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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: Keller, Damián; Costalonga, Leandro; Messina, Marcello;

    {"references": ["Abolhasani, M., Oakes, S., & Oakes, H. (2017). Music in advertising and consumer identity: The search for Heideggerian authenticity. Marketing Theory 17 (4), 473-490. (Doi: 10.1177/1470593117692021.)", "Aliel, L., Keller, D., & Alvim, V. (2019). A Soundtrack for Atravessamentos : Expanding ecologically grounded methods for ubiquitous music collaborations. In 14th International Symposium on Computer Music Multidisciplinary Research .", "Aliel, L., & Fornari, J. (2015). Creating an ecologically modeled performance through the remote manipulation of multiple soundscapes. NICS Reports , (12), 2.", "Brooks, R. A. (1991). Intelligence without representation. Artificial Intelligence 47 (1), 139-159.", "Brown, A. R., Stewart, D., Hansen, A., & Stewart, A. (2014). Making meaningful musical experiences accessible using the iPad. In Keller, D., Lazzarini, V., & Pimenta, M. S. (Eds.). Ubiquitous music (pp. 65-81). Cham, Springer.", "Carson, T. (2020). On Ecocomposition. Journal of Digital Media & Interaction , 3(5), 133-142.", "Keller, D. (2000). Compositional processes from an ecological perspective. Leonardo Music Journal , 55-60.", "Keller, D. (2001). Social and perceptual dynamics in ecologically-based composition. Electronic Musicological Review , 6.", "Keller, D., Gomes, C., & Aliel, L. (2019). The Handy Metaphor: Bimanual, touchless interaction for the internet of musical things. Journal of New Music Research, 48(4), 385-396.", "Keller, D., Messina, M., & Oliveira, F. Z. (2020). Second Wave Ubiquitous Music. Journal of Digital Media & Interaction , 3(5), 5-20.", "Messina, M., & Aliel, L. (2019). Ubiquitous Music, Gelassenheit and the Metaphysics of Presence: Hijacking the Live Score Piece Ntrallazzu 4. In 14th International Symposium on Computer Music Multidisciplinary Research , 685-695.", "Messina, M., Svidzinski, J., de Menezes Bezerra, D., & da Costa, D. F. (2019). Live Patching and Remote Interaction: A Practice-Based, Intercontinental Approach to Kiwi. In 14th International Symposium on Computer Music Multidisciplinary Research , 696-703.", "Mesz, B., Sigman, M., & Trevisan, M. (2012). A composition algorithm based on crossmodal taste-music correspondences. Frontiers in Human Neuroscience , 6, 71.", "Turchet, L., Fischione, C., Essl, G., Keller, D., & Barthet, M. (2018). Internet of musical things: Vision and challenges. IEEE Access , 6, 61994-62017."]} Picture a world with no mobility. Planes are landed. Urban transportation stopped. Large gatherings are non-existent and everybody is at home. That’s 2020, today. Most countries have reduced social interactions to a minimum. Food markets, drugstores and gas stations remain open. But shopping malls, cinemas, coffee shops and pubs have closed their doors for the foreseeable future. The Covid-19 pandemic is among us, ready to strike the most vulnerable and sometimes also the healthy, rich and posh. Covid-19 impacts every social strata. This is a key difference between this disease and the plagues that have been taking lives in the peripheral countries for decades. Pulmonary and respiratory diseases are among the leading causes of death worldwide. But according to the WHO 1 (2018), the so-called Group I conditions (communicable diseases, maternal conditions arising during pregnancy and childbirth, and nutritional deficiencies) are particularly devastating among the low-income populations. Until today, music making has predominantly been done through face-to-face, synchronous interactions. While it is true that some forms of music making ⎼ for instance, studio post-production or karaoké ⎼ rely on resources that are prepared offline, the implicit target of musical activity is to make sound together, if possible in person and at the same time. The current pandemic has turned the traditional forms of music making into high-risk and in some cases potentially deadly activities. So is music making becoming an activity for a select elite, secluded from the mundane buzz and divorced from community exchanges, again? The answer from the ubimus community is a strong no!

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    Authors: Séroussi, Brigitte; Guezennec, Gilles; Lamy, Jean-Baptiste; Muro, Naiara; +4 Authors

    Breast cancer is the most common cancer among women. DESIREE is a European project which aims at developing web-based services for the management of primary breast cancer by multidisciplinary breast units (BUs). We describe the guideline-based decision support system (GL-DSS) of the project. Various breast cancer clinical practice guidelines (CPGs) have been selected to be concurrently applied to provide state-of-the-art patient-specific recommendations. The aim is to reconcile CPG recommendations with the objective of complementarity to enlarge the number of clinical situations covered by the GL-DSS. Input and output data exchange with the GL-DSS is performed using FHIR. We used a knowledge model of the domain as an ontology on which relies the reasoning process performed by rules that encode the selected CPGs. Semantic web tools were used, notably the Euler/EYE inference engine, to implement the GL-DSS. “Rainbow boxes” are a synthetic tabular display used to visualize the inferred recommendations.

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  • Authors: Pelletier, C.; Salar, Pascal; Gillet, J.; Cloquemin, G.; +3 Authors

    Flavescence dorée (FD) and Bois noir (BN) are the two main yellows of grapevine in Europe and are caused by phytoplasmas of the 16SrV and 16SrXII-A groups respectively. A new triplex real-time PCR assay was developed in order to detect simultaneously the FD and BN phytoplasmas as well as grapevine chloroplastic DNA with TaqMan minor groove binder probes. Each set of designed primers and probes specifically detected the map gene of the FD and BN phytoplasmas, respectively and did not detect phytoplasmas from other phylogenetic groups. PCR efficiencies varied from 90 to 110 %. The PCR assay showed good intra-test and inter-test reproducibility. Triplex real-time PCR was compared to the conventional biplex nested-PCR method. The sensitivity of the real-time PCR, tested on several infected periwinkle and grapevine samples, was up to 5 and 100 times higher for the BN-P and the FD-P targets, respectively. Out of 109 grapevine samples analysed 10, which were negative with the nested PCR, turned to be FD-P positive with the real-time PCR. A decision scheme was set up according to the Ct values of the FD-P, BN-P and grapevine targets in order to assess the routine detection results. VITIS - Journal of Grapevine Research, Vol. 48 No. 2 (2009): Vitis

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    Authors: Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio; +1 Authors

    The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project.Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal-temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal-parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders.

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    Authors: Roost, Pauline; Gaudin, Mylène; Guillermier, Martine; Gubinelli, Francesco; +9 Authors

