A comparative study of two formal semantics of the SIGNAL language

International audienceSIGNAL is a part of the synchronous languages family, which are broadly used in the design of safety-critical real-time systems such as avionics, space systems, and nuclear power plants. There exist several semantics for SIGNAL, such as denotational semantics based on traces (called trace semantics), denotational semantics based on tags (called tagged model semantics), operational semantics presented by structural style through an inductive definition of the set of possible transitions, operational semantics defined by synchronous transition systems (STS), etc. However, there is little research about the equivalence between these semantics.In this work, we would like to prove the equivalence between the trace semantics and the tagged model semantics, to get a determined and precise semantics of the SIGNAL language. These two semantics have several different definitions respectively, we select appropriate ones and mechanize them in the Coq platform, the Coq expressions of the abstract syntax of SIGNAL and the two semantics domains, i.e., the trace model and the tagged model, are also given. The distance between these two semantics discourages a direct proof of equivalence. Instead, we transformthem to an intermediate model, which mixes the features of both the trace semantics and the tagged model semantics. Finally, we get a determined and precise semantics of SIGNAL

Speaking out about gender imbalance in invited speakers improves diversity.

Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees

Kahn Process Networks and a Reactive Extension

Kahn and MacQueen have introduced a generic class of determinate asynchronous data-flow applications, called Kahn Process Networks (KPNs) with an elegant mathematical model and semantics in terms of Scott-continuous functions on data streams together with an implementation model of independent asynchronous sequential programs communicating through FIFO buffers with blocking read and non-blocking write operations. The two are related by the Kahn Principle which states that a realization according to the implementation model behaves as predicted by the mathematical function. Additional steps are required to arrive at an actual implementation of a KPN to take care of scheduling of independent processes on a single processor and to manage communication buffers. Because of the expressiveness of the KPN model, buffer sizes and schedules cannot be determined at design time in general and require dynamic run-time system support. Constraints are discussed that need to be placed on such system support so as to maintain the Kahn Principle.We then discuss a possible extension of the KPN model to include the possibility for sporadic, reactive behavior which is not possible in the standard model. The extended model is called Reactive Process Networks. We introduce its semantics, look at analyzability and at more constrained data-flow models combined with reactive behavior

MicroRNA-31 is required for astrocyte specification

Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in part, by limiting the activity of NF-κB. Herein, we expand our previous studies by characterizing the role of miR-31 during neural precursor cell (NPC) to astrocyte differentiation. We demonstrate that miR-31 expression and activity is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4. However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which mediate astrocyte differentiation. We determined miR-31 is required for terminal astrocyte differentiation, and that the loss of miR-31 impairs this process and/or prevents astrocyte maturation. We demonstrate that miR-31 promotes astrocyte development, in part, by reducing the levels of Lin28, a stem cell factor implicated in NPC renewal. These data suggest that miR-31 deletions may disrupt astrocyte development and/or homeostasis

Long-term mortality in HIV patients virally suppressed for more than three years with incomplete CD4 recovery: A cohort study

<p>Abstract</p> <p>Background</p> <p>The mortality in patients with persistent low CD4 count despite several years of HAART with sustained viral suppression is poorly documented. We aimed to identify predictors for inadequate CD4 cell recovery and estimate mortality in patients with low CD4 count but otherwise successful HAART.</p> <p>Method</p> <p>In a nationwide cohort of HIV patients we identified all individuals who started HAART before 1 January 2005 with CD4 cell count ≤ 200 cells/μL and experienced three years with sustained viral suppression. Patients were categorized according to CD4 cell count after the three years suppressed period (≤ 200 cells/μL; immunological non-responders (INRs), >200 cells/μL; immunological responders (IRs)). We used logistic regression and Kaplan-Meier analysis to estimated risk factors and mortality for INRs compared to IRs.</p> <p>Results</p> <p>We identified 55 INRs and 236 IRs. In adjusted analysis age > 40 years and > one year from first CD4 cell count ≤ 200 cells/μL to start of the virologically suppressed period were associated with increased risk of INR. INRs had substantially higher mortality compared to IRs. The excess mortality was mainly seen in the INR group with > one year of immunological suppression prior to viral suppression and injection drug users (IDUs).</p> <p>Conclusion</p> <p>Age and prolonged periods of immune deficiency prior to successful HAART are risk factors for incomplete CD4 cell recovery. INRs have substantially increased long-term mortality mainly associated with prolonged immunological suppression prior to viral suppression and IDU.</p

Paraphrastic Reformulations in Spoken Corpora

International audienceOur work addresses the automatic detection of paraphrastic reformulation in French spoken corpora. The proposed approach is syn-tagmatic. It is based on specific markers and the specificities of the spoken language. Manual multi-dimensional annotation performed by two annotators provides fine-grained reference data. An automatic method is proposed in order to decide whether sentences contain or not paraphras-tic relations. The obtained results show up to 66.4% precision. Analysis of the manual annotations indicates that few paraphrastic segments show morphological modifications (inflection, derivation or compounding) and that the syntactic equivalence between the segments is seldom respected, as these usually belong to different syntactic categories

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Increase in Ocular Syphilis Cases at Ophthalmologic Reference Center, France, 2012–2015

We describe the frequency, demographic and clinical features, and visual outcomes of ocular syphilis infections observed during 2012–2015 at a tertiary reference center in Paris, France. Twenty-one cases (29 eyes) were identified. The occurrence of ocular syphilis increased from 1 case in 2012 to 5 cases in 2013, 6 cases in 2014, and 9 cases in 2015 (2.22–25.21/1,000 individual patients/year for the period). Among case-patients, an annual 20%–33% were co-infected with HIV. Seventy-six percent of ocular syphilis infections occurred in men who have sex with men. Seventy-five percent of case-patients had a good final visual outcome (best-corrected visual acuity >0.3 logMAR score). Visual outcome was worse for HIV-positive patients than for HIV-negative patients (p = 0.0139). At follow-up, the best visual outcomes were observed in patients whose mean time from first ocular symptom to consultation was 15 days (SD +19 days)

Perivascular spaces in the brain:anatomy, physiology and pathology

Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance