Coastal process modelling as an art and a science has progressed significantly over the last four decades. The main areas of progress have been the development of more realistic models of natural waves and the discovery of the wave thrust or radiation stress which enables the quantitative description of phenomena like longshore currents and wave setup. Progress has been slower in the area of quantitative morphodynamic modelling. The reason is that the quantitative link has been missing between the main flow and the rate of morphological change. The required link consists of efficient models of the boundary layer flow and the resulting sediment transport. These are the topics of the present book. The book has two main objectives. The first is to provide a review of coastal bottom boundary layer flow and sediment transport by summarising the presently available experimental data. The second objective is to provide the basic sediment transport models which can be used as building blocks for comprehensive models of coastal sediment transport. In order to address both of these objectives , the treatment of major topics like oscillatory boundary layer flow and sediment suspension are given in two parts each. The first parts each attempt to review the experimental evidence without reference to any particular theory. The second parts subsequently deal with state of the art of modelling. It is hoped that the book will be useful for Earth Scientists and Engineers who work in the general area of coastal process modelling and to graduate students in the areas of Marine Geology, Coastal Morphodynamics and Coastal Engineering. For such students, the book should help bridge the gap in the literature between general texts on Coastal Hydrodynamics and descriptive texts on coastal processes. It is also hoped that the student ' s supervisors will find something new and useful in the book. Indexing and many cross references are provided in order to make the book more efficient as a handbook for practising professionals.

The mb1 gene encodes the Ig-␣ signaling subunit of the B cell antigen receptor and is expressed exclusively in B cells beginning at the very early pro-B cell stage in the bone marrow. We examine here the efficacy of the mb1 gene as a host locus for cre recombinase expression in B cells. We show that by integrating a humanized cre recombinase into the mb1 locus we obtain extraordinarily efficient recombination of loxP sites in the B cell lineage. The results from a variety of reporter genes including the splicing factor SRp20 and the DNA methylase Dnmt1 suggest that mb1-cre is probably the best model so far described for pan-B cell-specific cre expression. The availability of a mouse line with efficient cre-mediated recombination at an early developmental stage in the B lineage provides an opportunity to study the role of various genes specifically in B cell development and function.Dnmt1 ͉ SRp20 ͉ loxP ͉ enhanced yellow fluorescent protein ͉ lymphocyte T he bacteriophage recombinase cre can efficiently delete DNA sequences that are flanked by loxP sites (floxed) even in eukaryotic cells (1). This feature has led to the frequent use of transgenic cre mice for the tissue-specific deletion or modification of floxed genes to access the function of a gene in a specific tissue (2).Development of a B lymphocyte can be separated into several ordered steps encompassing commitment to the B lineage, somatic recombination and expression of its heavy chain and light chain Ig genes, and selection of the B cell antigen receptor repertoire (for reviews, see refs. 3-5). In the B cell system there are several transgenic mouse lines available that express cre in defined stages of B lymphocyte development. For example, CD19-cre mice (6) express cre from the pre-B cell stage on, whereas CD21-cre mice (7) express cre only in mature B cells. However, a cre transgenic mouse line with efficient cre-mediated deletion from the earliest pro-B cell stage was missing so far. We asked whether expression of the cre recombinase from the murine mb-1 locus would provide an even more efficient model for studying gene function specifically in B cell precursors. The mb1 gene encodes the Ig-␣ signaling subunit of the B cell antigen receptor (8, 9). It is strongly expressed in the B cell lineage beginning at the very early pro-B cell stage in the bone marrow and continues to be expressed in all later stages except plasma cells (10). The mb1-cre line was tested by intercrossing it to a floxed enhanced yellow fluorescent protein (EYFP) reporter mouse line. The analysis showed a very efficient and B cell-specific recombination. To further test the mb1-cre line, we bred it to several different lines bearing floxed genes, some of which are believed to be essential genes in all cell types. We show results for the splicing factor SRp20 and the DNA methylase Dnmt1. SRp20 belongs to a family of serine-arginine-rich proteins important for a variety of cellular functions surrounding mRNA including constitutive and alternative splicing, transport, translation, an...

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Allergies to nickel (Ni(2+)) are the most frequent cause of contact hypersensitivity (CHS) in industrialized countries. The efficient development of CHS requires both a T lymphocyte-specific signal and a proinflammatory signal. Here we show that Ni(2+) triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Ni(2+)-induced TLR4 activation was species-specific, as mouse TLR4 could not generate this response. Studies with mutant TLR4 proteins revealed that the non-conserved histidines 456 and 458 of human TLR4 are required for activation by Ni(2+) but not by the natural ligand lipopolysaccharide. Accordingly, transgenic expression of human TLR4 in TLR4-deficient mice allowed efficient sensitization to Ni(2+) and elicitation of CHS. Our data implicate site-specific human TLR4 inhibition as a potential strategy for therapeutic intervention in CHS that would not affect vital immune responses.

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Semi‐empirical formulae for the size and shape of sand ripples are derived from an analysis of the water and sediment motion over a rippled bed in oscillatory flow. Simple physical arguments show that ripple steepness should be a function of the nondimensional shear stress θ′ and the angle of repose of the bed material. All available data seem to support this. The mechanisms that determine the ripple length are very complex, and at least four nondimensional parameters are important. However, for practical purposes the ripple length is well determined by the mobility number ψ. ψ is essentially the ratio of the water velocity amplitude to the sediment settling velocity. Both ripple length and ripple height are shown to depend mainly on ψ, when only quartz sand and natural wave periods are considered. The derived formulae apply well to the full range of flow conditions, where ripples occur. Natural ripples obey essentially the same rules as laboratory ripples; however, they are generally shorter and flatter owing to the irregularity of natural waves.

During signal transduction through the B cell antigen receptor (BCR), several signaling elements are brought together by the adaptor protein SLP-65. We have investigated the role of SLP-65 in B cell maturation and function in mice deficient for SLP-65. While the mice are viable, B cell development is affected at several stages. SLP-65-deficient mice show increased proportions of pre-B cells in the bone marrow and immature B cells in peripheral lymphoid organs. B1 B cells are lacking. The mice show lower IgM and IgG3 serum titers and poor IgM but normal IgG immune responses. Mutant B cells show reduced Ca2+ mobilization and reduced proliferative responses to B cell mitogens. We conclude that while playing an important role, SLP-65 is not always required for signaling from the BCR.

The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (Ig) molecule as antigen-binding subunit and the Ig-α/Ig-β heterodimer as signaling subunit. BCR signal transduction involves activation of protein tyrosine kinases (PTKs) and phosphorylation of several proteins, only some of which have been identified. The phosphorylation of these proteins can be induced by exposure of B cells either to antigen or to the tyrosine phosphatase inhibitor pervanadate/H2O2. One of the earliest substrates in B cells is a 65-kD protein, which we identify here as a B cell adaptor protein. This protein, named SLP-65, is part of a signaling complex involving Grb-2 and Vav and shows homology to SLP-76, a signaling element of the T cell receptor. In pervanadate/H2O2-stimulated cells, SLP-65 becomes phosphorylated only upon expression of the BCR. These data suggest that SLP-65 is part of a BCR transducer complex.