One of the most significant changes in the evolution of modern business management is that organizations no longer compete as individual entities in the market, but as interlocking supply chains. Markets are no longer simply trading desks but dynamic ecosystems where people, organizations and the environment interact. Products and associated materials and resources are links that bridge supply chains from upstream (sourcing and manufacturing) to downstream (delivering and consuming). The lifecycle of a product plays a critical role in supply chains. Supply chains may be composed by, designed around, and modified for products. Product-related issues greatly impact supply chains. Existing studies have advanced product management and product lifecycle management literature through dimensions of product innovation, product growth, product line extensions, product efficiencies, and product acquisition. Product deletion, rationalization, or reduction research is limited but is a critical issue for many reasons. Sustainability is an important reason for this managerial decision. This study, grounded from multiple literature streams in both marketing and supply chain fields, identified relations and propositions to form a firm-level analysis on the role of supply chains in organizational product deletion decisions. Interviews, observational and archival data from international companies (i.e.: Australia, China, India, and Iran) contributed to the empirical support as case studies through a grounded theory approach. Bayesian analysis, an underused empirical analysis tool, was utilized to provide insights into this underdeveloped research stream; and its relationship to qualitative research enhances broader methodological understanding. Gibbs sampler and reversible jump Markov chain Monte Carlo (MCMC) simulation were used for Bayesian analysis based on collected data. The integrative findings are exploratory but provide insights for a number of research propositions.

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Background: Prevalence of metabolic disturbances is higher among individuals with neurodevelopmental disorders (NDDs), yet this association has been poorly studied. Investigation into human disease remains challenging, as a complete pathophysiological understanding relies on accurate modeling and highly controlled variables. As such, genetically engineered mouse models are increasingly used to gain insight into the biology of human NDDs, but preclinical research focus has been mainly on behavioral and neurophysiological abnormalities. Mouse models engineered to embody human-equivalent genetic variations can display discrepancies to human phenotypes, therefore a thorough characterization of mouse phenotypes must be conducted in order to evaluate how accurately a mouse model embodies a human phenotype. Also, mouse models can help discover unsuspected abnormalities that can be further validated in humans. Objective: In this study, we sought to investigate the metabolic alterations derived from NDD-associated genetic polymorphisms in previously-validated genetic mouse models. Due to the similarities in NDD-associated phenotypic expression, we hypothesized that our NDDs of interest would express similar metabolic signatures. Further, we anticipated that we might uncover unknown metabolic anomalies, and that sex may alter these differences. Methods: We used the Comprehensive Lab Animal Monitoring System coupled to EchoMRI, as well as quantification of key plasma metabolites by liquid chromatography-mass spectrometry to characterize and compare basal metabolism in three mouse models of NDDs, namely Down syndrome (Dp(16)Yey/+ mice), 16p11.2 deletion syndrome (16p11.2df/+ mice) and Fragile X syndrome (Fmr1-/- KO mice) and their wild-type (WT) counterparts. Results: Our study reveals that each mouse model expresses a unique metabolic signature that is sex-specific, independent of the amount of food consumed and minimally influenced by physical activity. We found striking differences in body composition, respiratory exchange ratio, caloric expenditure and concentrations of circulating plasma metabolites related to mitochondrial function. Conclusion: Providing novel insight into NDD-associated metabolic alterations provides a basis for future studies aimed at understanding physiological mechanisms and provides a point of reference for research aimed at detecting changes in response to intervention.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21665号 / 医博第4471号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 浅野 雅秀, 教授 齊藤 博英, 教授 遊佐 宏介 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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The U.S. aquaculture industry has become well established in the last three decades, and channel catfish aquaculture is the most significant component of this industry. Virulent Aeromonas hydrophila has been a serious disease problem since 2009 in the U.S. catfish aquaculture, and Aeromonas veronii and Edwardsiella piscicida are emerging pathogens of catfish. Therefore, this study aims to address fundamental questions on virulence mechanisms of these three fish pathogens, which I expect to support the development of control measures for preventing these diseases. In this study, E. piscicida and virulent Aeromonas hydrophila (vAh) genomes were sequenced, and comparative analyses were conducted using the genome sequences. Average nucleotide identity (ANI) calculations showed that E. piscicida strains share high sequence identity, yet they are from diverse host species and geographic regions. vAh isolates share very high sequence identity, while the other A. hydrophila genomes are more distantly related to this clonal group. We applied several comparative genomics approaches to evaluate E. piscicida genomes and E. ictaluri genomes, providing valuable information about unique and shared features of these two important pathogens in the Edwardsiella genus. Comprehensive secretion system analysis of 55 A. hydrophila genomes and deletion of tssD and tssI core elements of T6SS from vAh isolate ML09-119 has provided new knowledge. We sequenced the genome of virulent Aeromonas veronii strain ML09-123 from catfish indicated that it was highly similar to an A. veronii strain from China. Evaluation of all 41 A. veronii genomes available in the National Center for Biotechnology Information (NCBI) provides a base platform to investigate in detail the molecular mechanism of A. veronii biology and virulence. Lastly, we constructed deletion mutants vAhΔsia, vAhΔent, vAhΔcol, vAhΔhfq1, vAhΔhfq2, and vAhΔhfq1Δhfq2 to determine roles of A. hydrophila secreted proteins and regulatory proteins on virulence in catfish. Results showed that sialidase (vAhΔsia) and enterotoxin (vAhΔent) mutants were significantly attenuated.

