214 research outputs found

    Summarizing and Comparing Story Plans

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    Branching story games have gained popularity for creating unique playing experiences by adapting story content in response to user actions. Research in interactive narrative (IN) uses automated planning to generate story plans for a given story problem. However, a story planner can generate multiple story plan solutions, all of which equally-satisfy the story problem definition but contain different story content. These differences in story content are key to understanding the story branches in a story problem\u27s solution space, however we lack narrative-theoretic metrics to compare story plans. We address this gap by first defining a story plan summarization model to capture the important story semantics from a story plan. Secondly, we define a story plan comparison metric that compares story plans based on the summarization model. Using the Glaive narrative planner and a simple story problem, we demonstrate the usefulness of using the summarization model and distance metric to characterize the different story branches in a story problem\u27s solution space

    The role of immunogenic cell death in oncolytic herpes simplex virus-1 infection of cancer cells

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    Patients living with many cancers, including ovarian cancer (OC), often suffer from a lack of adequate treatment options. In the case of OC, primary debulking surgery followed by platinum and paclitaxel chemotherapy has led to a vast improvement in patient survival over the past few decades, however, rates of drug-resistant recurrence remain high. Research into new, experimental treatment options is therefore warranted for OC and other cancers. Oncolytic viruses (OVs) are replication-competent viruses that can selectively infect and destroy cancerous cell types, while leaving healthy cells unharmed. OVs do this by exploiting differences between cancer and normal cell phenotypes. Herpes simplex virus (HSV)-1, strain 1716 is one example of this type of virus that has shown selectivity for cancer cells in previous preclinical studies, as well as high levels of safety in humans. One prominent area of current OV study seeks to investigate the ability of OVs to induce immunogenic cell death (ICD) – this term describes multiple modes of programmed death pathways that culminate in release of proimmunogenic factors, which facilitate a modification of the host immune system. Two of the most prominent of these pathways are necroptosis and immunogenic apoptosis (IA). Here, I show that while many OV cell lines express the necessary components for necroptosis, they are unable to undergo classical necroptotic death (induced by TSZ). Despite this, HSV-1716 can infect and kill a range of OC lines successfully. I showed that HSV-1716-induced cell death displays two markers of IA yet does not seem to rely solely on apoptosis to kill cells. In addition, it appears not to rely on any components of the necrosome in order to kill cells, even in cells that are competent to typical necroptosis. However, when RIPK3 is overexpressed in HeLa cells, virus-induced cell death increases, as do markers of both necroptosis and IA. To investigate the role of ICP6 in HSV-1716-induced ICD, viral and cell mutants were made possessing various forms of the protein. Full-length ICP6 protein expressed in cell lines had the effect of blocking cellular response to TSZ, but constructs lacking a region known as the RHIM did not. A functionally similar mutation was produced within the RHIM of live HSV-1716 using CRISPR/Cas9 technology, which was shown to have the effect of disrupting ICP6/RIPK3 binding – thought to be the determinant of necroptotic cell death. Despite this, no changes in cell death signalling could be determined between the viruses at all. Interestingly, when cells were infected in combination with TNF-α, or TNF-α in addition to SMAC mimetic, the RHIM-modified virus produced significantly more death than HSV-1716. This suggests that while loss of RIPK3 inhibition is not sufficient to lead to increased necrosis alone, cells infected with this virus are more sensitive to further necrosis induction. This finding may prove to have great utility for producing the next generation of oncolytic viral therapeutics which can induce greater levels of proimmunogenic cell death. From this we can conclude that HSV-1716 is capable of inducing IA in OC cells. Death is not dependent on necroptosis, however additional RIPK3 seems to sensitise cells to death by other means. Cellular binding of viral ICP6 and RIPK3 can be disrupted by modification of the RHIM, although this change has no bearing on ICD signalling alone but can sensitise cells to TNF-α-induced death

    Good Timing for Computational Models of Narrative Discourse

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    The temporal order in which story events are presented in discourse can greatly impact how readers experience narrative; however, it remains unclear how narrative systems can leverage temporal order to affect comprehension and experience. We define structural properties of discourse which provide a basis for computational narratologists to reason about good timing, such as when readers learn about event relationships

    Adsorption of benzyldimethyldodecylammonium chloride onto stainless steel using the quartz crystal microbalance and the depletion methods: An optimisation study

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    The adsorption behaviour of benzyldimethyldodecylammonium chloride (C12BDMAC) corrosion inhibitor from aqueous solutions onto a stainless steel surface has been investigated using the quartz crystal microbalance (QCM) technique and the depletion-HPLC method. Three different experimental procedures were used to carry out the adsorption measurements using the QCM. The results revealed that the employed experimental procedure had a marked influence on both of the measured frequency and dissipation energy changes. Additionally, the measured changes in the normalized frequency and dissipation changes were found to be overtone-dependent. The adsorbed amounts determined by QCM were higher than those determined by depletion due to strong contributions from the bulk liquid properties. The direct application of the measured frequency shifts corresponding to the lowest dissipation changes, ?flowestD, in the Sauerbrey equation was effective in minimising these contributions within an acceptable experimental tolerance. A correction procedure, based on the Kanazawa equation, has been proposed and applied successfully to separate the contribution from the bulk effects to the calculated adsorbed mass. The adsorption isotherms obtained from the corrected frequency shifts and the depletion method were perfectly matched over the whole range of concentrations investigated

    Pump-probe spectroscopy of photovoltaic materials

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    The study of photovoltaic materials is important so as to develop new solar energy technologies: in particular, quantum-confined semiconductors could offer increased quantum efficiencies at a much lower manufacture cost. This thesis contains results from a number of pump-probe experiments designed to probe the carrier dynamics in bulk and quantum-confined photovoltaics. A THz time-domain spectrometer was designed, built and commissioned. The THz refractive indices and absorption coefficients of toluene and hexane were determined, and the spectrometer was benchmarked using a photoexcited GaAs wafer. Results are presented of time-resolved THz spectroscopy of photoexcited bulk InP as a function of laser excitation wavelength. These data were used to extract the quantum efficiency of bulk InP in order to compare with recent results for InP quantum dots. The quantum efficiency in quantum dots increases when the incident photon energy is at least twice the band gap energy, whereasthe efficiency of the bulk material is found to decrease. This is because of surface recombination, and these measurements therefore verify the potential superiority of quantum dot materials over bulk materials for use in solar energy applications. Initial measurements of quantum dots using THz spectroscopy highlighted the various experimental challenges involved and the upgrades required to study such samples in the future.The time-dependence of the photoinduced surface photovoltage (SPV) in Si was studied on nanosecond timescales by synchronizing an ultrafast laser system to a synchrotron radiation source (the SRS at Daresbury, UK), and measuring the resulting shift in the photoelectron spectrum. The equilibrium band bending was determined, and the decay of the SPV was attributed to the recombination of charge carriers across the band gap. Results are presented for the SPV in bulk ZnO and for PbS quantum dot chemically attached to ZnO. The fact that the PbS quantum dots were chemically attached to the surface without becoming oxidized was verified using X-ray photoelectron spectroscopy (XPS). The changes caused by photoexcitation occur on much longer timescales in ZnO than Si (sub-milliseconds rather than nanoseconds), and these timescales were conveniently accessed using the time-resolved XPS facility at the TEMPO beamline at Synchrotron SOLEIL (Paris, France). This is due to oxygen adsorption and desorption processes at the ZnO surface affectingthe transfer of charge carriers. The addition of PbS quantum dots to the ZnO surface was found to increase the speed of this charge transfer due to injection of carriers directly from the PbS quantum dot to the bulk ZnO conduction band.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
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