Managing Epistemic Uncertainty in Design Models through Type-2 Fuzzy Logic Multidisciplinary Optimization

Humans have a natural ability to operate in dynamic environments and perform complex tasks with little perceived effort. An experienced ship designer can intuitively understand the general consequences of design choices and the general attributes of a good vessel. A person's knowledge is often ill-structured, subjective, and imprecise, but still incredibly effective at capturing general patterns of the real-world or of a design space. Computers on the other hand, can rapidly perform a large number of precise computations using well-structured, objective mathematical models, providing detailed analyses and formal evaluations of a specfic set of design candidates. In ship design, which involves generating knowledge for decision-making through time, engineers interactively use their own mental models and information gathered from computer-based optimization tools to make decisions which steer a vessel's design. In recent decades, the belief that large synthesis codes can help achieve cutting-edge ship performance has led to an increased popularity of optimization methods, potentially leading to rewarding results. And while optimization has proven fruitful to structural engineering and the aerospace industry, its applicability to early-stage design is more limited for three main reasons. First, mathematical models are by definition a reduction which cannot properly describe all aspects of the ship design problem. Second, in multidisciplinary optimization, a low-fidelity model may incorrectly drive a design, biasing the system level solution. Finally, early-stage design is plagued with limited information, limiting the designer's ability to develop models to inform decisions. This research extends previously done work by incorporating type-2 fuzzy logic into a human-centric multidisciplinary optimization framework. The original framework used type-1 fuzzy logic to incorporate human expertise into optimization models through linguistic variables. However, a type-1 system does not properly account for the uncertainty associated with linguistic terms, and thus does not properly represent the uncertainty associated with a human mental model. This limitation is corrected with the type-2 fuzzy logic multidisciplinary optimization presented in this work, which more accurately models a designer's ability to "communicate, reason and make rational decisions in an environment of imprecision, uncertainty, incompleteness of information and partiality of truth" (Mendel et al., 2010). It uses fuzzy definitions of linguistic variables and rule banks to incorporate "human intelligence" into design models, and better handles the linguistic uncertainty inherent to human knowledge and communication. A general mathematical optimization proof of concept and a planing craft case study are presented in this dissertation to show how mathematical models can be enhanced by incorporating expert opinion into them. Additionally, the planing craft case study shows how human mental models can be leveraged to quickly estimate plausible values of ship parameters when no model exists, increasing the designer's ability to run optimization methods when information is limited.PHDNaval Architecture & Marine EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/145891/1/doriancb_1.pd

