Enumerating constrained elementary flux vectors of metabolic networks

The concept of elementary vector is generalised to the case where the steady-state space of the metabolic network is not a flux cone but is a general polyhedron due to further inhomogeneous constraints on the flows through some of the reactions. On one hand, this allows to selectively enumerate elementary modes which satisfy certain optimality criteria and this can yield a large computational gain compared with full enumeration. On the other hand, in contrast to the single optimum found by executing a linear program, this enables a comprehensive description of the set of alternate optima often encountered in flux balance analysis. The concepts are illustrated on a metabolic network model of human cardiac mitochondria.

Inhibition of FcepsilonRI-dependent mediator release and calcium flux from human mast cells by sialic acid-binding immunoglobulin-like lectin 8 engagement

BACKGROUND: Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of glycan-binding inhibitory receptors, and among them, Siglec-8 is selectively expressed on human eosinophils, basophils, and mast cells. On eosinophils, Siglec-8 engagement induces apoptosis, but its function on mast cells is unknown. OBJECTIVE: We sought to study the effect of Siglec-8 engagement on human mast cell survival and mediator release responses. METHODS: Human mast cells were generated from CD34+ precursors. Apoptosis was studied by using flow cytometry. Mast cell mediator release or human lung airway smooth muscle contraction was initiated by FcepsilonRI cross-linking with or without preincubation with Siglec-8 or control antibodies, and release of mediators was analyzed along with Ca++ flux. RBL-2H3 cells transfected with normal and mutated forms of Siglec-8 were used to study how Siglec-8 engagement alters mediator release. RESULTS: Siglec-8 engagement failed to induce human mast cell apoptosis. However, preincubation with Siglec-8 mAbs significantly (P < .05) inhibited FcepsilonRI-dependent histamine and prostaglandin D(2) release, Ca++ flux, and anti-IgE-evoked contractions of human bronchial rings. In contrast, release of IL-8 was not inhibited. Siglec-8 ligation was also shown to inhibit beta-hexosaminidase release and Ca++ flux triggered through FcepsilonRI in RBL-2H3 cells transfected with full-length human Siglec-8 but not in cells transfected with Siglec-8 containing a tyrosine to phenylalanine point mutation in the membrane-proximal immunoreceptor tyrosine-based inhibitory motif domain. CONCLUSION: These data represent the first reported inhibitory effects of Siglec engagement on human mast cells.

Two Stable Equilibria of the Atlantic Subpolar Gyre

The cyclonic circulation of the Atlantic subpolar gyre is a key mechanism for North Atlantic climate variability on a wide range of time scales. It is generally accepted that it is driven by both cyclonic winds and buoyancy forcing, yet the individual importance and dynamical interactions of the two contributions remain unclear. The authors propose a simplified four-box model representing the convective basin of the Labrador Sea and its shallow and deep boundary current system, the western subpolar gyre. Convective heat loss drives a baroclinic flow of relatively light water around the dense center. Eddy salt flux from the boundary current to the center increases with a stronger circulation, favors the formation of dense waters, and thereby sustains a strong baroclinic flow, approximately 10%–25% of the total. In contrast, when the baroclinic flow is not active, surface waters may be too fresh to convect, and a buoyancy-driven circulation cannot develop. This situation corresponds to a second stable circulation mode. A hysteresis is found for variations in surface freshwater flux and the salinity of the near-surface boundary current. An analytical solution is presented and analyzed.

Flux and resident injection in gaseous advection experiments

The occurrence of gaseous pollutants in soils has stimulated many experimental activities, including forced ventilation in the field as well as laboratory transport experiments with gases. The dispersion coefficient in advective-dispersive gas phase transport is often dominated by molecular diffusion, which leads to a large overall dispersivity gamma. Under such conditions it is important to distinguish between flux and resident modes of solute injection and detection. The influence of the inlet type oil the macroscopic injection mode was tested in two series of column experiments with gases at different mean flow velocities nu. First we compared infinite resident and flux injections, and second, semi-infinite resident and flux injections. It is shown that the macroscopically apparent injection condition depends on the geometry of the inlet section. A reduction of the cross-sectional area of the inlet relative to that of the column is very effective in excluding the diffusive solute input, thus allowing us to use the solutions for a flux Injection also at rather low mean flow velocities nu. If the whole cross section of a column is exposed to a large reservoir like that of ambient air, a semi-infinite resident injection is established, which can be distinguished from a flux injection even at relatively high velocities nu, depending on the mechanical dispersivity of the porous medium.