The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.
NY-ESO-1 is a “cancer-testis” antigen expressed in many cancers. ISCOMATRIX is a saponin-based adjuvant that induces antibody and T cell responses. We performed a placebo-controlled clinical trial evaluating the safety and immunogenicity of recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant. Forty-six evaluable patients with resected NY-ESO-1-positive tumors received three doses of vaccine intramuscularly at monthly intervals. The vaccine was well tolerated. We observed high-titer antibody responses, strong delayed-type hypersensitivity reactions, and circulating CD8+ and CD4+ T cells specific for a broad range of NY-ESO-1 epitopes, including known and previously unknown epitopes. In an unplanned analysis, vaccinated patients appeared to have superior clinical outcomes to those treated with placebo or protein alone. The vaccine is safe and highly potent immunologically.
Images taken by the Stardust mission during its flyby of 81P/Wild 2 show the comet to be a 5-kilometer oblate body covered with remarkable topographic features, including unusual circular features that appear to be impact craters. The presence of high-angle slopes shows that the surface is cohesive and self-supporting. The comet does not appear to be a rubble pile, and its rounded shape is not directly consistent with the comet being a fragment of a larger body. The surface is active and yet it retains ancient terrain. Wild 2 appears to be in the early stages of its degradation phase as a small volatile-rich body in the inner solar system.
Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.
The lattice Boltzmann method is modified to allow the simulation of non-Newtonian shear-dependent viscosity models. Casson and Carreau-Yasuda non-Newtonian blood viscosity models are implemented and are used to compare two-dimensional Newtonian and non-Newtonian flows in the context of simple steady flow and oscillatory flow in straight and curved pipe geometries. It is found that compared to analogous Newtonian flows, both the Casson and Carreau-Yasuda flows exhibit significant differences in the steady flow situation. In the straight pipe oscillatory flows, both models exhibit differences in velocity and shear, with the largest differences occurring at low Reynolds and Womersley numbers. Larger differences occur for the Casson model. In the curved pipe Carreau-Yasuda model, moderate differences are observed in the velocities in the central regions of the geometries, and the largest shear rate differences are observed near the geometry walls. These differences may be important for the study of atherosclerotic progression.
Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(-5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 ± 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion. The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails.
We present a new rough‐surface thermophysical model (Advanced Thermophysical Model or ATPM) that describes the observed directional thermal emission from any atmosphereless planetary surface. It explicitly incorporates partial shadowing, scattering of sunlight, self‐heating and thermal–infrared beaming (re‐radiation of absorbed sunlight back towards the Sun as a result of surface roughness). The model is verified by accurately reproducing ground‐based directional thermal emission measurements of the lunar surface using surface properties that are consistent with the findings of the Apollo missions and roughness characterized by an rms slope of ∼32°. By considering the wide range of potential asteroid surface properties, the model implies a beaming effect that cannot be described by a simple parameter or function. It is highly dependent on the illumination and viewing angles as well as surface thermal properties and is predominantly caused by macroscopic rather than microscopic roughness. Roughness alters the effective Bond albedo and thermal inertia of the surface as well as moving the mean emission away from the surface normal. For accurate determination of surface properties from thermal–infrared observations of unresolved bodies or resolved surface elements, roughness must be explicitly modelled, preferably aided with thermal measurements at different emission angles and wavelengths.
Dendritic cells (DCs) are being evaluated for cancer immunotherapy due to their unique ability to induce tumor-directed T-cell responses. Here we report that the type of human DC, the mode of activation, and the strategy for delivery of antigen are 3 critical factors for efficient stimulation of tumor-specific CD8 ؉ and CD4 ؉ T cells. Only CD1c ؉ blood DCs and monocyte-derived DCs (MoDCs) were capable of presenting epitopes of the full-length tumor antigen NY-ESO-1 on both major histocompatibility complex (MHC) class I (cross-presentation) and MHC II, whereas plasmacytoid DCs were limited to MHC II presentation. Cross-presentation was inefficient for soluble protein, but highly efficient for antigen-antibody immune complexes (NY-ESO-1/IC) and for protein formulated with ISCOMATRIX adjuvant (NY-ESO-1/IMX). DC activation with CD40L further enhanced cross-presentation efficiency. The mode of antigen delivery was found to be a determining factor for cytosolic proteolysis by DCs. Immune complexes (ICs) targeted a slow, proteasomedependent cross-presentation pathway, whereas ISCOMATRIX (IMX) targeted a fast, proteasome-independent pathway. Both cross-presentation pathways resulted in a long-lived, T-cell stimulatory capacity, which was maintained for several days longer than for DCs pulsed with peptide. This may provide DCs with ample opportunities for sensitizing tumorspecific T cells against a broad array of tumor antigen epitopes in lymph nodes. IntroductionTo achieve tumor cell killing by cytotoxic CD8 ϩ T cells (CTLs), cancer vaccines target major histocompatibility complex (MHC) class Irestricted epitopes. CTL responses alone may not be sufficient for effective anticancer immunity, and additional help from CD4 ϩ T cells is required for optimal CTL priming and memory induction. [1][2][3][4] A variety of vaccine strategies are being developed to generate an integrated CD4 ϩ and CD8 ϩ T-cell response. One strategy uses dendritic cells (DCs), which have the unique capacity to not only present exogenous antigen on MHC II, but also to "cross-present" these on MHC I. 5 DC-based clinical trials have demonstrated "proof of concept" using primary DCs isolated directly from peripheral blood or DCs generated in vitro from monocytes (MoDCs) or CD34 ϩ progenitors, pulsed with MHC Irestricted peptides (reviewed in Davis et al 6 ). We and others have previously studied the functional profiles of different DC populations providing valuable insights into their potential clinical utility. [7][8][9] Despite this, the rational design of DC-based cancer vaccines still lacks some critical information. What are the optimal approaches to achieve antigen presentation on both MHC I and MHC II? Which DC population is best suited for this purpose? How should these DCs be matured or activated?We have used the tumor antigen NY-ESO-1 as a model antigen to address these questions. NY-ESO-1 is a 180 amino acid protein, which is absent in normal tissues apart from testis, but is expressed in a variety of common human cancers including melanoma, ...
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