742 research outputs found

    DIALOGIC: A Core Natural-Language Processing System

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    The DIALOGIC system translates English sentences into representations of their literal meaning in the context of an utterance. These representations, or "logical forms," are intended to be a purely formal language that is as close as possible to the structure of natural language, while providing the semantic compositionality necessary for meaning-dependent computational processing. The design of DIALOGIC (and of its constituent modules) was influenced by the goal of using it as the core language-processing component in a variety of systems, some of which are transportable to new domains of application.Engineering and Applied Science

    Variation in the reported management of canine prolapsed nictitans gland and feline herpetic keratitis

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    Treatment variation in medicine may be driven by evidence gaps, clinician factors, and patient preferences. Although well-documented in human medicine, variation in clinical management is relatively unexplored in veterinary practice. Clinical vignette questionnaires were administered to a cross section of general practitioners (GPs) and veterinarians with postgraduate training in ophthalmology (PGs) to survey recommended management of canine prolapsed nictitans gland (“cherry eye”, PNG) and feline herpesvirus (FHV-1) keratitis. The majority of veterinarians (96.2%) suggested surgical replacement of cherry eye, with a pocketing technique being the most frequently nominated procedure. GPs were more likely to suggest gland excision in the event of surgical failure, while PGs more frequently nominated techniques incorporating a periosteal anchor for salvage repair. Most respondents managed FHV-1 keratitis with topical antibiotics (76.4%), with a minority suggesting topical antivirals (32.2%). GPs favoured topical acyclovir whilst PGs more frequently recommended topical trifluorothymidine. A significantly larger proportion of PGs nominated systemic famciclovir and lysine supplement for FHV-1 keratitis. This survey revealed moderate treatment variation for these conditions, both between and within practitioner groups. Additional research is needed to assess the reasons for this variation, particularly for conditions in which high quality evidence is scant

    Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy

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    Inducing stable control of tumour growth by tumour reversion is an alternative approach to cancer treatment when eradication of the disease cannot be achieved. The process requires re-establishment of normal control mechanisms that are lost in cancer cells so that abnormal proliferation can be halted. Embryonic environments can reset cellular programmes and we previously showed that axolotl oocyte extracts can reprogram breast cancer cells and reverse their tumorigenicity. In this study, we analysed the gene expression profiles of oocyte extract-treated tumour xenografts to show that tumour reprogramming involves cell cycle arrest and acquisition of a quiescent state. Tumour dormancy is associated with increased P27 expression, restoration of RB function and downregulation of mitogen-activated signalling pathways. We also show that the quiescent state is associated with increased levels of H4K20me3 and decreased H4K20me1, an epigenetic profile leading to chromatin compaction. The epigenetic reprogramming induced by oocyte extracts is required for RB hypophosphorylation and induction of P27 expression, both occurring during exposure to the extracts and stably maintained in reprogrammed tumour xenografts. Therefore, this study demonstrates the value of oocyte molecules for inducing tumour reversion and for the development of new chemoquiescence-based therapies

    A simple heuristic for perishable inventory control under nonstationary stochastic demand

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    In this paper, we study the single-item single-stocking location non-stationary stochastic lot sizing problem for a perishable product. We consider fixed and proportional ordering cost, holding cost and penalty cost. The item features a limited shelf life, therefore we also take into account a variable cost of disposal. We derive exact analytical expressions to determine the expected value of the inventory of different ages. We also discuss a good approximation for the case in which the shelf-life is limited. To tackle this problem, we introduce two new heuristics that extend Silver’s heuristic and compare them to an optimal Stochastic Dynamic Programming policy in the context of a numerical study. Our results demonstrate the effectiveness of our approach

    Organization and Usage of Learning Objects within Personal Computers

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    Research report of the ProLearn Network of Excellence (IST 507310), Deliverable 7.6To promote the integration of Desktop related Knowledge Management and Technology Enhanced Learning this deliverable aims at increasing the awareness of Desktop research within the Professional Learning community and at familiarizing the e-Learning researchers with the state-of-the-art in the relevant areas of Personal Information Management (PIM), as well as with the currently on-going activities and some of the regular PIM publication venues

    Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell

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    ABSTRACT We report here the in vitro characterization of 1-(2-chlorophenyl)-6-[(2R)-3,3,3-trifluoro-2-methylpropyl]-1,5-dihydro-4H-pyrazolo [3,4-d]pyrimidine-4-one , the first potent and selective inhibitor of phosphodiesterase 9 (PDE9), which is currently under preclinical development for the treatment of Alzheimer's disease. This compound selectively inhibits human (IC 50 ϭ 55 nM) and murine (IC 50 ϭ 100 nM) PDE9 activity in vitro and shows only moderate activity against other cyclic nucleotide-specific phosphodiesterases. We also report the generation and characterization of a stably transfected PDE9 Chinese hamster ovary cell line, additionally expressing soluble guanylate cyclase (sGC), the olfactory cyclic nucleotide-gated cation channel CNGA2 and the photoprotein aequorin. In this cell line, intracellular cGMP levels can be monitored in real-time via aequorin luminescence induced by Ca 2ϩ influx through CNGA2, acting as the intracellular cGMP sensor. This simple and sensitive assay system was used for the characterization of the cellular activity of the new PDE9 inhibitor. BAY 73-6691 alone did not significantly increase basal cGMP levels in this experimental setting. However, in combination with submaximal stimulating concentrations of the sGC activator 4-[((4-carboxybutyl){2-[(4-phenethylbenzyl)oxy]phenethyl}amino)methyl] benzoic acid (BAY 58-2667), the compound induced concentration-dependent luminescence signals and intracellular cGMP accumulation. The PDE9 inhibitor significantly potentiated the cGMP signals generated by sGC activating compounds such as BAY 58-2667 or 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b]pyridin-3-yl]pyrimidin-4-ylamine (BAY 41-2272) and induced leftward shifts of the corresponding concentration-response curves. Using our newly generated PDE9 reporter cell line, we could show that BAY 73-6691 is able to efficiently penetrate cells and to inhibit intracellular PDE9 activity

    Исследования гидравлических сопротивлений при движении в трубах золошлаковых тампонажно- закладочных суспензий

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    Експериментально досліджено залежність гідравлічного опору від швидкості руху та концентрації золошлакових суспензій при течії по трубах. Встановлена критична швидкість руху концентрованих гідросумішей.Dependence of hydraulic resistance is experimentally set from the rate of movement of ash-slag suspensions at a flow on pipes. The critical speed of motion of the concentrated slurries is set

    Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4

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    AbstractMast cells (MCs) are found abundantly in the central nervous system and play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. In the present study, we show that MC-deficient KitW-sh/W-sh mice display significantly increased astrogliosis and T cell infiltration as well as significantly reduced functional recovery after spinal cord injury compared to wildtype mice. In addition, MC-deficient mice show significantly increased levels of MCP-1, TNF-α, IL-10 and IL-13 protein levels in the spinal cord. Mice deficient in mouse mast cell protease 4 (mMCP4), an MC-specific chymase, also showed increased MCP-1, IL-6 and IL-13 protein levels in spinal cord samples and a decreased functional outcome after spinal cord injury. A degradation assay using supernatant from MCs derived from either mMCP4−/− mice or controls revealed that mMCP4 cleaves MCP-1, IL-6, and IL-13 suggesting a protective role for MC proteases in neuroinflammation. These data show for the first time that MCs may be protective after spinal cord injury and that they may reduce CNS damage by degrading inflammation-associated cytokines via the MC-specific chymase mMCP4
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