Cell-cell communication in three dimensional microenvironments

Cellular behavior is dependent on a variety of extracellular cues required for normal tissue function, wound healing, and activation of the immune system. Removed from their in vivo microenvironment and cultured in vitro, cells lose many environmental cues and that may result in abberant behavior, making it difficult to study cellular processes. In order to mimic native tissue environments, optical tweezer and microfluidic technologies were used to place cells within defined areas of the culture environment. To provide three dimensional supports found in natural tissues, hydrogel scaffolds of poly (ethylene glycol) diacrylate and the basement membrane matrix Matrigel were used. Optical tweezer technology allowed precision placement and formation of homotypic and heterotypic arrays of human U937, HEK 293, and porcine mesenchymal stem cells. Alternatively, two microfluidic devices were designed to pattern Matrigel scaffolds. The first microfluidic device utilized laminar flow to spatially pattern multiple cell types within the device. Gradients of soluble molecules were then be formed and manipulated across the Matrigel scaffolds. Patterning Matrigel using laminar flow techniques require microfluidic expertise and do not produce consistent patterning conditions, limiting their use difficult in most cell culture laboratories. Thus, a buried Matrigel polydimethylsiloxane (PDMS) device was developed for spatial patterning of biological scaffolds. Matrigel is injected into micron sized channels of PDMS fabricated by soft lithography and allowed to thermally cure. Following curing, a second PDMS device was placed on top of the buried Matrigel channels to support media flow. In order to validate these systems, a cell-cell communication model system was developed utilizing LPS and TNFα signaling with fluorescent reporter systems to monitor communication in real time. We demonstrated the utility of microfluidic devices to support the cell-cell communication model system by co culturing three cell types within Matrigel scaffolds and monitoring signaling activity via fluorescent reporters.

From the human rights-based approach to an ecological approach on how to achieve successful inclusion in international disability education

The barriers that people with disabilities face around the world are not only inherent to the limitations resulting from the disability itself, but, more importantly, these barriers rest with the societal technologies of exclusion. Using a mixed methodology approach, I conduct a quest to revealing several societal factors that limit full participation of people with disabilities in their communities, which will contribute to understanding and developing a more comprehensive framework for full inclusion of people with disabilities into the society. First, I conduct a multiple regression analysis to seek whether there is a statistical relationship between the national level of development, the level of democratization, and the level of education within a country’s population on one hand, and expressed concern for and preparedness to improve the quality of life for people of disabilities on another hand. The results from the quantitative methodology reveal that people without disabilities are more prepared to take care of people with disabilities when the level of development of the country is higher, when the people have more freedom of expression and hold the government accountable for its actions, and when the level of corruption is under control. However, a greater concern for the well-being of people with disabilities is correlated with a high level of country development, a decreased value of political stability and absence of violence, a decreased level of government effectiveness, and a greater level of law enforcement. None of the dependent variables are significantly correlated with the level of education from a given country. Then, I delve into an interpretive analysis to understand multiple factors that contribute to the construction of attitudes and practices towards people with disabilities. In doing this, I build upon the four main principles outlined by the United Nations as strongly recommended to be embedded in all international programmes: (1) identification of claims of human rights and the corresponding obligations of governments, hence, I assess and analyze disability rights in education, looking at United Nation, United States, and European Union Perspectives Educational Rights Provisions for People with Disabilities (Ch. 3); (2) estimated capacity of individuals to claim their rights and of governments to fulfill their obligations, hence, I look at the people with disabilities as rights-holders and duty-bearers and discuss the importance of investing in special capital in the context of global development (Ch. 4); (3) programmes monitor and evaluate the outcomes and the processes under the auspices of human rights standards, hence, I look at the importance of evaluating the UN World Programme of Action Concerning People with Disabilities from multiple perspectives, as an example of why and how to monitor and evaluate educational human rights outcomes and processes (Ch. 5); and (4) programming should reflect the recommendations of international human rights bodies and mechanisms, hence, I focus on programming that fosters development of the capacity of people with disabilities, that is, planning for an ecology of disabilities and ecoducation for people with disabilities (Ch. 6). Results from both methodologies converge to a certain point, and they further complement each other. One common result for the two methodologies employed is that disability is an evolving concept when viewed in a broader context, which integrates the four spaces that the ecological framework incorporates. Another common result is that factors such as economic, social, legal, political, and natural resources and contexts contribute to the health, education and employment opportunities, and to the overall well-being of people with disabilities. The ecological framework sees all these factors from a meta-systemic perspective, where bi-directional interactions are expected and desired, and also from a human rights point of view, where the inherent value of people is upheld at its highest standard.