    ABSTRACT – HOPE 2018 Introduction Parkinson’s disease (PD) is the second most prevalent age-related neurodegenerative disorder, characterized by a tremor at rest, rigidity, and slowness, pathologically caused by a loss of the dopaminergic neurons in the substantia nigra (SN), resulting in a dopamine (DA) deficiency in the striatum [1]. Although it is over 200 years ago now that James Parkinson described this disease, to date there is still no treatment available that halts or slows dopaminergic neuron degeneration [2]. A necessity in finding such therapy is a pathologically relevant model to test new treatments. We developed a genetic rodent PD model with progressive, but significant DA loss through overexpressing WT or mutant (A53T) human alpha-synuclein protein in the SN [3], similar to the human pathology[1]. Our aims are to accelerate dopaminergic neuron loss in these rat models and evaluate DA pathology by two different presynaptic PET tracers and correlated this with behaviour and histological results. Materials & Methods A total of sixteen rats were unilaterally injected in the SN with a viral vector (AAV2/6-PGK; 1.00E+11 vgc) overexpressing WT human alpha-synuclein (WT-α-syn; n=8, 573±40gr) or mutated alpha-synuclein protein (A53T-α-syn; n=8, 589±39gr) and were studied at 10-12wpi. PET imaging was performed using a ligand substrate for AADC, 6-[18F]fluoro-L-m-tyrosine (“FMT”, 60min acquisition, 36.4-46.5MBq; pre-treatment by IP injection of 10mg/kg benserazide 30’ before imaging [4]), or a ligand after DA transporter (DAT), [18F]-LBT999 [5] (“LBT", 90min acquisition, 54.4-63.0MBq). For behaviour, rats were subjected for 5 minutes to the cylinder test, in which contralateral- and ipsilateral paw use was compared. After the in vivo studies rats were sacrificed for stereological counting studies in the SN using tyrosine hydroxylase immunohistochemistry. From LBT and FMT PET scans, quantitative uptake images (BPnd and Ki) were calculated using Logan and Patlak graphical methods, respectively, with the cerebellum as a reference, Ki images were subsequently smoothed. The striatum contralateral to the injection site served as internal control. Results are expressed as the mean ± SD, and compared using paired Student t-test for contra- and ipsilateral sides in imaging studies, while a one-way ANOVA and Scheffe F post-hoc test was used to compare contralateral paw use to a control group. Results Injection of benserazide was not effective in 37% of the animals, thus Ki (constant of accumulation) could not reasonably be estimated. Additionally, Ki parametric images showed lower contrast to background than binding potential (BPnd) images. At 12wpi we did not observed lower Ki in the ipsilateral caudate putamen compared to the contralateral side of quantifiable scans for the WT-α-syn (n=3, p=0.255) nor A53T-α-syn rats (n=2, p=0.336). However, LBT data showed a decreased BPnd in the ipsilateral caudate putamen of A53T-α-syn animals (n=4, p=0.003), while a near significant difference was observed in the WT-α-syn group (n=3, p=0.051). These results are in concordance with the behavioural observations, showing roughly only 30% use of the contralateral forepaw at this time point for A53T-α-syn (n=8, p=0.045), while the WT-α-syn rats showed no such difference (n=7, p=0.949). No significant correlations between PET data and behaviour were observed. All counts using stereological methods, and subsequent comparison, are still ongoing. Fig 1: Positron emission tomography and behavioural studies. (A) Graphical schematic of WT-α-syn and A53T-α-syn viral vectors. (B) Cylinder tests at 10wpi detected motor deficits in A53T-α-syn overexpressing rats (n=8) but not WT-α-syn rats (n=7). PET scans were obtained from WT-α-syn and A53T-α-syn rats 12wpi, using a tracer substrate of aromatic L-amino acid decarboxylase (AADC; 18F-FMTyr) (C), or a dopamine transporter ligand (DAT, 18F-LBT999) (D). (C) Neither for WT-α-syn (n=3) nor for A53T-α-syn (n=2) a difference was observed in AADC metabolism (FMT). (D) In contrast the DAT tracer (LBT999) showed a significant difference in A53T-α-syn (n=4) but not WT-α-syn animals (n=3). Discussion/Conclusion We have created two AAV-overexpression rat models of PD; WT-α-syn and A53T-α-syn. Only the latter showed significant DA deficiency and neuronal loss detectible by LBT PET imaging, this is in concordance with behavioural tests. However, in our experiment this difference might also arise from the lower number of subjects in the WT-α-syn group. Additionally, the inter-animal variability seems to be more prominent in the WT-α-syn as compared to A53T-α-syn. Research by Lazaro et al. [6] has shown that A53T mutated α-synuclein has increased presence of oligomers in the nucleus compared to the wildtype protein in HEK cells, and additionally A53T α-synuclein cells might possibly secrete oligomers [6]. Taken together, this might explain the more deleterious effect of A53T α-synuclein we found. Our parametric data suggest that the DAT tracer, LBT999, is more sensitive to detect a mild PD phenotype as compared to the AADC tracer, FMT. This phenomenon has previously been described, and is possibly due to a combination of reduced nerve terminal DAT binding sites and downregulation of DAT in surviving neurons, in an attempt to increase DA availability [7]. More FMT scans will have to be done to increase numbers and compensate for ineffective benserazide blocking. Further analysis of PET data will allow correlation of PET data to behavioural and histological measurements. Acknowledgements This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No. 676408. References 1. Dauer, W. and S. Przedborski, Parkinson's disease: mechanisms and models. Neuron, 2003. 39(6): p. 889-909. 2. Fahn, S., The 200-year journey of Parkinson disease: Reflecting on the past and looking towards the future. Parkinsonism Relat Disord, 2018. 46 Suppl 1: p. S1-S5. 3. Cresto, N., ; Gaillard M.C.; Joséphine, C.; Aurégan, G.; Guillermier, M.; Bernier, S.; Jan, C.; Petit, F. Gipchtein, P.; Joliot, A.; Hantraye, P.; Cambon, K.; Bemelmans, A.; Brouillet, E., THE LRRK2 G2019S MUTATION BUT NOT ITS DEAD KINASE FORM INCREASES THE NEUROTOXICITY OF MUTANT A53T A-SYNUCLEIN. Neurodegener Dis 2017;17(suppl 1):8-590 – Page 448, 2017. 4. Becker, G., et al., Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model. J Neurochem, 2017. 5. Serriere, S., et al., In vivo PET quantification of the dopamine transporter in rat brain with [(1)(8)F]LBT-999. Nucl Med Biol, 2014. 41(1): p. 106-13. 6. Lazaro, D.F., et al., Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation. PLoS Genet, 2014. 10(11): p. e1004741. 7. Arena, J.E. and A.J. Stoessl, Optimizing diagnosis in Parkinson's disease: Radionuclide imaging. Parkinsonism Relat Disord, 2016. 22 Suppl 1: p. S47-51. This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No. 676408.

