Immunocytes of the Atlantic bottlenose dolphin (Tursiops truncatus) and West Indian manatee (Trichechus manatus latirostris): Morphologic characterizations and correlations between healthy and disease states under free-ranging and captive conditions

Interest in the health of marine mammals has increased due, in part, to the attention given to human impact on the marine environment. Recent mass strandings of the Atlantic bottlenose dolphin (Tursiops truncatus) and rising mortalities of the endangered Florida manatee (Trichechus manatus latirostris) have raised questions on the extent to which pollution, infectious disease, "stress," and captivity influence the immune system of these animals. This study has provided the first in-depth characterization of immunocytes in the peripheral blood of dolphins (n = 190) and manatees (n = 56). Immunocyte morphology and baseline values were determined in clinically normal animals under free-ranging, stranded and captive living conditions as well as by age and sex. Additionally, immunocyte population dynamics were characterized in sick animals. This was accomplished with traditional cytochemical techniques and new lymphocyte phenotyping methodology which was validated in this study. Traditional cytochemical techniques demonstrated that blood immunocyte morphology and cell numbers are similar to terrestrial mammals with some notable exceptions. The manatee heterophilic granulocyte is a morphologically unique cell and probably functions similarly to the typical mammalian neutrophil. Eosinophils were rarely found in manatees but were uncommonly high in healthy and sick dolphins. Basophils were not identified. Manatees had higher total lymphocyte numbers compared to dolphins and most terrestrial mammals. Lymphocyte subsets identified in healthy animals included T$\rm\sb{h}$, T$\rm\sb{c/s}$, B and NK cells. Dolphin and manatee T and B cell values were higher than those reported in man and most terrestrial mammals. The manatee has extraordinarily high absolute numbers of circulating T$\rm\sb{h}$ cells which suggests an enhanced immunological response capability. With few exceptions, immunocyte types and absolute numbers were not significantly different between free-ranging, stranded and captive categories or between sex and age categories. The evaluation of immunocyte dynamics in various disease states demonstrated a wide variation in cellular responses which provided new insights into innate, humoral and cell-mediated immunity in these species. Additionally, this study demonstrated that lymphocyte phenotyping has diagnostic significance and could be developed into a potential indicator of immunocompetence in both free-ranging and captive dolphin and manatee populations.

Immunocytes of the Atlantic bottlenose dolphin (Tursiops truncatus) and West Indian manatee (Trichechus manatus latirostris) : morphologic characterizations and correlations between healthy and disease states under free-ranging and captive conditions

Interest in the health of marine mammals has increased due, in part, to the attention given to human impact on the marine environment. Recent mass strandings of the Atlantic bottlenose dolphin (Tursiops truncatus) and rising mortalities of the endangered Florida manatee (Trichechus manatus latirostris) have raised questions on the extent to which pollution, infectious disease, "stress," and captivity influence the immune system of these animals. This study has provided the first in-depth characterization of immunocytes in the peripheral blood of dolphins (n=180) and manatees (n=56). Immunocyte morphology and baseline values were determined in clinically normal animals under free-ranging, stranded and captive living conditions as well as by age and sex. Additionally, immuocyte population dynamics were characterized in sick animals. This was accomplished with traditional cytochemical techniques and new lymphocyte phenotyping methodology which was validated in this study. Traditional cytochemical techniques demonstrated that blood immunocyte morphology and cell numbers are similar to terrestrial mammals with some notable exceptions. The manatee heterophilic granulocyte is a morphologically unique cell and probably functions similarly to the typical mammalian neutrophil. Eosinophils were rarely found in manatees but were uncommonly high in healthy and sick dolphins. Basophils were not identified. Manatees had higher total lymphocyte numbers compared to dolphins and most terrestrial mammals. Lymphocyte subsets identified in healthy animals included Th, Tes, B and NK cells. Dolphin and manatee T and B cell values were higher than those reported in man and most terrestrial mammals. The manatee has extraordinarily high absolute numbers of circulating Th cells which suggests an enhanced immunological response capability. With few exceptions, immunocyte types and absolute numbers were not significantly different between free-ranging, stranded and captive categories or between sex and age categories. The evaluation of immunocyte dynamics in various disease states demonstrated a wide variation in cellular responses which provided new insights into innate, humoral and cell-mediated immunity in these species. Additionally, this study demonstrated that lymphocyte phenotyping has diagnostic significance and could be developed into a potential indicator of immunocompetence in both free-ranging and captive dolphin and manatee populations.

A Generic Model of Execution for Synthesizing Domain-Specific Models

Software engineering researchers are challenged to provide increasingly more pow- erful levels of abstractions to address the rising complexity inherent in software solu- tions. One new development paradigm that places models as abstraction at the fore- front of the development process is Model-Driven Software Development (MDSD). MDSD considers models as first class artifacts, extending the capability for engineers to use concepts from the problem domain of discourse to specify apropos solutions. A key component in MDSD is domain-specific modeling languages (DSMLs) which are languages with focused expressiveness, targeting a specific taxonomy of problems. The de facto approach used is to first transform DSML models to an intermediate artifact in a HLL e.g., Java or C++, then execute that resulting code. Our research group has developed a class of DSMLs, referred to as interpreted DSMLs (i-DSMLs), where models are directly interpreted by a specialized execution engine with semantics based on model changes at runtime. This execution engine uses a layered architecture and is referred to as a domain-specific virtual machine (DSVM). As the domain-specific model being executed descends the layers of the DSVM the semantic gap between the user-defined model and the services being provided by the underlying infrastructure is closed. The focus of this research is the synthesis engine, the layer in the DSVM which transforms i-DSML models into executable scripts for the next lower layer to process. The appeal of an i-DSML is constrained as it possesses unique semantics contained within the DSVM. Existing DSVMs for i-DSMLs exhibit tight coupling between the implicit model of execution and the semantics of the domain, making it difficult to develop DSVMs for new i-DSMLs without a significant investment in resources. At the onset of this research only one i-DSML had been created for the user- centric communication domain using the aforementioned approach. This i-DSML is the Communication Modeling Language (CML) and its DSVM is the Communication Virtual machine (CVM). A major problem with the CVM’s synthesis engine is that the domain-specific knowledge (DSK) and the model of execution (MoE) are tightly interwoven consequently subsequent DSVMs would need to be developed from inception with no reuse of expertise. This dissertation investigates how to decouple the DSK from the MoE and sub- sequently producing a generic model of execution (GMoE) from the remaining appli- cation logic. This GMoE can be reused to instantiate synthesis engines for DSVMs in other domains. The generalized approach to developing the model synthesis com- ponent of i-DSML interpreters utilizes a reusable framework loosely coupled to DSK as swappable framework extensions. This approach involves first creating an i-DSML and its DSVM for a second do- main, demand-side smartgrid, or microgrid energy management, and designing the synthesis engine so that the DSK and MoE are easily decoupled. To validate the utility of the approach, the SEs are instantiated using the GMoE and DSKs of the two aforementioned domains and an empirical study to support our claim of reduced developmental effort is performed.