2,034 research outputs found

    Pristup specifikaciji i generisanju proizvodnih procesa zasnovan na inženjerstvu vođenom modelima

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    In this thesis, we present an approach to the production process specification and generation based on the model-driven paradigm, with the goal to increase the flexibility of factories and respond to the challenges that emerged in the era of Industry 4.0 more efficiently. To formally specify production processes and their variations in the Industry 4.0 environment, we created a novel domain-specific modeling language, whose models are machine-readable. The created language can be used to model production processes that can be independent of any production system, enabling process models to be used in different production systems, and process models used for the specific production system. To automatically transform production process models dependent on the specific production system into instructions that are to be executed by production system resources, we created an instruction generator. Also, we created generators for different manufacturing documentation, which automatically transform production process models into manufacturing documents of different types. The proposed approach, domain-specific modeling language, and software solution contribute to introducing factories into the digital transformation process. As factories must rapidly adapt to new products and their variations in the era of Industry 4.0, production must be dynamically led and instructions must be automatically sent to factory resources, depending on products that are to be created on the shop floor. The proposed approach contributes to the creation of such a dynamic environment in contemporary factories, as it allows to automatically generate instructions from process models and send them to resources for execution. Additionally, as there are numerous different products and their variations, keeping the required manufacturing documentation up to date becomes challenging, which can be done automatically by using the proposed approach and thus significantly lower process designers' time.У овој дисертацији представљен је приступ спецификацији и генерисању производних процеса заснован на инжењерству вођеном моделима, у циљу повећања флексибилности постројења у фабрикама и ефикаснијег разрешавања изазова који се појављују у ери Индустрије 4.0. За потребе формалне спецификације производних процеса и њихових варијација у амбијенту Индустрије 4.0, креиран је нови наменски језик, чије моделе рачунар може да обради на аутоматизован начин. Креирани језик има могућност моделовања производних процеса који могу бити независни од производних система и тиме употребљени у различитим постројењима или фабрикама, али и производних процеса који су специфични за одређени систем. Како би моделе производних процеса зависних од конкретног производног система било могуће на аутоматизован начин трансформисати у инструкције које ресурси производног система извршавају, креиран је генератор инструкција. Такође су креирани и генератори техничке документације, који на аутоматизован начин трансформишу моделе производних процеса у документе различитих типова. Употребом предложеног приступа, наменског језика и софтверског решења доприноси се увођењу фабрика у процес дигиталне трансформације. Како фабрике у ери Индустрије 4.0 морају брзо да се прилагоде новим производима и њиховим варијацијама, неопходно је динамички водити производњу и на аутоматизован начин слати инструкције ресурсима у фабрици, у зависности од производа који се креирају у конкретном постројењу. Тиме што је у предложеном приступу могуће из модела процеса аутоматизовано генерисати инструкције и послати их ресурсима, доприноси се креирању једног динамичког окружења у савременим фабрикама. Додатно, услед великог броја различитих производа и њихових варијација, постаје изазовно одржавати неопходну техничку документацију, што је у предложеном приступу могуће урадити на аутоматизован начин и тиме значајно уштедети време пројектаната процеса.U ovoj disertaciji predstavljen je pristup specifikaciji i generisanju proizvodnih procesa zasnovan na inženjerstvu vođenom modelima, u cilju povećanja fleksibilnosti postrojenja u fabrikama i efikasnijeg razrešavanja izazova koji se pojavljuju u eri Industrije 4.0. Za potrebe formalne specifikacije proizvodnih procesa i njihovih varijacija u ambijentu Industrije 4.0, kreiran je novi namenski jezik, čije modele računar može da obradi na automatizovan način. Kreirani jezik ima mogućnost modelovanja proizvodnih procesa koji mogu biti nezavisni od proizvodnih sistema i time upotrebljeni u različitim postrojenjima ili fabrikama, ali i proizvodnih procesa koji su specifični za određeni sistem. Kako bi modele proizvodnih procesa zavisnih od konkretnog proizvodnog sistema bilo moguće na automatizovan način transformisati u instrukcije koje resursi proizvodnog sistema izvršavaju, kreiran je generator instrukcija. Takođe su kreirani i generatori tehničke dokumentacije, koji na automatizovan način transformišu modele proizvodnih procesa u dokumente različitih tipova. Upotrebom predloženog pristupa, namenskog jezika i softverskog rešenja doprinosi se uvođenju fabrika u proces digitalne transformacije. Kako fabrike u eri Industrije 4.0 moraju brzo da se prilagode novim proizvodima i njihovim varijacijama, neophodno je dinamički voditi proizvodnju i na automatizovan način slati instrukcije resursima u fabrici, u zavisnosti od proizvoda koji se kreiraju u konkretnom postrojenju. Time što je u predloženom pristupu moguće iz modela procesa automatizovano generisati instrukcije i poslati ih resursima, doprinosi se kreiranju jednog dinamičkog okruženja u savremenim fabrikama. Dodatno, usled velikog broja različitih proizvoda i njihovih varijacija, postaje izazovno održavati neophodnu tehničku dokumentaciju, što je u predloženom pristupu moguće uraditi na automatizovan način i time značajno uštedeti vreme projektanata procesa

