On the singular homology of one class of simply-connected cell-like spaces

In our earlier papers we constructed examples of 2-dimensional nonaspherical simply-connected cell-like Peano continua, called {\sl Snake space}. In the sequel we introduced the functor $SC(-,-)$ defined on the category of all spaces with base points and continuous mappings. For the circle $S^1$, the space $SC(S^1, \ast)$ is a Snake space. In the present paper we study the higher-dimensional homology and homotopy properties of the spaces $SC(Z, \ast)$ for any path-connected compact spaces $Z$

SPATIAL ACCESSIBILITY OF HEALTH CARE IN INDIANA

Healthy populations and access to health care services are significant factors influencing economic development and prosperity. Since geographic access is an essential feature of an overall health system, it is important for health service researchers to develop accurate measures of physical access to health. In this paper we develop a series of gravity-based health care accessibility measures for all the counties in Indiana. The measures go beyond local availability of health care services within a county and account for travel impedance via distance-discounted health care services accessible throughout the state. When applied to Indiana counties, the results show sharp disparities in health care accessibility with extensive pockets of poor accessibility in rural and peripheral areas. The research concludes with a demonstration of how spatial accessibility measures can be beneficially used to evaluate of policies indicative of changes in the provision of health services.spatial accessibility, health care, geographic information systems (GIS),

Predicting the Role of IL-10 in the Regulation of the Adaptive Immune Responses in Mycobacterium avium Subsp. paratuberculosis Infections Using Mathematical Models

Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular bacterial pathogen that causes Johne’s disease (JD) in cattle and other animals. The hallmark of MAP infection in the early stages is a strong protective cell-mediated immune response (Th1-type), characterized by antigen-specific γ-interferon (IFN-γ). The Th1 response wanes with disease progression and is supplanted by a non-protective humoral immune response (Th2-type). Interleukin-10 (IL-10) is believed to play a critical role in the regulation of host immune responses to MAP infection and potentially orchestrate the reversal of Th1/Th2 immune dominance during disease progression. However, how its role correlates with MAP infection remains to be completely deciphered. We developed mathematical models to explain probable mechanisms for IL-10 involvement in MAP infection. We tested our models with IL-4, IL-10, IFN-γ, and MAP fecal shedding data collected from calves that were experimentally infected and followed over a period of 360 days in the study of Stabel and Robbe-Austerman (2011). Our models predicted that IL-10 can have different roles during MAP infection, (i) it can suppress the Th1 expression, (ii) can enhance Th2 (IL-4) expression, and (iii) can suppress the Th1 expression in synergy with IL-4. In these predicted roles, suppression of Th1 responses was correlated with increased number of MAP. We also predicted that Th1-mediated responses (IFN-γ) can lead to high expression of IL-10 and that infection burden regulates Th2 suppression by the Th1 response. Our models highlight areas where more experimental data is required to refine our model assumptions, and further test and investigate the role of IL-10 in MAP infection

Can Immune Response Mechanisms Explain the Fecal Shedding Patterns of Cattle Infected with Mycobacterium avium Subspecies paratuberculosis?

Johne’s disease (JD) is a chronic disease in ruminants and is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). At late stages of the disease, MAP bacilli are shed via feces excretion and in turn create the potential for oral-fecal transmission. The role of the host immune response in MAP bacteria shedding patterns at different stages of JD is still unclear. We employed mathematical modeling to predict if the variation in MAP shedding could be correlated to the immune response in infected animals. We used a novel inverse modeling approach that assumed biological interactions among the antigen-specific lymphocyte proliferation response (cell-mediated response), antibody/humoral immune responses, and MAP bacteria. The modeling framework was used to predict and test possible biological interactions between the measured variables and returns only the essential interactions that are relevant in explaining the observed cattle MAP experimental infection data. Through confronting the models with data, we predicted observed effects (enhancement or suppression) and extents of interactions among the three variables. This analysis enabled classification of the infected cattle into three different groups that correspond to the unique predicted immune responses that are essential to explain the data from cattle within these groups. Our analysis highlights the strong and weak points of the modeling approach, as well as the key immune mechanisms predicted to be expressed in all animals and those that were different between animals, hence giving insight into how animals exhibit different disease dynamics and bacteria shedding patterns

Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Integrins are heterodimeric molecules that are composed of 18 α -subunits and 8 β -subunits. They exist in 24 distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases can result in enhanced tumorigenesis. Among several types of integrins, αvβ 3 and α 5 β 1 have gained importance in anti-angiogenesis studie

Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Integrins are heterodimeric molecules that are composed of 18 \ud α\ud -subunits and 8 \ud β\ud -subunits. They exist in 24\ud distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of\ud extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the\ud basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that\ud certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies\ud reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and\ud integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases\ud can result in enhanced tumorigenesis. Among several types of integrins, \ud αvβ\ud 3 and \ud α\ud 5\ud β\ud 1 \ud have gained importance in\ud anti-angiogenesis studie

On the homology of the Harmonic Archipelago

We calculate the singular homology and \v{C}ech cohomology groups of the Harmonic archipelago. As a corollary, we prove that this space is not homotopy equivalent to the Griffiths space. This is interesting in view of Eda's proof that the first singular homology groups of these spaces are isomorphic