10 research outputs found
Cognitive Frameworks that Enable South Carolina High School Principals to Implement Smaller Learning Communities
The demands of an ever-changing technological and diverse global society contribute to the need for systemic change in today\u27s secondary schools. Faced with these realities, American high schools must set course on a new mission for education. Not only must high schools require differentiated instructions to accommodate students\u27 needs, high school personnel must also be held accountable for student learning by producing a high quality education. Because of the variety of these diverse issues, high school principals are faced with overcoming the challenges and obstacles that confront high school reforms. The research regarding smaller learning communities is well-documented and encouraging. While the practice can become the focus for producing higher achievement, educators must create new paradigms of operations. In many cases, traditional standards and procedures must be abandoned in order to increase school-wide success. Little is known of South Carolina\u27s high school administrators as they attempt to find solutions to meet the needs of rapidly growing and diverse student populations. Little is also known of the experiences of South Carolina high school principals as they implement smaller learning communities, or the forces confronting those transitions. Therefore, the researcher examined the supporting and impeding forces experienced by South Carolina high school principals implementing smaller learning communities. In addition, the researcher analyzed the strategies used by administrators to overcome the forces, using Bolman and Deal\u27s (2008) four frames: human resources, political, structural, and symbolic. The researcher conducted in-depth interviews with administrators in seven South Carolina high schools located in five school districts. The researcher analyzed the forces as well as strategies used by administrators to overcome the forces at work. The researcher categorized the strategies used by administrators to deal with the forces into four frames: human resources, political, structural, and symbolic. In analyzing the cognitive frameworks commonly used by administrators in implementing smaller learning communities, the researcher found that the majority of cognitive frames fell within the human resource framework. The second largest group of responses fell within the structural framework followed by the symbolic framework and then the political framework
HLA Alleles Associated with Slow Progression to AIDS Truly Prefer to Present HIV-1 p24
Background: The mechanism behind the association between human leukocyte antigen (HLA) molecules and the rate of HIV-1
disease progression is still poorly understood. Recent data suggest that ‘‘protective’’ HLA molecules, i.e. those associated with
a low HIV-1 viral load and relatively slow disease progression, tend to present epitopes from the Gag capsid protein. Although
this suggests that preferential targeting of Gag delays disease progression, the apparent preference for Gag could also be
a side-effect of the relatively high immunogenicity of the protein. Methods and Findings: To separate cause and effect, we
predicted HIV-1 epitopes from the whole genome of HIV-1, and found that protective HLA alleles have a true preference for the
p24 Gag protein, while non-protective HLA alleles preferentially target HIV-1 Nef. In line with this, we found a significant
negative correlation between the predicted affinity of the best-binding p24 epitopes and the relative hazard of HIV-1 disease
progression for a large number of HLA molecules. When the epitopes targeted by protective HLA alleles were mapped to the
known p24 structure, we found that mutations in these epitopes are likely to disturb the p24 dimer structure, which is
expected to severely reduce the fitness of the virus. Conclusions: Our results suggest that the intrinsic preference of different
HLA molecules to present p24 peptides explains why some HLA molecules are more protective than others
Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting
<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p
HIV-1 Vaccine Trials: Evolving Concepts and Designs
An effective prophylactic HIV-1 vaccine is needed to eradicate the HIV/AIDS pandemic but designing such a vaccine is a challenge. Despite many advances in vaccine technology and approaches to generate both humoral and cellular immune responses, major phase-II and -III vaccine trials against HIV/AIDS have resulted in only moderate successes. The modest achievement of the phase-III RV144 prime-boost trial in Thailand re-emphasized the importance of generating robust humoral and cellular responses against HIV. While antibody-directed approaches are being pursued by some groups, others are attempting to develop vaccines targeting cell-mediated immunity, since evidence show CTLs to be important for the control of HIV replication. Phase-I and -IIa multi-epitope vaccine trials have already been conducted with vaccine immunogens consisting of known CTL epitopes conserved across HIV subtypes, but have so far fallen short of inducing robust and consistent anti-HIV CTL responses. The concepts leading to the development of T-cell epitope-based vaccines, the outcomes of related clinical vaccine trials and efforts to enhance the immunogenicity of cell-mediated approaches are summarized in this review. Moreover, we describe a novel approach based on the identification of SIV and FIV antigens which contain conserved HIV-specific T-cell epitopes and represent an alternative method for developing an effective HIV vaccine against global HIV isolates