    Chatbots for Modelling, Modelling of Chatbots

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    Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Escuela Politécnica Superior, Departamento de Ingeniería Informática. Fecha de Lectura: 28-03-202

    Measuring the impact of COVID-19 on hospital care pathways

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    Care pathways in hospitals around the world reported significant disruption during the recent COVID-19 pandemic but measuring the actual impact is more problematic. Process mining can be useful for hospital management to measure the conformance of real-life care to what might be considered normal operations. In this study, we aim to demonstrate that process mining can be used to investigate process changes associated with complex disruptive events. We studied perturbations to accident and emergency (A &E) and maternity pathways in a UK public hospital during the COVID-19 pandemic. Co-incidentally the hospital had implemented a Command Centre approach for patient-flow management affording an opportunity to study both the planned improvement and the disruption due to the pandemic. Our study proposes and demonstrates a method for measuring and investigating the impact of such planned and unplanned disruptions affecting hospital care pathways. We found that during the pandemic, both A &E and maternity pathways had measurable reductions in the mean length of stay and a measurable drop in the percentage of pathways conforming to normative models. There were no distinctive patterns of monthly mean values of length of stay nor conformance throughout the phases of the installation of the hospital’s new Command Centre approach. Due to a deficit in the available A &E data, the findings for A &E pathways could not be interpreted

    An evaluation of the role of biomarkers in Alzheimer’s disease and age-related cognitive decline

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    An ageing population will lead to an increase in age-related cognitive decline and dementia syndromes such as Alzheimer’s disease (AD), which can seriously limit an individual’s independence and quality of life. Identifying biomarkers associated with cognitive impairment in both ageing and AD are needed as they will improve our understanding of underlying pathophysiology and may eventually improve prognoses via the identification of at-risk individuals and the development of novel therapeutics. Several pathological changes in the brain which are typically seen in AD can be detected in the cerebrospinal fluid (CSF) and plasma of middle- and late-life adults without dementia. Previous work has identified associations between CSF markers and cognitive functions, although a synthesis of the large number of studies is needed. Furthermore CSF marker levels may also differ with AD risk factors, however evidence is mixed. Increasingly, research has shifted to focus on blood-based biomarkers which provide the benefit of being less invasive and more accessible. Several plasma biomarkers have been associated with cognitive functions in ageing, although few studies use appropriate cognitive tests, and even fewer have examined these proteins in the brain. There remains no gold-standard biomarkers associated with cognitive functions in either AD or age-related cognitive decline, therefore additional approaches are needed to fully understand their relationship. The aims of the current thesis are to: investigate CSF biomarkers associated with cognition in dementia and ageing; assess the relationship between CSF biomarkers and AD risk factors; examine whether plasma biomarkers are associated with age-related cognitive decline; and lastly, to examine the level of proteins (which have previously been investigated as biomarkers) in post-mortem brain tissue. Cerebrospinal fluid biomarkers associated with cognition have been investigated across a range of dementia syndromes and age-related cognitive decline. While much of the work has focused on tau and amyloid-beta (Aβ), there is burgeoning research around markers such as neurogranin and neurofilament-light. Due to a wide range of markers investigated across several dementia syndromes and ageing, the roles of each marker are less clear. Therefore, a systematic review was conducted examining the association between CSF synaptic/axonal markers, and cognitive functions across dementia syndromes and typical ageing. Sixty-seven studies were included in the review in Chapter 3. Despite substantial heterogeneity in the field, there was evidence for an association between CSF neurofilament-light and cognition in AD, frontotemporal dementia, and typical cognitive ageing. Cerebrospinal fluid neurogranin tended to be associated with cognition in those with CSF tau and CSF Aβ profiles indicative of AD. Chapter 4 focuses on the interaction between Apolipoprotein E (APOE) and sex on CSF tau levels in a middle-life cohort without dementia. Females account for an estimated 60% of those diagnosed with AD and the APOE4 allele is widely recognised to be the strongest genetic risk factor for late-onset AD. However, evidence for the interaction between these two risk factors is mixed. In this chapter, a significant interaction between APOE, sex, and CSF AD biomarkers was found, suggesting that tau accumulation may be independent of Ab in females, but not males. This has potential implications for the implementation of CSF AD biomarkers in clinical practice and pharmacological interventions which target cortical Ab. Chapter 5 focuses on the relationship between plasma biomarkers and cognitive functions in typical ageing. Previous studies have focused on this relationship, however, few use appropriate cognitive tests for a sample without dementia. In this chapter, the association between cognitive ability and plasma phosphor-tau 181 (ptau181), Ab, neurofilament-light (NfL), and glial fibrillary acidic protein (GFAP) were investigated in the Lothian Birth Cohort 1936. A significant relationship was observed between baseline p-tau181, NfL, GFAP and cognitive decline up to ~ 10-years later. Further, increasing levels of p-tau181 over time were associated with steeper cognitive decline. The results of this chapter suggest that plasma p-tau181, NfL, and GFAP may be useful biomarkers of age-related cognitive decline. In Chapter 6, several of the aforementioned markers that were previously investigated in the CSF and plasma are examined in post-mortem brain tissue. While previous work has focused on these markers in the CSF and plasma, few studies have investigated them in post-mortem tissue and how levels differ between AD and typically ageing participants. Relative differences in neurogranin, p-tau181, p-tau231, total tau, and SNAP-25 were examined by western blot in AD cases, healthy ageing cases, and mid-life cases. The results of this chapter provide evidence of a reduction of neurogranin and SNAP-25 at the synapse in AD, as well as an increase of p-tau231. This suggests that the elevations of CSF neurogranin, SNAP-25, and p-tau231 seen in AD may reflect both the loss of neurogranin/SNAP-25 and the accumulation of ptau231 in synapses. The final chapter of the thesis summarise the findings of the previous chapters, their limitations, and the impact of this work on the field

