Higher-order CpG-DNA stimulation reveals distinct activation requirements for marginal zone and follicular B cells in lupus mice

Mouse follicular B cells express TLR9 and respond vigorously to stimulation with single-stranded CpG-oligodeoxynucleotides (ODN). Surprisingly, follicular B cells do not respond to direct stimulation with other TLR9 ligands, such as bacterial DNA or class A(D) CpG-ODN capable of forming higher-order structures, unless other cell types are present. Here, we show that priming with interferons or with B cell-activating factor, or simultaneous co-engagement of the B cell receptor for antigen (BCR), can overcome this unresponsiveness. The effect of interferons occurs at the transcriptional level and is mediated through an autocrine/paracrine loop, which is dependent on IRF-1, IL-6 and IL-12 p40. We hypothesize that the lack of bystander activation of follicular B cells with more complex CpG ligands may be an important safety mechanism for avoiding autoimmunity. This will prevent resting B cells from responding to foreign or self-derived hypomethylated double-stranded CpG ligands unless these ligands are either delivered through the B cell receptor or under conditions where B cells are simultaneously co-engaged by activated plasmacytoid dendritic cells or TH1 cells. A corollary is that the heightened responsiveness of lupus B cells to TLR9-induced stimulation cannot be ascribed to unprimed follicular B cells, but is rather mediated by hypersensitive marginal zone B cells.

Geochemistry of late Archaean stromatolites from Zimbabwe: evidence for microbial life in restricted epicontinental seas

We report comprehensive trace element and Sr-isotope data for microbial carbonates from the Archaean Mushandike limestone, Masvingo Greenstone Belt, Zimbabwe. The stromatolites have very coherent REE + Y patterns and share the essential shale-normalised characteristics of other Archaean marine precipitates (positive La and Gd anomalies, absence of a negative Cc anomaly and a strongly superchondritic Y/Ho ratio). Mixing models constrain the maximum amount of shale contamination to 0.25-1% and calculated detritus-free carbonate REE + Y systematics require precipitation from seawater. In terms of light-REE over heavy-REE depletion, however, the studied samples are very different from all other known Archaean marine precipitates. In shale-normalised plots, the Mushandike samples yield a negative slope. A very restricted, regional input source of the dissolved load is indicated because normalisation with locally occurring tonalite gneiss REE + Y data yields a pattern closely resembling typical shale-normalised Archaean marine chemical sediments. The disappearance of a negative Eu anomaly when patterns are normalised with local tonalite gneiss strengthens this interpretation. Sr-isotope ratios are strongly correlated with trace element contents and ratios, which explains the modest scatter in Sr-isotope ratios as representing (minor) clastic contamination. Importantly, even the least contaminated samples have very radiogenic initial Sr-87/Sr-86 ratios (0.7184) implying Sr input from an ancient high Rb/Sr source, such as the early Archaean gneisses of south-central Zimbabwe. A local ancient (3.5-3.8 Ga) source is also indicated by previously published Pb-isotope datasets for the Mushandike stromatolites. This is entirely compatible with the occurrence of 3.7-3.8 Ga zircons in quartzites and metapelites from comparably old greenstone belts within less than 150 km of the studied locality. Comparison of the Pb-isotope ratios of the Mushandike stromatolites with 2.7 and 2.6 Ga old stromatolites from the neighbouring, Belingwe Greenstone Belt demonstrates differences in initial isotope composition that relate to the extent of exchange with the open ocean. The development of numerous basins on old continental crust, with water masses variably restricted from the open ocean. suggests a lack of strong vertical topography on this late Archaean craton. (C) 2004 Elsevier B.V. All rights reserved.

[0 0 1] zone-axis bright-field diffraction contrast from coherent Ge(Si) islands on Si(0 0 1): Dedicated to Professor Fang-hua Li on the occasion of her 70th birthday

Coherent Ge(Si)/Si(001) quantum dot islands grown by solid source molecular beam epitaxy at a growth temperature of 700degreesC were investigated using transmission electron microscopy working at 300 kV. The [001] zone-axis bright-field diffraction contrast images of the islands show strong periodicity with the change of the TEM sample substrate thickness and the period is equal to the effective extinction distance of the transmitted beam. Simulated images based on finite element models of the displacement field and using multi-beam dynamical diffraction theory show a high degree of agreement. Studies for a range of electron energies show the power of the technique for investigating composition segregation in quantum dot islands. (C) 2003 Elsevier B.V. All rights reserved.

Determination of protein charge by capillary zone electrophoresis

The feasibility of employing classical electrophoresis theory to determine the net charge (valence) of proteins by capillary zone electrophoresis is illustrated in this paper. An outline of a procedure to facilitate the interpretation of mobility measurements is demonstrated by its application to a published mobility measurement for Staphylococcal nuclease at pH 8.9 that had been obtained by capillary zone electrophoresis. The significantly higher valence of +7.5 (cf. 5.6 from the same series of measurements) that has been reported on the basis of a charge ladder approach for charge determination signifies the likelihood that the latter generic approach may be prone to error arising from nonconformity of the experimental system with an inherent assumption that chemical modification or mutation of amino acid residues has no effect on the overall three-dimensional size and shape of the protein. (C) 2004 Elsevier Inc. All rights reserved.

Explaining landholders' decisions about riparian zone management: The role of behavioural, normative, and control beliefs

Water quality is a key concern in the current global environment, with the need to promote practices that help to protect water quality, such as riparian zone management, being paramount. The present study used the theory of planned behaviour as a framework for understanding how beliefs influence decisions about riparian zone management. Respondents completed a survey that assessed their behavioural, normative, and control beliefs in relation to intentions to manage riparian zones on their property. The results of the study showed that, overall, landholders with strong intentions to manage their riparian zones differed significantly in terms of their beliefs compared to landholders who had weak intentions to manage their riparian zones. Strong intentions to manage riparian zones were associated with a favourable cost-benefit analysis, greater perceptions of normative support for the practice and lower perceptions of the extent to which barriers would impede management of riparian zones. It was also evident that willingness to comply with the recommendations of salient referents, beliefs about the benefits of riparian zone management and perceptions of the extent to which barriers would impede riparian zone management were most important for determining intentions to manage riparian zones. Implications for policy and extension practice are discussed. (c) 2005 Elsevier Ltd. All rights reserved.

Comparison of blast furnace raceway size with theory

A previously developed one-dimensional mathematical model, to explain raceway hysteresis, is used to predict the raceway diameter in operating blast furnaces and hot models. Raceway size obtained from the open literature under various conditions for various blast furnaces are compared with computed predictions. In addition the predictions are also compared with published outcomes from other hot models. Simulated results on raceway diameter are in very good agreement with published operating blast furnace and hot model data. The effect of various parameters such as tuyere and hearth diameter, coke size and density, void fraction and bed height on raceway diameter has been studied.

Long-term flow rates and biomat zone hydrology in soil columns receiving septic tank effluent

Soil absorption systems (SAS) are used commonly to treat and disperse septic tank effluent (STE). SAS can hydraulically fail as a result of the low permeable biomat zone that develops on the infiltrative surface. The objectives of this experiment were to compare the hydraulic properties of biomats grown in soils of different textures, to investigate the long-term acceptance rates (LTAR) from prolonged application of STE, and to assess if soils were of major importance in determining LTAR. The STE was applied to repacked sand, Oxisol and Vertisol soil columns over a period of 16 months, at equivalent hydraulic loading rates of 50, 35 and 8 L/m(2)/d, respectively Infiltration rates, soil matric potentials, and biomat hydraulic properties were measured either directly from the soil columns or calculated using established soil physics theory. Biomats 1 to 2 cm thick developed in all soils columns with hydraulic resistances of 27 to 39 d. These biomats reduced a 4 order of magnitude variation in saturated hydraulic conductivity (K.) between the soils to a one order of magnitude variation in LTAR. A relationship between biomat resistance and organic loading rate was observed in all soils. Saturated hydraulic conductivity influenced the rate and extent of biomat development. However, once the biomat was established, the LTAR was governed by the resistance of the biomat and the sub-biomat soil unsaturated flow regime induced by the biomat. Results show that whilst initial soil K. is likely to be important in the establishment of the biomat zone in a trench, LTAR is determined by the biomat resistance and the unsaturated soil hydraulic conductivity, not the K, of a soil. The results call into question the commonly used approach of basing the LTAR, and ultimately trench length in SAS, on the initial K, of soils. (c) 2006 Elsevier Ltd. All rights reserved.

Reweaving the Silk Road through outsourcing and offshoring: The need for an externalisation theory

The reweaving and repaving of the modern Silk Road passes through outsourcing and offshoring activities that have a profound impact on both global business psyche and landscape. Firms, in particular, and their global value chain are being shaped and reshaped through a complex concoction of vertical integration and disintegration. The boundary of the firm and the firm/market interface has been of interest to students of organisation and economics for some time. It has provided the context for Internalisation Theory. Within the new economy, the twin trends of globalisation and advancing technologies are giving rise to a hitherto unknown “worldwide market for market transactions? and increased opportunities for international expansion by firms via market-based modes of organisation. We describe these trends and offer an early modeling approach for explaining why some firm’s externalise the marginal transaction in the so-called new economy. The paper further draws attention on the need to articulate an “Externalisation Theory? that adequately accounts for the firm’s offshoring and outsourcing activities, and that parallels as well as complement “Internalisation Theory? for a full explanation of today’s firms behaviour.