18 research outputs found

    Distributed System Contract Monitoring

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    The use of behavioural contracts, to specify, regulate and verify systems, is particularly relevant to runtime monitoring of distributed systems. System distribution poses major challenges to contract monitoring, from monitoring-induced information leaks to computation load balancing, communication overheads and fault-tolerance. We present mDPi, a location-aware process calculus, for reasoning about monitoring of distributed systems. We define a family of Labelled Transition Systems for this calculus, which allow formal reasoning about different monitoring strategies at different levels of abstractions. We also illustrate the expressivity of the calculus by showing how contracts in a simple contract language can be synthesised into different mDPi monitors.Comment: In Proceedings FLACOS 2011, arXiv:1109.239

    Alpha-synuclein/synapsin III pathological interplay boosts the motor response to methylphenidate

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    : Loss of dopaminergic nigrostriatal neurons and fibrillary α-synuclein (α-syn) aggregation in Lewy bodies (LB) characterize Parkinson's disease (PD). We recently found that Synapsin III (Syn III), a phosphoprotein regulating dopamine (DA) release with α-syn, is another key component of LB fibrils in the brain of PD patients and acts as a crucial mediator of α-syn aggregation and toxicity. Methylphenidate (MPH), a monoamine reuptake inhibitor (MRI) efficiently counteracting freezing of gait in advanced PD patients, can bind α-syn and controls α-syn-mediated DA overflow and presynaptic compartmentalization. Interestingly, MPH results also efficient for the treatment of attention deficits and hyperactivity disorder (ADHD), a neurodevelopmental psychiatric syndrome associated with Syn III and α-syn polymorphisms and constituting a risk factor for the development of LB disorders. Here, we studied α-syn/Syn III co-deposition and longitudinal changes of α-syn, Syn III and DA transporter (DAT) striatal levels in nigrostriatal neurons of a PD model, the human C-terminally truncated (1-120) α-syn transgenic (SYN120 tg) mouse, in comparison with C57BL/6J wild type (wt) and C57BL/6JOlaHsd α-syn null littermates. Then, we analyzed the locomotor response of these animals to an acute administration of MPH (d-threo) and other MRIs: cocaine, that we previously found to stimulate Syn III-reliant DA release in the absence of α-syn, or the selective DAT blocker GBR-12935, along aging. Finally, we assessed whether these drugs modulate α-syn/Syn III interaction by fluorescence resonance energy transfer (FRET) and performed in silico studies engendering a heuristic model of the α-syn conformations stabilized upon MPH binding. We found that only MPH was able to over-stimulate a Syn III-dependent/DAT-independent locomotor activity in the aged SYN120 tg mice showing α-syn/Syn III co-aggregates. MPH enhanced full length (fl) α-syn/Syn III and even more (1-120) α-syn/Syn III interaction in cells exhibiting α-syn/Syn III inclusions. Moreover, in silico studies confirmed that MPH may reduce α-syn fibrillation by stabilizing a protein conformation with increased lipid binding predisposition. Our observations indicate that the motor-stimulating effect of MPH can be positively fostered in the presence of α-syn/Syn III co-aggregation. This evidence holds significant implications for PD and ADHD therapeutic management

    Binary systems and their nuclear explosions

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    Peer ReviewedPreprin

    Stress rapidly dysregulates the glutamatergic synapse in the prefrontal cortex of cocaine-withdrawn adolescent rats

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    Although several lines of evidence have shown that chronic cocaine use is associated with stress system dysregulation, the underlying neurochemical mechanisms are still elusive. To investigate whether the rapid stress-induced response of the glutamatergic synapse was influenced by a previous history of cocaine, rats were exposed to repeated cocaine injections during adolescence [from postnatal day (PND) 28-42], subjected to a single swim stress (5 minutes) three days later (PND 45) and sacrificed 15 minutes after the end of this stressor. Critical determinants of glutamatergic homeostasis were measured in the medial prefrontal cortex (mPFC) whereas circulating corticosterone levels were measured in the plasma. Exposure to stress in saline-treated animals did not show changes in the crucial determinants of the glutamatergic synapse. Conversely, in cocaine-treated animals, stress dynamically altered the glutamatergic synapse by: (1) enhancing the presynaptic vesicular mediators of glutamate release; (2) reducing the transporters responsible for glutamate clearance; (3) increasing the postsynaptic responsiveness of the N-methyl-D-aspartate subunit GluN1; and (4) causing hyperresponsive spines as evidenced by increased activation of the postsynaptic cdc42-Pak pathway. These findings indicate that exposure to cocaine during adolescence sensitizes mPFC glutamatergic synapses to stress. It is suggested that changes in glutamatergic signaling may contribute to the increased sensitivity to stress observed in cocaine users. Moreover, glutamatergic processes may play an important role in stress-induced reinstatement of cocaine seeking

    Diversidade genĂ©tica de Tadarida brasiliensis (Chiroptera: Molossidae) no extremo sul do Brasil: hĂĄ evidĂȘncias de segregação entre sexos?

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    EspĂ©cies de morcegos com dieta insetĂ­vora e abundantes possuem um papel fundamental no ecossistema (AGOSTA, 2002); principalmente por possuĂ­rem importantĂąncia na polinização e dispersĂŁo de sementes, assim como no controle de insetos pragas de agricultura. As populaçÔes da espĂ©cie com ocorrĂȘncia na AmĂ©rica do Norte foram estudadas acerca da diversidade genĂ©tica (RUSSELL et al., 2005), diferentemente das populaçÔes com ocorrĂȘncia na AmĂ©rica do Sul. PopulaçÔes de T. brasiliensis apresentam padrĂ”es migratĂłrios, de deslocamento ou de uso de poleiros de forma diferenciada entre os sexos. No presente estudo, testamos a hipĂłtese de que o comportamento de deslocamento ou migração distinto entre indivĂ­duos machos e fĂȘmeas reflita na diversidade genĂ©tica e na estruturação das populaçÔes. Portanto, objetivo do estudo Ă© avaliar a diversidade genĂ©tica e a estruturação da população de T. brasiliensis no extremo sul do Brasil

    Football player dominant region determined by a novel model based on instantaneous kinematics variables

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    Dominant regions are defned as regions of the pitch where a player can reach before any other and are commonly determined without considering the free-spaces in the pitch. We presented an approach to football players’ dominant regions analysis, based on movement models created from players’ positions, displacement, velocity, and acceleration vectors. 109 Brazilian male professional football players were analysed during ofcial matches, computing over 15 million positional data obtained by video-based tracking system. Movement models were created based on players’ instantaneous vectorial kinematics variables, then probabilities models and dominant regions were determined. Accuracy in determining dominant regions by the proposed model was tested for diferent timelag windows. We calculated the areas of dominant, free-spaces, and Voronoi regions. Mean correct predictions of dominant region were 96.56%, 88.64%, and 72.31% for one, two, and three seconds, respectively. Dominant regions areas were lower than the ones computed by Voronoi, with median values of 73 and 171 m2 , respectively. A median value of 5537 m2 was presented for free-space regions, representing a large part of the pitch. The proposed movement model proved to be more realistic, representing the match dynamics and can be a useful method to evaluate the players’ tactical behaviours during matches

    A Comprehensive, High-Resolution Genomic Transcript Map of Human Skeletal Muscle

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    We present the Human Muscle Gene Map (HMGM), the first comprehensive and updated high-resolution expression map of human skeletal muscle. The 1078 entries of the map were obtained by merging data retrieved from UniGene with the RH mapping information on 46 novel muscle transcripts, which showed no similarity to any known sequence. In the map, distances are expressed in megabase pairs. About one-quarter of the map entries represents putative novel genes. Genes known to be specifically expressed in muscle account for <4% of the total. The genomic distribution of the map entries confirmed the previous finding that muscle genes are selectively concentrated in chromosomes 17, 19, and X. Five chromosomal regions are suspected to have a significant excess of muscle genes. Present data support the hypothesis that the biochemical and functional properties of differentiated muscle cells may result from the transcription of a very limited number of muscle-specific genes along with the activity of a large number of genes, shared with other tissues, but showing different levels of expression in muscle. [The sequence data described in this paper have been submitted to the EMBL data library under accession nos. F23198–F23242.
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