Organizational Culture\u27s Impact on Job Satisfaction: A Reconceptualization of the Competing Values Framework

Academic job satisfaction has been decreasing in the U.S. which has profound negative impacts such as burnout and decreased well-being of employees. One way that job satisfaction can be increased is through understanding and changing organizational cultures through better communication. The Competing Values Framework (CVF; Quinn & Rohrbaugh, 1983; Belasen & Frank, 2010; Lund, 2003) has been used to understand how organizational cultures and their communicative norms relate to job satisfaction. However, the CVF relies on categorical measures sitting on two axes that are not orthogonal. As such, the study posits breaking these two axes into four dimensions of organizational culture from the van der Post et. al (1997) questionnaire that has better explanatory power towards job satisfaction. Utilizing a survey distributed to communication studies employees in the United States, this study found that identification with the organization and performance orientation positively impacted job satisfaction, while locus of authority negatively impacted job satisfaction and task structure had no significant impact on job satisfaction. Due to identification with the organization’s complex relationship with job satisfaction as well as other variables, future research should spend more time investigating identification with the organization as an organizational culture aspect

Optimization and Translation of MSC-Based Hyaluronic Acid Hydrogels for Cartilage Repair

Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 kPa, nearly 10-fold greater than previous reports of integration with MSC-based constructs. Furthermore, we demonstrated the durability of this repair system by applying dynamic loading and showed its functional contribution to the distribution of compressive loads across the repair space. Overall, the studies contained within this thesis offer the first MSC-based tissue engineering strategy that successfully recapitulates native mechanical function while also demonstrating the potential for complete functional cartilage repair

Assimilation of All-Weather GMI and ATMS Observations into HWRF

We propose a novel Bayesian Monte Carlo Integration (BMCI) technique to retrieve the profiles of temperature, water vapor, and cloud liquid/ice water content from microwave cloudy measurements in the presence of TCs. These retrievals then can either be directly used by meteorologists to analyze the structure of TCs or be assimilated to provide accurate initial conditions for the NWP models. The technique is applied to the data from the Advanced Technology Microwave Sounder (ATMS) onboard Suomi National Polar-orbiting Partnership (NPP) and Global Precipitation Measurement (GPM) Microwave Imager (GMI)

Transitioning from manual to stirred-tank bioreactor manufacturing of IDCT, An allogeneiccell therapy to treat lumbar degenerative disc disease

DiscGenics is a clinical stage regenerative medicine company focused on developing cell therapies that alleviate pain and restore function in patients with degenerative disc disease (DDD), a major cause of low back pain which is a driver of disability worldwide. The Company’s lead product candidate, IDCT, is a homologous, allogeneic, off-the-shelf, injectable cell therapy under investigational use in the US (ClinicalTrials.gov Identifier: NCT03347708). The manufacturing process for IDCT involves isolating cells from donated intervertebral disc tissue and expanding them into proprietary progenitor cells known as discogenic cells. For preclinical and early clinical testing, cell production was a manual process which relied on pooling individual flasks to achieve the desired lot size. For successful scale-up and commercial production, DiscGenics seeks to modify the IDCT manufacturing process to utilize one large, single vessel per lot, while also applying bioprocess controls and more robust analytical methods to ensure consistent and optimal production of drug product. Once these changes are implemented, the product critical quality attributes (CQAs) must be maintained. DiscGenics has engaged GE Healthcare (GEHC) and the Centre for Commercialization of Regenerative Medicine (CCRM) for assay, media, and process development at the Centre for Advanced Therapeutic Cell Technologies (CATCT) in Toronto, ON., Canada. In partnership with the Federal Economic Development Agency for Southern Ontario (FedDev Ontario), CATCT accelerates the development, industrialization, and adoption of cell manufacturing technologies to improve patient access to cell and gene therapies. In this collaborative project, discogenic cells were generated in traditional static culture using CellStacks (Corning), in PBS-MINI bioreactor systems (PBS Biotech), and in stirred-tank reactors (STRs) (Eppendorf), which was led by the GEHC/CCRM team. Parameters such as cell viability, fold growth, and identity via flow cytometry were compared across modalities. For the STRs, multiple control parameters were evaluated to improve cell growth and assess successful maintenance of a consistent environment for cell quality. In this study, we found that we are able to maintain CQAs between the production modalities, with cell growth being significantly improved in the STR platform. In the STRs, in-process measurements of metabolites aligned with cell growth found using a custom sampling method. Increased cell expansion was facilitated by modified agitation, inoculation, and perfusion feeding strategies. Additionally, the process-controlled STRs provide non-invasive, continuous process data monitoring which allow for development of specified control ranges of manufacturing parameters. The quality by design (QbD) approach taken for the STR process development and improvement has allowed an increase in the lot size, process knowledge, and data-driven process definition. This presentation describes the approach and benefits of transitioning from a manual process to a suspension-based, process-controlled, stirred-tank reactor to produce allogeneic cell therapies

