865 research outputs found

    Tension in the Eye: Milton and Surveillance

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    An Agent-Based Model of Cryoprotectant Equilibration in Secondary Stage Preantral Ovarian Follicles

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    Young cancer patients have limited options for fertility treatment when facing gonadotoxic treatment. One promising fertility treatment for young cancer patients is the cryopreservation of immature ovarian follicles followed by maturation and subsequent reimplantation. However, preantral ovarian follicles currently have lower post-thaw success rates compared to mature oocytes and embryos. Previous research suggests that damage to vital intercellular connections, Transzonal Projections (TZPs), occurs during the cryopreservation process and may account for the observed lower post-thaw success rate in this tissue. It is likely that cryoprotective agent (CPA) equilibration is the cryopreservation step during which TZP damage occurs. Constructing a biologically relevant model of CPA equilibration and the associated damage may allow for improved protocols as measured by increased post-thaw success rates. Agent-based models are a promising technique to capture steps in the cryopreservation process, such as CPA equilibration. In this thesis, I conducted a series of experiments with typical CPAs and nonpermeating solutes at different temperatures using preantral ovarian follicles from a non-human primate (Rhesus monkeys) to measure TZP damage. In these experiments, I also estimated relevant permeability parameters within the tissue. I found that the majority of TZP damage was likely the result of mechanical forces that occurred during the cell volume reduction phase of CPA equilibration. Furthermore, through these experiments, I demonstrate that for this tissue type, parameters collected either during monolayer or single-cell experiments can be used to construct full tissue models. Using the derived experimental parameters and available literature values, I constructed and validated a 3-D agent-based model to capture CPA equilibration in preantral ovarian follicles. My agent-based model utilizes parallel computing on an average desktop computer and allows for the rapid design and testing of CPA equilibration protocols. The model I constructed can account for both mechanical and toxic damage. Importantly, my model accurately captures the experimental damage to TZPs in the majority of simulations. Lastly, I propose several theoretically improved cryopreservation protocols for preantral ovarian follicles. The research presented in this thesis demonstrates that agent-based models can be utilized to capture steps in the cryopreservation in silico and represents a non-invasive, less costly means to test and improve CPA equilibration protocols

    Circles Minimize most Knot Energies

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    We define a new class of knot energies (known as renormalization energies) and prove that a broad class of these energies are uniquely minimized by the round circle. Most of O'Hara's knot energies belong to this class. This proves two conjectures of O'Hara and of Freedman, He, and Wang. We also find energies not minimized by a round circle. The proof is based on a theorem of G. Luko on average chord lengths of closed curves.Comment: 15 pages with 3 figures. See also http://www.math.sc.edu/~howard

    Make It Real - Undergraduate Research Opportunities

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    Theme one in the Quest for Distinction is for VCU to become a leader among national research universities in providing all students with high quality learning/living experiences focused on inquiry, discovery, and innovation in a global environment. Quest is grounded in a commitment to providing students with a diversity of experiences which are available at a premiere public research university. The goal of this project is to take advantage of the wealth of research resources at the Medical College of Virginia Campus, coordinate cross campus efforts to facilitate the use of these resources and increase faculty participation in mentoring undergraduate research projects

    A Mathematical Model for the Origin of Name Brands and Generics

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    Firms in the U.S. spend over 200 billion dollars each year advertising their products to consumers, around one percent of the country's gross domestic product. It is of great interest to understand how that aggregate expenditure affects prices, market efficiency, and overall welfare. Here, we present a mathematical model for the dynamics of competition through advertising and find a surprising prediction: when advertising is relatively cheap compared to the maximum benefit advertising offers, rational firms split into two groups, one with significantly less advertising (a "generic" group) and one with significantly more advertising (a "name brand" group). Our model predicts that this segmentation will also be reflected in price distributions; we use large consumer data sets to test this prediction and find good qualitative agreement.Comment: 24 pages, 11 figure

    Plasma microRNA levels following resection of metastatic melanoma

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    Melanoma remains the leading cause of skin cancer–related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection
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