Lack of Rbl1/p107 Effects on Cell Proliferation and Maturation in the Inner Ear

Loss of postnatal mammalian auditory hair cells (HCs) is irreversible. Earlier studies have highlighted the importance of the Retinoblastoma family of proteins (pRBs) (i.e., Rb1, Rbl1/p107, and Rbl2/p130) in the auditory cells’ proliferation and emphasized our lack of information on their specific roles in the auditory system. We have previously demonstrated that lack of Rbl2/p130 moderately affects HCs’ and supporting cells’ (SCs) proliferation. Here, we present evidence supporting multiple roles for Rbl1/p107 in the developing and mature mouse organ of Corti (OC). Like other pRBs, Rbl1/p107 is expressed in the OC, particularly in the Hensen’s and Deiters’ cells. Moreover, Rbl1/p107 impacts maturation and postmitotic quiescence of HCs and SCs, as evidenced by enhanced numbers of these cells and the presence of dividing cells in the postnatal Rbl1/p107−/− OC. These findings were further supported by microarray and bioinformatics analyses, suggesting downregulation of several bHLH molecules, as well as activation of the Notch/Hes/Hey signaling pathway in homozygous Rbl1/p107 mutant mice. Physiological assessments and detection of ectopic HC marker expression in postnatal spiral ganglion neurons (SGNs) provided evidence for incomplete cell maturation and differentiation in Rbl1/p107−/− OC. Collectively, the present study highlights an important role for Rbl1/p107 in OC cell differentiation and maturation, which is distinct from other pRBs

Investigating and Supporting Sensemaking within Online Health Communities

This dissertation focuses on understanding and supporting individual and collective sensemaking within online health communities (OHCs). This major goal was achieved in three aims. In Aim 1, this dissertation contributes a rich descriptive account of collective sensemaking in OHCs forums by describing how it occurs and develops, what triggers it, what elements constitute collective construction of meaning, and what conversational moves positively contribute to this process. Further, it describes how collective sensemaking in OHCs is impacted by the interplay between informational and socio-emotional needs of OHCs members. Moreover, it examines how design of different social computing platforms influences OHCs members’ ability to meet their informational and socio-emotional needs and engage in collective sensemaking. In Aim 2, this dissertation explores the design space of tools for supporting individual sensemaking through optimized information access. Through the design and evaluation of a prototype DisVis it examines the impact of such tools on OHCs members’ ability to understand information within discussion threads. In the final Aim 3, this dissertation proposes a novel approach for meeting the three main needs identified in Aims 1 and 2: promoting individual sensemaking, while at the same time encouraging collective sensemaking, and facilitating development of social awareness and ties among community members. The design and evaluation of the novel solution for visualizing discussion threads that synergistically addresses these three needs—dSense—provides insights for future research and design of interactive solutions for supporting individual and collective sensemaking within OHCs

AVATAR - Machine Learning Pipeline Evaluation Using Surrogate Model

© 2020, The Author(s). The evaluation of machine learning (ML) pipelines is essential during automatic ML pipeline composition and optimisation. The previous methods such as Bayesian-based and genetic-based optimisation, which are implemented in Auto-Weka, Auto-sklearn and TPOT, evaluate pipelines by executing them. Therefore, the pipeline composition and optimisation of these methods requires a tremendous amount of time that prevents them from exploring complex pipelines to find better predictive models. To further explore this research challenge, we have conducted experiments showing that many of the generated pipelines are invalid, and it is unnecessary to execute them to find out whether they are good pipelines. To address this issue, we propose a novel method to evaluate the validity of ML pipelines using a surrogate model (AVATAR). The AVATAR enables to accelerate automatic ML pipeline composition and optimisation by quickly ignoring invalid pipelines. Our experiments show that the AVATAR is more efficient in evaluating complex pipelines in comparison with the traditional evaluation approaches requiring their execution

The Phenomenology of Independent Living: Examining the Lived Experience of Young Adults From Out-of-Home Care in Wisconsin

Abstract: Interpretive Phenomenological Analysis was used to examine how young adults with prior out-of-home care experience make meaning of the Independent Living (IL) process (Smith, Flowers & Larkin, 2009). Participants had been in foster care, kinship care, and informal care settings. All participants were enrolled at the university or had recently graduated from the university. All participants were female, white, and from mixed geographic background. None registered as having disability, although evidence of Adverse Childhood Experiences (ACES) was shared. Only one study participant had prior experience with an IL contractor. Individual interviews were conducted, followed by a focus group. The how and what of the learning about topics of IL were explored. Additional questions probed how meaning was made from the formal or informal IL learning experience. Familiarity with New Public Service themes found in local, county, state government was also explored. While each participant pointed out the uniqueness of their experience, the study found similarities sufficient to identify themes, sub-themes and patterns in their experiences. Themes included context of Basic Needs, as well as content in Priority of Education/Work, Attention to Task/Organization, and Challenges with Health/Relationships. Patterns woven through the experience and meaning expressed by participants included safety, work ethic, and healthy relationships. The participants’ desire to impact public policy through the study was apparent. Recommendations for practice, research and policy were addressed, along with need for collaborative research among professionals in the field, academics, and the young adults whose voices of experience need to be at the policy table reinforcing the theme that grounded the study, “Nothing about us without us” (Charlton, 2000)

Neural Models of Subcortical Auditory Processing

An important feature of the auditory system is its ability to distinguish many simultaneous sound sources. The primary goal of this work was to understand how a robust, preattentive analysis of the auditory scene is accomplished by the subcortical auditory system. Reasonably accurate modelling of the morphology and organisation of the relevant auditory nuclei, was seen as being of great importance. The formulation of plausible models and their subsequent simulation was found to be invaluable in elucidating biological processes and in highlighting areas of uncertainty. In the thesis, a review of important aspects of mammalian auditory processing is presented and used as a basis for the subsequent modelling work. For each aspect of auditory processing modelled, psychophysical results are described and existing models reviewed, before the models used here are described and simulated. Auditory processes which are modelled include the peripheral system, and the production of tonotopic maps of the spectral content of complex acoustic stimuli, and of modulation frequency or periodicity. A model of the formation of sequential associations between successive sounds is described, and the model is shown to be capable of emulating a wide range of psychophysical behaviour. The grouping of related spectral components and the development of pitch perception is also investigated. Finally a critical assessment of the work and ideas for future developments are presented. The principal contributions of this work are the further development of a model for pitch perception and the development of a novel architecture for the sequential association of those groups. In the process of developing these ideas, further insights into subcortical auditory processing were gained, and explanations for a number of puzzling psychophysical characteristics suggested.Royal Naval Engineering College, Manadon, Plymout