Transferrin Binding to Peripheral Blood Lymphocytes Activated by Phytohemagglutinin Involves a Specific Receptor: Ligand Interaction

Immunohistological studies have indicated that membrane sites binding transferrin are present upon activated human peripheral blood lymphocytes. In this study, we have investigated transferrin uptake in human lymphocytes exposed to phytohemagglutinin (PHA), by quantitative radiobinding and immunofluorescence in parallel. In stimulated lymphocytes, binding was maximal after a 30-min incubation, being greatest at 37°C, and greater at 22°C than at 4°C. Although some shedding and endocytosis of transferrin occurred at 22° and 37°C, these factors, and resulting synthesis of new sites, did not affect measurement of binding which was found to be saturable, reversible, and specific for transferrin (Ka 0.5-2.5 x 10^8 M-1). Binding was greater after a 48-h exposure to PHA than after 24 h, and was maximal at 66 h. Sequential Scatchard analysis revealed no significant elevation in affinity of interaction. However, although the total number of receptors increased, the proportion of cells in which binding of ligand was detected immunohistologically increased in parallel, and after appropriate correction, the cellular density of receptors remained relatively constant throughout (60,000-80,000 sites/cell). Increments in binding during the culture period were thus due predominantly to expansion of a population of cells bearing receptors. Similar differences in binding were apparent upon comparison of cells cultured in different doses of PHA, and in unstimulated cells binding was negligible. Transferrin receptors appear, therefore, to be readily detectable only upon lymphocytes that have been activated

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

The Eleventh and Twelfth Data Releases of the Sloan Digital Sky Survey: Final Data from SDSS-III

The third generation of the Sloan Digital Sky Survey (SDSS-III) took data from 2008 to 2014 using the original SDSS wide-field imager, the original and an upgraded multi-object fiber-fed optical spectrograph, a new near-infrared high-resolution spectrograph, and a novel optical interferometer. All of the data from SDSS-III are now made public. In particular, this paper describes Data Release 11 (DR11) including all data acquired through 2013 July, and Data Release 12 (DR12) adding data acquired through 2014 July (including all data included in previous data releases), marking the end of SDSS-III observing. Relative to our previous public release (DR10), DR12 adds one million new spectra of galaxies and quasars from the Baryon Oscillation Spectroscopic Survey (BOSS) over an additional 3000 deg2 of sky, more than triples the number of H-band spectra of stars as part of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE), and includes repeated accurate radial velocity measurements of 5500 stars from the Multi-object APO Radial Velocity Exoplanet Large-area Survey (MARVELS). The APOGEE outputs now include the measured abundances of 15 different elements for each star. In total, SDSS-III added 5200 deg2 of ugriz imaging; 155,520 spectra of 138,099 stars as part of the Sloan Exploration of Galactic Understanding and Evolution 2 (SEGUE-2) survey; 2,497,484 BOSS spectra of 1,372,737 galaxies, 294,512 quasars, and 247,216 stars over 9376 deg2; 618,080 APOGEE spectra of 156,593 stars; and 197,040 MARVELS spectra of 5513 stars. Since its first light in 1998, SDSS has imaged over 1/3 of the Celestial sphere in five bands and obtained over five million astronomical spectra. \ua9 2015. The American Astronomical Society

Expression in Patients with Acquired Immune Deficiency Syndrome by Isoprinosine Treatment In Vitro

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-i absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration

The contribution of different components of working memory to knowledge transformation during writing

Outlining probably represents the most common strategy recommended to help novice writers improve their writing. However, although good evidence exists that it has beneficial effects, much less is known about how it achieves these effects. In this paper, we examine how ideas are developed during outlining and how this is related to the quality of the text that is subsequently produced. We focus particularly on how the different processes are coordinated in working memory and on the differences between more and less experienced writers, and consider the implications for educational practice. Two groups of writers, differing in educational level, were asked to write argumentative essays about a discussion topic. In order to investigate the contribution of different components of working memory to outlining, secondary tasks designed to load on the central executive and visual-spatial sketchpad components of working memory were imposed during outlining. Effects of educational level and secondary tasks on the ways novice writers generated and organized their ideas during outlining, and on the resulting quality of the text, were measured. The results suggest that the beneficial effects of planning on text content depend on the extent to which new ideas are introduced during the organizational phase of planning and on the extent to which rhetorical goals are incorporated in planning. However, less experienced writers showed much less evidence of this kind of knowledge-transforming activity during outlining, and we suggest that this aspect of outlining should be the target of educational interventions. Secondary-task effects suggested that the central executive and the spatial component of the visuo-spatial sketchpad play significant, but different roles in the transformation of knowledge, with the spatial component having a specific effect on the generation of new ideas during the organizational phase of planning. We suggest that teaching interventions with novice writers should therefore include attention to the spatial properties of outlines. Finally, some evidence indicates that, although outlining has a beneficial effect on content for all writers, it may reduce the quality of verbal expression for less experienced writers. We suggest that this aspect of their writing needs to be closely monitored. Furthermore, more research into the detailed nature of the processes involved in turning plans into text needs to be conducted

Simulated resilience of tropical rainforests to CO2-induced climate change

How tropical forest carbon stocks might alter in response to changes in climate and atmospheric composition is uncertain. However, assessing potential future carbon loss from tropical forests is important for evaluating the efficacy of programmes for reducing emissions from deforestation and degradation. Uncertainties are associated with different carbon stock responses in models with different representations of vegetation processes on the one hand 1, 2, 3, and differences in projected changes in temperature and precipitation patterns on the other hand 4, 5. Here we present a systematic exploration of these sources of uncertainty, along with uncertainty arising from different emissions scenarios for all three main tropical forest regions: the Americas (that is, Amazonia and Central America), Africa and Asia. Using simulations with 22 climate models and the MOSES–TRIFFID land surface scheme, we find that only in one 5 of the simulations are tropical forests projected to lose biomass by the end of the twenty-first century—and then only for the Americas. When comparing with alternative models of plant physiological processes 1, 2, we find that the largest uncertainties are associated with plant physiological responses, and then with future emissions scenarios. Uncertainties from differences in the climate projections are significantly smaller. Despite the considerable uncertainties, we conclude that there is evidence of forest resilience for all three regions