Alaya Preschool: A Culture of Care and Meaningful Work in Contemplative Early Childhood Education

The purpose of this ethnographic case study was to describe the culture of an early childhood educational preschool setting which was philosophically grounded in contemplative education and traditions — the Alaya Preschool at Naropa University in Boulder, Colorado. While much has been written about early education and contemplative education as separate topics, the current study fills a scholarship gap in the literature about contemplative early childhood education. Data were collected using the Mosaic Approach, and included shoulder-to-shoulder and walk-around methods for interviewing. Data types consisted of the observation of classroom and school activities; semi-structured face-to-face-interviews and informal interviews with adults and children; and the collection of artifacts, including paintings, drawings, photographs, and poetry generated by the researcher and participants, as well as school documents and audio recordings. Multimodal data analysis included inductive analysis and coding; the compilation of paintings and drawings; and research poetry. Both narrative and art forms generated with participatory tools were used for reporting. Findings about the culture and lived experiences of the learning community included contemplative practices of adults (staff meditation), children (practicing stones, sand trays, and Kalapa Ikebana), and the collective practice of holding and opening space. In addition, the learning community described their personal and professional cultural identities, as individuals and a collective, and spoke to the key Principles of Practice which served as their guide — a foundational belief in Basic Goodness, which cradled expressions of Genuine Relationships and Kindness. These findings were interpreted and discussed within the contexts of embodied presence, care theory, and the theory of work and human evolution. This research has the potential to inform early childhood educators, teacher educators, and contemplative practitioners. Key words: care theory, contemplative education, contemplative practices, early childhood education, embodied presence, ethnographic case study, qualitative, teacher education, theory of work and human evolution, transformative educatio

Redesigning specificity in miniproteins

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2006.Includes bibliographical references.This work focuses on designing specific miniprotein interactions using computational models and then testing these designs with experiments. Miniproteins are small, autonomously-folding proteins that are excellent for testing protein designs because they can be chemically synthesized and computationally modeled. Despite their diminutive size, miniproteins are used as minimal models to discern important features, such as folding and interaction specificity, in natural proteins. A 21-residue [beta][beta][alpha] homotetramer miniprotein (BBA) was computationally redesigned to interact as a heterotetramer. Protein design calculations revealed a large/small pattern of hydrophobic residues in the core and charge complementarity on the surface as a mechanism for attaining heterospecificity. Solution studies showed the designed protein is a tetramer and interacts in the same stoichiometry as its parent homotetramer. The x-ray crystal structure of the heterotetramer revealed a structure very close to the designed structure with near-perfect prediction of core side-chain packing. In a second round of design, the BBA heterotetramer was stabilized to near-native stability. Next, the coiled-coil region within the Bcr (breakpoint cluster region) oligomerization domain was used to probe antiparallel versus parallel helix-orientation specificity in coiled coils.(cont.) Based on the Bcr sequence, it is unclear why the oligomerization domain has an antiparallel orientation preference. The isolated Bcr coiled-coil region adopts an antiparallel orientation, so the orientation preference must be encoded in the Bcr coiled-coil sequence itself. Coiled-coil statistics and parallel and antiparallel model structures revealed an alanine and glutamate in the Bcr core as candidates that may be important for helix-orientation specificity. Both residues were mutated to leucine, a common core residue in parallel coiled coils. Based on solution studies of the mutant, both alanine and glutamate play an important role in oligomerization specificity, while glutamate may also be important for orientation specificity in Bcr. Finally, interaction partners to the Bcr oligomerization domain were computationally designed to act as dominant negative inhibitors. Four interaction partners were designed using different design techniques and energy functions. The inhibitors were expressed in E. coli and tested in a pull-down assay.by Christina Marie Taylor.Ph.D

Urban Dust Microbiome: Impact on Later Atopy and Wheezing

INTRODUCTION: Investigations in urban areas have just begun to explore how the indoor dust microbiome may affect the pathogenesis of asthma and allery. We aimed to investigate the early fungal and bacterial microbiome in house dust with allergic sensitization and wheezing later in childhood. METHODS: Individual dust samples from 189 homes of the LISAplus birth cohort study were collected shortly after birth from living room floors and profiled for fungal and bacterial microbiome. Fungal and bacterial diversity was assessed with terminal restriction fragment length polymorphism (tRFLP) and defined by the Simpson diversity index. Information on wheezing outcomes and co-variates until the age of 10 years was obtained by parental questionnaires. Information on specific allergic sensitization was available at 6 and 10 years. Logistic regression and General Estimation Equation (GEE) models were used to examine the relationship between microbial diversity and health outcomes. RESULTS: Logistic regression analyses revealed a significantly reduced risk of developing sensitization to aero-allergens at 6 years and ever wheezing until the age of 10 years for exposure to higher fungal diversity (adjusted Odds Ratio aOR (95%CI): 0.26 (0.10-0.70)), and 0.42 (0.18-0.96), respectively), in adjusted analyses. The associations were attenuated for the longitudinal analyses (GEE) until the age of 10 years. There was no association between higher exposure to bacterial diversity and the tested health outcomes. CONCLUSION: Higher early exposure to fungal diversity might help to prevent from developing sensitization to aero-allergens in early childhood, but the reasons for attenuated effects in later childhood require further prospective studies

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment