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This paper presents a multi-scale model of a solid oxide fuel cell (SOFC) stack consisting of five anode-supported cells. A two-dimensional isothermal elementary kinetic model is used to calculate the performance of single cells. Several of these models are thermally coupled to form the stack model. Simulations can be carried out at steady-state as well as dynamic operation. The model is validated over a wide range of operating conditions including variation of temperature, gas composition (both on anode and cathode side), and pressure. Validation is carried out using polarization curves and impedance spectra. The model is then used to explain the pressure-induced performance increase measured at constant fuel utilization of 40%. Results show that activation and concentration overpotentials are reduced with increasing pressure. [ABSTRACT FROM AUTHOR]

Synthetic lipopeptides carrying the head group of bacterial lipoproteins are specific ligands of Toll-like receptors (TLR). The three fatty acids containing lipopeptides with the tripalmitoyl-S-glyceryl-cysteinyl N-terminus (Pam3Cys) are agonists of TLR2. The structurally related lipopeptides with a head group lacking the fatty acyl residue at the amino-terminus (Pam2Cys) stimulate TLR2 and 6. To investigate the influence of the peptide chain of lipohexapeptides with a free N-terminus with regard to their ability to enhance B-cell proliferation, a randomizedS-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amide collection Pam2CysXXXXX and 5 × 19 subcollections (Pam2CysOXXXX, Pam2CysXOXXX, Pam2CysXXOXX, Pam2CysXXXOX, Pam2CysXXXXO, O: all protein amino acids except Cys) were prepared by parallel solid-phase synthesis. The collection represents synthetic lipopeptide analogues of the numerous bacterial lipoproteins and of mycoplasma lipoprotein. Each of the 95 subcollections is characterized by one defined and four degenerated amino acid positions thus comprising 194 individual lipopeptides with free N-terminal amino groups. High-performance liquid chromatography electrospray mass spectrometry (HPLC–ESI-MS) was applied for the analytical characterization of the lipohexapeptide amide subcollections and for the individual lipohexapeptide amides. The subcollections were tested for polyclonal activation of murine spleen cells, deconvolution led to highly active singleS-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amides. [ABSTRACT FROM AUTHOR]

Monocytes (MO) and macrophages (MAC) are important producers of cytokines involved in the pathophysiology of bacterial sepsis. Most studies concentrate on the effects of bacterial lipopoly-saccharides (LPS) regarding the induction of cytokine gene expression and secretion in MO/MAC. Here we report that besides LPS, the synthetic lipoprotein analogue lipopeptide N-palmitoyl-S-( 2,3-bis (palmitoyl)-(2RS)-propyl)-(R)cysteinyl-alanyl-glycine (Pam 3-Cys-Ala-Gly), another component of the outer membrane of Gram-negative bacteria, as well as heat-killed Staphyloccocus aureus (S. aureus/SAC) are potent stimuli for cytokines in human MO. For all three investigated stimuli we found an individual pattern of cytokine induction: LPS was most potent in inducing interleukin-6 (IL-6) synthesis, whereas for tumour necrosis factor-α (TNF-α) secretion SAC was the best stimulus. Comparable amounts of IL-8 were induced by either LPS or Pam3-Cys-AlaGly, with SAC being less effective even at higher concentrations. The addition of serum led to an increase in LPS-, SAC- and Pam3-Cys-Ala-Gly-stimulated TNT-α secretion, indicating that the presence of serum is critical not just for LPS stimulation. Furthermore, as is known for LPS, Pam3-Cys-Ala-Gly and SAC rendered MO refractory to a second bacterial stimulus. Pam3-Cys-Ala-Gly and SAC induced tolerance for itself, but LPS could partially overcome this effect. As the CD14 molecule is discussed as a common receptor for different bacterial components, we investigated whether the TNF-α response of MO could be blocked by anti-CD 14 antibodies. MY4, a CD14 antibody, selectively blocked the TNF-α secretion induced by LPS but not by Pam3-Cys-AIa-Gly or SAC. In summary, we conclude that besides LPS, lipopeptide Pam3-Cys- Ala-Gly and SAC are potent stimuli for human MO, while the mechanisms of activation seem to be partially different from LPS. [ABSTRACT FROM AUTHOR]

This study shows that stimulating bone marrow-derived macrophages with either Iipopolysaccharide (LPS) or the lipopeptide N-palmitoyl-S-(2.3-bis(palmitoyloxy)-(2RS)-propyl (R)-cysteinyl-alanyl-glycine (Pam3Cys-Ala-Gly), a synthetic analogue of the N-terminal part of bacterial lipoprotein, leads to the formation of nitric oxide (NO) and nitrite (NO2), a stable analogue of NO. NO was detected by applying the chemiluminescence method and by measuring the activity olexogenously added soluble guanylate cyclase (GC), which is strongly and selectively activated by NO. Synthesis of NO and NO2 occurs via activation of the L-arginine and NADPH-dependent enzyme(s) present in the cytosol of bone marrow-derived macrophages. NO produced by this non-constitutive L-arginine pathway is thought to be responsible for the cytostatic and killing properties of macrophages (Stuehr & Nathan, 1989). Macrophages stimulated either with LPS or Pam3Cys-Ala-Gly exhibited a 6-hr lag time before engaging in nitrite synthesis, a time at which expression of the NO-forming enzyme had already reached its maximum. The regulation of NO and NO2 synthesis during macrophage development seems to differ from that of cytokine synthesis. Whereas cytokine release varies during a culture period up to 20 days. NO synthesis and expression of the NO-forming enzyme remain unaltered. These studies show that, similar to LPS. Pam3-Cys-Ala-Gly is a potent activator of `the oxidative L-arginine pathway' in bone marrow-derived macrophages. Whether both stimuli use the same signal transfer mechanism to induce this pathway and whether NO synthesized by this pathway is involved in the activation of the enzyme guanylate cyclase in macrophages requires clarification. [ABSTRACT FROM AUTHOR]

The reactivity of 38 murine strains to a synthetic analogue of bacterial lipoprotein, tripalmitoyl-pentapeptide (TPP), was tested and compared with the reactivity to lipopolysaccharide (LPS). These strains include common laboratory mice and H-2 recombinant inbred lines, as well as some newly bred lines originating from animals recently captured in different regions of Europe. All animals analysed were reactive to TPP and polyclonally activated to proliferation and immunoglobulin synthesis. Large differences in mitogen reactivities of various H-2 recombinant inbred strains suggest that MHC or closely linked gene products influence the reactivity to the LPS and TPP mitogens. By analyzing the frequencies of precursor cells reactive to TPP or LPS and the isotype patterns obtained after stimulation, we demonstrated that both mitogens activate individual B cells in different ways. [ABSTRACT FROM AUTHOR]

We recently showed that synthetic lipopeptides, analogues of the N-terminal region of bacterial lipoprotein, induce DNA synthesis in B lymphocytes in the absence of enhanced phosphatidylinositol 4,5-bisphosphate hydrolysis and protein kinase C translocation. Here we demonstrate that lipopeptides are capable of inducing enhanced expression of MHC class II molecules and early increases in the intracellular free calcium concentration ([Ca2+]1) in B cells. However, they do not effect Tcells. The increase in [Ca2+ seen in B cells is due primarily to Ca2+ release from intracellular stores. Since lipopeptides differ in their capability to induce early increases in [Ca22+]1 and since the calcium response does not correlate with the ability of lipopeptides to induce proliferation and expression of MHC class II molecules, we suggest that this biochemical event may not be essential for lipopeptide-mediated B-cell activation. [ABSTRACT FROM AUTHOR]