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  • Authors: G, Remington; J, Lee; O, Agid; H, Takeuchi; +5 Authors

    Clozapine was first introduced as an antipsychotic in the 1970's but a cluster of deaths, later linked to the drug's risk of agranulocytosis, led to its withdrawal in most countries. However, work in the 1980's established its unique efficacy in treatment resistant schizophrenia (TRS), which constitutes as many as 30% of those with the illness. Clozapine was reintroduced with this indication shortly thereafter, but because of this risk its use requires routine hematologic monitoring.An update is provided regarding clozapine's risk of neutropenia, agranulocytosis, and associated mortality. In addition, updates are provided on other side effects, specifically myocarditis and bowel obstruction, as evidence suggests these are more common than agranulocytosis and associated with higher mortality rates.Clozapine remains the only treatment indicated in TRS, but it is dramatically underutilized. Clearly there are serious side effects associated with its use, and while the focus has historically been on hematologic concerns, we highlight other side effects that also demand systematic monitoring. Because it is the only effective treatment option we have for TRS, though, efforts must be implemented that ensure its use in this population while maximizing safety.

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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Will Featherstone; Petr Vaníček;

    This paper reviews the fundamental definitions of geodetic and geocentric coordinate systems, whilst clarifying the distinction between coordinates and coordinate systems. It is then argued that the transformation of coordinates from a local geodetic datum to a geocentric datum should first employ a change of the coordinate system using a six- or four-parameter transformation, followed by further modeling of the distortion in the coordinates. It is also argued that the horizontal coordinate transformation should not include height information, since this forms an entirely different coordinate in another coordinate system.

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    Australian Surveyor
    Article . 1999
    Data sources: Crossref
    Australian Surveyor
    Article . 1999
    Data sources: Crossref
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      Australian Surveyor
      Article . 1999
      Data sources: Crossref
      Australian Surveyor
      Article . 1999
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  • Authors: Katherine Frear; Samantha C. Paustian-Underdahl; Natalya M. Alonso; Shannon Cheng; +11 Authors

    Women’s inclusion in the workplace has continued to improve since the gender “revolution” of the 1960s, yet women are far from reaching parity with men and improvements have not been equal for all ...

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    Authors: Patrick P L, Tam; Janet, Rossant;

    Embryonic chimeras of the mouse are well-established tools for studying cell lineage and cell potential. They are also a key part of the analysis of complex phenotypes of mutant mice. By combining embryonic stem cell technology, molecularly tagged mutations and sensitive cell lineage markers,chimeras can provide invaluable insights into the tissue-specific requirement and the mode of action of many mouse genes.

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    Development
    Article
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    Article . 2003
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    Development
    Article . 2003
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      Article . 2003
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      Development
      Article . 2003
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Mariann Oemisch; Stephanie Westendorff; Stefan Everling; Thilo Womelsdorf;

    The anterior cingulate cortex (ACC) and prefrontal cortex (PFC) are believed to coactivate during goal-directed behavior to identify, select, and monitor relevant sensory information. Here, we tested whether coactivation of neurons across macaque ACC and PFC would be evident at the level of pairwise neuronal correlations during stimulus selection in a spatial attention task. We found that firing correlations emerged shortly after an attention cue, were evident for 50–200 ms time windows, were strongest for neuron pairs in area 24 (ACC) and areas 8 and 9 (dorsal PFC), and were independent of overall firing rate modulations. For a subset of cell pairs from ACC and dorsal PFC, the observed functional spike-train connectivity carried information about the direction of the attention shift. Reliable firing correlations were evident across area boundaries for neurons with broad spike waveforms (putative excitatory neurons) as well as for pairs of putative excitatory neurons and neurons with narrow spike waveforms (putative interneurons). These findings reveal that stimulus selection is accompanied by slow time scale firing correlations across those ACC/PFC subfields implicated to control and monitor attention. This functional coupling was informative about which stimulus was selected and thus indexed possibly the exchange of task-relevant information. We speculate that interareal, transient firing correlations reflect the transient coordination of larger, reciprocally interacting brain networks at a characteristic 50–200 ms time scale.SIGNIFICANCE STATEMENTOur manuscript identifies interareal spike-train correlations between primate anterior cingulate and dorsal prefrontal cortex during a period where attentional stimulus selection is likely controlled by these very same circuits. Interareal correlations emerged during the covert attention shift to one of two peripheral stimuli, proceeded on a slow 50–200 ms time scale, and occurred between putative pyramidal and putative interneurons. Spike-train correlations emerged particularly for cell pairs tuned to similar contralateral target locations, thus indexing the interareal coordination of attention-relevant information. These findings characterize a possible way by which prefrontal and anterior cingulate cortex circuits implement their control functions through coordinated firing when macaque monkeys select and monitor relevant stimuli for goal-directed behaviors.

