Modulation of HIV-1 macrophage-tropism among R5 envelopes occurs before detection of neutralizing antibodies

HIV-1 R5 viruses vary widely in their capacity to infect primary macrophages. R5 macrophage-tropism is associated with an increased envelope:CD4 affinity that partly results from an increased exposure of CD4 contact residues on gp120 and allows the use of low levels of CD4 for infection. The selective pressures in vivo that modulate R5 macrophage-tropism are not understood. It is possible that different R5 variants adapt for replication in either T-cells (high CD4) or in macrophages (low CD4). However, other selective pressures in vivo (e.g. neutralizing antibodies) may also impact R5 tropism. Here, we measured macrophage infectivity conferred by gp120 sequences amplified sequentially from subjects in London followed from the acute stage of infection. We report wide variation in the capacity of these envelopes to confer macrophage infection in the complete absence of both autologous and heterologous neutralizing antibodies. Our data show that the variation in macrophage tropism observed at early times cannot have been influenced by neutralizing antibodies

Improved frame synchronization schemes for INMARSAT-B/M SCPC and TDM channels

This paper proposes faster, more robust, frame synchronization schemes for various Inmarsat-B and Inmarsat-M communication and signalling channels. Equations are developed which permit frame synchronization strategies of the type specified by Inmarsat to be evaluated in terms of average true lock time, average false maintenance time, and average search time. Evaluation of the currently specified framing schemes shows that a significant performance improvement is obtained by optimizing the threshold parameters of the scheme. The optimization seeks a compromise between the conflicting requirements of maximizing true lock time and minimizing search time

Cross-presentation of Disialoganglioside GD3 to Natural Killer T Cells

GD3, a ganglioside expressed on human melanoma, can be recognized by the humoral immune system. In this paper, we demonstrate that immunizing mice with the human melanoma cell line SK-MEL-28 (GD3+ GM2− CD1−) or with syngeneic APCs loaded with GD3 can induce a GD3-reactive natural killer T (NKT) cell response. GD3-reactive NKT cells were detected among splenocytes of immunized mice at frequencies of ∼1:2,000 both by ELISPOT and GD3-loaded mouse CD1d tetramer analysis. GD3-reactive NKT cells did not react with GM2, a closely related ganglioside, and were not detectable in unimmunized mice. GD3-reactive NKT cells initially produced IL-4 and IFN-γ followed by IL-10. They were CD1d restricted in that reactivity was abrogated when APCs were blocked with anti-CD1d monoclonal antibody before being loaded with GD3 or when APCs from CD1d knockout mice were used. Because SK-MEL-28 does not express any isoform of human CD1, GD3 must be cross-presented by murine APCs in vivo. This is the first analysis of a natural ligand for mouse NKT cells and the first definitive paper of cross-presentation to NKT cells. This could be a mechanism for NKT cell recognition of tumor gangliosides in CD1− tumors

Infall and Outflow around the HH 212 protostellar system

HH 212 is a highly collimated jet discovered in H2 powered by a young Class 0 source, IRAS 05413-0104, in the L1630 cloud of Orion. We have mapped around it in 1.33 mm continuum, 12CO ($J=2-1$), 13CO ($J=2-1$), C18O ($J=2-1$), and SO ($J_K = 6_5-5_4$) emission at $\sim$ \arcs{2.5} resolution with the Submillimeter Array. A dust core is seen in the continuum around the source. A flattened envelope is seen in C18O around the source in the equator perpendicular to the jet axis, with its inner part seen in 13CO. The structure and kinematics of the envelope can be roughly reproduced by a simple edge-on disk model with both infall and rotation. In this model, the density of the disk is assumed to have a power-law index of $p=-1.5$ or -2, as found in other low-mass envelopes. The envelope seems dynamically infalling toward the source with slow rotation because the kinematics is found to be roughly consistent with a free fall toward the source plus a rotation of a constant specific angular momentum. A 12CO outflow is seen surrounding the H2 jet, with a narrow waist around the source. Jetlike structures are also seen in 12CO near the source aligned with the H2 jet at high velocities. The morphological relationship between the H2 jet and the 12CO outflow, and the kinematics of the 12CO outflow along the jet axis are both consistent with those seen in a jet-driven bow shock model. SO emission is seen around the source and the H2 knotty shocks in the south, tracing shocked emission around them.Comment: 17 pages, 11 figures, Accepted by the Ap

An examination of business occupier relocation decision making : distinguishing small and large firm behaviour

This paper explores how business occupiers decide whether and where to relocate. It captures the experience and behaviour of a range of sizes and types of business occupier and subjects their decision-making processes to detailed scrutiny. A linear three-stage decision model is used to sequence and structure interviews with individuals who have intimate involvement with the relocation of 28 firms and organizations in Tyne and Wear, in the north-east of England. The 'constant comparative' method is used to analyse the interview data, from which emerges 18 key concepts, comprising 51 characteristic components. Using an axial approach, these are organized into 10 cross-cutting themes that represent the main areas of consideration or influence on the thinking of the people involved in determining whether a firm or organization should relocate and, if so, where to. The resulting analysis finds that organizations adopt varying degrees of sophistication when making relocation decisions; small firms are more inclined to make decisions based on constrained information; larger organizations adopt a more complex approach. Regardless of firm size, key individuals exert considerable influence over the decision-making process and its outcome

The Structure of IR Luminous Galaxies at 100 Microns

We have observed twenty two galaxies at 100 microns with the Kuiper Airborne Observatory in order to determine the size of their FIR emitting regions. Most of these galaxies are luminous far-infrared sources, with L_FIR > 10^11 L_sun. This data constitutes the highest spatial resolution ever achieved on luminous galaxies in the far infrared. Our data includes direct measurements of the spatial structure of the sources, in which we look for departures from point source profiles. Additionally, comparison of our small beam 100 micron fluxes with the large beam IRAS fluxes shows how much flux falls beyond our detectors but within the IRAS beam. Several sources with point- like cores show evidence for such a net flux deficit. We clearly resolved six of these galaxies at 100 microns and have some evidence for extension in seven others. Those galaxies which we have resolved can have little of their 100 micron flux directly emitted by a point-like active galactic nucleus (AGN). Dust heated to ~40 K by recent bursts of non-nuclear star formation provides the best explanation for their extreme FIR luminosity. In a few cases, heating of an extended region by a compact central source is also a plausible option. Assuming the FIR emission we see is from dust, we also use the sizes we derive to find the dust temperatures and optical depths at 100 microns which we translate into an effective visual extinction through the galaxy. Our work shows that studies of the far infrared structure of luminous infrared galaxies is clearly within the capabilities of new generation far infrared instrumentation, such as SOFIA and SIRTF.Comment: 8 tables, 23 figure

The Spitzer Survey of Interstellar Clouds in the Gould Belt. VI. The Auriga-California Molecular Cloud observed with IRAC and MIPS

We present observations of the Auriga-California Molecular Cloud (AMC) at 3.6, 4.5, 5.8, 8.0, 24, 70 and 160 micron observed with the IRAC and MIPS detectors as part of the Spitzer Gould Belt Legacy Survey. The total mapped areas are 2.5 sq-deg with IRAC and 10.47 sq-deg with MIPS. This giant molecular cloud is one of two in the nearby Gould Belt of star-forming regions, the other being the Orion A Molecular Cloud (OMC). We compare source counts, colors and magnitudes in our observed region to a subset of the SWIRE data that was processed through our pipeline. Using color-magnitude and color-color diagrams, we find evidence for a substantial population of 166 young stellar objects (YSOs) in the cloud, many of which were previously unknown. Most of this population is concentrated around the LkHalpha 101 cluster and the filament extending from it. We present a quantitative description of the degree of clustering and discuss the fraction of YSOs in the region with disks relative to an estimate of the diskless YSO population. Although the AMC is similar in mass, size and distance to the OMC, it is forming about 15 - 20 times fewer stars.Comment: (30 pages, 17 figures (2 multipage figures), accepted for publication in ApJ

Cystatin C deficiency in human atherosclerosis and aortic aneurysms

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease

Liquid-Solid Transition of Hard Spheres Under Gravity

We investigate the liquid-solid transition of two dimensional hard spheres in the presence of gravity. We determine the transition temperature and the fraction of particles in the solid regime as a function of temperature via Even-Driven molecular dynamics simulations and compare them with the theoretical predictions. We then examine the configurational statistics of a vibrating bed from the view point of the liquid-solid transition by explicitly determining the transition temperature and the effective temperature, T, of the bed, and present a relation between T and the vibration strength.Comment: 14 total pages, 4 figure

Therapeutic benefit for late, but not early, passage mesenchymal stem cells on pain behaviour in an animal model of osteoarthritis

Background: Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims of this study were to determine the influence of a passage number on the effects of MSCs on pain behaviour and cartilage and bone features in a rodent model of OA. Methods: Rats underwent either medial meniscal transection (MNX) or sham surgery under anaesthesia. Rats received intra-articular injection of either 1.5×106 late passage MSCs labelled with 10 μg/ml SiMAG, 1.5×106 late passage mesenchymal stem cells, the steroid Kenalog (200 μg/20 μL), 1.5×106 early passage MSCs, or serum-free media (SFM). Sham-operated rats received intra-articular injection of SFM. Pain behaviour was quantified until day 42 postmodel induction. Magnetic resonance imaging (MRI) was used to localise the labelled cells within the knee joint. Results: Late passage MSCs and Kenalog attenuated established pain behaviour in MNX rats, but did not alter MNX-induced joint pathology at the end of the study period. Early passage MSCs exacerbated MNX-induced pain behaviour for up to one week postinjection and did not alter joint pathology. Conclusion: Our data demonstrate for the first time the role of a passage number in influencing the therapeutic effects of MSCs in a model of OA pain