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“Attractive” Treatment for Abdominal Aortic Aneurysm: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles
No full textAbdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter 50% or more of its normal size of about 2 cm. Treatment of AAAs requires either open surgery or endovascular repair, which is not clinically recommended until the diameter of the aneurysm has reached a critical threshold (taken as 5.5 cm in men or 5.0 cm in women). Thus, patients with AAA sized below this threshold are monitored until they are eligible for surgery; however, there have been cases where the AAA ruptures before this surgical threshold can be met, indicating a clear need for a treatment for small AAAs.
Previous work in our lab has utilized adipose tissue derived mesenchymal stem cells (AT MSCs) to locally treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This dissertation presents an extension of that previous work, creating a delivery system for therapeutic extracellular vesicles (MSC-EVs) secreted by AT MSCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of MSC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the microparticles and release their encapsulated MSC-EVs to exert their regenerative effects.
Magnetic moveability was tested through solution and within a polymerizing hydrogel, and MSC-EV release and uptake were demonstrated using 3D SMC-seeded fibrin gel constructs. MSC-
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EVs and SIPEs were tested in vitro for proteolytic activity and stimulation of elastin and collagen synthesis. For in vivo analysis, testing was performed in an AAA mouse model (and preliminarily a AAA rat model) wherein SIPEs were delivered locally to the site of the aneurysm to assess their potential regenerative effects
Health Education Sessions: Implementation, Lessons Learned and Sustainability: The ReCAST Study
No full textAs part of an ongoing community-partnered study on community resiliency, we implemented a series of community health education sessions across five neighborhoods in the Greater Pittsburgh region. Intended as a ‘light-touch comparison intervention’ to another more intensive training program on building collective efficacy, these neighborhood-based sessions exceeded our expectations in terms of partnership building. This poster will focus on implementation of these sessions: what makes these community gatherings so impactful and what we’ve learned so far. We will explore several factors including: collaborating with community members to plan session topics and logistics; thanking participants for attending with a small stipend; and sharing a meal together at each session. Every action, from development of the sessions to our last meeting with the community, has received positive feedback from people attending. We will reflect on lessons learned and plan for sustainability
Parallels in the Regulatory Landscape of Dimorphic Female and Male Genital Structures in Drosophila melanogaster
No full textUnderstanding how morphological structures evolve via changes to their development is an ongoing pursuit in biology. Comparative approaches examine changes in the expression or function of key developmental molecules within homologous structures, and correlate these changes with structural divergence across species, populations, the sexes, or even between different body parts within individuals. The female and male genitalia of Drosophila offer an excellent opportunity to investigate homology and trait evolution, as fruit fly genital structures are developmentally tractable and evolve rapidly. While previous work has characterized gene regulatory networks operating in the development and evolution of male genital structures in Drosophila, female pupal genitalia are comparatively understudied. Here, we traced the development of female pupal genitalia to determine when and how individual structures form. We then measured the expression patterns of 29 transcription factors in both female and male genital structures at high resolution using hybridization chain reaction and confocal microscopy. We found that these transcription factors are highly patterned in both sexes, and some serve as marker genes for distinct genital structures in females. Our results suggest that the same transcription factors may control developmental processes in female and male genitalia, and this data enables future studies that interrogate how developmental gene regulatory networks specialize and evolve in both sexes.
Please view the "Read Me" for an explanation of the file names
Acoustic Emission Data for Delayed Failure of Rock and Bone
No full textDatasets indicating time of each event along with waveform metrics for rock beam experiments published in Winner et al. (2018) with advanced analysis in the submitted article "Acoustic Emission Cascade Predicting Progression to Failure of Rock and Bone" by AP Bunger, Y Lu, A Mustafa, and MM McDowell.
Winner, R. A., Lu, G., Prioul, R., Aidagulov, G., & Bunger, A. P. (2018). Acoustic emission and kinetic fracture theory for time-dependent breakage of granite. Engineering Fracture Mechanics, 199, 101-113
The Future of Nonprofits: Leveraging Technology and Regional Networks for Transformative, Regenerative Impact
No full textTechnology is reshaping how nonprofits operate, connect, and scale their impact, recognizing that the goal of their work is to move our region from surviving to thriving. This discussion will highlight emerging tools, regional networks, and strategic approaches to maximizing the role of AI, data, and digital transformation in the nonprofit sector are made possible through The Forbes Funds’ Sixth Pivot.
