Proving Determinacy of the PharOS Real-Time Operating System

International audienceExecutions in the PharOS real-time system are deterministic in the sense that the sequence of local states for every process is independent of the order in which processes are scheduled. The essential ingredient for achieving this property is that a temporal window of execution is associated with every instruction. Messages become visible to receiving processes only after the time window of the sending message has elapsed. We present a high-level model of PharOS in TLA+ and formally state and prove determinacy using the TLA+ Proof System

Temporal perception deficits in schizophrenia: integration is the problem, not deployment of attentions

Patients with schizophrenia are known to have impairments in sensory processing. In order to understand the specific temporal perception deficits of schizophrenia, we investigated and determined to what extent impairments in temporal integration can be dissociated from attention deployment using Attentional Blink (AB). Our findings showed that there was no evident deficit in the deployment of attention in patients with schizophrenia. However, patients showed an increased temporal integration deficit within a hundred-millisecond timescale. The degree of such integration dysfunction was correlated with the clinical manifestations of schizophrenia. There was no difference between individuals with/without schizotypal personality disorder in temporal integration. Differently from previous studies using the AB, we did not find a significant impairment in deployment of attention in schizophrenia. Instead, we used both theoretical and empirical approaches to show that previous findings (using the suppression ratio to correct for the baseline difference) produced a systematic exaggeration of the attention deficits. Instead, we modulated the perceptual difficulty of the task to bring the baseline levels of target detection between the groups into closer alignment. We found that the integration dysfunction rather than deployment of attention is clinically relevant, and thus should be an additional focus of research in schizophrenia

Analytic fluid theory of beam spiraling in high-intensity cyclotrons

Using a two-dimensional fluid description, we investigate the nonlinear radial-longitudinal dynamics of intense beams in isochronous cyclotrons in the nonrelativistic limit. With a multiscale analysis separating the time scale associated with the betatron motion and the slower time scale associated with space-charge effects, we show that the longitudinal-radial vortex motion can be understood in the frame moving with the charged beam as the nonlinear advection of the beam by the E×B velocity field, where E is the electric field due to the space charge and B is the external magnetic field. This interpretation provides simple explanations for the stability of round beams and for the development of spiral halos in elongated beams. By numerically solving the nonlinear advection equation for the beam density, we find that it is also in quantitative agreement with results obtained in particle-in-cell simulations

Evidence for the predictive remapping of visual attention

When attending an object in visual space, perception of the object remains stable despite frequent eye movements. It is assumed that visual stability is due to the process of remapping, in which retinotopically organized maps are updated to compensate for the retinal shifts caused by eye movements. Remapping is predictive when it starts before the actual eye movement. Until now, most evidence for predictive remapping has been obtained in single cell studies involving monkeys. Here, we report that predictive remapping affects visual attention prior to an eye movement. Immediately following a saccade, we show that attention has partly shifted with the saccade (Experiment 1). Importantly, we show that remapping is predictive and affects the locus of attention prior to saccade execution (Experiments 2 and 3): before the saccade was executed, there was attentional facilitation at the location which, after the saccade, would retinotopically match the attended location

Effect of stimulus type and pitch salience on pitch-sequence processing

Using a same-different discrimination task, it has been shown that discrimination performance for sequences of complex tones varying just detectably in pitch is less dependent on sequence length (1, 2, or 4 elements) when the tones contain resolved harmonics than when they do not [Cousineau, Demany, and Pessnitzer (2009). J. Acoust. Soc. Am. 126, 3179-3187]. This effect had been attributed to the activation of automatic frequency-shift detectors (FSDs) by the shifts in resolved harmonics. The present study provides evidence against this hypothesis by showing that the sequence-processing advantage found for complex tones with resolved harmonics is not found for pure tones or other sounds supposed to activate FSDs (narrow bands of noise and wide-band noises eliciting pitch sensations due to interaural phase shifts). The present results also indicate that for pitch sequences, processing performance is largely unrelated to pitch salience per se: for a fixed level of discriminability between sequence elements, sequences of elements with salient pitches are not necessarily better processed than sequences of elements with less salient pitches. An ideal-observer model for the same-different binary-sequence discrimination task is also developed in the present study. The model allows the computation of d' for this task using numerical methods

EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases

EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention

MEG/EEG Group Analysis With Brainstorm

Brainstorm is a free, open-source Matlab and Java application for multimodal electrophysiology data analytics and source imaging [primarily MEG, EEG and depth recordings, and integration with MRI and functional near infrared spectroscopy (fNIRS)]. We also provide a free, platform-independent executable version to users without a commercial Matlab license. Brainstorm has a rich and intuitive graphical user interface, which facilitates learning and augments productivity for a wider range of neuroscience users with little or no knowledge of scientific coding and scripting. Yet, it can also be used as a powerful scripting tool for reproducible and shareable batch processing of (large) data volumes. This article describes these Brainstorm interactive and scripted features via illustration through the complete analysis of group data from 16 participants in a MEG vision study

PARP1 suppresses homologous recombination events in mice in vivo

Recent studies suggest that PARP1 inhibitors, several of which are currently in clinical trial, may selectively kill BRCA1/2 mutant cancers cells. It is thought that the success of this therapy is based on immitigable lethal DNA damage in the cancer cells resultant from the concurrent loss or inhibition of two DNA damage repair pathways: single-strand break (SSB) repair and homologous recombination repair (HRR). Presumably, inhibition of PARP1 activity obstructs the repair of SSBs and during DNA replication, these lesions cause replication fork collapse and are transformed into substrates for HRR. In fact, several previous studies have indicated a hyper-recombinogenic phenotype in the absence of active PARP1 in vitro or in response to DNA damaging agents. In this study, we demonstrate an increased frequency of spontaneous HRR in vivo in the absence of PARP1 using the pun assay. Furthermore, we found that the HRR events that occur in Parp1 nullizygous mice are associated with a significant increase in large, clonal events, as opposed to the usually more frequent single cell events, suggesting an effect in replicating cells. In conclusion, our data demonstrates that PARP1 inhibits spontaneous HRR events, and supports the model of DNA replication transformation of SSBs into HRR substrates