An application of Hirschfelder-Silbey perturbation theory to the H2 plus ion

Hirschfelder-Silbey perturbation theory applied to positive hydrogen io

Mapping our way out? Critical reflections on historical research and the 1972 Faure report

Contributions to the literature have postulated an historical shift in policy narratives from the Faure report’s formulation of “lifelong education” for UNESCO in 1972 to a focus on “lifelong learning” since the mid-1990s. It has also been argued that the policy narrative articulated by de-schoolers in the early 1970s was incorporated in the Faure report. This paper critically examines the empirical foundations for such arguments and is based on a re-reading of the policy repertoire articulated by Faure’s report together with an analysis of the de-schoolers’ reception of the report in the early 1970s. Based upon a re-reading of primary texts and secondary sources from the 1970s, the analysis demonstrates that these widely accepted arguments constitute a problematic interpretation of the historical relationships between the key policy narratives in the 1970s. The conclusions identify a number of significant areas for further empirical research regarding the historical relationships between first generation policy narratives. (DIPF/Orig.

Modeling effects of L-type ca(2+) current and na(+)-ca(2+) exchanger on ca(2+) trigger flux in rabbit myocytes with realistic T-tubule geometries.

The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+) current affects intracellular Ca(2+) dynamics. Our model includes a realistic 3D geometry of a single t-tubule and its surrounding half-sarcomeres for rabbit ventricular myocytes. The effects of spatially distributed membrane ion-transporters (LCC, Na(+)/Ca(2+) exchanger, sarcolemmal Ca(2+) pump, and sarcolemmal Ca(2+) leak), and stationary and mobile Ca(2+) buffers (troponin C, ATP, calmodulin, and Fluo-3) are also considered. We used a coupled reaction-diffusion system to describe the spatio-temporal concentration profiles of free and buffered intracellular Ca(2+). We obtained parameters from voltage-clamp protocols of L-type Ca(2+) current and line-scan recordings of Ca(2+) concentration profiles in rabbit cells, in which the sarcoplasmic reticulum is disabled. Our model results agree with experimental measurements of global Ca(2+) transient in myocytes loaded with 50 μM Fluo-3. We found that local Ca(2+) concentrations within the cytosol and sub-sarcolemma, as well as the local trigger fluxes of Ca(2+) crossing the cell membrane, are sensitive to details of t-tubule micro-structure and membrane Ca(2+) flux distribution. The model additionally predicts that local Ca(2+) trigger fluxes are at least threefold to eightfold higher than the whole-cell Ca(2+) trigger flux. We found also that the activation of allosteric Ca(2+)-binding sites on the Na(+)/Ca(2+) exchanger could provide a mechanism for regulating global and local Ca(2+) trigger fluxes in vivo. Our studies indicate that improved structural and functional models could improve our understanding of the contributions of L-type and Na(+)/Ca(2+) exchanger fluxes to intracellular Ca(2+) dynamics

Pregnancy has a minimal impact on the acute transcriptional signature to vaccination.

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety

Evidence for multiband superconductivity in the heavy fermion compound UNi2Al3

Epitaxial thin films of the heavy fermion superconductor UNi2Al3 with Tc{max}=0.98K were investigated. The transition temperature Tc depends on the current direction which can be related to superconducting gaps opening at different temperatures. Also the influence of the magnetic ordering at TN=5K on R(T) is strongly anisotropic indicating different coupling between the magnetic moments and itinerant charge carriers on the multi-sheeted Fermi surface. The upper critical field Hc2(T) suggests an unconventional spin-singlet superconducting state.Comment: 4 pages, 6 figures revised version: inset of fig. 2 changed, fig. 3 added accepted for pub. in Phys. Rev. Lett. (estimated 9/04

2,4,5-Tris(pyridin-4-yl)-4,5-dihydro-1,3-oxazole

In the title compound, C18H14N4O, the mol­ecules are disordered about a crystallographic twofold axis, leading to 50:50 disorder of the O- and N-atom sites within the oxazole ring. As a consequence, symmetry-related oxazole C—N and C—O bonds are averaged. The oxazole ring makes a dihedral angle of 6.920 (1)° with the pyridyl ring in the 2-position and 60.960 (2)° with the pyridyl rings in the 4- and 5-positions

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes

Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes

DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono-and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes