Development of lubricating oils suitable for use with liquid oxidizers Final summary report, 4 Mar. 1968 - 4 Mar. 1969

Lubricating properties and impact stability of polyfluoroalcohol derivatives at low temperatur

Reuse as heuristic : from transmission to nurture in learning activity design

In recent years a combination of ever more flexible and sophisticated Web technologies and an explosion in the quantity of online content has sparked learning technologists around the world to pursue the promise of the 'reusable learning object' or RLO with the idea that RLOs could be reused in different educational contexts, thereby providing greater overall flexibility and return on investment. In 2002 the ACETS Project undertook a three-year study in the UK to investigate whether RLOs worked in practice and how the pursuit of reuse affected the teacher and their teaching. Teachers working in healthcare-related subjects in Higher and Further Education were asked to create an original learning design or activity from third-party digital resources and to reflect both on the process and its outcomes. The expectation was that teachers would be the ones selecting and reusing third-party materials. This paper describes how one of the ACETS exemplifiers reinterpreted this remit, challenged the anticipated transmissive model of learning, and instead, gave their students an opportunity to create their own original learning designs and learning activities from third-party digital resources. By describing the educational enhancements, the resulting heightened levels of critical thinking, and sensitivity to patient needs, 'reuse' will be shown to be an effective heuristic for student self-direction and professional development

What clonal hematopoiesis can teach us about MDS

Clonal hematopoiesis (CH), defined as the clonal expansion of mutated hematopoietic stem and progenitor cells (HSPCs), is a common aging process. CH is a risk factor for the development of hematologic malignancies, most commonly myeloid neoplasms (MNs) including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasm (MPN). Recent work has elucidated how the development and cellular fitness of CH is shaped by aging, environmental exposures, and the germline (inherited) genetic background of an individual. This in turn has provided valuable insights into the pathogenesis of MNs including MDS. Here, in this review, we discuss the genetic origins of CH, the environmental stressors that influence CH, and the implications of CH on health outcomes including MDS. Since MNs have shared risk factors and underlying biology, most of our discussion regarding the implications of CH surrounds MN in general rather than focusing specifically on MDS. We conclude with future directions and areas of investigation including how intervention studies of CH might inform future therapeutic approaches to MN including MDS

Ten myths about character, virtue and virtue education – plus three well-founded misgivings

Initiatives to cultivate character and virtue in moral education at school continue to provoke sceptical responses. Most of those echo familiar misgivings about the notions of character, virtue and education in virtue – as unclear, redundant, old-fashioned, religious, paternalistic, anti-democratic, conservative, individualistic, relative and situation dependent. I expose those misgivings as ‘myths’, while at the same time acknowledging three better-founded historical, methodological and practical concerns about the notions in question

Genomic islands of divergence in the Yellow Tang and the Brushtail Tang Surgeonfishes.

The current ease of obtaining thousands of molecular markers challenges the notion that full phylogenetic concordance, as proposed by phylogenetic species concepts, is a requirement for defining species delimitations. Indeed, the presence of genomic islands of divergence, which may be the cause, or in some cases the consequence, of speciation, precludes concordance. Here, we explore this issue using thousands of RAD markers on two sister species of surgeonfishes (Teleostei: Acanthuridae), Zebrasoma flavescens and Z. scopas, and several populations within each species. Species are readily distinguished based on their colors (solid yellow and solid brown, respectively), yet populations and species are neither distinguishable using mitochondrial markers (cytochrome c oxidase 1), nor using 5193 SNPs (pairwise Φst = 0.034). In contrast, when using outlier loci, some of them presumably under selection, species delimitations, and strong population structure follow recognized taxonomic positions (pairwise Φst = 0.326). Species and population delimitation differences based on neutral and selected markers are likely due to local adaptation, thus being consistent with the idea that these genomic islands of divergence arose as a consequence of isolation. These findings, which are not unique, raise the question of a potentially important pathway of divergence based on local adaptation that is only evident when looking at thousands of loci

Molecular subclasses of clear cell ovarian carcinoma and their impact on disease behavior and outcomes

PURPOSE: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes. EXPERIMENTAL DESIGN: We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival. RESULTS: We detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy. CONCLUSIONS: Our study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness. See related commentary by Lheureux, p. 4838

Modulation of the equilibrative nucleoside transporter by inhibitors of DNA synthesis.

Expression of the equilibrative, S-(p-nitrobenzyl)-6-thioinosine (NBMPR)-sensitive nucleoside transporter (es), a component of the nucleoside salvage pathway, was measured during unperturbed growth and following exposure to various antimetabolites at growth-inhibitory concentrations. The probe 5-(SAENTA-x8)-fluorescein is a highly modified form of adenosine incorporating a fluorescein molecule. It binds. with high affinity and specificity to the (es) nucleoside transporter at a 1:1 stoichiometry, allowing reliable estimates of es expression by flow cytometry. Using a dual labelling technique which combined the vital DNA dye Hoechst-33342 and 5-(SAENTA-x8)-fluorescein, we found that surface expression of es approximately doubled between G1 and G2 + M phases of the cell cycle. To address the question of whether es expression could be modulated in cells exposed to drugs which inhibit de novo synthesis of nucleotides, cells were exposed to antimetabolite drugs having different modes of action. Hydroxyurea and 5-fluorouracil (5-FU), which inhibit the de novo synthesis of DNA precursors, produced increases in the expression of es. In contrast, cytosine arabinoside (ara-C) and aphidicolin, which directly inhibit DNA synthesis, produced no significant increase in es expression. Thymidine (TdR), which is an allosteric inhibitor of ribonucleotide reductase that depletes dATP, dCTP and dGTP pools while repleting the dTTP pool, had no significant effect on es expression. These data suggest that surface expression of the es nucleoside transporter is regulated by a mechanism which is sensitive to the supply of deoxynucleotides. Because 5-FU (which specifically depletes dTTP pools) causes a large increase in expression whereas TdR (which depletes all precursors except dTTP) does not, this mechanism might be particularly sensitive to dTTP pools

Impacts of agricultural land use on biological integrity: a causal analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116919/1/eap20112183128.pd

Structural Analysis and Testing of the Inflatable Re-entry Vehicle Experiment (IRVE)

The Inflatable Re-entry Vehicle Experiment (IRVE) is a 3.0 meter, 60 degree half-angle sphere cone, inflatable aeroshell experiment designed to demonstrate various aspects of inflatable technology during Earth re-entry. IRVE will be launched on a Terrier-Improved Orion sounding rocket from NASA s Wallops Flight Facility in the fall of 2006 to an altitude of approximately 164 kilometers and re-enter the Earth s atmosphere. The experiment will demonstrate exo-atmospheric inflation, inflatable structure leak performance throughout the flight regime, structural integrity under aerodynamic pressure and associated deceleration loads, thermal protection system performance, and aerodynamic stability. Structural integrity and dynamic response of the inflatable will be monitored with photogrammetric measurements of the leeward side of the aeroshell during flight. Aerodynamic stability and drag performance will be verified with on-board inertial measurements and radar tracking from multiple ground radar stations. In addition to demonstrating inflatable technology, IRVE will help validate structural, aerothermal, and trajectory modeling and analysis techniques for the inflatable aeroshell system. This paper discusses the structural analysis and testing of the IRVE inflatable structure. Equations are presented for calculating fabric loads in sphere cone aeroshells, and finite element results are presented which validate the equations. Fabric material properties and testing are discussed along with aeroshell fabrication techniques. Stiffness and dynamics tests conducted on a small-scale development unit and a full-scale prototype unit are presented along with correlated finite element models to predict the in-flight fundamental mo