SNS Timing System

This poster describes the timing system being designed for Spallation Neutron Source being built at Oak Ridge National lab

Macropolyhedral boron-containing cluster chemistry. Ligand-induced two-electron variations of intercluster bonding intimacy. Structures of nineteen-vertex[(eta(5)-C5Me5) HIrB18H19(PMe2Ph)] and the related carbene complex [(eta(5)-C5Me5)HIrB18H19{C(NHMe)(2)}]

Addition of PMe2Ph to fused-cluster syn-[(η5-C5Me5)IrB18H20] 1 to give [(η5-C5Me5)HIrB18H19(PMe2Ph)] 3 entails a diminution in the degree of intimacy of the intercluster fusion, rather than retention of inter-subcluster binding intimacy and a nido → arachno conversion of the character of either of the subclusters. Reaction with MeNC gives [(η5-C5Me5)HIrB18H19{C(NHMe)2}] 4 which has a similar structure, but with the ligand now being the carbene {:C(NHMe)2}, resulting from a reductive assembly reaction involving two MeNC residues and the loss of a carbon atom

Macropolyhedral boron-containing cluster chemistry: two-electron variations in intercluster bonding intimacy. Contrasting structures of 19-vertex [(eta(5)-C5Me5)HIrB18H19(PHPh2)] and [(eta(5) -C5Me5)IrB18H18(PH2Ph)]

Fused double-cluster [(5-C5Me5)IrB18H18(PH2Ph)]8, from syn-[(5-C5Me5)IrB18H20] 1 and PH2Ph, retains the three-atoms-in-common cluster fusion intimacy of 1, in contrast to [(5-C5Me5)HIrB18H19(PHPh2)]6, from PHPh2 with 1, which exhibits an opening to a two atoms-in-common cluster fusion intimacy. Compound 8 forms via spontaneous dihydrogen loss from its precursor [(5-C5Me5)HIrB18H19(PH2Ph)]7, which has two-atoms-in-common cluster-fusion intimacy and is structurally analogous to 6

But What About... Cosmic Rays, Magnetic Fields, Conduction, & Viscosity in Galaxy Formation

We present a suite of high-resolution cosmological simulations, using the FIRE-2 feedback physics together with explicit treatment of magnetic fields, anisotropic conduction and viscosity, and cosmic rays (CRs) injected by supernovae (including anisotropic diffusion, streaming, adiabatic, hadronic and Coulomb losses). We survey systems from ultra-faint dwarf ($M_{\ast}\sim 10^{4}\,M_{\odot}$, $M_{\rm halo}\sim 10^{9}\,M_{\odot}$) through Milky Way masses, systematically vary CR parameters (e.g. the diffusion coefficient $\kappa$ and streaming velocity), and study an ensemble of galaxy properties (masses, star formation histories, mass profiles, phase structure, morphologies). We confirm previous conclusions that magnetic fields, conduction, and viscosity on resolved ($\gtrsim 1\,$pc) scales have small effects on bulk galaxy properties. CRs have relatively weak effects on all galaxy properties studied in dwarfs ($M_{\ast} \ll 10^{10}\,M_{\odot}$, $M_{\rm halo} \lesssim 10^{11}\,M_{\odot}$), or at high redshifts ($z\gtrsim 1-2$), for any physically-reasonable parameters. However at higher masses ($M_{\rm halo} \gtrsim 10^{11}\,M_{\odot}$) and $z\lesssim 1-2$, CRs can suppress star formation by factors $\sim 2-4$, given relatively high effective diffusion coefficients $\kappa \gtrsim 3\times10^{29}\,{\rm cm^{2}\,s^{-1}}$. At lower $\kappa$, CRs take too long to escape dense star-forming gas and lose energy to hadronic collisions, producing negligible effects on galaxies and violating empirical constraints from $\gamma$-ray emission. But around $\kappa\sim 3\times10^{29}\,{\rm cm^{2}\,s^{-1}}$, CRs escape the galaxy and build up a CR-pressure-dominated halo which supports dense, cool ($T\ll 10^{6}$ K) gas that would otherwise rain onto the galaxy. CR heating (from collisional and streaming losses) is never dominant.Comment: 35 pages, 23 figures. Updated to match published (MNRAS) versio

Centrifugation and capillarity integrated into a multiple analyte whole blood analyser

A unique clinical chemistry analyser is described which processes 90 μl of whole blood (fingerstick or venous) into multiple aliquots of diluted plasma and reports the results of 12 tests in 14 min. To perform a panel of tests, the operator applies the unmetered sample directly into a single use, 8 cm diameter plastic rotor which contains the required liquid diluent and dry reagents. Using centrifugal and capillary forces, the rotor meters the required amount of blood, separates the red cells, meters the plasma, meters the diluent, mixes the fluids, distributes the fluid to the reaction cuvettes and mixes the reagents and the diluted plasma in the cuvettes. The instrument monitors the reagent reactions simultaneously using nine wavelengths, calculates the results from the absorbance data, and reports the results

Dynamic microRNA activity identifies therapeutic targets in trastuzumab‐resistant HER2+ breast cancer