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    Journal of Neuroscience
    Article . 2015
    License: CC BY NC SA
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    Europe PubMed Central
    Other literature type . 2016
    Data sources: PubMed Central
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    Journal of Neuroscience
    Article . 2016
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    Europe PubMed Central
    Other literature type . 2015
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      Journal of Neuroscience
      Article . 2015
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      Other literature type . 2016
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      Journal of Neuroscience
      Article . 2016
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      Europe PubMed Central
      Other literature type . 2015
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  • image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Authors: Samuel N. Cohen; Robert J. Elliott;

    We now come to one of the key objects in stochastic analysis, and what fundamentally distinguishes the theory from classical calculus. This is the notion of the quadratic variation of a process.

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    https://doi.org/10.1007/978-1-...
    Part of book or chapter of book . 2015
    License: Springer Nature TDM
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      https://doi.org/10.1007/978-1-...
      Part of book or chapter of book . 2015
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    Authors: Radtke, G; Maunders, C; Lazar, S; de Groot, FMF; +3 Authors

    The energy loss near edge structure (ELNES) of the O-K, Ti-L-23 and Mn-L-23 edges have been recorded in hexagonal Ba(3)Ti(2)NlnO(9) with an energy resolution of 0.10-0.20eV using a monochromator on a commercial transmission electron microscope (TEM) and compared with a tetragonal BaTiO3 reference sample. The formal valency and symmetry of Mn have been determined using atomic multiplets calculations and its effect on the electronic structure of BaTiO3 has been interpreted through a molecular-orbital model. (c) 2005 Elsevier Inc. All rights reserved.

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    NARCIS
    Article . 2005
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    Journal of Solid State Chemistry
    Article . 2005
    License: Elsevier TDM
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      Article . 2005
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      Journal of Solid State Chemistry
      Article . 2005
      License: Elsevier TDM
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    Authors: Mangé, Alain; Coyaud, Etienne; Desmetz, Caroline; Laurent, Estelle; +4 Authors

    Purpose: Among the FKBP family members, FKBP4 has been described to have a potential role in tumorigenesis, and as a putative tissue marker. We previously showed that FKBP4, an HSP90-associated co-chaperone, can elicit immune response as a tumor-specific antigen, and are overexpressed in breast cancer. Experimental design: In this study, we examined how loss of FKBP4 affect breast cancer progression and exploited protein interactomics to gain mechanistic insight into this process. Results: We found that FKBP4 expression is associated with breast cancer progression and prognosis, especially of ER-negative breast cancer. Furthermore, FKBP4 depletion specifically reduces cell growth and proliferation of triple negative breast cancer cell model and xenograft tumor model. Using specific protein interactome strategy by BirA proximity-dependent biotin identification, we demonstrated that FKBP4 is a novel PI3K-Akt-mTOR proximal interacting protein. Conclusion: Our results suggest that FKBP4 interacts with PI3K and can enhance Akt activation through PDK1 and mTORC2. International audience

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    Europe PubMed Central
    Article . 2019
    Data sources: PubMed Central
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      Europe PubMed Central
      Article . 2019
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    Authors: Jiapeng Qu; Denis Réale; Quinn E. Fletcher; Yanming Zhang;

    Abstract Background Animals inhabiting high altitudes consistently show slow life-histories. The pace-of-life syndrome (POLS) hypothesis posits behavioural, physiological and/or morphological traits that mediate the trade-off between current and future reproduction or survival, which have coevolved along a slow-fast life history continuum. Previous studies have shown that the life histories of plateau pikas varied across altitude, high-altitude individuals showed slow pace of life which were characterized by few litters per year with small litter sizes. Thus, we hypothesized that pikas populations at higher altitudes would also express personalities characteristic associated with slow life history, such as high sociability, low activity or aggressiveness. We tested this hypothesis by comparing the activity and docility of three plateau pika (Ochotona curzoniae) populations distributed along an altitudinal gradient of the Tibetan Plateau. We predicted that high-altitude pika would be more docile and less active. Results The behaviour of 556 pikas, from which 120 individuals were measured at least twice, was quantified. We observed that plateau pikas at high altitudes were less active and more docile than pika at lower altitudes. Activity and docility were significantly and negatively correlated in populations from high altitudes but not in populations from low altitudes. Conclusions Our results support the POLS hypothesis, highlight the existence of personality variation among populations distributed along an altitudinal gradient and emphasise the importance of environmental selection on personality divergence.

