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CD5(+) B-cell origins and their predisposition to lymphoma are long-standing issues. Transfer of fetal and adult liver BM Pro-B cells generates B cells with distinct phenotypes: fetal cells generate IgM(high) IgD(low) CD5(+) , whereas adult cells IgM(low) IgD(high) CD5(-) . This suggests a developmental switch in B lymphopoiesis, similar to the switch in erythropoiesis. Comparison of mRNA and miRNA expression in fetal and adult Pro-B cells revealed differential expression of Lin28b mRNA and Let-7 miRNA, providing evidence that this regulatory axis functions in the switch. Recent work has shown that Arid3a is a key transcription factor mediating fetal-type B-cell development. Lin28b-promoted fetal development generates CD5(+) B cells as a consequence of positively selected self-reactivity. CD5(+) B cells play important roles in clearance of apoptotic cells and in protective immune responses, but also pose a risk of progression to leukemia/lymphoma. Differential Lin28b expression in fetal and adult human B-cell precursors showed that human B-cell development may resemble mouse, with self-reactive "innate-like" B cells generated early in life. It remains to be determined whether such human B cells have a higher propensity to leukemic progression. This review describes our recent research with CD5(+) B cells and presents our perspective on their role in disease.

Patient characteristics of the 6,248 patients shown by trial. Table S2. National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 2. Table S3. Case-control classification method for the 13 CRTs investigated. Table S4. Neutropenia and fatigue in relation to outcome, split by different treatment components. Figure S1. Trial objectives, outcomes and treatment regimens of the contributing clinical trials. (DOCX 82 kb)

To date, published studies of alluvial bar architecture in large rivers have been restricted mostly to case studies of individual bars and single locations. Relatively little is known about how the depositional processes and sedimentary architecture of kilometre-scale bars vary within a multi-kilometre reach or over several hundreds of kilometres downstream. This study presents Ground Penetrating Radar and core data from 11, kilometre-scale bars from the Río Paraná, Argentina. The investigated bars are located between 30 km upstream and 540 km downstream of the Río Paraná – Río Paraguay confluence, where a significant volume of fine-grained suspended sediment is introduced into the network. Bar-scale cross-stratified sets, with lengths and widths up to 600 m and thicknesses up to 12 m, enable the distinction of large river deposits from stacked deposits of smaller rivers, but are only present in half the surface area of the bars. Up to 90% of bar-scale sets are found on top of finer-grained ripple-laminated bar-trough deposits. Bar-scale sets make up as much as 58% of the volume of the deposits in small, incipient mid-channel bars, but this proportion decreases significantly with increasing age and size of the bars. Contrary to what might be expected, a significant proportion of the sedimentary structures found in the Río Paraná is similar in scale to those found in much smaller rivers. In other words, large river deposits are not always characterized by big structures that allow a simple interpretation of river scale. However, the large scale of the depositional units in big rivers causes small-scale structures, such as ripple sets, to be grouped into thicker cosets, which indicate river scale even when no obvious large-scale sets are present. The results also show that the composition of bars differs between the studied reaches upstream and downstream of the confluence with the Río Paraguay. Relative to other controls on downstream fining, the tributary input of fine-grained suspended material from the Río Paraguay causes a marked change in the composition of the bar deposits. Compared to the upstream reaches, the sedimentary architecture of the downstream reaches in the top ca 5 m of mid-channel bars shows: (i) an increase in the abundance and thickness (up to metre-scale) of laterally extensive (hundreds of metres) fine-grained layers; (ii) an increase in the percentage of deposits comprised of ripple sets (to >40% in the upper bar deposits); and (iii) an increase in bar-trough deposits and a corresponding decrease in bar-scale cross-strata (

Analysis of the effects on nonsmokers of breathing exhaled smoke precedes recommendations for action to assert nonsmokers' rights to breathe clean air. (GW)

Recent technological advances in remote sensing have enabled investigation of the morphodynamics and hydrodynamics of large rivers. However, measuring topography and flow in these very large rivers is time consuming and thus often constrains the spatial resolution and reach-length scales that can be monitored. Similar constraints exist for computational fluid dynamics (CFD) studies of large rivers, requiring maximization of mesh- or grid-cell dimensions and implying a reduction in the representation of bedform-roughness elements that are of the order of a model grid cell or less, even if they are represented in available topographic data. These "subgrid" elements must be parameterized, and this paper applies and considers the impact of roughness-length treatments that include the effect of bed roughness due to "unmeasured" topography. CFD predictions were found to be sensitive to the roughness-length specification. Model optimization was based on acoustic Doppler current profiler measurements and estimates of the water surface slope for a variety of roughness lengths. This proved difficult as the metrics used to assess optimal model performance diverged due to the effects of large bedforms that are not well parameterized in roughness-length treatments. However, the general spatial flow patterns are effectively predicted by the model. Changes in roughness length were shown to have a major impact upon flow routing at the channel scale. The results also indicate an absence of secondary flow circulation cells in the reached studied, and suggest simpler two-dimensional models may have great utility in the investigation of flow within large rivers Fil: Sandbach, Steven D.. Durham University - Department Of Geography; Reino Unido Fil: Lane, Stuart N.. Universite´ de Lausanne, Lausanne, Switzerland; Suiza Fil: Hardy, Richard J.. Durham University - Department Of Geography; Reino Unido Fil: Amsler, Mario Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina Fil: Ashworth, Philip J.. University Of Brighton - School Of The Envirom And Tech; Reino Unido Fil: Best, James L.. University Of Illinois - Dept. Of Geology And Geography; Estados Unidos Fil: Nicholas, Andrew P.. University Of Exeter - Department Of Geography; Argentina Fil: Orfeo, Oscar. Centro de Ecología Aplicada, Conicet; Argentina Fil: Parsons, Daniel R.. University Of Hull, Hull, Uk; Argentina Fil: Reesink, Arjan. University Of Brighton - School Of The Envirom And Tech; Argentina Fil: Szupiany, Ricardo Nicolas. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Departamento de Hidráulica; Argentina

