DEVELOPMENT OF A NUCLEIC ACID-BASED SPECIFIC GROWTH MODEL FOR JUVENILE BLUE CRAB, CALLINECTES SAPIDUS

The evaluation and identification of habitats that function as nurseries for marine species has the potential to improve conservation and management. A key assessment of nursery habitat is estimating individual growth. However, the discrete growth of crustaceans presents a challenge for many traditional in situ techniques to accurately estimate growth over a short temporal scale. To evaluate the use of nucleic acid ratios (R:D) for juvenile blue crab (Callinectes sapidus), I developed and validated an R:D-based index of growth in the laboratory. R:D based growth estimates of crabs collected in the Patuxent River, MD indicated growth ranged from 0.8-25.9 (mg·g-1·d-1). Overall, there was no effect of size on growth, whereas there was a weak, but significant effect of date. These data provide insight into patterns of habitat-specific growth. These results highlight the complexity of the biological and physical factors which regulate growth of juvenile blue crabs in the field.

Applying Mathematical Models to Study the Role of the Immune System in Chronic Myelogenous Leukemia

Although tyrosine kinase inhibitors (TKIs) such as imatinib have transformed chronic myelogenous leukemia (CML) into a chronic condition, these therapies are not curative in the majority of cases. Most patients must continue TKI therapy indefinitely, a requirement that is both expensive and that compromises a patient's quality of life. While TKIs are known to reduce leukemic cells' proliferative capacity and to induce apoptosis, their effects on leukemic stem cells, the immune system, and the microenvironment are not fully understood. A more complete understanding of their global therapeutic effects would help us to identify any limitations of TKI monotherapy and to address these issues through novel combination therapies. Mathematical models are a complementary tool to experimental and clinical data that can provide valuable insights into the underlying mechanisms of TKI therapy. Previous modeling efforts have focused on CML patients who show biphasic and triphasic exponential declines in BCR-ABL ratio during therapy. However, our patient data indicates that many patients treated with TKIs show fluctuations in BCR-ABL ratio yet are able to achieve durable remissions. To investigate these fluctuations, we construct a mathematical model that integrates CML with a patient's autologous immune response to the disease. In our model, we define an immune window, which is an intermediate range of leukemic concentrations that lead to an effective immune response against CML. While small leukemic concentrations provide insufficient stimulus, large leukemic concentrations actively suppress a patient's immune system, thus limiting it's ability to respond. Our patient data and modeling results suggest that at diagnosis, a patient's high leukemic concentration is able to suppress their immune system. TKI therapy drives the leukemic population into the immune window, allowing the patient's immune cells to expand and eventually mount an efficient response against the residual CML. This response drives the leukemic population below the immune window, causing the immune population to contract and allowing the leukemia to partially recover. The leukemia eventually reenters the immune window, thus stimulating a sequence of weaker immune responses as the two populations approach equilibrium. We hypothesize that a patient's autologous immune response to CML may explain the fluctuations in BCR-ABL ratio that are regularly seen during TKI therapy. These fluctuations may serve as a signature of a patient's individual immune response to CML. By applying our modeling framework to patient data, we are able to construct an immune profile that can then be used to propose patient-specific combination therapies aimed at further reducing a patient's leukemic burden. Our characterization of a patient's anti-leukemia immune response may be especially valuable in the study of drug resistance, treatment cessation, and combination therapy.

Regenerative Stormwater Conveyance: Design Implications of an Urban Case Demonstration in Baltimore, Maryland

This research-design thesis explores the implementation of Regenerative Stormwater Conveyance (RSC) as a retrofit of an existing impervious drainage system in a small catchment in the degraded Jones Falls watershed in Baltimore City. An introduction to RSC is provided, placing its development within a theoretical context of novel ecosystems, biomimicry and Nassauer and Opdam’s (2008) model of landscape innovation. The case site is in Baltimore’s Hampden neighborhood on City-owned land adjacent to rowhomes, open space and an access point to a popular wooded trail along a local stream. The design proposal employs RSC to retrofit an ill-performing stormwater system, simultaneously providing a range of ecological, social and economic services; water quantity, water quality and economic performance of the proposed RSC are quantified. While the proposed design is site-specific the model is adaptable for retrofitting other small-scale impervious drainage systems, providing a strategic tool in addressing Baltimore City’s stormwater challenges.