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      Other literature type . Article . Conference object . 2018
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    Authors: Fu, Hongjun; Possenti, Andrea; Freer, Rosie; Nakano, Yoshikazu; +11 Authors

    Excitatory neurons are preferentially impaired in early Alzheimer's disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place predominantly in excitatory neurons compared to inhibitory neurons, not only in the entorhinal cortex, a brain region affected in early Alzheimer's disease, but also in areas affected later by the disease. By analyzing RNA transcripts from single-nucleus RNA datasets, we identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons. One of the genes, BCL2-associated athanogene 3 (BAG3), a facilitator of autophagy, was identified as a hub, or master regulator, gene. We verified that reducing BAG3 levels in primary neurons exacerbated pathological tau accumulation, whereas BAG3 overexpression attenuated it. These results define a tau homeostasis signature that underlies the cellular and regional vulnerability of excitatory neurons to tau pathology.

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  • Authors: Huss, Brigitte; Walter, Bernard; Etienne, Lucien; van Regenmortel, M.;

    Monoclonal antibodies prepared with grapevine fanleaf virus (GFV) are useful for detecting the virus in plant extracts. In this paper we describe comparisons between different ELISA techniques using rabbit and chicken immunoglobulins as weil as monoclonal antibodies (MCA). The technique using chicken immunoglobulins for coating the plates followed by MCA and goat anti-mouse phosphatase conjugate was the best one for detecting GFV in plant sap. In this technique, ascitic fluids containing MCA could be diluted up to 10-6. Our experiments clearly demonstrate that the detection of GFV is possible in grapevine not only from leaves or rootlets, but also from wood shavings, without grinding them. We replaced the classical nicotine containing extraction medium by a harmless phosphate or Tris-HCl buffer. To detect GFV with these media it is essential that the buffer should contain polyvinylpyrrolidone and that its molarity should not be less than 0.1 M. VITIS - Journal of Grapevine Research, Vol. 25 No. 3 (1986): VITIS

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    Authors: Gevensleben, Holger; Albrecht, Björn; Lütcke, Henry; Auer, Tibor; +5 Authors

    To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials (SCPs) by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCPs training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post) fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT). Performance-data during the sessions (regulation performance) in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz) at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition. In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group. Furthermore, we found a localized increase of activity in the anterior cingulate cortex (ACC). Analyses of the estimation of treatment assignment by the participants indicate feasibility of blinding. Participants could not assess treatment assignment confidently. Participants of the SCP-group improved regulation capability during treatment sessions (in contrast to the participants of the placebo-group), although regulation capability appeared to be instable, presumably due to diminished confidence in the training (SCP- or sham-training). Our results indicate that SCP training in healthy adults might lead to functional changes in neuronal circuits serving cognitive preparation even after a limited number of sessions. Frontiers in Human Neuroscience, 8 ISSN:1662-5161

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    Frontiers in Human Neuroscience
    Article . 2014 . Peer-reviewed
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    ETH Zürich Research Collection
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      Frontiers in Human Neuroscience
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      ETH Zürich Research Collection
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    Authors: Ince, PG; Minett, T; Forster, G; Brayne, C; +2 Authors

    INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship to dementia, mobility and cerebrovascular disease in an older population-representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n=331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95%CI 1.02; 1.96, p=0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95%CI 1.05 - 1.74; p 0.018) and falls (OR 1.96, 95%CI 1.11 - 3.43; p= 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions, lacunes and significant arteriosclerosis, was assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of white matter lesions, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on white matter lesions, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis. This article is protected by copyright. All rights reserved.

