was followed by a decrease. Malmquist Index analysis showed a significant decline in the TFP between 2006 and 2011. The financial improvement of medium-sized hospitals was not associated with enhancement of efficiency. Hospital efficiency was not significantly different among ownership structure and law-application system groups, but it was significantly affected by hospital location. The results indicate a need for region-tailored health care policies and for a more comprehensive reform to overcome the systemic constraints that might contribute to the decline of the TFP. © Health Research and Educational Trust.

  14. Injection barrel with a tapered structure for a low speed and small size cryogenic hydrogen pellet in medium-sized plasma fusion devices

    NASA Astrophysics Data System (ADS)

    Motojima, G.; Sakamoto, R.; Okada, H.; Nagasaki, K.; Yamada, H.; Nakamura, Y.; Kado, S.; Kobayashi, S.; Konoshima, S.; Minami, T.; Ohshima, S.; Yamamoto, S.; Mizuuchi, T.; Mutoh, T.

    2016-10-01

    An injection barrel was designed and fabricated for a small size 0.8 mm cryogenic pellet with a low speed of 200-300 m/s in medium-sized plasma fusion devices. Pellet injection with pneumatic acceleration was examined using a conventional in situ technique. A tapered structure was applied in the downstream side of the injection barrel to satisfy the requirement of pellet speed reduction by expansion of the propellant gas. Shadowgraph and light gate measurements show that the intact pellets have speeds of 260 ± 30 m/s and a typical size of 1.1-1.2 mm. The pellet ablation code based on a neutral gas shielding model shows that the penetration depth of the measured pellet parameters does not cross the plasma center, even in medium-sized plasma devices such as the Heliotron J helical device. The injection barrel with a tapered structure developed in this study is feasible for low speed pellet injection.

  15. Injection barrel with a tapered structure for a low speed and small size cryogenic hydrogen pellet in medium-sized plasma fusion devices.

    PubMed

    Motojima, G; Sakamoto, R; Okada, H; Nagasaki, K; Yamada, H; Nakamura, Y; Kado, S; Kobayashi, S; Konoshima, S; Minami, T; Ohshima, S; Yamamoto, S; Mizuuchi, T; Mutoh, T

    2016-10-01

    An injection barrel was designed and fabricated for a small size 0.8 mm cryogenic pellet with a low speed of 200-300 m/s in medium-sized plasma fusion devices. Pellet injection with pneumatic acceleration was examined using a conventional in situ technique. A tapered structure was applied in the downstream side of the injection barrel to satisfy the requirement of pellet speed reduction by expansion of the propellant gas. Shadowgraph and light gate measurements show that the intact pellets have speeds of 260 ± 30 m/s and a typical size of 1.1-1.2 mm. The pellet ablation code based on a neutral gas shielding model shows that the penetration depth of the measured pellet parameters does not cross the plasma center, even in medium-sized plasma devices such as the Heliotron J helical device. The injection barrel with a tapered structure developed in this study is feasible for low speed pellet injection.

  16. Chemical management and control strategies: experiences from the GTZ pilot project on chemical safety in Indonesian small and medium-sized enterprises.

    PubMed

    Tischer, M; Scholaen, S

    2003-10-01

    In 1998 the Deutsche Gesellschaft für Technische Zusammenarbeit (GTZ) launched the Convention Project on Chemical Safety in developing countries. The project aims to support developing countries in the implementation of the Rotterdam and Stockholm Conventions, create human resources and institutional capacities and to demonstrate via pilot measures how chemical safety in the partner countries can be improved and sustainably implemented in line with international standards. With this objective the development of a Chemical Management Guide (CM Guide) for small and medium-sized enterprises in developing countries has been initiated. The guide describes a step-by-step approach which is based on identifying 'hot-spots' as a first step, and making a chemical inventory as a second step. The third step is the continuous improvement of chemical management. In total, there are six tools that aim to support the chemical management process: basic concepts for risk assessment; description of control approaches; using material safety data sheets (MSDSs); risk phrases for hazardous substances; safety phrases for hazardous substances; symbols used for labelling hazardous substances. In the course of the test-implementation of the CM Guide in Indonesia, it was found that MSDSs were not available in most of the smaller companies. In contrast, medium-sized and larger companies do have more MSDSs available. It was also found that the way to engage the minds of company owners and managers is with economic arguments related to the loss, waste and expiry of materials, and quality standards expected from importing countries.

  17. Cost-effectiveness analysis of different devices used for the closure of small-to-medium-sized patent ductus arteriosus in pediatric patients.

    PubMed

    El-Saiedi, Sonia A; El Sisi, Amal M; Mandour, Rodina Sobhy; Abdel-Aziz, Doaa M; Attia, Wael A

    2017-01-01

    In this study, we examined the differences in cost and effectiveness of various devices used for the closure of small to medium sized patent ductus arteriosus (PDA). We retrospectively studied 116 patients who underwent closure of small PDAs between January 2010 and January 2015. Three types of devices were used: the Amplatzer duct occluder (ADO) II, the cook detachable coil and the Nit Occlud coil (NOC). Immediate and late complications were recorded and patients were followed up for 3 months after the procedure. All statistical calculations were performed using Statistical Package for the Social Science software. P <0.05 were considered significant. We successfully deployed ADO II devices in 33 out of 35 cases, cook detachable coils in 36 out of 40 cases and NOCs in 38 out of 41 cases. In the remaining nine cases, the first device was unsuitable or embolized and required retrieval and replacement with another device. Eleven patients (9.5%) developed vascular complications and required anticoagulation therapy. Patients who had hemolysis or vascular complications remained longer in the intensive care unit, with consequently higher total cost (P = 0.016). Also, the need for a second device increased the cost per patient. The cook detachable coil is the most cost-effective device for closure of small-to medium-sized PDAs. Calculations of the incremental cost-effectiveness. (ICE) revealed that the Cook detachable coil had less ICE than the ADO II and NOC. The NOC was more effective with fewer complications.

  18. Development of a large-scale isolation chamber system for the safe and humane care of medium-sized laboratory animals harboring infectious diseases*

    PubMed Central

    Pan, Xin; Qi, Jian-cheng; Long, Ming; Liang, Hao; Chen, Xiao; Li, Han; Li, Guang-bo; Zheng, Hao

    2010-01-01

    The close phylogenetic relationship between humans and non-human primates makes non-human primates an irreplaceable model for the study of human infectious diseases. In this study, we describe the development of a large-scale automatic multi-functional isolation chamber for use with medium-sized laboratory animals carrying infectious diseases. The isolation chamber, including the transfer chain, disinfection chain, negative air pressure isolation system, animal welfare system, and the automated system, is designed to meet all biological safety standards. To create an internal chamber environment that is completely isolated from the exterior, variable frequency drive blowers are used in the air-intake and air-exhaust system, precisely controlling the filtered air flow and providing an air-barrier protection. A double door transfer port is used to transfer material between the interior of the isolation chamber and the outside. A peracetic acid sterilizer and its associated pipeline allow for complete disinfection of the isolation chamber. All of the isolation chamber parameters can be automatically controlled by a programmable computerized menu, allowing for work with different animals in different-sized cages depending on the research project. The large-scale multi-functional isolation chamber provides a useful and safe system for working with infectious medium-sized laboratory animals in high-level bio-safety laboratories. PMID:20872984

  19. New technique: Development of a large-scale isolation chamber system for the safe and humane care of medium-sized laboratory animals harboring infectious diseases.

    PubMed

    Pan, Xin; Qi, Jian-cheng; Long, Ming; Liang, Hao; Chen, Xiao; Li, Han; Li, Guang-bo; Zheng, Hao

    2010-10-01

    The close phylogenetic relationship between humans and non-human primates makes non-human primates an irreplaceable model for the study of human infectious diseases. In this study, we describe the development of a large-scale automatic multi-functional isolation chamber for use with medium-sized laboratory animals carrying infectious diseases. The isolation chamber, including the transfer chain, disinfection chain, negative air pressure isolation system, animal welfare system, and the automated system, is designed to meet all biological safety standards. To create an internal chamber environment that is completely isolated from the exterior, variable frequency drive blowers are used in the air-intake and air-exhaust system, precisely controlling the filtered air flow and providing an air-barrier protection. A double door transfer port is used to transfer material between the interior of the isolation chamber and the outside. A peracetic acid sterilizer and its associated pipeline allow for complete disinfection of the isolation chamber. All of the isolation chamber parameters can be automatically controlled by a programmable computerized menu, allowing for work with different animals in different-sized cages depending on the research project. The large-scale multi-functional isolation chamber provides a useful and safe system for working with infectious medium-sized laboratory animals in high-level bio-safety laboratories.

  20. Report: Maximizing recycling participation to reduce waste to landfill: a study of small to medium-sized enterprises in Hobart, Tasmania, Australia.

    PubMed

    Parsons, Sam; Kriwoken, Lorne K

    2010-05-01

    Small to medium-sized enterprises (SMEs) in Hobart, Tasmania, Australia face many barriers to recycling participation. This study first investigated the volumes and types of waste produced by SMEs. Significant barriers were then identified and key motivators to recycle examined. Using the Australia New Zealand Standard of Industrial Classification, stratified sampling of SMEs (n = 436) was undertaken. Inadequate storage space, paucity of readily available information on recycling services and the lack of staff allocated to sort and recycle were identified as major barriers. Cardboard, paper and plastic waste were produced in large volumes with only a small percentage being recycled and these were identified as target areas for local government. Recommendations include the appointment of a dedicated recycling officer to maximize recycling participation for the reduction of waste to landfill and to undertake further research on minimizing recycling costs.