150 research outputs found

    Exploring Business Process Deviance with Declare

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    See töö tutvustab äriprotsessi hälbe kaevandust, mis kuulub protsessi\n\rkaevandamise gruppi ja annab ülevaate mitme hälbivaga kaevandamise lähenemisviisidest.\n\rKeskendutakse ka hälbiva kaevandamise kasutamise diskrimineerivatele mustritele, mis kuulub kontserni järjestikumustrite kaevandustehnoloogiatega samasse gruppi. Selles töös vaadeldakse uute diskrimineerivate mustrite kaevandamise algoritmi, mis põhineb Declare keelel. Rakendati plug-in lähenemisviisi protsessi kaevandamise näitajaga ProMile. Kirjeldatakse kogu protsessi kuni klassifitseerimiseni. Töö lõpus hinnati algoritmi tõhusust ja eksperimente erinevates variatsioonides.This thesis introduces business process deviance mining, which belongs to the group\n\rof process mining, and gives an overview on multiple deviance mining approaches. After that\n\rwe focus on deviance mining using discriminative patterns, which belongs to the group of\n\rsequential patterns mining techniques. In this work we propose new discriminative pattern\n\rmining algorithm based on the Declare language. We implemented the approach as a plug-in\n\rof the Process Mining tool ProM. We describe the whole proposed approach from the labelling\n\rof the event logs until building the classifier and classifying the test logs. In the end of the\n\rthesis we evaluate the effectiveness of our proposed algorithm on variety of experiments on\n\revent logs

    INVESTIGATION OF MANIFOLDS AND OPTIMIZED TRAJECTORIES IN THE THREE-BODY PROBLEM

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    Manifolds and optimal control were used to better understand trajectories in the circular restricted three-body problem (CR3BP). CR3BP equations were used to generate two-dimensional stable and unstable manifolds. Optimized trajectory solutions were found using the Hamilton-Jacobi-Bellman equation applied to the third body traveling from L1 toward m2. Three sets of optimal trajectories with various fixed final positions were compared to the L1 manifold. The cases with final positions closest to the manifold remained close and had lower costs. Trajectories with low time allowances took more direct paths to their final positions, leaving the manifold and resulting in higher costs. Large time allowances caused increased trajectory length and early departure from the manifold, resulting in increased cost. For the intermediate time constrained cases, the trajectories stay longer on the manifold and cost less. From this investigation, optimized trajectories were shown to use manifolds when finding the optimal trajectory in the CR3BP

    Proline biosynthesis regulates proline transport in Staphylococcus aureus.

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    Staphylococcus aureus is metabolically diverse with the ability to rapidly adapt to a vast array of nutrient sources. This allows the pathogen to colonize a variety of niches in the host. For instance, S. aureus is the leading cause of skin and soft tissue infections, a niche that has been shown to become glucose-depleted over the course of an infection. Previous studies have shown that in niches where glucose is deficient, S. aureus utilizes peptides and free amino acids as nutrient sources. Primarily, these amino acids include glutamate and amino acids that can serve as substrates for glutamate synthesis. While arginine and histidine serve as substrates in glutamate synthesis, proline is the primary source of glutamate. Indeed, S. aureus utilizes proline as a secondary carbon source only when glucose is absent, and it can be synthesized from arginine or acquired via proline transporters from its environment. Although S. aureus encodes two putative pathways for proline biosynthesis, it has been shown that pyrroline-5-carboxylate reductase (encoded by proC) is the sole proline biosynthetic pathway in S. aureus. Studies from our laboratory have revealed that despite encoding five putative proline transporters (B7H15_03660, opuC, opuD, proP, putP), only two of the transporters, PutP and B7H15_03660 are responsible for a majority of proline transport under the laboratory conditions tested. Surprisingly, when we introduced the proC mutation into the B7H15_03660 putP double mutant, we observed proline-dependent growth, even though the primary proline transporters and proline biosynthetic pathway were knocked-out. In contrast, a transporter null ΔproC strain was unable to grow. These data suggest that inhibiting proline biosynthesis alters proline transport, and therefore one or more of the additional transporters, OpuC, OpuD, and/or ProP, are activated under these conditions. After introducing opuC, opuD, and/or proP mutations into the Δ03660 ΔputP ΔproC strain, we found that both OpuC and ProP are important for proline transport. Additionally, we observed proline-dependent growth in a proline transporter null ΔproC strain when high amounts of exogenous proline are added to the media. This growth appears to be due to an acquired mutation and will be studied more in the future. Overall these studies have revealed that proline transport is tightly linked to proline biosynthesis.https://digitalcommons.unmc.edu/surp2021/1021/thumbnail.jp

    Meeting Report: Mode(s) of Action of Asbestos and Related Mineral Fibers

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    Background: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease-causing potential, and the mode of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood

    Workshop to identify critical windows of exposure for children's health: immune and respiratory systems work group summary.

