216 research outputs found
New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer
A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naΓ―ve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies
Global modelling studies of hydrogen and its isotopomers using STOCHEM-CRI:Likely radiative forcing consequences of a future hydrogen economy
A global chemistry-transport model has been employed to describe the global sources and sinks of hydrogen (H2) and its isotopomer (HD). The model is able to satisfactorily describe the observed tropospheric distributions of H2 and HD and deliver budgets and turnovers which agree with literature studies. We than go on to quantify the methane and ozone responses to emission pulses of hydrogen and their likely radiative forcing consequences. These radiative forcing consequences have been expressed on a 1 Tg basis and integrated over a hundred-year time horizon. When compared to the consequences of a 1 Tg emission pulse of carbon dioxide, 1 Tg of hydrogen causes 5 Β± 1 times as much time-integrated radiative forcing over a hundred-year time horizon. That is to say, hydrogen has a global warming potential (GWP) of 5 Β± 1 over a hundred-year time horizon. The global warming consequences of a hydrogen-based low-carbon energy system therefore depend critically on the hydrogen leakage rate. If the leakage of hydrogen from all stages in the production, distribution, storage and utilisation of hydrogen is efficiently curtailed, then hydrogen-based energy systems appear to be an attractive proposition in providing a future replacement for fossil-fuel based energy systems
The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the βΌ120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella
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Observations of Coupling between Surface Wind Stress and Sea Surface Temperature in the Eastern Tropical Pacific
Satellite measurements of surface wind stress from the QuikSCAT scatterometer and sea surface temperature (SST) from the Tropical Rainfall Measuring Mission Microwave Imager are analyzed for the three-month period 21 Julyβ20 October 1999 to investigate oceanβatmosphere coupling in the eastern tropical Pacific. Oceanic tropical instability waves (TIWs) with periods of 20β40 days and wavelengths of 1000β2000 km perturb the SST fronts that bracket both sides of the equatorial cold tongue, which is centered near 1Β°S to the east of 130Β°W. These perturbations are characterized by cusp-shaped features that propagate systematically westward on both sides of the equator. The spaceβtime structures of these SST perturbations are reproduced with remarkable detail in the surface wind stress field. The wind stress divergence is shown to be linearly related to the downwind component of the SST gradient with a response on the south side of the cold tongue that is about twice that on the north side. The wind stress curl is linearly related to the crosswind component of the SST gradient with a response that is approximately half that of the wind stress divergence response to the downwind SST gradient. The perturbed SST and wind stress fields propagate synchronously westward with the TIWs. This close coupling between SST and wind stress supports the Wallace et al. hypothesis that surface winds vary in response to SST modification of atmospheric boundary layer stability
Association of cord blood digitalis-like factor and necrotizing enterocolitis
Endogenous digoxin-like factor (EDLF) has been linked to vasoconstriction, altered membrane transport and apoptosis. Our objective was to determine whether increased EDLF in the cord sera of preterm infants was associated with an increased incidence of necrotizing enterocolitis (NEC)
Hox10 Genes Function in Kidney Development in the Differentiation and Integration of the Cortical Stroma
Organogenesis requires the differentiation and integration of distinct populations of cells to form a functional organ. In the kidney, reciprocal interactions between the ureter and the nephrogenic mesenchyme are required for organ formation. Additionally, the differentiation and integration of stromal cells are also necessary for the proper development of this organ. Much remains to be understood regarding the origin of cortical stromal cells and the pathways involved in their formation and function. By generating triple mutants in the Hox10 paralogous group genes, we demonstrate that Hox10 genes play a critical role in the developing kidney. Careful examination of control kidneys show that Foxd1-expressing stromal precursor cells are first observed in a cap-like pattern anterior to the metanephric mesenchyme and these cells subsequently integrate posteriorly into the kidney periphery as development proceeds. While the initial cap-like pattern of Foxd1-expressing cortical stromal cells is unaffected in Hox10 mutants, these cells fail to become properly integrated into the kidney, and do not differentiate to form the kidney capsule. Consistent with loss of cortical stromal cell function, Hox10 mutant kidneys display reduced and aberrant ureter branching, decreased nephrogenesis. These data therefore provide critical novel insights into the cellular and genetic mechanisms governing cortical cell development during kidney organogenesis. These results, combined with previous evidence demonstrating that Hox11 genes are necessary for patterning the metanephric mesenchyme, support a model whereby distinct populations in the nephrogenic cord are regulated by unique Hox codes, and that differential Hox function along the AP axis of the nephrogenic cord is critical for the differentiation and integration of these cell types during kidney organogenesis
SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally Does Not Involve Resistant Viruses
Maraviroc (MVC) gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0) but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294Β±0.027%; limited entropy changes were noted across the envelope (gp160). No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14β21, the time of first detectable viremia, nor selected at later time points, days 42β70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC50] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC50 1.18 nM, 1.69 nM, and 1.53 nM, respectively). Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants
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