Observations of loading-unloading process at Saturn distant magnetotail

peer reviewe

Characterizing Abundances of Volatiles in Comets Through Multiwavelength Observations

Recently, there have been complimentary observations from multiple facilities to try to unravel the chemical complexity of comets. Incorporating results from various techniques, including: single-dish millimeter wavelength observations, interferometers, and/or IR spectroscopy, one can gain further insight into the abundances, production rates, distributions, and formation mechanisms of molecules in these objects [I]. Such studies have provided great detail towards molecules with a-typical chemistries, such as H2CO [2]. We report spectral observations of C/2007 N3 (Lulin), C/2009 R1 (McNaught), 103P/Hartley 2, and C/2009 P1 (Garradd) with the Arizona Radio Observatory's SMT and 12-m telescopes, as well as the NRAO Greenbank telescope and IRTF-CSHELL. Multiple parent volatiles (HCN, CH3OH, CO, CH4, C2H6, and H2O) as well as a number of daughter products (CS and OH) have been detected in these objects. We will present a comparison of molecular abundances in these comets to those observed in others, supporting a long-term effort of building a comet taxonomy based on composition. Previous work has revealed a range of abundances of parent species (from "organics-poor" to "organics-rich") with respect to water among comets [3,4,5], however the statistics are still poorly constrained and interpretations of the observed compositional diversity are uncertain. We gratefully acknowledge support from the NSF Astronomy and Astrophysics Program, the NASA Planetary Astronomy Program, NASA Planetary Atmospheres Program, and the NASA Astrobiology Program

Capacitating Community: The Writing Innovation Symposium

The topic of this symposium, capacitating community, invites CLJ readers to consider what makes a community possible. This piece showcases one means, small conferences, via a retrospective on the Writing Innovation Symposium (WIS), a regional event with national scope that has hosted writers and writing educators annually in Milwaukee, WI, since 2018. Through a quilted conversation pieced from hours of small-group discussion, twenty-nine participants across academic and nonacademic ranks, roles, and ranges of experience offer insight into the WIS as well as the nature and value of professional community

Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors

The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures –8 determined here– of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The grail of life; an anthology on heroic death and immortal life,

Mode of access: Internet

Modeling the role of negative cooperativity in metabolic regulation and homeostasis.

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous

Coordination cages as permanently porous ionic liquids.

Porous materials are widely used in industry for applications that include chemical separations and gas scrubbing. These materials are typically porous solids, although the liquid state can be easier to manipulate in industrial settings. The idea of combining the size and shape selectivity of porous domains with the fluidity of liquids is a promising one and porous liquids composed of functionalized organic cages have recently attracted attention. Here we describe an ionic-liquid, porous, tetrahedral coordination cage. Complementing the gas binding observed in other porous liquids, this material also encapsulates non-gaseous guests-shape and size selectivity was observed for a series of isomeric alcohols. Three gaseous chlorofluorocarbon guests, trichlorofluoromethane, dichlorodifluoromethane and chlorotrifluoromethane, were also shown to be taken up by the liquid coordination cage with an affinity that increased with their size. We hope that these findings will lead to the synthesis of other porous liquids whose guest-uptake properties may be tailored to fulfil specific functions.L.M., A.B.G., C.J.E.H., and A.T. acknowledge support from the UK Engineering and Physical Sciences Research Council (EPSRC EP/P027067/1) and the European Research Council (ERC 695009). C.C.P. (EPSRC DTP grant EP/M508007/1) acknowledges the Engineering and Physical Sciences Research Council for funding. L.L. acknowledges an EPSRC Departmental Studentship. A.W. and A.R.S. acknowledge the National Centre for Research and Development for funding (LIDER/024/391/L-5/13/NCBR/2014 and PRELUDIUM UMO-2016/21/N/ST5/00851). T.D.B. would like to thank the Royal Society for a University Research Fellowship (UF150021), and for a Research Grant (RSG\R1\180395)