T and B lymphocytes are developmentally and functionally related cells of the immune system, representing the two major branches of adaptive immunity. Although originating from a common precursor, they play very different roles: T cells contribute to and drive cell-mediated immunity, while B cells secrete antibodies. Because of their functional importance and well-characterized differentiation pathways, T and B lymphocytes are ideal cell-types with which to understand how functional differences are encoded at the transcriptional level. Although there has been a great deal of interest in defining regulatory factors that distinguish T and B cells, a truly genome-wide view of the transcriptional differences between these two cells types has not yet been taken. To obtain a more global perspective of the transcriptional differences underlying T and B cells, we exploited the statistical power of combinatorial profiling on different microarray platforms, and the breadth of the Immunological Genome Project (ImmGen) gene-expression database, to generate robust differential signatures. We find that differential expression in T and B cells is pervasive, the majority of transcripts showing statistically significant differences. These distinguishing characteristics are acquired gradually, though all stages of B and T differentiation. On the other hand, very few T vs. B signature genes are uniquely expressed in these lineages, but are shared throughout immune cells.

The links between large‐scale turbulence and the suspension of sediment over alluvial bedforms have generated considerable interest in the last few decades, with past studies illustrating the origin of such turbulence and its influence on flow resistance, sediment transport and bedform morphology. In this study of turbulence and sediment suspension over large sand dunes in the Río Paraná, Argentina, time series of three‐dimensional velocity, and at‐a‐point suspended sediment concentration and particle‐size, were measured with an acoustic Doppler current profiler and laser in situ scattering transmissometer, respectively. These time series were decomposed using wavelet analysis to investigate the scales of covariation of flow velocity and suspended sediment. The analysis reveals an inverse relationship between streamwise and vertical velocities over the dune crest, where streamwise flow deceleration is linked to the vertical flux of fluid towards the water surface in the form of large turbulent fluid ejections. Regions of high suspended sediment concentration are found to correlate well with such events. The frequencies of these turbulent events have been assessed from wavelet analysis and found to concentrate in two zones that closely match predictions from empirical equations. Such a finding suggests that a combination and interaction of vortex shedding and wake flapping/changing length of the lee‐side separation zone are the principal contributors to the turbulent flow field associated with such large alluvial sand dunes. Wavelet analysis provides insight upon the temporal and spatial evolution of these coherent flow structures, including information on the topology of dune‐related turbulent flow structures. At the flow stage investigated, the turbulent flow events, and their associated high suspended sediment concentrations, are seen to grow with height above the bed until a threshold height (ca 0·45 flow depth) is reached, above which they begin to decay and dissipate. Fil: Shugar, Dan H.. University of Guelph; Canadá Fil: Kostaschuk, Ray. University of Guelph; Canadá Fil: Best, James L.. University of Illinois; Estados Unidos Fil: Parsons, Daniel R.. University of Leeds; Reino Unido Fil: Lane, Stuart N.. University Of Durham; Reino Unido Fil: Orfeo, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Centro de Ecología Aplicada del Litoral. Universidad Nacional del Nordeste. Centro de Ecología Aplicada del Litoral; Argentina Fil: Hardy, Richard J.. University Of Durham; Reino Unido

[1] Most past studies of river dune dynamics have concentrated on two-dimensional (2-D) bed forms, with constant heights and straight crest lines transverse to the flow, and their associated turbulent flow structure. This morphological simplification imposes inherent limitations on the interpretation and understanding of dune form and flow dynamics in natural channels, where dune form is predominantly three-dimensional. For example, studies over 2-D forms neglect the significant influence that lateral flows and secondary circulation may have on the flow structure and thus dune morphology. This paper details a field study of a swath of 3-D dunes in the Rio Paraná, Argentina. A large (0.35 km wide, 1.2 km long) area of dunes was surveyed using a multibeam echo sounder (MBES) that provided high-resolution 3-D detail of the river bed. Simultaneous with the MBES survey, 3-D flow information was obtained with an acoustic Doppler current profiler (ADCP), revealing a complicated pattern of dune morphology and associated flow structure within the swath. Dune three-dimensionality appears intimately connected to the morphology of the upstream dune, with changes in crest line curvature and crest line bifurcations/junctions significantly influencing the downstream dune form. Dunes with lobe or saddle-shaped crest lines were found to have larger, more structured regions of vertical velocity with smaller separation zones than more 2-D straight-crested dunes. These results represent the first integrated study of 3-D dune form and mean flow structure from the field and show several similarities to recent laboratory models of flow over 3-D dunes. Copyright 2005 by the American Geophysical Union. Fil: Parsons, Daniel R.. University Of Leeds; Fil: Best, James L.. University Of Leeds; Fil: Orfeo, Oscar. Centro de Ecologica Applicada del Littoral; Argentina Fil: Hardy, Richard J.. University Of Durham; Reino Unido Fil: Kostaschuk, R.. University of Guelph; Canadá Fil: Lane, Stuart N.. University Of Durham; Reino Unido