Browsing by Author "Arciero, Julia C."

Now showing 1 - 9 of 9
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    Bifurcation study of blood flow control in the kidney.
    (Elsevier, 2015-05) Ford Versypt, Ashlee N.; Makrides, Elizabeth; Arciero, Julia C.; Ellwein, Laura; Layton, Anita T.; Department of Mathematical Sciences, School of Science
    Renal blood flow is maintained within a narrow window by a set of intrinsic autoregulatory mechanisms. Here, a mathematical model of renal hemodynamics control in the rat kidney is used to understand the interactions between two major renal autoregulatory mechanisms: the myogenic response and tubuloglomerular feedback. A bifurcation analysis of the model equations is performed to assess the effects of the delay and sensitivity of the feedback system and the time constants governing the response of vessel diameter and smooth muscle tone. The results of the bifurcation analysis are verified using numerical simulations of the full nonlinear model. Both the analytical and numerical results predict the generation of limit cycle oscillations under certain physiologically relevant conditions, as observed in vivo.
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    Combining Theoretical and Experimental Techniques to Study Murine Heart Transplant Rejection
    (Frontiers Media SA, 2016) Arciero, Julia C.; Maturo, Andrew; Arun, Anirudh; Oh, Byoung Chol; Brandacher, Gerald; Raimondi, Giorgio; Department of Mathematical Sciences, School of Science
    The quality of life of organ transplant recipients is compromised by complications associated with life-long immunosuppression, such as hypertension, diabetes, opportunistic infections, and cancer. Moreover, the absence of established tolerance to the transplanted tissues causes limited long-term graft survival rates. Thus, there is a great medical need to understand the complex immune system interactions that lead to transplant rejection so that novel and effective strategies of intervention that redirect the system toward transplant acceptance (while preserving overall immune competence) can be identified. This study implements a systems biology approach in which an experimentally based mathematical model is used to predict how alterations in the immune response influence the rejection of mouse heart transplants. Five stages of conventional mouse heart transplantation are modeled using a system of 13 ordinary differential equations that tracks populations of both innate and adaptive immunity as well as proxies for pro- and anti-inflammatory factors within the graft and a representative draining lymph node. The model correctly reproduces known experimental outcomes, such as indefinite survival of the graft in the absence of CD4(+) T cells and quick rejection in the absence of CD8(+) T cells. The model predicts that decreasing the translocation rate of effector cells from the lymph node to the graft delays transplant rejection. Increasing the starting number of quiescent regulatory T cells in the model yields a significant but somewhat limited protective effect on graft survival. Surprisingly, the model shows that a delayed appearance of alloreactive T cells has an impact on graft survival that does not correlate linearly with the time delay. This computational model represents one of the first comprehensive approaches toward simulating the many interacting components of the immune system. Despite some limitations, the model provides important suggestions of experimental investigations that could improve the understanding of rejection. Overall, the systems biology approach used here is a first step in predicting treatments and interventions that can induce transplant tolerance while preserving the capacity of the immune system to protect against legitimate pathogens.
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    Editorial: Transplant Rejection and Tolerance—Advancing the Field through Integration of Computational and Experimental Investigation
    (Frontiers Media S.A., 2017-05-30) Raimondi, Giorgio; Wood, Kathryn J.; Perelson, Alan S.; Arciero, Julia C.; Mathematical Sciences, School of Science
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    Mathematical methods for modeling the microcirculation
    (AIMS, 2017) Arciero, Julia C.; Causin, Paola; Malgaroli, Francesca; Mathematical Sciences, School of Science
    The microcirculation plays a major role in maintaining homeostasis in the body. Alterations or dysfunctions of the microcirculation can lead to several types of serious diseases. It is not surprising, then, that the microcirculation has been an object of intense theoretical and experimental study over the past few decades. Mathematical approaches offer a valuable method for quantifying the relationships between various mechanical, hemodynamic, and regulatory factors of the microcirculation and the pathophysiology of numerous diseases. This work provides an overview of several mathematical models that describe and investigate the many different aspects of the microcirculation, including geometry of the vascular bed, blood flow in the vascular networks, solute transport and delivery to the surrounding tissue, and vessel wall mechanics under passive and active stimuli. Representing relevant phenomena across multiple spatial scales remains a major challenge in modeling the microcirculation. Nevertheless, the depth and breadth of mathematical modeling with applications in the microcirculation is demonstrated in this work. A special emphasis is placed on models of the retinal circulation, including models that predict the influence of ocular hemodynamic alterations with the progression of ocular diseases such as glaucoma.
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    Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents
    (American Scientific, 2013) Guidoboni, Giovanna; Harris, Alon; Arciero, Julia C.; Siesky, Brent A.; Amireskandari, Annahita; Gerber, Austin L.; Huck, Andrew H.; Kim, Nathaniel J.; Cassani, Simone; Carichino, Lucia; Mathematical Sciences, School of Science
    Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.
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    Modeling the Potential of Treg-Based Therapies for Transplant Rejection: Effect of Dose, Timing, and Accumulation Site
    (Frontiers Media, 2022-04-11) Lapp, Maya M.; Lin, Guang; Komin, Alexander; Andrews, Leah; Knudson, Mei; Mossman, Lauren; Raimondi, Giorgio; Arciero, Julia C.; Mathematical Sciences, School of Science
    Introduction: The adoptive transfer of regulatory T cells (Tregs) has emerged as a method to promote graft tolerance. Clinical trials have demonstrated the safety of adoptive transfer and are now assessing their therapeutic efficacy. Strategies that generate large numbers of antigen specific Tregs are even more efficacious. However, the combinations of factors that influence the outcome of adoptive transfer are too numerous to be tested experimentally. Here, mathematical modeling is used to predict the most impactful treatment scenarios. Methods: We adapted our mathematical model of murine heart transplant rejection to simulate Treg adoptive transfer and to correlate therapeutic efficacy with Treg dose and timing, frequency of administration, and distribution of injected cells. Results: The model predicts that Tregs directly accumulating to the graft are more protective than Tregs localizing to draining lymph nodes. Inhibiting antigen-presenting cell maturation and effector functions at the graft site was more effective at modulating rejection than inhibition of T cell activation in lymphoid tissues. These complex dynamics define non-intuitive relationships between graft survival and timing and frequency of adoptive transfer. Conclusion: This work provides the framework for better understanding the impact of Treg adoptive transfer and will guide experimental design to improve interventions.
