Sequential induction of NF-κB/Rel family proteins during B-cell terminal differentiation

The NF-kappa B/Rel family of at least five transcription factor polypeptides is thought to function both as a developmental regulator in B cells and as a rapid response system in all cells. To examine this notion in more detail, we determined the protein contents of both the inducible and constitutive NF-kappa B/Rel activities in a pre-B-cell line, 70Z/3, and a mature B-cell line, WEHI 231. NF-kappa B p50/p65 is the major inducible nuclear complex after lipopolysaccharide or phorbol myristate acetate treatment of 70Z/3 cells. The constitutive and inducible complexes in WEHI 231 cells are mainly composed of p50 and Rel. The constitutive or induced activities are all sensitive to I kappa B-alpha, but this inhibitor is very short-lived in WEHI 231 cells, suggesting that the balance between synthesis and degradation of I kappa B-alpha determines whether a particular cell lineage has constitutive activity. A patterned expression of the NF-kappa B/Rel activator proteins emerges from an analysis of other B-lineage cell lines and splenic B cells: mainly p50 and p65 in pre-B (and non-B) cells, a predominance of Rel and p50 in mature B cells, and expression of p52 and RelB in plasmacytoma lines. This ordered pattern of regulators may reflect the requirement for expression of different genes during terminal B-cell differentiation because different combinations of NF-kappa B/Rel family members preferentially activate distinct kappa B sites in reporter constructs

Oxygen Hydration Mechanism for the Oxygen Reduction Reaction at Pt and Pd Fuel Cell Catalysts

We report the reaction pathways and barriers for the oxygen reduction reaction (ORR) on platinum, both for gas phase and in solution, based on quantum mechanics calculations (PBE-DFT) on semi-infinite slabs. We find a new mechanism in solution: O_2 → 2O_(ad) (E_(act) = 0.00 eV), O_(ad) + H_2O_(ad) → 2OH_(ad) (E_(act) = 0.50 eV), OH_(ad) + H_(ad) → H_2O_(ad) (E_(act) = 0.24 eV), in which OH_(ad) is formed by the hydration of surface O_(ad). For the gas phase (hydrophilic phase of Nafion), we find that the favored step for activation of the O_2 is H_(ad) + O_(2ad) → HOO_(ad) (E_(act) = 0.30 eV) → HO_(ad) + O_(ad) (E_(act) = 0.12 eV) followed by O_(ad) + H_2O_(ad) → 2OH_(ad) (E_(act) = 0.23 eV), OH_(ad) + H_(ad) → H_2O_(ad) (E_(act) = 0.14 eV). This suggests that to improve the efficiency of ORR catalysts, we should focus on decreasing the barrier for Oad hydration while providing hydrophobic conditions for the OH and H_2O formation steps

Theoretical Study of Solvent Effects on the Platinum-Catalyzed Oxygen Reduction Reaction

We report here density functional theory (DFT) studies (PBE) of the reaction intermediates and barriers involved in the oxygen reduction reaction (ORR) on a platinum fuel cell catalyst. Solvent effects were taken into account by applying continuum Poisson−Boltzmann theory to the bound adsorbates and to the transition states of the various reactions on the platinum (111) surface. Our calculations show that the solvent effects change significantly the reaction barriers compared with those in the gas-phase environment (without solvation). The O_2 dissociation barrier decreases from 0.58 to 0.27 eV, whereas the H + O → OH formation barrier increases from 0.73 to 1.09 eV. In the water-solvated phase, OH formation becomes the rate-determining step for both ORR mechanisms, O_2 dissociation and OOH association, proposed earlier for the gas-phase environment. Both mechanisms become significantly less favorable for the platinum catalytic surface in water solvent, suggesting that alternative mechanisms must be considered to describe properly the ORR on the platinum surface

Mechanism for Degradation of Nafion in PEM Fuel Cells from Quantum Mechanics Calculations

We report results of quantum mechanics (QM) mechanistic studies of Nafion membrane degradation in a polymer electrolyte membrane (PEM) fuel cell. Experiments suggest that Nafion degradation is caused by generation of trace radical species (such as OH^●, H^●) only when in the presence of H_2, O_2, and Pt. We use density functional theory (DFT) to construct the potential energy surfaces for various plausible reactions involving intermediates that might be formed when Nafion is exposed to H_2 (or H^+) and O_2 in the presence of the Pt catalyst. We find a barrier of 0.53 eV for OH radical formation from HOOH chemisorbed on Pt(111) and of 0.76 eV from chemisorbed OOH_(ad), suggesting that OH might be present during the ORR, particularly when the fuel cell is turned on and off. Based on the QM, we propose two chemical mechanisms for OH radical attack on the Nafion polymer: (1) OH attack on the S–C bond to form H_2SO_4 plus a carbon radical (barrier: 0.96 eV) followed by decomposition of the carbon radical to form an epoxide (barrier: 1.40 eV). (2) OH attack on H_2 crossover gas to form hydrogen radical (barrier: 0.04 eV), which subsequently attacks a C–F bond to form HF plus carbon radicals (barrier as low as 1.00 eV). This carbon radical can then decompose to form a ketone plus a carbon radical with a barrier of 0.86 eV. The products (HF, OCF_2, SCF_2) of these proposed mechanisms have all been observed by F NMR in the fuel cell exit gases along with the decrease in pH expected from our mechanism

The Method of Moments and the Energy Levels of Molecules and Solids

The method of moments is used to derive the energy levels of a representative series of molecules, crystalline and noncrysta-1- line solids. It provides a direct link between the density of states of the eigenvalue spectrum and the connectivity and topology of the molecular or solid state network

The combined absence of NF-kappa B1 and c-Rel reveals that overlapping roles for these transcription factors in the B cell lineage are restricted to the activation and function of mature cells

Transcription factors NF-KB1 and c-Rel, individually dispensable during embryogenesis, serve similar, yet distinct, roles in the function of mature hemopoietic cells. Redundancy among Rel/ NF-KB family members prompted an examination of the combined roles of c-Rel and NF-KB1 by using mice that lack both proteins. Embryonic development and the maturation of hemopoietic progenitors were unaffected in nfkb1(-/-)c-rel(-/-) mice. Peripheral T cell populations developed normally, but follicular, marginal zone, and CD5(+) peritoneal B cell populations all were reduced. In culture, a failure of mitogen-stimulated nfkb1(-/-)c-rel(-/-) B cells to proliferate was caused by a cell cycle defect in early G(1) that prevented growth. In vivo, defects in humoral immunity and splenic architecture seen in nfkbl(-/-) and c-rel(-/-) mice were exacerbated in the double mutant mice. These findings demonstrate that in the B lineage overlapping roles for NF-K81 and c-Rel appear to be restricted to regulating the activation and function of mature cells