Help your organization move beyond crisis response and short-term fixes to build enduring, strategic collaborations. We’ll explore the role of coaching, point-in-time capacity-building, and leadership development in ensuring long-term resilience. Nonprofits and their partners must rethink how they invest in capacity building, leadership, and technology. This discussion will highlight best practices in strategic investment, regional network-building, and ecosystem development for long-term sustainability
The heart of community engagement: exploring respect, reflexivity, reciprocity and responsiveness in practice
No full textThis workshop centers Elias & Bui’s (2001) guiding principles of community-engaged research (i.e., Respectfulness, Reflexivity, Reciprocity, Responsiveness) to present a case study and engage attendees in a thoughtful reflection of their own community-engaged work. We will present the Healthy Communities, Services, and Lifestyle Project, highlighting the process from planning to implementation of a community-engaged research study to co-create the mission/vision of Pitt’s Healthy Lifestyle Institute. Through this research we have hired, engaged, and trained three graduate students and two community partners as co-researchers. Our workshop will include our community partners’ perspectives to share why they chose to be involved, their experiences, and their dreams for engaged research moving forward. Workshop activities will include reading scenarios and discussing how the principles apply and ask attendees to consider how they can or are applying them in their own work
Data associated with publication: "Mechanical behavior and size–dependent strength of small noble-metal nanoparticles" by R. Ding, A. Martini, T.D.B. Jacobs, published in Acta Materialia, 2025
No full textWhile metal nanoparticles are foundational to many advanced technologies, the instability of small particles limits their performance and lifetime. Extensive prior work has demonstrated size-dependent behavior, including “smaller-is-stronger”, “smaller-is-weaker”, and “liquid-like deformation”. However, mechanistic understanding of deformation processes has been hampered by the difficulty of characterizing nanoparticles as they fail. Here, we have compressed nanoparticles to failure with in situ transmission electron microscopy, linking their strength to direct observation of failure mechanisms. More than 250 tests, conducted on particles of Au, Ag, and Pt with sizes ranging from 3 to 130 nm, reveal a complex, non-monotonic dependence of strength on particle size. Deformation in larger particles (130 nm down to approximately 15 nm) is carried by dislocations nucleating from the surface. Without any observable change in mechanism, the nanoparticles first exhibit strengthening with decreasing size, reach a peak strength at around 30–60 nm, then show weakening. Deformation in intermediate-size particles (15 to approximately 5 nm) exhibits a mix of plasticity and diffusive deformation. Finally, the very smallest particles, with single-digit-nanometer sizes, exhibit homogeneous diffusive deformation that contradicts recent theories, and is instead well described by the zero-creep analysis. Overall, this work reveals the regimes and mechanisms underlying nanoparticle failure, across sizes and across materials
Uncovering the mechanism of neoadjuvant Vidutolimod and Nivolumab for the treatment of melanoma using multi-omics
No full textIntratrumoral injections of the TLR9 agonist Vidutolimod (Vidu) combined with the anti-PD-1 Nivolumab has the potential to improve patient outcomes. A single-arm phase II clinical trial of neoadjuvant Vidutolimod combined with Nivolumab in high-risk resectable melanoma demonstrated a major pathologic response (MPR) rate of 55% in 31 evaluable patients. The tumor microenvironment and peripheral circulating immune cells were evaluated using a multi-omics approach that included scRNASeq, scTCRSeq, and spatial transcriptomics.
Post-treatment samples from MPR patients showed increased infiltration of pDCs and immune cells with elevated necrosis and melanophagocytosis in the tumor bed. MPR was associated with an elevated post-treatment gene signature of CD8+ T cells, pDCs, myeloid cells, phagocytosis, and macrophage activation. A distinct pre-treatment gene signature for myeloid cells was observed in tumor of MPR patients. Spatial transcriptomics demonstrated a myeloid and macrophage activation gene signature that was elevated in necrosis and histocyte rich regions. In addition, a signature of activated tertiary lymphoid structure (TLS) observed using spatial transcriptomics was elevated due to treatment in bulk RNASeq samples of Vidu/Nivo MPR patients.
MPR patients showed elevated CD8+ tumor-infiltrating lymphocytes (TILs) by IHC. ScRNAseq revealed a subset of CD8+ TILs associated with MPR that highly expresses cytotoxicity and MHC class II genes. A similar subset of MPR post-treatment enriched MHC Class II expressing CD8+ T cells was observed in the scRNASeq of PBMC samples. A subset of PBMC Ki67+CD8+ T cells expressing HLA-DR was also elevated in MPRs on-treatment by flow cytometry.
This work supports the finding that combined intratumoral injections of vidutolimod with nivolumab produces a broad anti-tumor immune response. Vidu/Nivo strongly activates B cells and macrophages in human melanoma in addition to the previously established pDC activation. This new information may prove critical for the further development of TLR9 agonists like Vidu as a treatment for melanoma and other cancers
Bridging Gaps and Building Connections: Islandora Integrations at Pitt
No full textA presentation about three Islandora 2.x integrations that were identified during a gap analysis done in 2022