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    Potential measurement error from vessel reflex and multiple light paths in dual-wavelength retinal oximetry
    (Wiley, 2024-05) Beach, James M.; Shoemaker, Benjamin; Eckert, George J.; Harris, Alon; Siesky, Brent; Arciero, Julia C.; Mathematical Sciences, School of Science
    Purpose This study aims to characterize the dependence of measured retinal arterial and venous saturation on vessel diameter and central reflex in retinal oximetry, with an ultimate goal of identifying potential causes and suggesting approaches to improve measurement accuracy. Methods In 10 subjects, oxygen saturation, vessel diameter and optical density are obtained using Oxymap Analyzer software without diameter correction. Diameter dependence of saturation is characterized using linear regression between measured values of saturation and diameter. Occurrences of negative values of vessel optical densities (ODs) associated with central vessel reflex are acquired from Oxymap Analyzer. A conceptual model is used to calculate the ratio of optical densities (ODRs) according to retinal reflectance properties and single and double-pass light transmission across fixed path lengths. Model-predicted values are compared with measured oximetry values at different vessel diameters. Results Venous saturation shows an inverse relationship with vessel diameter (D) across subjects, with a mean slope of −0.180 (SE = 0.022) %/μm (20 < D < 180 μm) and a more rapid saturation increase at small vessel diameters reaching to over 80%. Arterial saturation yields smaller positive and negative slopes in individual subjects, with an average of −0.007 (SE = 0.021) %/μm (20 < D < 200 μm) across all subjects. Measurements where vessel brightness exceeds that of the retinal background result in negative values of optical density, causing an artifactual increase in saturation. Optimization of model reflectance values produces a good fit of the conceptual model to measured ODRs. Conclusion Measurement artefacts in retinal oximetry are caused by strong central vessel reflections, and apparent diameter sensitivity may result from single and double-pass transmission in vessels. Improvement in correction for vessel diameter is indicated for arteries however further study is necessary for venous corrections.
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    Using a continuum model to predict closure time of gaps in intestinal epithelial cell layers
    (Wiley Blackwell (Blackwell Publishing), 2013-03) Arciero, Julia C.; Mi, Qi; Branca, Maria; Hackam, David; Swigon, David; Department of Mathematical Sciences, School of Science
    A two-dimensional continuum model of collective cell migration is used to predict the closure of gaps in intestinal epithelial cell layers. The model assumes that cell migration is governed by lamellipodia formation, cell-cell adhesion, and cell-substrate adhesion. Model predictions of the gap edge position and complete gap closure time are compared with experimental measures from cell layer scratch assays (also called scratch wound assays). The goal of the study is to combine experimental observations with mathematical descriptions of cell motion to identify effects of gap shape and area on closure time and to propose a method that uses a simple measure (e.g., area) to predict overall gap closure time early in the closure process. Gap closure time is shown to increase linearly with increasing gap area; however, gaps of equal areas but different aspect ratios differ greatly in healing time. Previous methods that calculate overall healing time according to the absolute or percent change in gap area assume that the gap area changes at a constant rate and typically underestimate gap closure time. In this study, data from scratch assays suggest that the rate of change of area is proportional to the first power or square root power of area.
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    Using a Theoretical Model to Assess the Impact of Vascular Risk Factors on Autoregulation in the Retina
    (Association for Research in Vision and Ophthalmology, 2025) Fry, Brendan C.; Arciero, Julia C.; Gyurek, Croix; Albright, Amanda; Siesky, Brent; Verticchio, Alice; Harris, Alon; Mathematical Sciences, School of Science
    Purpose: Vascular impairments, including reduced capillary density (CD), impaired autoregulation capacity (Reg), and elevated intraocular pressure (IOP), have been identified as significant contributors to glaucomatous disease. This study implemented a theoretical model to quantify the impact of these impairments on retinal blood flow and oxygenation as intraluminal pressure (Pa) is varied. Methods: A theoretical model of the retinal vasculature was used to simulate reductions in CD by 10% (early glaucoma) and 30% to 50% (advanced glaucoma), a range in autoregulation capacity from 0% (totally impaired) to 100% (totally functional), and normal (15 mm Hg) and elevated (25 mm Hg) levels of IOP. Results: Under baseline conditions of CD = 500 mm-2, Reg = 100%, and IOP = 15 mm Hg, an autoregulation plateau was predicted for Pa = 28 to 44 mm Hg. Decreased CD, impaired flow regulation mechanisms, and increased IOP all cause a loss of the autoregulation plateau and a corresponding decrease in tissue oxygenation in this pressure range. Although the detrimental effects of small decreases in CD or elevations in IOP are mostly offset by functional flow regulation, larger changes and/or combinations of vascular impairments lead to a significant drop in retinal oxygenation. Conclusions: Model predictions indicate that isolated or combined vascular impairments in CD, flow regulation, and IOP contribute to poor retinal tissue oxygenation, which could lead to vision loss in advanced glaucoma patients. This study motivates early identification of vascular changes to prevent a substantially worse effect of these factors on retinal oxygenation during the progression of glaucoma.