The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing

BACKGROUND: The clinical outcomes following intrasynovial flexor tendon repair are highly variable. Excessive inflammation is a principal factor underlying the formation of adhesions at the repair surface and affecting matrix regeneration at the repair center that limit tendon excursion and impair tendon healing. A previous in-vitro study revealed that adipose-derived mesenchymal stromal cells (ASCs) modulate tendon fibroblast response to macrophage-induced inflammation. The goal of the current study was therefore to explore the effectiveness of autologous ASCs on the inflammatory stage of intrasynovial tendon healing in vivo using a clinically relevant animal model. METHODS: Zone II flexor tendon transections and suture repairs were performed in a canine model. Autologous ASC sheets were delivered to the surface of repaired tendons. Seven days after repair, the effects of ASCs on tendon healing, with a focus on the inflammatory response, were evaluated using gene expression assays, immunostaining, and histological assessments. RESULTS: ASCs delivered via the cell sheet infiltrated the host tendon, including the repair surface and the space between the tendon ends, as viewed histologically by tracking GFP-expressing ASCs. Gene expression results demonstrated that ASCs promoted a regenerative/anti-inflammatory M2 macrophage phenotype and regulated tendon matrix remodeling. Specifically, there were significant increases in M2-stimulator (IL-4), marker (CD163 and MRC1), and effector (VEGF) gene expression in ASC-sheet treated tendons compared with nontreated tendons. When examining changes in extracellular matrix expression, tendon injury caused a significant increase in scar-associated COL3A1 expression and reductions in COL2A1 and ACAN expression. The ASC treatment effectively counteracted these changes, returning the expression levels of these genes closer to normal. Immunostaining further confirmed that ASC treatment increased CD163(+) M2 cells in the repaired tendons and suppressed cell apoptosis at the repair site. CONCLUSIONS: This study provides a novel approach for delivering ASCs with outcomes indicating potential for substantial modulation of the inflammatory environment and enhancement of tendon healing after flexor tendon repair

Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis

Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133–134, 141, 152–153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.info:eu-repo/semantics/publishedVersio

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

Background Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30). Results Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance. Conclusions The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship

A shared role for RBF1 and dCAP-D3 in the regulation of transcription with consequences for innate immunity

Previously, we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase. The Drosophila melanogaster homologs RBF1 and dCAP-D3 co-localize on non-dividing polytene chromatin, suggesting the existence of a shared, non-mitotic role for these two proteins. Here, we show that the absence of RBF1 and dCAP-D3 alters the expression of many of the same genes in larvae and adult flies. Strikingly, most of the genes affected by the loss of RBF1 and dCAP-D3 are not classic cell cycle genes but are developmentally regulated genes with tissue-specific functions and these genes tend to be located in gene clusters. Our data reveal that RBF1 and dCAP-D3 are needed in fat body cells to activate transcription of clusters of antimicrobial peptide (AMP) genes. AMPs are important for innate immunity, and loss of either dCAP-D3 or RBF1 regulation results in a decrease in the ability to clear bacteria. Interestingly, in the adult fat body, RBF1 and dCAP-D3 bind to regions flanking an AMP gene cluster both prior to and following bacterial infection. These results describe a novel, non-mitotic role for the RBF1 and dCAP-D3 proteins in activation of the Drosophila immune system and suggest dCAP-D3 has an important role at specific subsets of RBF1-dependent genes

Global Analysis of Extracytoplasmic Stress Signaling in Escherichia coli

The Bae, Cpx, Psp, Rcs, and σE pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response

Global modeling of aerosol dynamics: Model description, evaluation, and interactions between sulfate and nonsulfate aerosols

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95258/1/jgrd12001.pd