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    DOAJ
    Article . 2019
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    Frontiers in Zoology
    Article . 2019
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    Frontiers in Zoology
    Article . 2019
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    Frontiers in Zoology
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      Frontiers in Zoology
      Article . 2019
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      Frontiers in Zoology
      Article . 2019
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213,672 Research products
  • Authors: G, Remington; J, Lee; O, Agid; H, Takeuchi; +5 Authors

    Clozapine was first introduced as an antipsychotic in the 1970's but a cluster of deaths, later linked to the drug's risk of agranulocytosis, led to its withdrawal in most countries. However, work in the 1980's established its unique efficacy in treatment resistant schizophrenia (TRS), which constitutes as many as 30% of those with the illness. Clozapine was reintroduced with this indication shortly thereafter, but because of this risk its use requires routine hematologic monitoring.An update is provided regarding clozapine's risk of neutropenia, agranulocytosis, and associated mortality. In addition, updates are provided on other side effects, specifically myocarditis and bowel obstruction, as evidence suggests these are more common than agranulocytosis and associated with higher mortality rates.Clozapine remains the only treatment indicated in TRS, but it is dramatically underutilized. Clearly there are serious side effects associated with its use, and while the focus has historically been on hematologic concerns, we highlight other side effects that also demand systematic monitoring. Because it is the only effective treatment option we have for TRS, though, efforts must be implemented that ensure its use in this population while maximizing safety.

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    Authors: Will Featherstone; Petr Vaníček;

    This paper reviews the fundamental definitions of geodetic and geocentric coordinate systems, whilst clarifying the distinction between coordinates and coordinate systems. It is then argued that the transformation of coordinates from a local geodetic datum to a geocentric datum should first employ a change of the coordinate system using a six- or four-parameter transformation, followed by further modeling of the distortion in the coordinates. It is also argued that the horizontal coordinate transformation should not include height information, since this forms an entirely different coordinate in another coordinate system.

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    Australian Surveyor
    Article . 1999
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    Australian Surveyor
    Article . 1999
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      Australian Surveyor
      Article . 1999
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      Australian Surveyor
      Article . 1999
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  • Authors: Katherine Frear; Samantha C. Paustian-Underdahl; Natalya M. Alonso; Shannon Cheng; +11 Authors

    Women’s inclusion in the workplace has continued to improve since the gender “revolution” of the 1960s, yet women are far from reaching parity with men and improvements have not been equal for all ...

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    Authors: Patrick P L, Tam; Janet, Rossant;

    Embryonic chimeras of the mouse are well-established tools for studying cell lineage and cell potential. They are also a key part of the analysis of complex phenotypes of mutant mice. By combining embryonic stem cell technology, molecularly tagged mutations and sensitive cell lineage markers,chimeras can provide invaluable insights into the tissue-specific requirement and the mode of action of many mouse genes.

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    Development
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    Article . 2003
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    Development
    Article . 2003
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      Article . 2003
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    Authors: Mariann Oemisch; Stephanie Westendorff; Stefan Everling; Thilo Womelsdorf;

    The anterior cingulate cortex (ACC) and prefrontal cortex (PFC) are believed to coactivate during goal-directed behavior to identify, select, and monitor relevant sensory information. Here, we tested whether coactivation of neurons across macaque ACC and PFC would be evident at the level of pairwise neuronal correlations during stimulus selection in a spatial attention task. We found that firing correlations emerged shortly after an attention cue, were evident for 50–200 ms time windows, were strongest for neuron pairs in area 24 (ACC) and areas 8 and 9 (dorsal PFC), and were independent of overall firing rate modulations. For a subset of cell pairs from ACC and dorsal PFC, the observed functional spike-train connectivity carried information about the direction of the attention shift. Reliable firing correlations were evident across area boundaries for neurons with broad spike waveforms (putative excitatory neurons) as well as for pairs of putative excitatory neurons and neurons with narrow spike waveforms (putative interneurons). These findings reveal that stimulus selection is accompanied by slow time scale firing correlations across those ACC/PFC subfields implicated to control and monitor attention. This functional coupling was informative about which stimulus was selected and thus indexed possibly the exchange of task-relevant information. We speculate that interareal, transient firing correlations reflect the transient coordination of larger, reciprocally interacting brain networks at a characteristic 50–200 ms time scale.SIGNIFICANCE STATEMENTOur manuscript identifies interareal spike-train correlations between primate anterior cingulate and dorsal prefrontal cortex during a period where attentional stimulus selection is likely controlled by these very same circuits. Interareal correlations emerged during the covert attention shift to one of two peripheral stimuli, proceeded on a slow 50–200 ms time scale, and occurred between putative pyramidal and putative interneurons. Spike-train correlations emerged particularly for cell pairs tuned to similar contralateral target locations, thus indexing the interareal coordination of attention-relevant information. These findings characterize a possible way by which prefrontal and anterior cingulate cortex circuits implement their control functions through coordinated firing when macaque monkeys select and monitor relevant stimuli for goal-directed behaviors.

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    Journal of Neuroscience
    Article . 2015
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    Other literature type . 2016
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    Article . 2016
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    Other literature type . 2015
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