45 research outputs found

    Cut elimination in multifocused linear logic

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    We study cut elimination for a multifocused variant of full linear logic in the sequent calculus. The multifocused normal form of proofs yields problems that do not appear in a standard focused system, related to the constraints in grouping rule instances in focusing phases. We show that cut elimination can be performed in a sensible way even though the proof requires some specific lemmas to deal with multifocusing phases, and discuss the difficulties arising with cut elimination when considering normal forms of proofs in linear logic.Comment: In Proceedings LINEARITY 2014, arXiv:1502.0441

    DNA methylation in glioblastoma: impact on gene expression and clinical outcome

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    International audienceBACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key biological pathways have been reported in glioblastoma. Genome-wide assessments of DNA methylation levels are now required to decipher the epigenetic events involved in the aggressive phenotype of glioblastoma, and to guide new treatment strategies. RESULTS: We performed a whole-genome integrative analysis of methylation and gene expression profiles in 40 newly diagnosed glioblastoma patients. We also screened for associations between the level of methylation of CpG sites and overall survival in a cohort of 50 patients uniformly treated by surgery, radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter of which was differentially expressed in a concordant way. Thirteen of the genes with concordant CpG sites displayed an inverse correlation between promoter methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival analysis identified six CpG sites associated with overall survival. SOX10 promoter methylation status (two CpG sites) stratified patients similarly to MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters identified patients with MGMT-methylated tumors that did not respond to STUPP treatment (p-value < 1e-04). CONCLUSIONS: This study provides the first genome-wide integrative analysis of DNA methylation and gene expression profiles obtained from the same GBM cohort. We also present a methylome-based survival analysis for one of the largest uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We have identified genes whose expression may be tightly regulated by epigenetic mechanisms and markers that may guide treatment decisions

    Foreign language ictal speech automatisms in nondominant temporal lobe epilepsy.

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    International audienceBACKGROUND: Foreign language ictal speech automatism (FLISA) is a rare ictal sign that has been hitherto reported in five unilingual patients, all right handed men with right temporal lobe epilepsy (TLE), only one of whom has benefited from an intracerebral EEG investigation. METHODS: We report three unilingual French patients who consistently presented English spoken ictal speech automatisms and were investigated with intracerebral EEG recordings. RESULTS: All three patients were right-handed men with nondominant TLE originating in the right amygdala. However, FLISA only occurred when the ictal EEG discharge spread to the ipsilateral temporal neocortex or frontal operculum. In addition, FLISA were emotionally salient, referring to the patient's parents or to the intensity of the ongoing seizure. CONCLUSION: Our findings, together with previously published data, suggest that foreign language ictal speech automatisms are more likely to occur in men with nondominant amygdala onset seizures, an observation that might reflect the sexual dimorphism observed in the right amygdala during emotional processing

    Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin-containing monooxygenases

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    Stereotactic recordings of median nerve somatosensory-evoked potentials in the human pre-supplementary motor area

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    International audienceMedian nerve somatosensory-evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface-to-depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so-called pre-SMA. Intracortical responses were analysed in two latency ranges: 0--50 ms and 50--150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20--N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre-SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50--150 ms latency range, contacts implanted in the pre-SMA recorded a negative potential in the 60--70 ms latency range which, in five patients, was followed by a positive response peaking 80--110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre-SMA in the first 50 ms after stimulation, while some potentials peaking in the 60--100 ms after stimulus are likely to originate from this cortical area. The latency of the pre-SMA responses recorded in our patients supports the hypothesis that the pre-SMA does not receive short-latency somatosensory inputs via direct thalamocortical projections. More probably the pre-SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas

    Responses of the supra-sylvian (SII) cortex in humans to painful and innocuous stimuli

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    International audienceIn this study we compare the intrinsic characteristics and localization of nociceptive CO(2) laser evoked potential (LEP) and non-nociceptive electrical EP (SEP) sources recorded by deep electrodes (one to two electrodes per patient, 10-15 contacts per electrode) directly implanted in the supra-sylvian cortex of 15 epileptic patients. Early CO(2) laser (N140-P170) and electrical (N60-P90) evoked potentials were recorded by all of the electrodes implanted in the supra-sylvian cortex contralateral to stimulation. SEPs and LEPs had similar waveforms and inter-peak latencies. The LEPs appeared 84+/-15 ms later and were, on average, 14.2+/-22.2 microV smaller than the SEPs. These differences may be accounted for by the characteristics and the sizes of the different peripheral fibers (Adelta vs. Abeta) activated by the two types of stimuli. The stereotactic Talairach coordinates of the SEP and LEP sources covered the pre- and post-rolandic upper bank of the sylvian fissure, and were not significantly different for noxious and non-noxious stimuli. The spatial distribution of these contralateral responses fits with that of the modeled sources of scalp CO(2) LEPs, magneto-encephalographic studies, and PET data from pain and vibrotactile activation studies. These results permit us to define the SII cortex as a cortical integration area of non-nociceptive and nociceptive inputs. This is supported by: (i) anatomical data reporting that the SII area receives inputs from both posterior columns and spino-thalamic pathways conveying the non-noxious and noxious information, respectively, and (ii) single cell recordings in monkeys, demonstrating that the SII area contains both nociceptive-specific neurons and wide-dynamic-range neurons receiving convergent input from nociceptive and non-nociceptive somatosensory afferents

    Online training of data-driven POD-based surrogates for optimization

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