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    Authors: Kieliba, I.; Tonnesen, T.; Huger, Marc; Telle, R.;

    Acoustic Emission temperature dependent behavior of alumina-spinel refractory materials

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    Authors: Keller, Damián; Costalonga, Leandro; Messina, Marcello;

    {"references": ["Abolhasani, M., Oakes, S., & Oakes, H. (2017). Music in advertising and consumer identity: The search for Heideggerian authenticity. Marketing Theory 17 (4), 473-490. (Doi: 10.1177/1470593117692021.)", "Aliel, L., Keller, D., & Alvim, V. (2019). A Soundtrack for Atravessamentos : Expanding ecologically grounded methods for ubiquitous music collaborations. In 14th International Symposium on Computer Music Multidisciplinary Research .", "Aliel, L., & Fornari, J. (2015). Creating an ecologically modeled performance through the remote manipulation of multiple soundscapes. NICS Reports , (12), 2.", "Brooks, R. A. (1991). Intelligence without representation. Artificial Intelligence 47 (1), 139-159.", "Brown, A. R., Stewart, D., Hansen, A., & Stewart, A. (2014). Making meaningful musical experiences accessible using the iPad. In Keller, D., Lazzarini, V., & Pimenta, M. S. (Eds.). Ubiquitous music (pp. 65-81). Cham, Springer.", "Carson, T. (2020). On Ecocomposition. Journal of Digital Media & Interaction , 3(5), 133-142.", "Keller, D. (2000). Compositional processes from an ecological perspective. Leonardo Music Journal , 55-60.", "Keller, D. (2001). Social and perceptual dynamics in ecologically-based composition. Electronic Musicological Review , 6.", "Keller, D., Gomes, C., & Aliel, L. (2019). The Handy Metaphor: Bimanual, touchless interaction for the internet of musical things. Journal of New Music Research, 48(4), 385-396.", "Keller, D., Messina, M., & Oliveira, F. Z. (2020). Second Wave Ubiquitous Music. Journal of Digital Media & Interaction , 3(5), 5-20.", "Messina, M., & Aliel, L. (2019). Ubiquitous Music, Gelassenheit and the Metaphysics of Presence: Hijacking the Live Score Piece Ntrallazzu 4. In 14th International Symposium on Computer Music Multidisciplinary Research , 685-695.", "Messina, M., Svidzinski, J., de Menezes Bezerra, D., & da Costa, D. F. (2019). Live Patching and Remote Interaction: A Practice-Based, Intercontinental Approach to Kiwi. In 14th International Symposium on Computer Music Multidisciplinary Research , 696-703.", "Mesz, B., Sigman, M., & Trevisan, M. (2012). A composition algorithm based on crossmodal taste-music correspondences. Frontiers in Human Neuroscience , 6, 71.", "Turchet, L., Fischione, C., Essl, G., Keller, D., & Barthet, M. (2018). Internet of musical things: Vision and challenges. IEEE Access , 6, 61994-62017."]} Picture a world with no mobility. Planes are landed. Urban transportation stopped. Large gatherings are non-existent and everybody is at home. That’s 2020, today. Most countries have reduced social interactions to a minimum. Food markets, drugstores and gas stations remain open. But shopping malls, cinemas, coffee shops and pubs have closed their doors for the foreseeable future. The Covid-19 pandemic is among us, ready to strike the most vulnerable and sometimes also the healthy, rich and posh. Covid-19 impacts every social strata. This is a key difference between this disease and the plagues that have been taking lives in the peripheral countries for decades. Pulmonary and respiratory diseases are among the leading causes of death worldwide. But according to the WHO 1 (2018), the so-called Group I conditions (communicable diseases, maternal conditions arising during pregnancy and childbirth, and nutritional deficiencies) are particularly devastating among the low-income populations. Until today, music making has predominantly been done through face-to-face, synchronous interactions. While it is true that some forms of music making ⎼ for instance, studio post-production or karaoké ⎼ rely on resources that are prepared offline, the implicit target of musical activity is to make sound together, if possible in person and at the same time. The current pandemic has turned the traditional forms of music making into high-risk and in some cases potentially deadly activities. So is music making becoming an activity for a select elite, secluded from the mundane buzz and divorced from community exchanges, again? The answer from the ubimus community is a strong no!

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    Authors: Séroussi, Brigitte; Guezennec, Gilles; Lamy, Jean-Baptiste; Muro, Naiara; +4 Authors

    Breast cancer is the most common cancer among women. DESIREE is a European project which aims at developing web-based services for the management of primary breast cancer by multidisciplinary breast units (BUs). We describe the guideline-based decision support system (GL-DSS) of the project. Various breast cancer clinical practice guidelines (CPGs) have been selected to be concurrently applied to provide state-of-the-art patient-specific recommendations. The aim is to reconcile CPG recommendations with the objective of complementarity to enlarge the number of clinical situations covered by the GL-DSS. Input and output data exchange with the GL-DSS is performed using FHIR. We used a knowledge model of the domain as an ontology on which relies the reasoning process performed by rules that encode the selected CPGs. Semantic web tools were used, notably the Euler/EYE inference engine, to implement the GL-DSS. “Rainbow boxes” are a synthetic tabular display used to visualize the inferred recommendations.

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  • Authors: Pelletier, C.; Salar, Pascal; Gillet, J.; Cloquemin, G.; +3 Authors

    Flavescence dorée (FD) and Bois noir (BN) are the two main yellows of grapevine in Europe and are caused by phytoplasmas of the 16SrV and 16SrXII-A groups respectively. A new triplex real-time PCR assay was developed in order to detect simultaneously the FD and BN phytoplasmas as well as grapevine chloroplastic DNA with TaqMan minor groove binder probes. Each set of designed primers and probes specifically detected the map gene of the FD and BN phytoplasmas, respectively and did not detect phytoplasmas from other phylogenetic groups. PCR efficiencies varied from 90 to 110 %. The PCR assay showed good intra-test and inter-test reproducibility. Triplex real-time PCR was compared to the conventional biplex nested-PCR method. The sensitivity of the real-time PCR, tested on several infected periwinkle and grapevine samples, was up to 5 and 100 times higher for the BN-P and the FD-P targets, respectively. Out of 109 grapevine samples analysed 10, which were negative with the nested PCR, turned to be FD-P positive with the real-time PCR. A decision scheme was set up according to the Ct values of the FD-P, BN-P and grapevine targets in order to assess the routine detection results. VITIS - Journal of Grapevine Research, Vol. 48 No. 2 (2009): Vitis

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    Authors: Riccelli, Roberta; Toschi, Nicola; Nigro, Salvatore; Terracciano, Antonio; +1 Authors

    The five-factor model (FFM) is a widely used taxonomy of human personality; yet its neuro anatomical basis remains unclear. This is partly because past associations between gray-matter volume and FFM were driven by different surface-based morphometry (SBM) indices (i.e. cortical thickness, surface area, cortical folding or any combination of them). To overcome this limitation, we used Free-Surfer to study how variability in SBM measures was related to the FFM in n = 507 participants from the Human Connectome Project.Neuroticism was associated with thicker cortex and smaller area and folding in prefrontal-temporal regions. Extraversion was linked to thicker pre-cuneus and smaller superior temporal cortex area. Openness was linked to thinner cortex and greater area and folding in prefrontal-parietal regions. Agreeableness was correlated to thinner prefrontal cortex and smaller fusiform gyrus area. Conscientiousness was associated with thicker cortex and smaller area and folding in prefrontal regions. These findings demonstrate that anatomical variability in prefrontal cortices is linked to individual differences in the socio-cognitive dispositions described by the FFM. Cortical thickness and surface area/folding were inversely related each others as a function of different FFM traits (neuroticism, extraversion and consciousness vs openness), which may reflect brain maturational effects that predispose or protect against psychiatric disorders.

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    Authors: Roost, Pauline; Gaudin, Mylène; Guillermier, Martine; Gubinelli, Francesco; +9 Authors

    ABSTRACT – HOPE 2018 Introduction Parkinson’s disease (PD) is the second most prevalent age-related neurodegenerative disorder, characterized by a tremor at rest, rigidity, and slowness, pathologically caused by a loss of the dopaminergic neurons in the substantia nigra (SN), resulting in a dopamine (DA) deficiency in the striatum [1]. Although it is over 200 years ago now that James Parkinson described this disease, to date there is still no treatment available that halts or slows dopaminergic neuron degeneration [2]. A necessity in finding such therapy is a pathologically relevant model to test new treatments. We developed a genetic rodent PD model with progressive, but significant DA loss through overexpressing WT or mutant (A53T) human alpha-synuclein protein in the SN [3], similar to the human pathology[1]. Our aims are to accelerate dopaminergic neuron loss in these rat models and evaluate DA pathology by two different presynaptic PET tracers and correlated this with behaviour and histological results. Materials & Methods A total of sixteen rats were unilaterally injected in the SN with a viral vector (AAV2/6-PGK; 1.00E+11 vgc) overexpressing WT human alpha-synuclein (WT-α-syn; n=8, 573±40gr) or mutated alpha-synuclein protein (A53T-α-syn; n=8, 589±39gr) and were studied at 10-12wpi. PET imaging was performed using a ligand substrate for AADC, 6-[18F]fluoro-L-m-tyrosine (“FMT”, 60min acquisition, 36.4-46.5MBq; pre-treatment by IP injection of 10mg/kg benserazide 30’ before imaging [4]), or a ligand after DA transporter (DAT), [18F]-LBT999 [5] (“LBT", 90min acquisition, 54.4-63.0MBq). For behaviour, rats were subjected for 5 minutes to the cylinder test, in which contralateral- and ipsilateral paw use was compared. After the in vivo studies rats were sacrificed for stereological counting studies in the SN using tyrosine hydroxylase immunohistochemistry. From LBT and FMT PET scans, quantitative uptake images (BPnd and Ki) were calculated using Logan and Patlak graphical methods, respectively, with the cerebellum as a reference, Ki images were subsequently smoothed. The striatum contralateral to the injection site served as internal control. Results are expressed as the mean ± SD, and compared using paired Student t-test for contra- and ipsilateral sides in imaging studies, while a one-way ANOVA and Scheffe F post-hoc test was used to compare contralateral paw use to a control group. Results Injection of benserazide was not effective in 37% of the animals, thus Ki (constant of accumulation) could not reasonably be estimated. Additionally, Ki parametric images showed lower contrast to background than binding potential (BPnd) images. At 12wpi we did not observed lower Ki in the ipsilateral caudate putamen compared to the contralateral side of quantifiable scans for the WT-α-syn (n=3, p=0.255) nor A53T-α-syn rats (n=2, p=0.336). However, LBT data showed a decreased BPnd in the ipsilateral caudate putamen of A53T-α-syn animals (n=4, p=0.003), while a near significant difference was observed in the WT-α-syn group (n=3, p=0.051). These results are in concordance with the behavioural observations, showing roughly only 30% use of the contralateral forepaw at this time point for A53T-α-syn (n=8, p=0.045), while the WT-α-syn rats showed no such difference (n=7, p=0.949). No significant correlations between PET data and behaviour were observed. All counts using stereological methods, and subsequent comparison, are still ongoing. Fig 1: Positron emission tomography and behavioural studies. (A) Graphical schematic of WT-α-syn and A53T-α-syn viral vectors. (B) Cylinder tests at 10wpi detected motor deficits in A53T-α-syn overexpressing rats (n=8) but not WT-α-syn rats (n=7). PET scans were obtained from WT-α-syn and A53T-α-syn rats 12wpi, using a tracer substrate of aromatic L-amino acid decarboxylase (AADC; 18F-FMTyr) (C), or a dopamine transporter ligand (DAT, 18F-LBT999) (D). (C) Neither for WT-α-syn (n=3) nor for