We describe an 11 year old girl with a de novo unbalanced t(X;10) that resulted in a deletion of Xq26→Xqter and a trisomy of 10q21→10qter. Her clinical features were of distal trisomy 10q, but she lacked the cardiovascular and renal malformations observed in duplications of 10q24→10qter and had only moderate mental retardation. X inactivation was assessed on peripheral blood lymphocytes by late replication with BrdU (LR) and the human androgen receptor assay (HAR). By LR the der(X) was inactive without spreading to 10q21→10qter in all cells. The HAR assay showed skewed methylation of the paternal allele (90%). The correlation of HAR and LR suggests that the der(X) was paternally inherited and is consistent with data from other de novo balanced and unbalanced X;autosome translocations detected in females. This is the first report of parental origin of a de novo trisomy 10q.

Sound reduction and deletion have been studied across many languages for some time. Usage-based approaches suggest that the more often a word is used, the more likely it is that some of the sounds are reduced. Phonetic environment, stress, and speech rate have all been studied as reasons for sound reduction or deletion. Most recently, frequency in reducing context (FRC) has been included when studying sound reduction and deletion. FRC in this thesis measures the portion of word tokens of a given word type that are followed by a reducing context. This thesis focuses on word-final /t/ reduction and deletion in German. Audio and transcriptions of six native German speakers were time aligned with the Montreal Forced Aligner for the analysis. Word frequency, phonetic environment, stress, and FRC were analyzed as factors that condition reduction and deletion. A linear mixed-effects regression model with the dependent variable of word-final /t/ duration found significance between a shorter /t/ duration and (1) a shorter duration of the preceding sound and (2) a consonant preceding the reduced /t/. A logistic mixed-effects regression model with the dependent variable of word-final /t/ deletion found significance between deletion and (1) a consonant preceding the deleted /t/ and (2) word frequency. Though FRC was not found to be significant in this study, perhaps measuring FRC with a different reducing context would be significant in a future study.

In order to remain competitive in the marketplace, all motor vehicle manufacturers face difficult decisions with regard to balancing cost vs. feature. That is to say that the manufacturer must balance the cost of the product to the customer to remain competitive whilst offering appropriate technology and standard features required by that customer. All motor manufacturers are therefore under pressure to keep costs of nonfeature items to a minimum. One of the cost reductions items prevalent on most vehicles is the deletion of the structural member that attaches the rear bumper, known as the bumper beam (RBB), which is researched in this Thesis. This generates average vehicle savings of $20 and, as this is invisible to the customer, should enable the manufacturers to realise a significant saving or allow this revenue to be spent on additional feature without loss of vehicle function. However, in nearly all cases, deletion of the rear bumper beam has the effect of degrading the steering responses of the vehicle by 1 to 1½ rating points (out of 10), which is contrary to the premise of cost reductions; which is to ensure that vehicle function is unaffected. Initial analysis of vehicles with deleted rear bumper beams cannot show an objective measurable difference in any vehicle behaviours with or without the beam fitted, and hence CAE studies using ADAMS models cannot verify the effects of the bumper beam. It was necessary to employ unconventional modelling and testing methods such as rigid body, flexible body model techniques as well as experimental studies included driving robots and expert driver appraisals. The research demonstrated that vehicle modelling methods currently used, cannot establish or predict the complete vehicle ride and handling status. A total vehicle model approach should be used without separating the body CAE model and vehicle dynamics ADAMS model into separate entities. Furthermore, it was concluded that the determination to the effects of body hysteresis rather than pure stiffness is of crucial importance and that the steering attribute could be maintained with the deletion of the RBB analytically.

Sleep is vital for optimal physical and mental health, as well as cognitive and social functioning. Young adults with developmental disabilities (DD) are at greater risk for physical and mental health disorders and experience limitations in cognitive and social functioning in ways that can prevent participation in meaningful activities associated with young adulthood. Sleep literature has reflected that persons with DD experience worse sleep than persons without DD. Suboptimal sleep could compromise functionality and thus participation in young adulthood activities. Not much is known however of the nature of sleep problems experienced by young adults with DD. This study is a short-term longitudinal descriptive study on the sleep of young adults with DD using actigraphy. Results identify potential sleep problems with getting enough sleep and maintaining sleep. With a better understanding of sleep issues, efforts can be made to improve the sleep, functionality, and outcomes for young adults with DD.