The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.

CD2, a cell surface glycoprotein expressed on T cells and natural killer cells, can couple to signaling pathways that result in T cell proliferation. An Src-like protein tyrosine kinase, p56lck, coprecipitates with CD2, and perturbation of CD2 by monoclonal antibodies results in an increase in the activity of p56lck, suggesting that an interaction with p56lck contributes to CD2-mediated signaling. Herein, we investigate the mechanism by which CD2 associates with p56lck. We demonstrate that CD2 and p56lck associate when coexpressed in nonlymphoid cells, that this association requires the cytoplasmic domain of CD2, and that the SH3 domain of p56lck mediates its interactions with CD2. Using truncation mutants of CD2, we identify two regions in the cytoplasmic domain of CD2 involved in binding p56lck. Each region contains a proline-rich sequence that, in the form of a synthetic peptide, directly binds p56lck. Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck

The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line.

The MRC OX-44 molecule, which is expressed on all peripheral leukocytes, identifies the subset of thymocytes capable of proliferating in response to alloantigens and lectins (Paterson, D.J., J.R. Green, W.A. Jefferies, M. Puklavec, and A.F. Williams. 1987. J. Exp. Med. 165:1). When we isolated monoclonal antibodies (mAbs) on the basis of their ability to activate the phosphatidylinositol signaling pathway in RNK-16 cells (a rat leukemia line with natural killer activity), three of the resulting mAbs recognized the OX-44 molecule. Addition of these mAbs to RNK-16 elicits protein tyrosine phosphorylation, generates inositol phosphates, and increases the concentration of cytoplasmic free calcium. These responses require the addition of intact mAb and are not observed with F(ab')2 fragments. One of these mAbs (7D2) is mitogenic for freshly isolated rat splenic T cells and synergizes with a mAb to the T cell antigen receptor in this activation. A 50-60-kD glycoprotein coprecipitates with the OX-44 molecule from RNK-16 cells and rat splenic T cells. Peptide mapping and reprecipitation studies indicate that the coprecipitating molecule is CD2. Thus, the OX-44 molecule can couple to multiple signaling pathways and associates with CD2 on both RNK-16 and rat T cells

An international, multicentre evaluation and description of Burkholderia pseudomallei infection in cystic fibrosis

BACKGROUND: Several cases of Burkholderia pseudomallei infection in CF have been previously reported. We aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies. METHODS: We performed a literature search to identify all published cases of B. pseudomallei infection in CF. In addition we hand-searched respiratory journals, and contacted experts in infectious diseases and CF around the world. Supervising clinicians for identified cases were contacted and contemporaneous clinical data was requested. RESULTS: 25 culture-confirmed cases were identified. The median age at acquisition was 21 years, mean FEV(1) % predicted was 60 %, and mean BMI was 19.5 kg/m(2). The location of acquisition was northern Australia or south-east Asia for most. 19 patients (76 %) developed chronic infection, which was usually associated with clinical decline. Successful eradication strategies included a minimum of two weeks of intravenous ceftazidime, followed by a consolidation phase with trimethoprim/sulfamethoxazole, and this resulted in a higher chance of success when instituted early. Three cases of lung transplantation have been recorded in the setting of chronic B. pseudomallei infection. CONCLUSION: Chronic carriage of B. pseudomallei in patients with CF appears common after infection, in contrast to the non-CF population. This is often associated with an accelerated clinical decline. Lung transplantation has been performed in select cases of chronic B. pseudomallei infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-015-0109-9) contains supplementary material, which is available to authorized users

The temporary marketing organization

Increasingly, marketing activity is carried out within temporary organizations, where teams are assembled to complete a specific task within a predetermined timeframe. Such organizations are uniquely suited to promoting various marketing outcomes but are not well understood. From a practical standpoint, their inherent characteristics create organizational challenges which, if not appropriately managed, can compromise performance. Drawing on agency theory and research on embedded ties, we conceptualize these challenges in terms of particular selection and enforcement problems. We identify three different forms of temporary marketing organizations that vary in their selection and enforcement qualities. Next, we develop a conceptual framework which shows the selection and enforcement implications of a temporary organization’s task, timeline and team composition. We also show how selection and enforcement mechanisms have portable qualities and can be “imported” to a given temporary organization, either from a prior temporary organization or from a larger permanent one

Turbulent jets with off-source heating

Motivated by anomalous entrainment behaviour in cumulus clouds, Bhat et al. (Exp. Fluids, vol. 7, 1989, pp. 99–102) pioneered a laboratory experiment to study turbulent jets subjected to a volumetric heating away from the momentum source. The study concluded that the use of a constant entrainment coefficient was insufficient for the flow, and that the results did not confirm the analysis of Hunt (Recent Research Advances in the Fluid Mechanics of Turbulent Jets and Plumes, 1994, pp. 309–334, Kluwer Academic), which suggested that an increase in relative turbulent transport of streamwise momentum could lead to a decrease in entrainment. The present paper re-evaluates theoretical aspects of both studies, and includes a decomposition of the factors contributing to entrainment. The reworked analysis is then used to examine three-dimensional numerical simulations of turbulent jets with off-source heating. The data are consistent with previous work, but give deeper insight not easily obtainable through experiment. Specifically, direct measurement of flux integrals shows that previous inference from experimental measurements of centreline velocity and profile widths under the assumption of self-similarity can lead to underestimation of the mass flux by over 50 % in some cases. Radial profiles of temperature, radial velocity and turbulent correlations show significant departures from self-similarity. The flux measurements show that there is actually an increase in the entrainment coefficient with heating, and that it is locally enhanced by positive forcing and decreased by an increase in turbulent transport of streamwise momentum, thereby confirming the essence of the original proposal of Hunt.A.J.A. was first supported by a CASE Fellowship from the EPSRC and AWE, and then a Glenn T. Seaborg Fellowship from LBNL, and would consequently like to thank D. Youngs and R. Williams for support and computational resources. A.J.A. would also like to thank J. Hunt for motivating this work, along with C. Caulfield, M. Andrews and A. Almgren. J.B.B. was supported by the DOE Applied Mathematics Research Program of the DOE Office of Advanced Scientific Computing Research under the U.S. Department of Energy Contract no. DE-AC02-05CH11231, which included computational resources at the National Energy Research Scientific Computing Center (NERSC)

Benthic Carbon fixation and cycling in diffuse hydrothermal and background sediments in the Bransfield Strait, Antarctica

Sedimented hydrothermal vents are likely to be widespread compared to hard substrate hot vents. They host chemosynthetic microbial communities which fix inorganic carbon (C) at the seafloor, as well as a wide range of macroinfauna, including vent-obligate and background non-vent taxa. There are no previous direct observations of carbon cycling at a sedimented hydrothermal vent. We conducted 13C isotope tracing experiments at three sedimented sites in the Bransfield Strait, Antarctica, which showed different degrees of hydrothermalism. Two experimental treatments were applied, with 13C added as either algal detritus (photosynthetic C), or as bicarbonate (substrate for benthic C fixation). Algal 13C was taken up by both bacteria and metazoan macrofaunal, but its dominant fate was respiration, as observed at deeper and more food-limited sites elsewhere. Rates of 13C uptake and respiration suggested that the diffuse hydrothermal site was not the hot spot of benthic C cycling that we hypothesised it would be. Fixation of inorganic C into bacterial biomass was observed at all sites, and was measurable at two out of three sites. At all sites, newly fixed C was transferred to metazoan macrofauna. Fixation rates were relatively low compared with similar experiments elsewhere; thus, C fixed at the seafloor was a minor C source for the benthic ecosystem. However, as the greatest amount of benthic C fixation occurred at the “Off Vent” (non-hydrothermal) site (0.077±0.034 mg C m−2 fixed during 60 h), we suggest that benthic fixation of inorganic C is more widespread than previously thought, and warrants further study

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P  = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort

Gravitational Collapse and Fragmentation in Molecular Clouds with Adaptive Mesh Refinement

We describe a powerful methodology for numerical solution of 3-D self-gravitational hydrodynamics problems with extremely high resolution. Our method utilizes the technique of local adaptive mesh refinement (AMR), employing multiple grids at multiple levels of resolution. These grids are automatically and dynamically added and removed as necessary to maintain adequate resolution. This technology allows for the solution of problems in a manner that is both more efficient and more versatile than other fixed and variable resolution methods. The application of AMR to simulate the collapse and fragmentation of a molecular cloud, a key step in star formation, is discussed. Such simulations involve many orders of magnitude of variation in length scale as fragments form. In this paper we briefly describe the methodology and present an illustrative application for nonisothermal cloud collapse. We describe the numerical Jeans condition, a criterion for stability of self-gravitational hydrodynamics problems. We show the first well-resolved nonisothermal evolutionary sequence beginning with a perturbed dense molecular cloud core that leads to the formation of a binary system consisting of protostellar cores surrounded by distinct protostellar disks. The scale of the disks, of order 100 AU, is consistent with observations of gaseous disks surrounding single T-Tauri stars and debris disks surrounding systems such as $\beta$ Pictoris.Comment: 10 pages, 6 figures (color postscript). To appear in the proceedings of Numerical Astrophysics 1998, Tokyo, March 10-13, 199

Radiographic Image Enhancement by Wiener Decorrelation

The primary focus of the application of image processing to radiography is the problem of segmentation. The general segmentation problem has been attacked on a broad front [1, 2], and thresholding, in particular, is a popular method [1, 3-6]. Unfortunately, geometric unsharpness destroys the crisp edges needed for unambiguous decisions, and this difficulty can be considered a problem in filtering in which the object is to devise a high-pass (sharpening) filter. This approach has been studied for more than 20 years [7-13]