Learning environments : redefining the discourse on school architecture

The thesis maintains that the physical environment of the school is only one component, although an important one, of learning environments suitable for learner-centered, consiructivist approaches to learning. Accordingly, school architecture should relate to both, the physical as well as the social environmental contexts. This perspective could invite educators and architects to participate in a collaborative discourse for realizing most effective and sustainable learning environments, one school at a time. In search of learning factors, factors that could influence learning and engage educators and architects in a collaborative discourse, the study addresses the following: a) A review of literature related to education, school architecture, and environmental psychology; b) Interviews with school architects and educators; c) Case studies of schools that exemplify distinctive approaches to the design of learning environments. Among the findings, the thesis identifies three learning factors: classroom organization, learning technologies, and school climate, as components of a conceptual framework that could advance a common language between educators and architects. Overall, the thesis confirms the importance of an environmental approach1 and moves to redefine the discourse on school architecture, by suggesting interdisciplinary research related to the findings, as a strategy to advance knowledge and shared understanding of effective learning environments

Building a better model of cancer

The 2006 Cold Spring Harbor Laboratory meeting on the Mechanisms and Models of Cancer was held August 16–20. The meeting featured several hundred presentations of many short talks (mostly selected from the abstracts) and posters, with the airing of a number of exciting new discoveries. We will focus this meeting review on models of cancer (primarily mouse models), highlighting recent advances in new mouse models that better recapitulate sporadic tumorigenesis, demonstrations of tumor addiction to tumor suppressor inactivation, new insight into senescence as a tumor barrier, improved understanding of the evolutionary paths of cancer development, and environmental/immunological influences on cancer

Optimal Aerodynamic Design of Scramjet Facility Nozzles

An hybrid approach to optimization is applied to the aerodynamic design of a device that acts as a facility nozzle and inlet distortion generator for a direct-connect scramjet combustor test-rig. The solution of the design problem is sought by using different approaches of CFD analysis and optimization tools. The initial design is based on the solution of an inverse problem coupled to optimization by genetic algorithms. The result of the optimization is then tested by CFD simulations of the direct-connect facility and the shock reflection patterns are compared toat of the in-flight configuration. The verification of nozzle design and the assessment of the prescribed flow distortion are then carried out by numerical simulations of the flowfield of the whole direct-connect facility by an URANS solver. The proposed procedure is checked by designing a facility nozzle and distortion generator system for a scramjet model available in the open literature

The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging-related disease

Aging represents the major risk factor for the development of cancer and many other diseases. Recent findings show that normal tissues become riddled with expanded clones that are frequently driven by cancer-associated mutations in an aging-dependent fashion. Additional studies show how aged tissue microenvironments promote the initiation and progression of malignancies, while young healthy tissues actively suppress the outgrowth of malignant clones. Here, we discuss conserved mechanisms that eliminate poorly functioning or potentially malignant cells from our tissues to maintain organismal health and fitness. Natural selection acts to preserve tissue function and prevent disease to maximize reproductive success but these mechanisms wane as reproduction becomes less likely. The ensuing age-dependent tissue decline can impact the shape and direction of clonal somatic evolution, with lifestyle and exposures influencing its pace and intensity. We also consider how aging- and exposure-dependent clonal expansions of "oncogenic" mutations might both increase cancer risk late in life and contribute to tissue decline and non-malignant disease. Still, we can marvel at the ability of our bodies to avoid cancers and other diseases despite the accumulation of billions of cells with cancer-associated mutations

Gene trap mutagenesis of hnRNP A2/B1: a cryptic 3' splice site in the neomycin resistance gene allows continued expression of the disrupted cellular gene

BACKGROUND: Tagged sequence mutagenesis is a process for constructing libraries of sequenced insertion mutations in embryonic stem cells that can be transmitted into the mouse germline. To better predict the functional consequences of gene entrapment on cellular gene expression, the present study characterized the effects of a U3Neo gene trap retrovirus inserted into an intron of the hnRNP A2/B1 gene. The mutation was selected for analysis because it occurred in a highly expressed gene and yet did not produce obvious phenotypes following germline transmission. RESULTS: Sequences flanking the integrated gene trap vector in 1B4 cells were used to isolate a full-length cDNA whose predicted amino acid sequence is identical to the human A2 protein at all but one of 341 amino acid residues. hnRNP A2/B1 transcripts extending into the provirus utilize a cryptic 3' splice site located 28 nucleotides downstream of the neomycin phosphotransferase start codon. The inserted Neo sequence and proviral poly(A) site function as an 3' terminal exon that is utilized to produce hnRNP A2/B1-Neo fusion transcripts, or skipped to produce wild-type hnRNP A2/B1 transcripts. This results in only a modest disruption of hnRNPA2/B1 gene expression. CONCLUSIONS: Expression of the occupied hnRNP A2/B1 gene and utilization of the viral poly(A) site are consistent with an exon definition model of pre-mRNA splicing. These results reveal a mechanism by which U3 gene trap vectors can be expressed without disrupting cellular gene expression, thus suggesting ways to improve these vectors for gene trap mutagenesis