A53T-α-syn (n=2) a difference was observed in AADC metabolism (FMT). (D) In contrast the DAT tracer (LBT999) showed a significant difference in A53T-α-syn (n=4) but not WT-α-syn animals (n=3). Discussion/Conclusion We have created two AAV-overexpression rat models of PD; WT-α-syn and A53T-α-syn. Only the latter showed significant DA deficiency and neuronal loss detectible by LBT PET imaging, this is in concordance with behavioural tests. However, in our experiment this difference might also arise from the lower number of subjects in the WT-α-syn group. Additionally, the inter-animal variability seems to be more prominent in the WT-α-syn as compared to A53T-α-syn. Research by Lazaro et al. [6] has shown that A53T mutated α-synuclein has increased presence of oligomers in the nucleus compared to the wildtype protein in HEK cells, and additionally A53T α-synuclein cells might possibly secrete oligomers [6]. Taken together, this might explain the more deleterious effect of A53T α-synuclein we found. Our parametric data suggest that the DAT tracer, LBT999, is more sensitive to detect a mild PD phenotype as compared to the AADC tracer, FMT. This phenomenon has previously been described, and is possibly due to a combination of reduced nerve terminal DAT binding sites and downregulation of DAT in surviving neurons, in an attempt to increase DA availability [7]. More FMT scans will have to be done to increase numbers and compensate for ineffective benserazide blocking. Further analysis of PET data will allow correlation of PET data to behavioural and histological measurements. Acknowledgements This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No. 676408. References 1. Dauer, W. and S. Przedborski, Parkinson's disease: mechanisms and models. Neuron, 2003. 39(6): p. 889-909. 2. Fahn, S., The 200-year journey of Parkinson disease: Reflecting on the past and looking towards the future. Parkinsonism Relat Disord, 2018. 46 Suppl 1: p. S1-S5. 3. Cresto, N., ; Gaillard M.C.; Joséphine, C.; Aurégan, G.; Guillermier, M.; Bernier, S.; Jan, C.; Petit, F. Gipchtein, P.; Joliot, A.; Hantraye, P.; Cambon, K.; Bemelmans, A.; Brouillet, E., THE LRRK2 G2019S MUTATION BUT NOT ITS DEAD KINASE FORM INCREASES THE NEUROTOXICITY OF MUTANT A53T A-SYNUCLEIN. Neurodegener Dis 2017;17(suppl 1):8-590 – Page 448, 2017. 4. Becker, G., et al., Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model. J Neurochem, 2017. 5. Serriere, S., et al., In vivo PET quantification of the dopamine transporter in rat brain with [(1)(8)F]LBT-999. Nucl Med Biol, 2014. 41(1): p. 106-13. 6. Lazaro, D.F., et al., Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation. PLoS Genet, 2014. 10(11): p. e1004741. 7. Arena, J.E. and A.J. Stoessl, Optimizing diagnosis in Parkinson's disease: Radionuclide imaging. Parkinsonism Relat Disord, 2016. 22 Suppl 1: p. S47-51. This project has been funded by the European Union Horizon 2020 Programme (H2020-MSCA-ITN-2015) under the Marie Skłodowska-Curie Innovative Training Network and Grant Agreement No. 676408.

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    Authors: Fu, Hongjun; Possenti, Andrea; Freer, Rosie; Nakano, Yoshikazu; +11 Authors

    Excitatory neurons are preferentially impaired in early Alzheimer's disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place predominantly in excitatory neurons compared to inhibitory neurons, not only in the entorhinal cortex, a brain region affected in early Alzheimer's disease, but also in areas affected later by the disease. By analyzing RNA transcripts from single-nucleus RNA datasets, we identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons. One of the genes, BCL2-associated athanogene 3 (BAG3), a facilitator of autophagy, was identified as a hub, or master regulator, gene. We verified that reducing BAG3 levels in primary neurons exacerbated pathological tau accumulation, whereas BAG3 overexpression attenuated it. These results define a tau homeostasis signature that underlies the cellular and regional vulnerability of excitatory neurons to tau pathology.

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