U.S. Commission on Immigration Reform

The U.S. Commission on Immigration Reform was created by Congress to assess U.S. immigration policy and make recommendations regarding its implementation and effects. Mandated in the Immigration Act of 1990 to submit an interim report in 1994 and a final report in 1997, the Commission has undertaken public hearings, fact-finding missions, and expert consultations to identify the major immigration-related issues facing the United States today.LBJ School of Public Affair

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here, in both murine and human PDA, we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through tumor-associated collagen signatures (TACS). This results in early dissemination from histologically premalignant lesions and continual invasion from well-differentiated disease, and it suggests TACS as a biomarker to aid in the pathologic assessment of early disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in potentially novel microfluidic-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to reengineer and normalize tumor microenvironments may have roles not only in very early disease, but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma-targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination

Capturing Cell Dynamics in Live Pancreatic Adenocarcinoma

University of Minnesota M.S. thesis.January 2020. Major: Biomedical Engineering. Advisor: Paolo Provenzano. 1 computer file (PDF); x, 64 pages + 1 folder of supplementary media files.Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive and lethal cancers and is associated with a robust fibroinflammatory stromal response termed desmoplastic reaction. This stromal response causes the local microenvironment to significantly aid disease progression by providing drug free sanctuaries, immunosuppressive niches, and suppressing cytotoxic T lymphocyte infiltration and distribution, due in part to the increased intra-tumoral pressure and robust extracellular matrix proteins (ECM) density. In order for CD8+ cytotoxic T cells to infiltrate and eliminate cancer cells, they need to migrate efficiently through the dense tumor microenvironment (TME). Thus, altering external (ECM content/architecture) and internal (modulating microtubule (MT) dynamics in immune cell) factors has the potential to enhance efficient infiltration of native or engineered cytotoxic T lymphocytes so they effectively sample the tumor volume to combat disease. Therefore, to analyze the infiltration capabilities in a dense tumor environment, we optimized an approach to culture live tumor slices over 1-4 days in order to perform live cell imaging of carcinoma and immune cell dynamics in complex TMEs with nonlinear optical imaging platforms. From human peripheral blood or tumor-bearing mouse model of PDA, CD4+ or CD8+ cytotoxic T lymphocytes, respectively, were isolated, activated, labeled and later introduced to 3D collagen matrices and live murine PDA tumor slice explants, which has a complex multi-cellular environment and contains elements of the original TME and architecture. Furthermore, we used CRISPR technology to engineer T cells to lack GEF-H1 and alter MT→GEF-H1→RhoA pathway to determine its effect on cell motility. We employed two-photon excitation and second harmonic generation (SHG) imaging to visualize cell dynamics and ECM architecture, and quantify T cell migration behavior through 3D collagen matrices and the native PDA tumor architectures. To test approaches to re-engineer TMEs, we are specifically altering ECM composition and architecture in PDA and quantifying changes in T cell behavior. Thus, combined, these live measures and quantitative analysis will form the basis for our understanding of cell migration in the complex microenvironment and set the mark for our objective to modulate immunity in tumors

Direct Observation of Localized Radial Oxygen Migration in Functioning Tantalum Oxide Memristors.

Oxygen migration in tantalum oxide, a promising next-generation storage material, is studied using in operando X-ray absorption spectromicroscopy. This approach allows a physical description of the evolution of conduction channel and eventual device failure. The observed ring-like patterns of oxygen concentration are modeled using thermophoretic forces and Fick diffusion, establishing the critical role of temperature-driven oxygen migration

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here, in both murine and human PDA, we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through tumor-associated collagen signatures (TACS). This results in early dissemination from histologically premalignant lesions and continual invasion from well-differentiated disease, and it suggests TACS as a biomarker to aid in the pathologic assessment of early disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in potentially novel microfluidic-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to reengineer and normalize tumor microenvironments may have roles not only in very early disease, but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma-targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination