Designing novel abstraction networks for ontology summarization and quality assurance

Biomedical ontologies are complex knowledge representation systems. Biomedical ontologies support interdisciplinary research, interoperability of medical systems, and Electronic Healthcare Record (EHR) encoding. Ontologies represent knowledge using concepts (entities) linked by relationships. Ontologies may contain hundreds of thousands of concepts and millions of relationships. For users, the size and complexity of ontologies make it difficult to comprehend “the big picture” of an ontology\u27s content. For ontology editors, size and complexity make it difficult to uncover errors and inconsistencies. Errors in an ontology will ultimately affect applications that utilize the ontology. In prior studies abstraction networks (AbNs) were developed to provide a compact summary of an ontology\u27s content and structure. AbNs have been shown to successfully support ontology summarization and quality assurance (QA), e.g., for SNOMED CT and NCIt. Despite the success of these previous studies, several major, unaddressed issues affect the applicability and usability of AbNs. This thesis is broken into five major parts, each addressing one issue. The first part of this dissertation addresses the scalability of AbN-based QA techniques to large SNOMED CT hierarchies. Previous studies focused on relatively small hierarchies. The QA techniques developed for these small hierarchies do not scale to large hierarchies, e.g., Procedure and Clinical finding. A new type of AbN, called a subtaxonomy, is introduced to address this problem. Subtaxonomies summarize a subset of an ontology\u27s content. Several types of subtaxonomies and subtaxonomy-based QA studies are discussed. The second part of this dissertation addresses the need for summarization and QA methods for the twelve SNOMED CT hierarchies with no lateral relationships. Previously developed SNOMED CT AbN derivation methodologies, which require lateral relationships, cannot be applied to these hierarchies. The Tribal Abstraction Network (TAN) is a new type of AbN derived using only hierarchical relationships. A TAN-based QA methodology is introduced and the results of a QA review of the Observable entity hierarchy are reported. The third part focuses on the development of generic AbN derivation methods that are applicable to groups of structurally similar ontologies, e.g., those developed in the Web Ontology Language (OWL) format. Previously, AbN derivation techniques were applicable to only a single ontology at a time. AbNs that are applicable to many OWL ontologies are introduced, a preliminary study on OWL AbN granularity is reported on, and the results of several QA studies are presented. The fourth part describes Diff Abstraction Networks, which summarize and visualize the structural differences between two ontology releases. Diff Area Taxonomy and Diff Partial-area Taxonomy derivation methodologies are introduced and Diff Partial-area taxonomies are derived for three OWL ontologies. The Diff Abstraction Network approach is compared to the traditional ontology diff approach. Lastly, tools for deriving and visualizing AbNs are described. The Biomedical Layout Utility Framework is introduced to support the automatic creation, visualization, and exploration of abstraction networks for SNOMED CT and OWL ontologies

A microparticle assembly

A microarray, comprising a plurality of bead constructs disposed thereon, wherein the bead constructs comprise: (a) a bead; (b) a fluorophore molecule, wherein the fluorophore molecule comprises at least two subunits connected to each other by at least one internal linker that provides conformational freedom to the at least two subunits, and wherein the optical signal emitted by the flurophore changes when reducing the conformational freedom of the at least two subunits to each other; (c) a first linker molecule connected to the bead and to one of the subunits of the flurophore molecule; (d) a second linker molecule connected to another subunit of the fluorophore molecule; and (e) a ligand molecule connected to the second linker

Friends of the Vermillion River Water Trail Study

At the time of this report, Friends of the Vermillion River Water Trail (FVRWT) was working toward getting the river designated as an official canoe route by the Minnesota Department of Natural Resources. This report contains a concept plan for the route, including put-in and take-out access sites.Prepared in partnership with the Friends of the Vermillion River Water Trail by the Community Assistantship Program (CAP), administered by the Center for Urban and Regional Affairs (CURA) at the University of Minnesota

2D-Visualisierung des zellulären Sauerstoff verbrauchs in Mikrofluidiksystemen

A new imaging system allows visualizing oxygen distributions in 2D. Combining sensor foils with microfluidic devices enables online monitoring of cellular oxygen consumption in whole chip areas. Furthermore, suitable device materials depending on application and cell line can be determined. Numerically simulated oxygen consumption of rat lung microvascular endothelial cells and rat hepatocytes was experimentally validated

Oxygen levels in thermoplastic microfluidic devices during cell culture

We developed a computational model to predict oxygen levels in microfluidic plastic devices during cell culture. This model is based on experimental evaluation of oxygen levels. Conditions are determined that provide adequate oxygen supply to two cell types, hepatocytes and endothelial cells, either by diffusion through the plastic device, or by supplying a low flow rate of medium

Exploring Potential Opportunities for the Fire Equipment Maintenance Program

This paper presents opportunities for expansion of the Country Fire Authority\u27s (CFA) Fire Equipment Maintenance (FEM) program in Victoria, Australia. These opportunities were identified through interviews of CFA personnel and are intended to enhance community safety and, where possible, increase the revenue of brigades participating in the FEM program. The opportunities were researched and organised into areas of products and services, training, emergency management, and post-incident analysis. These suggestions were then presented to the CFA via a computer program and a detailed written report

A novel microfluidic platform for high-resolution imaging of a three-dimensional cell culture under a controlled hypoxic environment

Low oxygen tensions experienced in various pathological and physiological conditions are a major stimulus for angiogenesis. Hypoxic conditions play a critical role in regulating cellular behaviour including migration, proliferation and differentiation. This study introduces the use of a microfluidic device that allows for the control of oxygen tension for the study of different three-dimensional (3D) cell cultures for various applications. The device has a central 3D gel region acting as an external cellular matrix, flanked by media channels. On each side, there is a peripheral gas channel through which suitable gas mixtures are supplied to establish a uniform oxygen tension or gradient within the device. The effects of various parameters, such as gas and media flow rates, device thickness, and diffusion coefficients of oxygen were examined using numerical simulations to determine the characteristics of the microfluidic device. A polycarbonate (PC) film with a low oxygen diffusion coefficient was embedded in the device in proximity above the channels to prevent oxygen diffusion from the incubator environment into the polydimethylsiloxane (PDMS) device. The oxygen tension in the device was then validated experimentally using a ruthenium-coated (Ru-coated) oxygen-sensing glass cover slip which confirmed the establishment of low uniform oxygen tensions (<3%) or an oxygen gradient across the gel region. To demonstrate the utility of the microfluidic device for cellular experiments under hypoxic conditions, migratory studies of MDA-MB-231 human breast cancer cells were performed. The microfluidic device allowed for imaging cellular migration with high-resolution, exhibiting an enhanced migration in hypoxia in comparison to normoxia. This microfluidic device presents itself as a promising platform for the investigation of cellular behaviour in a 3D gel scaffold under varying hypoxic conditions

Transcellular diapedesis is initiated by invasive podosomes

Producción CientíficaDiapedesis is critical for immune system function and inflammatory responses. This occurs by migration of blood leukocytes either directly through individual microvascular endothelial cells (the “transcellular” route) or between them (the “paracellular” route). Mechanisms for transcellular pore formation in endothelium remain unknown. Here we demonstrate that lymphocytes used podosomes and extended “invasive podosomes” to palpate the surface of, and ultimately form transcellular pores through, the endothelium. In lymphocytes, these structures were dependent on Src kinase and the actin regulatory protein WASP; inhibition of podosome formation selectively blocked the transcellular route of diapedesis. In endothelium, membrane fusion events dependent on the SNARE-containing membrane fusion complex and intracellular calcium were required for efficient transcellular pore formation in response to podosomes. These findings provide insights into basic mechanisms for leukocyte trafficking and the functions of podosomes

Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women’s Health Initiative

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis. In a sample of 11,084 postmenopausal women from the Women’s Health Initiative (WHI; mean age 63.3â years, SD = 7.4), we performed a crossâ sectional study of the association of selfâ reported usual hours of sleep and sleep quality (WHI Insomnia Rating Score) with whole body, total hip, femoral neck, and spine BMD using linear regression models. We also studied the association of sleep duration and quality with dualâ energy Xâ ray absorptiometry (DXA)â defined low bone mass (Tâ scoreâ <â â 2.5 to <â 1) and osteoporosis (Tâ scoreâ â ¤â â 2.5) using multinomial regression models. We adjusted for age, DXA machine, race, menopausal symptoms, education, smoking, physical activity, body mass index, alcohol use, physical function, and sleep medication use. In adjusted linear regression models, women who reported sleeping 5â hours or less per night had on average 0.012 to 0.018â g/cm2 significantly lower BMD at all four sites compared with women who reported sleeping 7â hours per night (reference). In adjusted multinomial models, women reporting 5â hours or less per night had higher odds of low bone mass and osteoporosis of the hip (odds ratio [OR] =â 1.22; 95% confidence interval [CI] 1.03â 1.45, and 1.63; 1.15â 2.31, respectively). We observed a similar pattern for spine BMD, where women with 5â hours or less per night had higher odds of osteoporosis (adjusted OR = 1.28; 95% CI 1.02â 1.60). Associations of sleep quality and DXA BMD failed to reach statistical significance. Short sleep duration was associated with lower BMD and higher risk of osteoporosis. Longitudinal studies are needed to confirm the crossâ sectional effects of sleep duration on bone health and explore associated mechanisms. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154418/1/jbmr3879_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154418/2/jbmr3879.pd

Rapid Multiplexed Proteomic Screening for Primary Immunodeficiency Disorders From Dried Blood Spots

Background: Primary immunodeficiency disorders (PIDD) comprise a group of life-threatening congenital diseases characterized by absent or impaired immune responses. Despite the fact that effective, curative treatments are available with optimal clinical outcomes when diagnosed early, newborn screening does not exist for the majority of these diseases due to the lack of detectable, specific biomarkers or validated methods for population-based screening. Peptide immunoaffinity enrichment coupled with selected reaction monitoring mass spectrometry (immuno-SRM) is a sensitive proteomic assay, involving antibody-mediated peptide capture, that allows for concurrent quantification of multiple analytes. This assay has promise for use in potential newborn screening of PIDDs that lead to diminished or absent target proteins in the majority of cases.Objective: To determine and evaluate if a multiplex assay based on immuno-SRM is able to reliably and precisely distinguish affected patients with X-linked agammaglobulinemia (XLA), Wiskott-Aldrich Syndrome (WAS), and CD3ϵ-associated severe combined immunodeficiency (SCID) from one another and from unaffected normal control dried blood spot (DBS) samples.Methods: We performed a blinded, multiplexed analysis of proteolytically-generated peptides from WASp, BTK, and CD3ϵ (for WAS, XLA, and SCID, respectively) in DBS samples from 42 PIDD patients, 40 normal adult controls, and 62 normal newborns. The peptide ATPase copper transporting protein (ATP7B) 1056 was simultaneously monitored for quality assurance purposes.Results: The immuno-SRM assays reliably quantified the target peptides in DBS and accurately distinguished affected patients from normal controls. Analysis of signature peptides found statistically significant reduction or absence of peptide levels in affected patients compared to control groups in each case (WASp and BTK: p = 0.0001, SCID: p = 0.05). Intra and inter-assay precision ranged from 11 to 22% and 11 to 43% respectively; linearity (1.39–2000 fmol peptide), and stability (≤ 0.09% difference in 72 h) showed high precision for the multiplexed assay. Inter-laboratory assay comparison showed high concordance for measured peptide concentrations, with R2 linearity ≥ 0.97 for the WASp 274, CD3ϵ 197, BTK 407, and ATP7B 1056 peptides.Conclusion: Immuno-SRM-based quantification of proteotypic peptides from WASp, BTK, and CD3ϵ in DBS distinguishes relevant PIDD cases from one another and from controls, raising the possibility of employing this approach for large-scale multiplexed newborn screening of selective PIDDs