MicroRNAs (miRNAs) are implicated in numerous physiologic and pathologic processes, such as the development of resistance to chemotherapy. Determining the role of miRNAs in these processes is often accomplished through measuring miRNA abundance by polymerase chain reaction, sequencing, or microarrays. We have developed a system for the large‐scale monitoring of dynamic miRNA activity and have applied this system to identify the contribution miRNA activity to the development of trastuzumab resistance in a cell model of HER2+ breast cancer. MiRNA activity measurements identified significantly different activity levels between BT474 cells (HER2+ breast cancer) and BT474R cells (HER2+ breast cancer cells selected for resistance to trastuzumab). We created a library of 32 miRNA reporter constructs, which were delivered by lentiviral transduction into cells, and miRNA activity was quantified by bioluminescence imaging. Upon treatment with the bioimmune therapy, trastuzumab, the activity of 11 miRNAs were significantly altered in parental BT474 cells, and 20 miRNAs had significantly altered activity in the therapy‐resistant BT474R cell line. A combination of statistical, network and classification analysis was applied to the dynamic data, which identified miR‐21 as a controlling factor in trastuzumab response. Our data suggested downregulation of miR‐21 activity was associated with resistance, which was confirmed in an additional HER2+ breast cancer cell line, SKBR3. Collectively, the dynamic miRNA activity measurements and analysis provided a system to identify new potential therapeutic targets in treatment‐resistant cancers.MicroRNAs (miRNAs) are often dysrgulated in cancer and can give rise to drug resistance. Identifying the mechanisms for resistance may lead to new This work used an array of miRNA activity reporters to identify miR‐21 as a mediator of trastuzumab resistance in breast cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/1/bit26791.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146392/2/bit26791_am.pd

Contrasting Development of Canopy Structure and Primary Production in Planted and Naturally Regenerated Red Pine Forests

Globally, planted forests are rapidly replacing naturally regenerated stands but the implications for canopy structure, carbon (C) storage, and the linkages between the two are unclear. We investigated the successional dynamics, interlinkages and mechanistic relationships between wood net primary production (NPPw) and canopy structure in planted and naturally regenerated red pine (Pinus resinosa Sol. ex Aiton) stands spanning ≥ 45 years of development. We focused our canopy structural analysis on leaf area index (LAI) and a spatially integrative, terrestrial LiDAR-based complexity measure, canopy rugosity, which is positively correlated with NPPw in several naturally regenerated forests, but which has not been investigated in planted stands. We estimated stand NPPw using a dendrochronological approach and examined whether canopy rugosity relates to light absorption and light–use efficiency. We found that canopy rugosity increased similarly with age in planted and naturally regenerated stands, despite differences in other structural features including LAI and stem density. However, the relationship between canopy rugosity and NPPw was negative in planted and not significant in naturally regenerated stands, indicating structural complexity is not a globally positive driver of NPPw. Underlying the negative NPPw-canopy rugosity relationship in planted stands was a corresponding decline in light-use efficiency, which peaked in the youngest, densely stocked stand with high LAI and low structural complexity. Even with significant differences in the developmental trajectories of canopy structure, NPPw, and light use, planted and naturally regenerated stands stored similar amounts of C in wood over a 45-year period. We conclude that widespread increases in planted forests are likely to affect age-related patterns in canopy structure and NPPw, but planted and naturally regenerated forests may function as comparable long-term C sinks via different structural and mechanistic pathways

SOX17 Regulates Conversion of Human Fibroblasts Into Endothelial Cells and Erythroblasts by Dedifferentiation Into CD34+ Progenitor Cells

BACKGROUND: The mechanisms underlying the dedifferentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast dedifferentiation recapitulates the generation of multipotent progenitors during embryonic development, which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bilineage conversion of fibroblasts by the generation of intermediate progenitors. METHODS: CD34+ progenitors were generated after the dedifferentiation of human adult dermal fibroblasts by overexpression of pluripotency transcription factors. Sorted CD34+ cells were transdifferentiated into induced endothelial cells and induced erythroblasts using lineage-specific growth factors. The therapeutic potential of the generated cells was assessed in an experimental model of myocardial infarction. RESULTS: Induced endothelial cells expressed specific endothelial cell surface markers and also exhibited the capacity for cell proliferation and neovascularization. Induced erythroblasts expressed erythroid surface markers and formed erythroid colonies. Endothelial lineage conversion was dependent on the upregulation of the developmental transcription factor SOX17, whereas suppression of SOX17 instead directed the cells toward an erythroid fate. Implantation of these human bipotential CD34+ progenitors into nonobese diabetic/severe combined immunodeficiency (NOD-SCID) mice resulted in the formation of microvessels derived from human fibroblasts perfused with mouse and human erythrocytes. Endothelial cells generated from human fibroblasts also showed upregulation of telomerase. Cell implantation markedly improved vascularity and cardiac function after myocardial infarction without any evidence of teratoma formation. CONCLUSIONS: Dedifferentiation of fibroblasts to intermediate CD34+ progenitors gives rise to endothelial cells and erythroblasts in a SOX17-dependent manner. These findings identify the intermediate CD34+ progenitor state as a critical bifurcation point, which can be tuned to generate functional blood vessels or erythrocytes and salvage ischemic tissue

Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

Social presence in the 21st Century: an adjustment to the Community of Inquiry framework

The Community of Inquiry framework, originally proposed by Garrison, Anderson and Archer (2000) identifies teaching, social and cognitive presences as central to a successful online educational experience. This article presents the findings of a study conducted in Uruguay between 2007 and 2010. The research aimed to establish the role of cognitive, social and teaching presences in the professional development of 40 English language teachers on Continuous Professional Development (CPD) programmes delivered in blended learning settings. The findings suggest that teaching presence and cognitive presence have themselves 'become social'. The research points to social presence as a major lever for engagement, sense-making and peer support. Based on the patterns identified in the study, this article puts forward an adjustment to the Community of Inquiry framework, which shows social presence as more prominent within the teaching and cognitive constructs than the original version of the framework suggests