Identifizierung von Effektoren der Pheromon-MAPK-Kaskade in Ustilago maydis

Die sexuelle Entwicklung von Ustilago maydis, dem Erreger des Maisbeulenbrandes, wird durch die Fusion zweier haploider Sporidien eingeleitet. Das aus der Zellfusion hervorgehende Dikaryon ist dann in der Lage die Maispflanze zu infizieren. Diese Entwicklungsprozesse werden durch die beiden Paarungstyploci a und b kontrolliert. Der biallelische a-Locus kodiert für ein Pheromon-Pheromonrezeptorsystem, das die Zell-Zellerkennung und die anschließende Zellfusion gewährleistet. Der multiallelische b-Locus kodiert für zwei Homeodomänenproteine, bE und bW, die nur in bestimmten Kombinationen heterodimerisieren und weitere Entwicklungsschritte ermöglichen. Während der Zell-Zellerkennung induziert das Pheromonsignal die Ausbildung von Konjugationshyphen und die Transkription der a- und b-Paarungstypgene. Die Induktion der a- und b-Gene erfolgt über den Transkriptionsfaktor Prf1, der über den cAMP-Signalweg und das Pheromon-MAPK-Modul posttranskriptionell aktiviert wird. Das aktive MAPK-Modul induziert zusätzlich die Transkription von prf1 und ist außerdem für die Ausbildung der Konjugationshyphen verantwortlich. Prf1 wird für die Konjugationshyphenbildung jedoch nicht benötigt. Diese Ergebnisse früherer Arbeiten deuteten auf die Existenz von weiteren unterhalb des MAPK-Moduls agierenden Regulatoren der Pheromonantwort hin. In dieser Arbeit wurden mit Rop1 und Hmg3 zwei HMG-Domänen-Transkriptionsfaktoren identifiziert, die wie Prf1 zur sequenzspezifisch DNA-bindenden Klasse dieser Proteinfamilie gehören. Während hmg3-Deletionsmutanten zwar einen schwachen Zellfusions- und Pathogenitätsdefekt zeigten, jedoch nach Pheromonstimulation Konjugationshyphen bildeten und lediglich eine leicht reduzierte Expression des Pheromongens aufwiesen, führte die Deletion von rop1 zum Verlust der Pheromon-induzierten Genexpression sowie der Konjugationshyphenbildung. Weitere Untersuchungen zeigten, dass rop1 selbst in Stämmen, die eine konstitutiv aktive Variante der MAPKK Fuz7 exprimieren für die Transkription von prf1 sowie die a- und b-Genexpression erforderlich ist. Dieser Ansatz ergab auch, dass rop1 an der Ausbildung von Konjugationshyphen nur indirekt beteiligt ist. Desweiteren wurden die starken Zellfusions- und Filamentationsdefekte von Drop1-Stämmen durch die konstitutive Expression von prf1 komplementiert, was darauf hindeutete, dass Rop1 einen entscheidenden Regulator der prf1-Expression darstellt. Gelretardationsexperimente ergaben dann, dass Rop1 in vitro spezifisch an den prf1-Promotor bindet und ermöglichten ferner die Identifizierung eines DNA-Bindemotivs, das sich in einer Reihe weiterer putativer Promotorregionen des U. maydis Genoms findet. In Northern-Analysen konnte gezeigt werden, dass das genetisch aktivierte MAPK-Modul die rop1-Expression über die MAPK Kpp2 induziert. Im Gegensatz dazu führte die genetische Aktivierung des cAMP-Signalweges zur Repression der rop1-Expression. Überraschenderweise exprimierten rop1-Deletionsmutanten auf der Pflanzenoberfläche ausreichend prf1, um alle Entwicklungsstadien zu durchlaufen und volle Pathogenität zu entwickeln. Dies deutet auf die Existenz von zusätzlichen Regulatoren der prf1-Expression auf der Pflanze hin

Identifizierung von Effektoren der Pheromon-MAPK-Kaskade in Ustilago maydis

Die sexuelle Entwicklung von Ustilago maydis, dem Erreger des Maisbeulenbrandes, wird durch die Fusion zweier haploider Sporidien eingeleitet. Das aus der Zellfusion hervorgehende Dikaryon ist dann in der Lage die Maispflanze zu infizieren. Diese Entwicklungsprozesse werden durch die beiden Paarungstyploci a und b kontrolliert. Der biallelische a-Locus kodiert für ein Pheromon-Pheromonrezeptorsystem, das die Zell-Zellerkennung und die anschließende Zellfusion gewährleistet. Der multiallelische b-Locus kodiert für zwei Homeodomänenproteine, bE und bW, die nur in bestimmten Kombinationen heterodimerisieren und weitere Entwicklungsschritte ermöglichen. Während der Zell-Zellerkennung induziert das Pheromonsignal die Ausbildung von Konjugationshyphen und die Transkription der a- und b-Paarungstypgene. Die Induktion der a- und b-Gene erfolgt über den Transkriptionsfaktor Prf1, der über den cAMP-Signalweg und das Pheromon-MAPK-Modul posttranskriptionell aktiviert wird. Das aktive MAPK-Modul induziert zusätzlich die Transkription von prf1 und ist außerdem für die Ausbildung der Konjugationshyphen verantwortlich. Prf1 wird für die Konjugationshyphenbildung jedoch nicht benötigt. Diese Ergebnisse früherer Arbeiten deuteten auf die Existenz von weiteren unterhalb des MAPK-Moduls agierenden Regulatoren der Pheromonantwort hin. In dieser Arbeit wurden mit Rop1 und Hmg3 zwei HMG-Domänen-Transkriptionsfaktoren identifiziert, die wie Prf1 zur sequenzspezifisch DNA-bindenden Klasse dieser Proteinfamilie gehören. Während hmg3-Deletionsmutanten zwar einen schwachen Zellfusions- und Pathogenitätsdefekt zeigten, jedoch nach Pheromonstimulation Konjugationshyphen bildeten und lediglich eine leicht reduzierte Expression des Pheromongens aufwiesen, führte die Deletion von rop1 zum Verlust der Pheromon-induzierten Genexpression sowie der Konjugationshyphenbildung. Weitere Untersuchungen zeigten, dass rop1 selbst in Stämmen, die eine konstitutiv aktive Variante der MAPKK Fuz7 exprimieren für die Transkription von prf1 sowie die a- und b-Genexpression erforderlich ist. Dieser Ansatz ergab auch, dass rop1 an der Ausbildung von Konjugationshyphen nur indirekt beteiligt ist. Desweiteren wurden die starken Zellfusions- und Filamentationsdefekte von Drop1-Stämmen durch die konstitutive Expression von prf1 komplementiert, was darauf hindeutete, dass Rop1 einen entscheidenden Regulator der prf1-Expression darstellt. Gelretardationsexperimente ergaben dann, dass Rop1 in vitro spezifisch an den prf1-Promotor bindet und ermöglichten ferner die Identifizierung eines DNA-Bindemotivs, das sich in einer Reihe weiterer putativer Promotorregionen des U. maydis Genoms findet. In Northern-Analysen konnte gezeigt werden, dass das genetisch aktivierte MAPK-Modul die rop1-Expression über die MAPK Kpp2 induziert. Im Gegensatz dazu führte die genetische Aktivierung des cAMP-Signalweges zur Repression der rop1-Expression. Überraschenderweise exprimierten rop1-Deletionsmutanten auf der Pflanzenoberfläche ausreichend prf1, um alle Entwicklungsstadien zu durchlaufen und volle Pathogenität zu entwickeln. Dies deutet auf die Existenz von zusätzlichen Regulatoren der prf1-Expression auf der Pflanze hin

An apoplastic peptide signal activates salicylic acid signalling in maize

Control of plant pathogen resistance or susceptibility largely depends on the promotion of either cell survival or cell death. In this context, papain-like cysteine proteases (PLCPs) regulate plant defence to drive cell death and protection against biotrophic pathogens. In maize (Zea mays), PLCPs are crucial in the orchestration of salicylic acid (SA)-dependent defence signalling. Despite this central role in immunity, it remains unknown how PLCPs are activated, and which downstream signals they induce to trigger plant immunity. Here, we present the discovery of an immune signalling peptide, Zea mays immune signalling peptide 1 (Zip1). A mass spectrometry approach identified the Zip1 peptide being produced after salicylic acid (SA) treatment. In vitro studies using recombinant proteins demonstrate that PLCPs are required to release bioactive Zip1 from its propeptide precursor (PROZIP1). Strikingly, Zip1 treatment strongly elicits SA accumulation in maize leaves. Moreover, RNAseq based transcriptome analyses revealed that Zip1 and SA treatments induce highly overlapping transcriptional changes. Consequently, Zip1 promotes the infection of the necrotrophic pathogen Botrytis cinerea in maize, while it reduces virulence of the biotrophic fungus Ustilago maydis. Together, Zip1 represents the previously missing signal that is released by PLCPs to activate SA defence signalling

The General Transcriptional Repressor Tup1 Is Required for Dimorphism and Virulence in a Fungal Plant Pathogen

A critical step in the life cycle of many fungal pathogens is the transition between yeast-like growth and the formation of filamentous structures, a process known as dimorphism. This morphological shift, typically triggered by multiple environmental signals, is tightly controlled by complex genetic pathways to ensure successful pathogenic development. In animal pathogenic fungi, one of the best known regulators of dimorphism is the general transcriptional repressor, Tup1. However, the role of Tup1 in fungal dimorphism is completely unknown in plant pathogens. Here we show that Tup1 plays a key role in orchestrating the yeast to hypha transition in the maize pathogen Ustilago maydis. Deletion of the tup1 gene causes a drastic reduction in the mating and filamentation capacity of the fungus, in turn leading to a reduced virulence phenotype. In U. maydis, these processes are controlled by the a and b mating-type loci, whose expression depends on the Prf1 transcription factor. Interestingly, Δtup1 strains show a critical reduction in the expression of prf1 and that of Prf1 target genes at both loci. Moreover, we observed that Tup1 appears to regulate Prf1 activity by controlling the expression of the prf1 transcriptional activators, rop1 and hap2. Additionally, we describe a putative novel prf1 repressor, named Pac2, which seems to be an important target of Tup1 in the control of dimorphism and virulence. Furthermore, we show that Tup1 is required for full pathogenic development since tup1 deletion mutants are unable to complete the sexual cycle. Our findings establish Tup1 as a key factor coordinating dimorphism in the phytopathogen U. maydis and support a conserved role for Tup1 in the control of hypha-specific genes among animal and plant fungal pathogens

