Relative energetics and structural properties of zirconia using a self-consistent tight-binding model

We describe an empirical, self-consistent, orthogonal tight-binding model for zirconia, which allows for the polarizability of the anions at dipole and quadrupole levels and for crystal field splitting of the cation d orbitals. This is achieved by mixing the orbitals of different symmetry on a site with coupling coefficients driven by the Coulomb potentials up to octapole level. The additional forces on atoms due to the self-consistency and polarizabilities are exactly obtained by straightforward electrostatics, by analogy with the Hellmann-Feynman theorem as applied in first-principles calculations. The model correctly orders the zero temperature energies of all zirconia polymorphs. The Zr-O matrix elements of the Hamiltonian, which measure covalency, make a greater contribution than the polarizability to the energy differences between phases. Results for elastic constants of the cubic and tetragonal phases and phonon frequencies of the cubic phase are also presented and compared with some experimental data and first-principles calculations. We suggest that the model will be useful for studying finite temperature effects by means of molecular dynamics.Comment: to be published in Physical Review B (1 march 2000

Free energy and molecular dynamics calculations for the cubic-tetragonal phase transition in zirconia

The high-temperature cubic-tetragonal phase transition of pure stoichiometric zirconia is studied by molecular dynamics (MD) simulations and within the framework of the Landau theory of phase transformations. The interatomic forces are calculated using an empirical, self-consistent, orthogonal tight-binding (SC-TB) model, which includes atomic polarizabilities up to the quadrupolar level. A first set of standard MD calculations shows that, on increasing temperature, one particular vibrational frequency softens. The temperature evolution of the free energy surfaces around the phase transition is then studied with a second set of calculations. These combine the thermodynamic integration technique with constrained MD simulations. The results seem to support the thesis of a second-order phase transition but with unusual, very anharmonic behaviour above the transition temperature

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

Allergen Uptake, Activation, and IL-23 Production by Pulmonary Myeloid DCs Drives Airway Hyperresponsiveness in Asthma-Susceptible Mice

Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs “pro-asthmatic”, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness

Methane emissions from permafrost thaw lakes limited by lake drainage.

Thaw lakes in permafrost areas are sources of the strong greenhouse gas methane. They develop mostly in sedimentary lowlands with permafrost and a high excess ground ice volume, resulting in large areas covered with lakes and drained thaw-lake basins (DTLBs; refs,). Their expansion is enhanced by climate warming, which boosts methane emission and contributes a positive feedback to future climate change. Modelling of thaw-lake growth is necessary to quantify this feedback. Here, we present a two-dimensional landscape-scale model that includes the entire life cycle of thaw lakes; initiation, expansion, drainage and eventual re-initiation. Application of our model to past and future lake expansion in northern Siberia shows that lake drainage strongly limits lake expansion, even under conditions of continuous permafrost. Our results suggest that methane emissions from thaw lakes in Siberia are an order of magnitude less alarming than previously suggested, although predicted lake expansion will still profoundly affect permafrost ecosystems and infrastructure. © 2011 Macmillan Publishers Limited

Prostaglandin E(2) is a potent regulator of interleukin-12- and interleukin-18-induced natural killer cell interferon-γ synthesis

Synthesis of interferon (IFN)-γ by natural killer (NK) cells is an important pro-inflammatory event with interleukin (IL)-12 and IL-18 playing major inductive roles. However, other temporal events are likely to regulate such processes and as prostaglandin E(2) (PGE(2)) is ubiquitous during inflammation this study tested the hypothesis that PGE(2) was capable of directly modulating cytokine-induced NK cell IFN-γ synthesis in the absence of other immune cells. Using homogenous NK cell lines to establish direct effects, PGE(2) (0·1–1 µm) was found to suppress NK cell IFN-γ synthesis and antagonized the potent synergistic IFN-γ-inducing effects of IL-12 and IL-18. The actions of PGE(2) were mimicked by synthetic PGE(2) analogues including misoprostol and butaprost. The selective EP(2) receptor agonist butaprost, but not the EP(1)/EP(3) agonist sulprostone, suppressed IFN-γ synthesis and exclusively competed with PGE(2) for receptor binding on NK cells. Further analysis showed that PGE(2) did not modulate IL-12 receptor mRNA expression and the effects of PGE(2) could be mimicked by the phosphodiesterase inhibitor 3-iosobutyl-1-methylxanthine. The absence of demonstrable receptor modulation coupled with the observed suppression of IFN-γ synthesis by both EP(2) receptor-selective agonists and IBMX suggest that PGE(2) acts directly on NK cells via EP(2) receptors with its downstream effects on cAMP metabolism. This conclusion is further supported by findings that PGE(2) and its analogues consistently elevated levels of cAMP in NK cells. The ability of PGE(2) to antagonize the potent inductive signal provided by the combination of IL-12 and IL-18 supports the concept that PGE(2) may play an important role in limiting innate inflammatory processes in vivo through direct suppression of NK cell IFN-γ synthesis