NASA GEOS Composition Forecast Modeling System GEOS-CF v1.0: Stratospheric Composition.

The NASA Goddard Earth Observing System (GEOS) Composition Forecast (GEOS-CF) provides recent estimates and 5-day forecasts of atmospheric composition to the public in near-real time. To do this, the GEOS Earth system model is coupled with the GEOS-Chem tropospheric-stratospheric unified chemistry extension (UCX) to represent composition from the surface to the top of the GEOS atmosphere (0.01 hPa). The GEOS-CF system is described, including updates made to the GEOS-Chem UCX mechanism within GEOS-CF for improved representation of stratospheric chemistry. Comparisons are made against balloon, lidar, and satellite observations for stratospheric composition, including measurements of ozone (O3) and important nitrogen and chlorine species related to stratospheric O3 recovery. The GEOS-CF nudges the stratospheric O3 toward the GEOS Forward Processing (GEOS FP) assimilated O3 product; as a result the stratospheric O3 in the GEOS-CF historical estimate agrees well with observations. During abnormal dynamical and chemical environments such as the 2020 polar vortexes, the GEOS-CF O3 forecasts are more realistic than GEOS FP O3 forecasts because of the inclusion of the complex GEOS-Chem UCX stratospheric chemistry. Overall, the spatial patterns of the GEOS-CF simulated concentrations of stratospheric composition agree well with satellite observations. However, there are notable biases-such as low NO x and HNO3 in the polar regions and generally low HCl throughout the stratosphere-and future improvements to the chemistry mechanism and emissions are discussed. GEOS-CF is a new tool for the research community and instrument teams observing trace gases in the stratosphere and troposphere, providing near-real-time three-dimensional gridded information on atmospheric composition.

Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes.

A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA (gp100(280)), with or without a modified T-helper epitope from tetanus toxoid AQYIKANSKFIGITEL, has been evaluated in a Phase I trial to assess safety and immunological response. The vaccines were administered s.c. in either of two adjuvants, Montanide ISA-51 or QS-21, to 22 patients with high-risk resected melanoma (stage IIB-IV). Local and systemic toxicities were mild and transient. We detected CTL responses to the gp100(280) peptide in peripheral blood in 14% of patients. Helper T-cell responses to the tetanus helper peptide were detected in 79% of patients and had a Th1 cytokine profile. One patient with a CTL response to gp100 had a recurrence in a lymph node 2 years later; her nodes contained CD8+ cells reactive to gp100(280) (0.24%), which proliferated in response to peptide. The overall survival of patients is 75% (95% confidence interval, 57-94%) at 4.7 years follow-up, which compares favorably with expected survival. Four of 14 patients who completed at least six vaccines subsequently developed metastases, all of which were solitary and surgically resectable. They remain alive and clinically free of disease at last follow-up. Data from this trial demonstrate immunogenicity of the gp100(280) peptide and suggest that immune responses may persist long-term in some patients. The frequency and magnitude of the CTL response may be improved with more aggressive vaccination regimens. Although this Phase I study was not intended to evaluate clinical benefit, the excellent survival of patients on this protocol suggests the possibility of a benefit that should be assessed in future studies.

Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients.

Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified from melanocytic differentiation proteins. Vaccine trials with these peptides have been limited mostly to those associated with HLA-A2, and immune responses have been detected inconsistently. Cases of clinical regression have been observed after peptide vaccination in some trials, but melanoma regressions have not correlated well with T-cell responses measured in peripheral blood lymphocytes (PBLs). We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. CTL responses were assessed in PBLs and in a lymph node draining a vaccine site (sentinel immunized node, SIN). We found CTL responses to vaccinating peptides in the SIN in 5/5 patients (100%). Equivalent assays detected peptide-reactive CTLs in PBLs of 2 of these 5 patients (40%). CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100. We demonstrated immunogenicity for peptides restricted by HLA-A1 and -A3 and for 1 HLA-A2 restricted peptide, YMDGTMSQV. Immune monitoring of clinical trials by evaluation of PBLs alone may under-estimate immunogenicity; evaluation of SIN provides a new and sensitive approach for defining responses to tumor vaccines and correlating these responses with clinical outcomes. This combination of an immunogenic vaccine strategy with a sensitive analysis of CTL responses demonstrates the potential for inducing and detecting anti-tumor immune responses in the majority of melanoma patients.

Listeners' discrimination of real and human-imitated animal sounds.

To determine if listeners can accurately distinguish between real and human-imitated animal sounds, a total of 165 recorded sounds (55 real and 110 human-imitated) of cats, cows, dogs, pigs, and sheep were randomly arranged on a master tape and presented to 30 listeners for discriminative judgments. Results indicate that, in general, listeners can accurately discriminate real from human-imitated animal sounds. Suggestions for future research are discussed.

Listeners' identification of human-imitated animal sounds.

To determine whether listeners can accurately identify human-imitated animal sounds, 20 speakers (10 females and 10 males) recorded their imitations of cows, cats, dogs, pigs, and sheep. These recordings were randomly arranged on a master tape and presented to 30 judges for identification. Analysis indicates that listeners can accurately identify various human-imitated animal sounds. Implications and suggestions for future research are discussed.

Listeners' identification of environmental sounds.

To determine if listeners can accurately identify various environmental sounds, a total of 40 sounds, including animal, inanimate, musical, and human sounds, were recorded, randomly arranged on a master tape, and presented to 30 judges for identification. Analysis indicated that, in general, listeners can accurately identify environmental sounds. However, their accuracy was not equal for all four classes of sounds investigated: human sounds yielded the highest accuracy, followed by musical and inanimate sounds, and animal sounds were least accurately identified. Implications and suggestions for research are discussed.