    Exploring annotations for deductive verification

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    IMP-BLAST : Desenvolupament i Integració d'un Traductor Bidireccional entre SQL i Lògica de Primer Ordre

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    SQL és el principal llenguatge utilitzat per consultar i interactuar amb dades de bases de dades relacionals. Tot i això, SQL no permet raonar sobre les consultes tal com es pot fer des del càlcul relacional, que permet expressar consultes sobre el model relacional directament amb lògica de primer ordre. Gràcies a l'equivalència d'expressivitat entre l'àlgebra relacional i el càlcul relacional, però, es poden fer traduccions d'expressions entre SQL i lògica de primer ordre. Això és molt útil perquè permet raonar sobre consultes SQL sense haver de dependre dels matisos sintàctics de les seves implementacions. En aquesta tesi es presenta IMP-BLAST, un traductor automàtic i bidireccional entre expressions d'SQL i lògica de primer ordre. El traductor compta amb dues estratègies de traducció diferents i es centren concretament a poder expressar assercions SQL com a restriccions lògiques i viceversa. També forma part del projecte l'especificació d'un metamodel d'SQL estàndard, necessari per al traductor, i la seva implementació amb l'eina IMP-SQL. Finalment, i per demostrar el valor de les eines desenvolupades s'han integrat amb l'eina de comprovació incremental d'assercions SQL TINTIN, substituint les traduccions antigues per les ofertes per IMP-BLAST.SQL is the main language used to query data in relational databases and interact with them. However, languages like relational calculus are far superior at reasoning and interacting with relational queries due to the proximity with first order logic. Thanks to the equivalence in expression power between relational algebra and relational calculus, expressions can be translated between SQL and first-order logic. This is very useful as it allows you to reason about SQL queries without having to depend on the nuances of their implementations. This thesis presents IMP-BLAST, an automatic and bidirectional translator between SQL expressions and first-order logic. The translator has two different translation strategies and they focus specifically on mapping SQL assertions as logical constraints and vice versa. The specification of a standard SQL metamodel is also included in the project since it is needed by the translator. Its implementation, the IMP-SQL tool, is also documented. Finally, and to demonstrate the value of the developed tools, both have been integrated with the incremental integrity checking tool over SQL assertions TINTIN, replacing the old translations with the ones offered by IMP-BLAST

    Validation and Verification of Safety-Critical Systems in Avionics

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    This research addresses the issues of safety-critical systems verification and validation. Safety-critical systems such as avionics systems are complex embedded systems. They are composed of several hardware and software components whose integration requires verification and testing in compliance with the Radio Technical Commission for Aeronautics standards and their supplements (RTCA DO-178C). Avionics software requires certification before its deployment into an aircraft system, and testing is mandatory for certification. Until now, the avionics industry has relied on expensive manual testing. The industry is searching for better (quicker and less costly) solutions. This research investigates formal verification and automatic test case generation approaches to enhance the quality of avionics software systems, ensure their conformity to the standard, and to provide artifacts that support their certification. The contributions of this thesis are in model-based automatic test case generations approaches that satisfy MC/DC criterion, and bidirectional requirement traceability between low-level requirements (LLRs) and test cases. In the first contribution, we integrate model-based verification of properties and automatic test case generation in a single framework. The system is modeled as an extended finite state machine model (EFSM) that supports both the verification of properties and automatic test case generation. The EFSM models the control and dataflow aspects of the system. For verification, we model the system and some properties and ensure that properties are correctly propagated to the implementation via mandatory testing. For testing, we extended an existing test case generation approach with MC/DC criterion to satisfy RTCA DO-178C requirements. Both local test cases for each component and global test cases for their integration are generated. The second contribution is a model checking-based approach for automatic test case generation. In the third contribution, we developed an EFSM-based approach that uses constraints solving to handle test case feasibility and addresses bidirectional requirements traceability between LLRs and test cases. Traceability elements are determined at a low-level of granularity, and then identified, linked to their source artifact, created, stored, and retrieved for several purposes. Requirements’ traceability has been extensively studied but not at the proposed low-level of granularity

    Glycolytic Inhibitors as Leads for Drug Discovery in the Pathogenic Free-Living Amoebae

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    The free-living amoeba, Naegleria fowleri, can cause a rare yet usually lethal infection of the brain called primary amebic meningoencephalitis. Because of poor diagnostics and limited treatment options, the mortality rate associated with the disease is \u3e97%. Due to our finding that glucose is critical for trophozoite growth in culture, we have been interested in exploiting amoebae glucose metabolism to identify new potential drug targets. We have characterized the first enzyme of the glycolytic pathway, glucokinase (Glck), from N. fowleri and two other pathogenic free-living amoeba, Acanthamoeba castellanii and Balamuthia mandrillaris. We have assessed their biochemical properties and tested potential inhibitors on the recombinant Glcks, which revealed that these enzymes are sufficiently different from one another that developing pan-amoeba inhibitors may be challenging. However, their individual differences from the human host enzyme suggests that species-specific Glck inhibitors could be identified. We have also explored targeting the glucose metabolizing enzyme enolase in N. fowleri using a series of phosphonate human enolase 2 (ENO-2) specific inhibitors that were developed to treat human cancer. These compounds are curative for ENO-1 deleted glioblastoma in a rodent model, can cross the blood-brain barrier, and are of limited toxicity to non-human primates. The phosphonate inhibitors were toxic to N. fowleri in vitro with (1-hydroxy-2-oxopiperidin-3-yl) phosphonic acid (HEX) being the most potent, with an EC50 value of 0.21 ± 0.02 µM, almost 1500-fold lower than the concentration required to impact human cells. Unbiased metabolomics indicates that glycolytic intermediates upstream of NfENO accumulate in HEX treated amoebae. In an effort to genetically validate new targets for therapeutic intervention, we have initiated efforts to develop molecular tools for use in N. fowleri. We have designed a vector for transient transfection of the amoebae that harbors portions of the 5’UTR of actin 1 (NF0111190) upstream of both eYFP and a hygromycin resistance gene, termed pJMJM1. We have tested a variety of approaches used in other parasite systems for plasmid delivery including the transfection reagent SuperFect, Amaxa Nucleofector technologies, and various electroporation settings. Transfection of N. fowleri flagellates with 5 µg pJMJM1 by electroporation (100 V, 500 µF, 400 Ω) yielded a population of fluorescent cells seven days after being treated with 300 µg/mL hygromycin, but this expression of eYFP was lost over time. More recently, we have used CRISPR/Cas9- mediated gene editing to successfully introduce an eYFP repair template into a predicted protein locus. While fluorescent cells were not noted in the culture, editing was confirmed by PCR analysis. Development of these molecular techniques will provide an important tool for uncovering potential target genes and allow for a better understanding of amoeba biology

    2011 GREAT Day Program

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    SUNY Geneseo’s Fifth Annual GREAT Day.https://knightscholar.geneseo.edu/program-2007/1005/thumbnail.jp
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