Service Oriented Big Data Management for Transport

International audienceThe increasing power of computer hardware and the sophistication of computer software have brought many new possibilities to information world. On one side the possibility to analyse massive data sets has brought new insight, knowledge and information. On the other, it has enabled to massively distribute computing and has opened to a new programming paradigm called Service Oriented Computing particularly well adapted to cloud computing. Applying these new technologies to the transport industry can bring new understanding to town transport infrastructures. The objective of our work is to manage and aggregate cloud services for managing big data and assist decision making for transport systems. Thus this paper presents our approach to propose a service oriented architecture for big data analytics for transport systems based on the cloud. Proposing big data management strategies for data produced by transport infra‐ structures, whilst maintaining cost effective systems deployed on the cloud, is a promising approach. We present the advancement for developing the Data acquisition service and Information extraction and cleaning service as well as the analysis for choosing a sharding strategy

Genetic deletion of α7 nicotinic acetylcholine receptors induces an age-dependent Alzheimer's disease-like pathology

none8siThe accumulation of amyloid-beta peptide (Aβ) and the failure of cholinergic transmission are key players in Alzheimer's disease (AD). However, in the healthy brain, Aβ contributes to synaptic plasticity and memory acting through α7 subtype nicotinic acetylcholine receptors (α7nAChRs). Here, we hypothesized that the α7nAChR deletion blocks Aβ physiological function and promotes a compensatory increase in Aβ levels that, in turn, triggers an AD-like pathology. To validate this hypothesis, we studied the age-dependent phenotype of α7 knock out mice. We found that α7nAChR deletion caused an impairment of hippocampal synaptic plasticity and memory at 12 months of age, paralleled by an increase of Amyloid Precursor Protein expression and Aβ levels. This was accompanied by other classical AD features such as a hyperphosphorylation of tau at residues Ser 199, Ser 396, Thr 205, a decrease of GSK-3β at Ser 9, the presence of paired helical filaments and neurofibrillary tangles, neuronal loss and an increase of GFAP-positive astrocytes. Our findings suggest that α7nAChR malfunction might precede Aβ and tau pathology, offering a different perspective to interpret the failure of anti-Aβ therapies against AD and to find novel therapeutical approaches aimed at restoring α7nAChRs-mediated Aβ function at the synapse.openTropea M.R.; Li Puma D.D.; Melone M.; Gulisano W.; Arancio O.; Grassi C.; Conti F.; Puzzo D.Tropea, M. R.; Li Puma, D. D.; Melone, M.; Gulisano, W.; Arancio, O.; Grassi, C.; Conti, F.; Puzzo, D

Dopaminergic-GABAergic interplay and alcohol binge drinking

© 2019 Elsevier Ltd The dopamine D 3 receptor (D 3 R), in the nucleus accumbens (NAc), plays an important role in alcohol reward mechanisms. The major neuronal type within the NAc is the GABAergic medium spiny neuron (MSN), whose activity is regulated by dopaminergic inputs. We previously reported that genetic deletion or pharmacological blockade of D 3 R increases GABA A α6 subunit in the ventral striatum. Here we tested the hypothesis that D 3 R-dependent changes in GABA A α6 subunit in the NAc affect voluntary alcohol intake, by influencing the inhibitory transmission of MSNs. We performed in vivo and ex vivo experiments in D 3 R knockout (D 3 R −/− ) mice and wild type littermates (D 3 R +/+ ). Ro 15-4513, a high affinity α6-GABA A ligand was used to study α6 activity. At baseline, NAc α6 expression was negligible in D 3 R +/+ , whereas it was robust in D 3 R −/− ; other relevant GABA A subunits were not changed. In situ hybridization and qPCR confirmed α6 subunit mRNA expression especially in the NAc. In the drinking-in-the-dark paradigm, systemic administration of Ro 15-4513 inhibited alcohol intake in D 3 R +/+ , but increased it in D 3 R −/− ; this was confirmed by intra-NAc administration of Ro 15-4513 and furosemide, a selective α6-GABA A antagonist. Whole-cell patch-clamp showed peak amplitudes of miniature inhibitory postsynaptic currents in NAc medium spiny neurons higher in D 3 R −/− compared to D 3 R +/+ ; Ro 15-4513 reduced the peak amplitude in the NAc of D 3 R −/− , but not in D 3 R +/+ . We conclude that D 3 R-dependent enhanced expression of α6 GABA A subunit inhibits voluntary alcohol intake by increasing GABA inhibition in the NAc

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders

Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

<p>Abstract</p> <p>Background</p> <p>PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor^®EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration.</p> <p>Methods</p> <p>In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC.</p> <p>Results</p> <p>NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested.</p> <p>Conclusion</p> <p>These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.</p

Use of water-Cherenkov detectors to detect Gamma-Ray-Bursts at the Large Aperture GRB Observatory (LAGO)

The Large Aperture GRB Observatory (LAGO) project aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique in ground-based water-Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Me´ rida, 4765 m a.s.l.). We report on detector calibration and operation at high altitude, search for bursts in 4 months of preliminary data, as well as search for signal at ground level when satellites report a burst.Fil: Allard, D.. Université Paris Diderot - Paris 7; FranciaFil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, C.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Asorey, Hernán Gonzalo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Barros, H.. Universidad Simon Bolivar; VenezuelaFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Burgoa, O.. Instituto de Investigaciones Fisicas; BoliviaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Martinez, O.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Miranda Loza, P.. Instituto de Investigaciones Fısicas; BoliviaFil: Murrieta, T.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Perez, G.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Rivera, H.. Instituto de Investigaciones Fısicas; BoliviaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Saavedra, O.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Salazar, H.. Facultad de Ciencias Fısico-Matematicas ; MéxicoFil: Tello, J. C.. Universidad Simon Bolıvar; VenezuelaFil: Ticona Peralda, R.. Instituto de Investigaciones Fısicas; BoliviaFil: Velarde, A.. Instituto de Investigaciones Fısicas; BoliviaFil: Villaseñor, L.. Universidad de Michoacan; MéxicoFil: Areso, Omar Antonio. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Arnaldi, Luis Horacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Dasso, Sergio Ricardo. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Gonzalez, M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Gulisano, Adriana Maria. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Martin, R.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Masías Meza, Jimmy Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sidelnik, Iván Pedro. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, W.. Universidad de San Carlos; GuatemalaFil: The LAGO Collaboration

Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology