Trusting our Students

PRESENTATION 2 ABSTRACT: Trusting Our Students: How Standard Setting Makes or Breaks a Team - Katrina M. Schell, Burke Library. An effective student employment program requires consistent standard setting. Employers set standards not just through employment contracts or performance reviews, but also with the day-to-day assignment of work and well-structured pathways for professional development. When student employees are given meaningful tasks with clearly-communicated importance, buy-in among the workforce will increase. Conversely, when tasks have poorly explained goals, it gives the impression that increased effort will not add value. Our presentation details how the meaningfulness of tasks can be demonstrated to students in two key ways: by involving students in the policy-making process and by giving students a range of growth opportunities that promote diverse skills. Growth opportunities on our team include student employees being given additional responsibilities or advancing into senior positions in Circulation, ILL, or courier roles. We also provide insight into the tangible consequences of breakdowns in communicating standards to our students, and what we’ve learned from them

Construction and Verification of a Bayesian Network for Third-Party Excavation Risk Assessment (BaNTERA)

According to the Pipeline and Hazardous Material Safety Administration (PHMSA), thirdparty damage is a leading cause of natural gas pipeline accidents. Although the risk of third-party damage has been widely studied in the literature, current models do not capture a sufficiently comprehensive set of up-to-date root cause factors and their dependencies. This limits their ability to achieve an accurate risk assessment that can be traced to meaningful elements of an excavation. This paper presents the construction, verification, and validation of a probabilistic Bayesian network model for third-party excavation risk assessment, BaNTERA. The model was constructed and its performance verified using the best available industry data and previous models from multiple sources. Historical industry data and nationwide statistics were compared with BaNTERA’s damage rate predictions to validate the model. The result of this work is a comprehensive risk model for the third-party damage problem in natural gas pipelines.U.S. Department of Transportation Pipeline and Hazardous Materials Safety Administratio

Competency for Nonsense-Mediated Reduction in Collagen X mRNA Is Specified by the 3′ UTR and Corresponds to the Position of Mutations in Schmid Metaphyseal Chondrodysplasia

Nonsense-mediated decay (NMD) is a eukaryotic cellular RNA surveillance and quality-control mechanism that degrades mRNA containing premature stop codons (nonsense mutations) that otherwise may exert a deleterious effect by the production of dysfunctional truncated proteins. Collagen X (COL10A1) nonsense mutations in Schmid-type metaphyseal chondrodysplasia are localized in a region toward the 3′ end of the last exon (exon 3) and result in mRNA decay, in contrast to most other genes in which terminal-exon nonsense mutations are resistant to NMD. We introduce nonsense mutations into the mouse Col10a1 gene and express these in a hypertrophic-chondrocyte cell line to explore the mechanism of last-exon mRNA decay of Col10a1 and demonstrate that mRNA decay is spatially restricted to mutations occurring in a 3′ region of the exon 3 coding sequence; this region corresponds to where human mutations have been described. This localization of mRNA-decay competency suggested that a downstream region, such as the 3′ UTR, may play a role in specifying decay of mutant Col10a1 mRNA containing nonsense mutations. We found that deleting any of the three conserved sequence regions within the 3′ UTR (region I, 23 bp; region II, 170 bp; and region III, 76 bp) prevented mutant mRNA decay, but a smaller 13 bp deletion within region III was permissive for decay. These data suggest that the 3′ UTR participates in collagen X last-exon mRNA decay and that overall 3′ UTR configuration, rather than specific linear-sequence motifs, may be important in specifying decay of Col10a1 mRNA containing nonsense mutations

Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.

Organ fibrosis is a shared endpoint of many diseases, yet underlying mechanisms are not well understood. Several pathways governed by the primary cilium, a sensory antenna present on most vertebrate cells, have been linked with fibrosis. Ciliopathies usually start early in life and represent a considerable disease burden. We performed massively parallel sequencing by using cohorts of genetically unsolved individuals with unexplained liver and kidney failure and correlated this with clinical, imaging, and histopathological analyses. Mechanistic studies were conducted with a vertebrate model and primary cells. We detected bi-allelic deleterious variants in TULP3, encoding a critical adaptor protein for ciliary trafficking, in a total of 15 mostly adult individuals, originating from eight unrelated families, with progressive degenerative liver fibrosis, fibrocystic kidney disease, and hypertrophic cardiomyopathy with atypical fibrotic patterns on histopathology. We recapitulated the human phenotype in adult zebrafish and confirmed disruption of critical ciliary cargo composition in several primary cell lines derived from affected individuals. Further, we show interaction between TULP3 and the nuclear deacetylase SIRT1, with roles in DNA damage repair and fibrosis, and report increased DNA damage ex vivo. Transcriptomic studies demonstrated upregulation of profibrotic pathways with gene clusters for hypertrophic cardiomyopathy and WNT and TGF-β signaling. These findings identify variants in TULP3 as a monogenic cause for progressive degenerative disease of major organs in which affected individuals benefit from early detection and improved clinical management. Elucidation of mechanisms crucial for DNA damage repair and tissue maintenance will guide novel therapeutic avenues for this and similar genetic and non-genomic diseases