The importance of moisture distribution for the growth and energetics of mid-latitude systems

A primitive equation model is used to study the sensitivity of baroclinic wave life cycles to the initial latitude-height distribution of humidity. Diabatic heating is parametrized only as a consequence of condensation in regions of large-scale ascent. Experiments are performed in which the initial relative humidity is a simple function of model level, and in some cases latitude bands are specified which are initially relatively dry. It is found that the presence of moisture can either increase or decrease the peak eddy kinetic energy of the developing wave, depending on the initial moisture distribution. A relative abundance of moisture at mid-latitudes tends to weaken the wave, while a relative abundance at low latitudes tends to strengthen it. This sensitivity exists because competing processes are at work. These processes are described in terms of energy box diagnostics. The most realistic case lies on the cusp of this sensitivity. Further physical parametrizations are then added, including surface fluxes and upright moist convection. These have the effect of increasing wave amplitude, but the sensitivity to initial conditions of relative humidity remains. Finally, 'control' and 'doubled CO2' life cycles are performed, with initial conditions taken from the time-mean zonal-mean output of equilibrium GCM experiments. The attenuation of the wave resulting from reduced baroclinicity is more pronounced than any effect due to changes in initial moisture.

A radial basis function network classifier to maximise leave-one-out mutual information

tWe develop an orthogonal forward selection (OFS) approach to construct radial basis function (RBF)network classifiers for two-class problems. Our approach integrates several concepts in probabilisticmodelling, including cross validation, mutual information and Bayesian hyperparameter fitting. At eachstage of the OFS procedure, one model term is selected by maximising the leave-one-out mutual infor-mation (LOOMI) between the classifier’s predicted class labels and the true class labels. We derive theformula of LOOMI within the OFS framework so that the LOOMI can be evaluated efficiently for modelterm selection. Furthermore, a Bayesian procedure of hyperparameter fitting is also integrated into theeach stage of the OFS to infer the l2-norm based local regularisation parameter from the data. Since eachforward stage is effectively fitting of a one-variable model, this task is very fast. The classifier construc-tion procedure is automatically terminated without the need of using additional stopping criterion toyield very sparse RBF classifiers with excellent classification generalisation performance, which is par-ticular useful for the noisy data sets with highly overlapping class distribution. A number of benchmarkexamples are employed to demonstrate the effectiveness of our proposed approach.

EphB2 regulates contact-dependent and independent signalling to control platelet function

The Eph kinases, EphA4 and EphB1 and their ligand, ephrinB1 have been previously reported to be present in platelets where they contribute to thrombus stability. While thrombus formation allows for Eph-ephrin engagement and bidirectional signalling, the importance specifically of Eph kinase or ephrin signalling in regulating platelet function remained unidentified. In the present study, a genetic approach was used in mice to establish the contribution of signalling orchestrated by the cytoplasmic domain of EphB2 (a newly discovered Eph kinase in platelets) in platelet activation and thrombus formation. We conclude that EphB2 signalling is involved in the regulation of thrombus formation and clot retraction. Furthermore, the cytoplasmic tail of this Eph kinase regulates initial platelet activation in a contact-independent manner in the absence of Eph-ephrin ligation between platelets. Together these data demonstrate that EphB2 signalling not only modulates platelet function within a thrombus but is also involved in the regulation of the function of isolated platelets in a contact-independent manner.

A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function

Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnA(loxP/loxP) females with GATA1-Cre males. FlnA(loxP/y) GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbalpha because they lack the normal cytoskeletal linkage of GPIbalpha to underlying actin filaments. This results in approximately 70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like-mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased alpha-granule secretion, integrin alphaIIbbeta3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C-gamma2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA-Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like-containing receptor signaling and platelet function.