424 research outputs found

    Don’t Want to Get Caught? Don’t Say It: The Use of EMOJIS in Online Human Sex Trafficking Ads

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    Technology has dramatically changed the way criminals conduct their illicit activities. Specifically, the Internet has become a major facilitator of online human sex trafficking. Traffickers are using these technologies to market their victims which presents new challenges for efforts to combat sex trafficking. This study used knowledge management principles and natural language processing methods to develop an improved ontology of online sex trafficking ads. The language of these ads is constantly evolving; therefore, this study explored the role of a new type of indicator, emoticons, to the ontology of human trafficking indicators

    Enhanced understanding of protein glycosylation in CHO cells through computational tools and experimentation

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    Chinese hamster ovary (CHO) cells are the workhorse of the multibillion-dollar biopharmaceuticals industry. They have been extensively harnessed for recombinant protein synthesis, as they exhibit high titres and human-like post translational modifications (PTM), such as protein N-linked glycosylation. More specifically, N-linked glycosylation is a crucial PTM that includes the addition of an oligosaccharide in the backbone of the protein and strongly affects therapeutic efficacy and immunogenicity. In addition, the Quality by Design (QbD) paradigm that is broadly applied in academic research, necessitates a comprehensive understanding of the underlying biological relationships between the process parameters and the product quality attributes. To that end, computational tools have been vastly employed to elucidate cellular functions and predict the effect of process parameters on cell growth, product synthesis and quality. This thesis reports several advancements in the use of mathematical models for describing and optimizing bioprocesses. Firstly, a kinetic mathematical model describing CHO cell growth, metabolism, antibody synthesis and N-linked glycosylation was proposed, in order to capture the effect of galactose and uridine supplementation on cell growth and monoclonal antibody (mAb) glycosylation. Subsequently, the model was utilized to optimize galactosylation, a desired quality attribute of therapeutic mAbs. Following the QbD paradigm for ensuring product titre and quality, the kinetic model was subsequently used to identify an in silico Design Space (DS) that was also experimentally verified. An elaborate parameter estimation methodology was also developed in order to adapt the existing model to data from a newly introduced CHO cell line, without altering model structure. In an effort to reduce the burden of parameter estimation, the N-linked glycosylation submodel was replaced with an artificial neural network that was used as a standalone machine learning algorithm to predict the effect of feeding alterations and genetic engineering on the glycan distribution of several therapeutic proteins. In addition, a hybrid model configuration (HyGlycoM) incorporating the ANN-glycosylation model was also formulated to link extracellular process conditions to glycan distribution. The latter was found to outperform its fully kinetic equivalent when compared to experimental data. Finally, a comprehensive investigation of mAb galactosylation bottlenecks was carried out. Five fed-batch experiments with different concentrations of galactose and uridine supplemented throughout the culturing period, were carried out and were found to present similar mAb galactosylation. In order to identify the bottlenecks that limit galactosylation, further experimental analysis, including the investigation of glycans microheterogeneity of CHO host cell proteins (HCPs), was conducted. The experimental results were used to parameterize a novel and significant extension of the kinetic glycosylation model that simultaneously describes the N-linked glycosylation of both HCPs and the mAb product. Flux balance analysis was also used to analyse carbon and nitrogen metabolism using the experimental amino acid concentration profiles. In addition to the expression levels of the beta-1,4-galactosyltransferase enzyme, constraints imposed by the transport of the galactosylation sugar donor in the Golgi compartments and the consumption of resources towards HCPs glycosylation, were found to considerably influence mAb galactosylation.Open Acces

    Mining complex trees for hidden fruit : a graph–based computational solution to detect latent criminal networks : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Information Technology at Massey University, Albany, New Zealand.

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    The detection of crime is a complex and difficult endeavour. Public and private organisations – focusing on law enforcement, intelligence, and compliance – commonly apply the rational isolated actor approach premised on observability and materiality. This is manifested largely as conducting entity-level risk management sourcing ‘leads’ from reactive covert human intelligence sources and/or proactive sources by applying simple rules-based models. Focusing on discrete observable and material actors simply ignores that criminal activity exists within a complex system deriving its fundamental structural fabric from the complex interactions between actors - with those most unobservable likely to be both criminally proficient and influential. The graph-based computational solution developed to detect latent criminal networks is a response to the inadequacy of the rational isolated actor approach that ignores the connectedness and complexity of criminality. The core computational solution, written in the R language, consists of novel entity resolution, link discovery, and knowledge discovery technology. Entity resolution enables the fusion of multiple datasets with high accuracy (mean F-measure of 0.986 versus competitors 0.872), generating a graph-based expressive view of the problem. Link discovery is comprised of link prediction and link inference, enabling the high-performance detection (accuracy of ~0.8 versus relevant published models ~0.45) of unobserved relationships such as identity fraud. Knowledge discovery uses the fused graph generated and applies the “GraphExtract” algorithm to create a set of subgraphs representing latent functional criminal groups, and a mesoscopic graph representing how this set of criminal groups are interconnected. Latent knowledge is generated from a range of metrics including the “Super-broker” metric and attitude prediction. The computational solution has been evaluated on a range of datasets that mimic an applied setting, demonstrating a scalable (tested on ~18 million node graphs) and performant (~33 hours runtime on a non-distributed platform) solution that successfully detects relevant latent functional criminal groups in around 90% of cases sampled and enables the contextual understanding of the broader criminal system through the mesoscopic graph and associated metadata. The augmented data assets generated provide a multi-perspective systems view of criminal activity that enable advanced informed decision making across the microscopic mesoscopic macroscopic spectrum

    Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery

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    The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy

    The illicit business of terrorism

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    This dissertation addresses a key variable determining the threat posed by terrorist groups. It relates the threat posed by terrorist attacks to how capable a terrorist group is to carry out attacks. As such, it links the threat not to the willingness of a terrorist group to conduct attacks but to its ability to do so. I maintain that for any active terrorist group the willingness to commit attacks is a necessary requirement. A terrorist group’s capability, in contrast, depends on a variety of internal and external factors. Study- ing how differences in those endowments or constraints induce varying capabilities offers a tangible approach to understand the threat posed by a specific terrorist group
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