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    Fetuses, infants, and juveniles (preadults) should not be considered simply "small adults" when it comes to toxicological risk. We present specific examples of developmental toxicants that are more toxic to children than to adults, focusing on effects on the immune and respiratory systems. We describe differences in both the pharmacokinetics of the developing immune and respiratory systems as well as changes in target organ sensitivities to toxicants. Differential windows of vulnerability during development are identified in the context of available animal models. We provide specific approaches to directly investigate differential windows of vulnerability. These approaches are based on fundamental developmental biology and the existence of discrete developmental processes within the immune and respiratory systems. The processes are likely to influence differential developmental susceptibility to toxicants, resulting in lifelong toxicological changes. We also provide a template for comparative research. Finally, we discuss the application of these data to risk assessment

    Xenbase: a Xenopus biology and genomics resource

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    Xenbase (www.xenbase.org) is a model organism database integrating a diverse array of biological and genomic data on the frogs, Xenopus laevis and Xenopus (Silurana) tropicalis. Data is collected from other databases, high-throughput screens and the scientific literature and integrated into a number of database modules covering subjects such as community, literature, gene and genomic analysis. Gene pages are automatically assembled from data piped from the Entrez Gene, Gurdon Institute, JGI, Metazome, MGI, OMIM, PubMed, Unigene, Zfin, commercial suppliers and others. These data are then supplemented with in-house annotation. Xenbase has implemented the Gbrowse genome browser and also provides a BLAST service that allows users to specifically search either laevis or tropicalis DNA or protein targets. A table of Xenopus gene synonyms has been implemented and allows the genome, genes, publications and high-throughput gene expression data to be seamlessly integrated with other Xenopus data and to external database resources, making the wealth of developmental and functional data from the frog available to the broader research community

    Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials

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    The increasing use of multi-walled carbon nanotubes (MWCNTs) in consumer products and their potential to induce adverse lung effects following inhalation has lead to much interest in better understanding the hazard associated with these nanomaterials (NMs). While the current regulatory requirement for substances of concern, such as MWCNTs, in many jurisdictions is a 90-day rodent inhalation test, the monetary, ethical, and scientific concerns associated with this test led an international expert group to convene in Washington, DC, USA, to discuss alternative approaches to evaluate the inhalation toxicity of MWCNTs. Pulmonary fibrosis was identified as a key adverse outcome linked to MWCNT exposure, and recommendations were made on the design of an in vitro assay that is predictive of the fibrotic potential of MWCNTs. While fibrosis takes weeks or months to develop in vivo, an in vitro test system may more rapidly predict fibrogenic potential by monitoring pro-fibrotic mediators (e.g., cytokines and growth factors). Therefore, the workshop discussions focused on the necessary specifications related to the development and evaluation of such an in vitro system. Recommendations were made for designing a system using lung-relevant cells co-cultured at the air–liquid interface to assess the pro-fibrogenic potential of aerosolized MWCNTs, while considering human-relevant dosimetry and NM life cycle transformations. The workshop discussions provided the fundamental design components of an air–liquid interface in vitro test system that will be subsequently expanded to the development of an alternative testing strategy to predict pulmonary toxicity and to generate data that will enable effective risk assessment of NMs

    Alternative approaches for acute inhalation toxicity testing to address global regulatory and non-regulatory data requirements: an international workshop report

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    Inhalation toxicity testing, which provides the basis for hazard labeling and risk management of chemicals with potential exposure to the respiratory tract, has traditionally been conducted using animals. Significant research efforts have been directed at the development of mechanistically based, non-animal testing approaches that hold promise to provide human-relevant data and an enhanced understanding of toxicity mechanisms. A September 2016 workshop, “Alternative Approaches for Acute Inhalation Toxicity Testing to Address Global Regulatory and Non-Regulatory Data Requirements”, explored current testing requirements and ongoing efforts to achieve global regulatory acceptance for non-animal testing approaches. The importance of using integrated approaches that combine existing data with in vitro and/or computational approaches to generate new data was discussed. Approaches were also proposed to develop a strategy for identifying and overcoming obstacles to replacing animal tests. Attendees noted the importance of dosimetry considerations and of understanding mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Recommendations were made to (1) develop a database of existing acute inhalation toxicity data; (2) prepare a state-of-the-science review of dosimetry determinants, mechanisms of toxicity, and existing approaches to assess acute inhalation toxicity; (3) identify and optimize in silico models; and (4) develop a decision tree/testing strategy, considering physicochemical properties and dosimetry, and conduct proof-of-concept testing. Working groups have been established to implement these recommendations
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