628 research outputs found

    Therapy for Tuberculous Meningitis

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    Flight Guidance System Validation Using SPIN

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    To verify the requirements for the mode control logic of a Flight Guidance System (FGS) we applied SPIN, a widely used software package that supports the formal verification of distributed systems. These requirements, collectively called the FGS specification, were developed at Rockwell Avionics & Communications and expressed in terms of the Consortium Requirements Engineering (CoRE) method. The properties to be verified are the invariants formulated in the FGS specification, along with the standard properties of consistency and completeness. The project had two stages. First, the FGS specification and the properties to be verified were reformulated in PROMELA, the input language of SPIN. This involved a semantics issue, as some constructs of the FGS specification do not have well-defined semantics in CoRE. Then we attempted to verify the requirements' properties using the automatic model checking facilities of SPIN. Due to the large size of the state space of the FGS specification an exhaustive state space analysis with SPIN turned out to be impossible. So we used the supertrace model checking procedure of SPIN that provides for a partial analysis of the state space. During this process, we found some subtle errors in the FGS specification

    Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

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    <p>Abstract</p> <p>Background</p> <p>Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these <it>Pax6</it><sup>-/- </sup>ES cells died rapidly after neuronal differentiation in vitro.</p> <p>Results</p> <p>Here we report the derivation of new lines of <it>Pax6</it><sup>-/- </sup>ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new <it>Pax6</it><sup>-/- </sup>lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported <it>Pax6</it><sup>-/- </sup>ES cell lines. The new lines of <it>Pax6</it><sup>-/-</sup>ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate <it>Pax6</it><sup>-/- </sup>↔ <it>Pax6</it><sup>+/+ </sup>chimeras in which the mutant cells survived and displayed the same phenotypes as <it>Pax6</it><sup>-/- </sup>cells in <it>Pax6</it><sup>-/- </sup>↔ <it>Pax6</it><sup>+/+ </sup>chimeras made by embryo aggregation.</p> <p>Conclusions</p> <p>We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.</p

    Cooperative Adaptive Cruise Control in Real Traffic Situations

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    International audienceIntelligent vehicle cooperation based on reliable communication systems contributes not only to reducing traffic accidents, but also to improving traffic flow. Adaptive Cruise Con-trol (ACC) systems can gain enhanced performance by adding vehicle-vehicle wireless communication to provide additional information to augment range sensor data, leading to Cooperative ACC (CACC). This paper presents the design, development, implementation and testing of a CACC system. It consists of two controllers, one to manage the approaching maneuver to the leading vehicle and the other to regulate car-following once the vehicle joins the platoon. The system has been implemented on four production Infiniti M56s vehicles, and this paper details the results of experiments to validate the performance of the controller and its improvements with respect to the commercially available ACC system

    Single-cell analysis of long non-coding RNAs in the developing human neocortex

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    Single cell transcriptomics of lncRNA expression in K562 cell cultures. A Distributions of median lncRNA expression to median mRNA expression ratios (lncRNA:mRNA) in populations, in silico merged single cells, and single cells from K562 cultures. B Proportion of K562 cells that expressed each lncRNA (blue) and mRNA (red), separated by maximum expression in single cells. C Same as in (B) but grouped by maximum expression quantile. D Distributions of non-zero lncRNA (blue) and mRNA (red) expression in 46 single K562 cells. Green squares, housekeeping genes; black triangles, ERCC Spike-In Controls. (PDF 454 kb

    Genetic architecture of EEG power spectra in early life

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    We measured the electroencephalogram (EEG) in 209 5 year old monozygotic (MZ) and dizygotic (DZ) twin pairs to estimate the relative contribution of genetic and environmental factors to EEG power spectra in early life. Data from same-sex and from opposite-sex twin pairs were used to test for sex differences in genetic influences. Results showed high concordance for EEGs of MZ twins for absolute and relative power in δ, θ, α1, α2, β1 and β2 bands. A model with additive genetic and unique environmental influences explained individual differences in both absolute and relative power in almost all bands and all electrode positions. Heritability of EEG power spectra was high. For absolute power the highest heritabilities were observed in θ, α1, α2 and β1 power bands (mean heritability 81, 81, 78, and 73%, respectively). Somewhat lower heritabilities were found in δ and β2 bands (mean heritability 55 and 64%, respectively). For relative power heritabilities were 63, 76, 71, 72, 68, and 65 for δ, θ, α1, α2, β1, and β2, respectively. Virtually no sex differences in heritability were found. These findings indicate that the background EEG is one of the most heritable characteristics in early life

    AUGMENT : a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma

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    PURPOSE Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile

    Introducing the Brassica Information Portal: Towards integrating genotypic and phenotypic Brassica crop data [version 1; referees: 2 approved]

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    The Brassica Information Portal (BIP) is a centralised repository for Brassica phenotypic data. Trait data associated with Brassica research and breeding experiments conducted on Brassica crops, used as vegetables, for livestock fodder and biofuels, is hosted on the site, together with information on the experimental plant materials used, as well as trial design. BIP is an open access and open source project, built on the schema of CropStoreDB, and as such can provide trait data management strategies for any crop data. A new user interface and programmatic submission/retrieval system helps to simplify data access for scientists and breeders. BIP opens up the opportunity to apply big data analyses to data generated by the Brassica Research Community. Here, we present a short description of the current status of the repository

    Diagnostic challenges of early Lyme disease: Lessons from a community case series

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    <p>Abstract</p> <p>Background</p> <p>Lyme disease, the most common vector-borne infection in North America, is increasingly reported. When the characteristic rash, erythema migrans, is not recognized and treated, delayed manifestations of disseminated infection may occur. The accuracy of diagnosis and treatment of early Lyme disease in the community is unknown.</p> <p>Methods</p> <p>A retrospective, consecutive case series of 165 patients presenting for possible early Lyme disease between August 1, 2002 and August 1, 2007 to a community-based Lyme referral practice in Maryland. All patients had acute symptoms of less than or equal to 12 weeks duration. Patients were categorized according to the Centers for Disease Control and Prevention criteria and data were collected on presenting history, physical findings, laboratory serology, prior diagnoses and prior treatments.</p> <p>Results</p> <p>The majority (61%) of patients in this case series were diagnosed with early Lyme disease. Of those diagnosed with early Lyme disease, 13% did not present with erythema migrans; of those not presenting with a rash, 54% had been previously misdiagnosed. Among those with a rash, the diagnosis of erythema migrans was initially missed in 23% of patients whose rash was subsequently confirmed. Of all patients previously misdiagnosed, 41% had received initial antibiotics likely to be ineffective against Lyme disease.</p> <p>Conclusion</p> <p>For community physicians practicing in high-risk geographic areas, the diagnosis of Lyme disease remains a challenge. Failure to recognize erythema migrans or alternatively, viral-like presentations without a rash, can lead to missed or delayed diagnosis of Lyme disease, ineffective antibiotic treatment, and the potential for late manifestations.</p
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