An architectural framework for distributed naval ship systems

This paper introduces a framework for analyzing distributed ship systems. The increase in interconnected and interdependent systems aboard modern naval vessels has significantly increased their complexity, making them more vulnerable to cascading failures and emergent behavior that arise only once the system is complete and in operation. There is a need for a systematic approach to describe and analyze distributed systems at the conceptual stage for naval vessels. Understanding the relationships between various aspects of these distributed systems is crucial for uninterrupted naval operations and vessel survivability. The framework introduced in this paper decomposes information about an individual system into three views: the physical, logical, and operational architectural representations. These representations describe the spatial and functional relationships of the system, together with their temporal behavior characteristics. This paper defines how these primary architectural representations are used to describe a system, the interrelations between the architectural blocks, and how those blocks fit together. A list of defined terms is presented, and a preliminary set of requirements for specific design tools to model these architectures is discussed. A practical application is introduced to illustrate how the framework can be used to describe the delivery of power to a high energy weapon

Long-distance endosome trafficking drives fungal effector production during plant infection

To cause plant disease, pathogenic fungi can secrete effector proteins into plant cells to suppress plant immunity and facilitate fungal infection. Most fungal pathogens infect plants using very long strand-like cells, called hyphae, that secrete effectors from their tips into host tissue. How fungi undergo long-distance cell signalling to regulate effector production during infection is not known. Here we show that long-distance retrograde motility of early endosomes (EEs) is necessary to trigger transcription of effector-encoding genes during plant infection by the pathogenic fungus Ustilago maydis. We demonstrate that motor-dependent retrograde EE motility is necessary for regulation of effector production and secretion during host cell invasion. We further show that retrograde signalling involves the mitogen-activated kinase Crk1 that travels on EEs and participates in control of effector production. Fungal pathogens therefore undergo long-range signalling to orchestrate host invasion

Identification of O-mannosylated Virulence Factors in Ustilago maydis

The O-mannosyltransferase Pmt4 has emerged as crucial for fungal virulence in the animal pathogens Candida albicans or Cryptococcus neoformans as well as in the phytopathogenic fungus Ustilago maydis. Pmt4 O-mannosylates specific target proteins at the Endoplasmic Reticulum. Therefore a deficient O-mannosylation of these target proteins must be responsible for the loss of pathogenicity in pmt4 mutants. Taking advantage of the characteristics described for Pmt4 substrates in Saccharomyces cerevisiae, we performed a proteome-wide bioinformatic approach to identify putative Pmt4 targets in the corn smut fungus U. maydis and validated Pmt4-mediated glycosylation of candidate proteins by electrophoretic mobility shift assays. We found that the signalling mucin Msb2, which regulates appressorium differentiation upstream of the pathogenicity-related MAP kinase cascade, is O-mannosylated by Pmt4. The epistatic relationship of pmt4 and msb2 showed that both are likely to act in the same pathway. Furthermore, constitutive activation of the MAP kinase cascade restored appressorium development in pmt4 mutants, suggesting that during the initial phase of infection the failure to O-mannosylate Msb2 is responsible for the virulence defect of pmt4 mutants. On the other hand we demonstrate that during later stages of pathogenic development Pmt4 affects virulence independently of Msb2, probably by modifying secreted effector proteins. Pit1, a protein required for fungal spreading inside the infected leaf, was also identified as a Pmt4 target. Thus, O-mannosylation of different target proteins affects various stages of pathogenic development in U. maydis