Upper Atmosphere Research Satellite Validation Workshop III: Temperature and Constituents Validation

The Upper Atmosphere Research Satellite (UARS) was launched in September 1991. Since that time data have been retrieved continuously from the various instruments on the UARS spacecraft. These data have been processed by the respective instrument science teams and subsequently archived in the UARS Central Data Handling Facility (CDHF) at the NASA Goddard Space Flight Center, Greenbelt, Maryland. This report contains the proceedings from one of the three workshops held to evaluate the progress in validating UARS constituents and temperature data and to document the quality of that data. The first workshop was held in Oxford, England, in March 1992, five and one-half months after UARS launch. The second workshop was held in Boulder, Colorado in October 1992. Since launch, the various data have undergone numerous revisions. In many instances these revisions are a result of data problems identified during the validation workshops. Thus, the formal validation effort is a continually ongoing process

Stratospheric dynamics and transport studies

A three dimensional General Circulation Model/Transport Model is used to simulate stratospheric circulation and constituent distributions. Model simulations are analyzed to interpret radiative, chemical, and dynamical processes and their mutual interactions. Concurrent complementary studies are conducted using both global satellite data and other appropriate data. Comparisons of model simulations and data analysis studies are used to aid in understanding stratospheric dynamics and transport processes and to assess the validity of current theory and models

Analysis of observations of the middle atmosphere from satellites

Satellite data are being used to investigate problems in middle atmosphere chemistry and dynamics. Efforts have been focused primarily on studies to determine the quality of observed distributions of trace species and derived dynamical quantities. Those data have been used as diagnostics for model-derived constituent profiles and fields and for improving our understanding of some of the fundamental processes occurring in the middle atmosphere. Temperatures and derived winds from Nimbus 7 Limb Infrared Monitoring of the Stratosphere (LIMS) data were compared with long-time series of rawinsonde data at Invercargill, New Zealand, and Berlin, West Germany, and the results are excellent for both quantities. It was also demonstrated that more highly-derived dynamical quantities can be obtained reliably from those LIMS fields. Furthermore, both the diabatic and residual-mean circulations derived using LIMS data agree qualitatively with changes in the distribution of trace species determined independently with the Nimbus 7 SAMS and LIMS experiments. Subsequently, an examination of LIMS data at mid to high latitudes of the Southern Hemisphere has revealed a synoptic-scale, upper stratospheric instability during late autumn that is associated with the development of the stratospheric polar jet. Investigation of this phenomenon continues with Stratospheric Sounding Unit (SSU) data sets

The atmospheric effects of stratospheric aircraft: A fourth program report

This document presents the fourth report from the Atmospheric Effects of Stratospheric Aircraft (AESA) component of NASA's High-Speed Research Program (HSRP). Market and technology considerations continue to provide an impetus for high-speed civil transport research. A recent AESA interim assessment report and a review of that report have shown that considerable uncertainty still exists about the possible impact of aircraft on the atmosphere. The AESA has been designed to develop the body of scientific knowledge necessary for the evaluation of the impact of stratospheric aircraft on the atmosphere. The first Program report presented the basic objectives and plans for AESA. This fourth report comes after the interim assessment and sets forth directions for the 1995 assessment at the end of AESA Phase 1. It also sets forth the goals and directions for AESA Phase 2, as reported at the 1994 Atmospheric Effects of Aviation Project (AEAP) annual meeting held in June. The focus of the Phase 2 effort is to obtain the best possible closure on the outstanding problems identified in the interim assessment and NASA/NRC review. Topics discussed in this report include how high-speed civil transports (HSCT) might affect stratospheric ozone, emissions scenarios and databases to assess potential atmospheric effects from HSCT's, calculated results from 2-D zonal mean models using emissions data, engine trace constituent measurements

Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency following AAV5 Gene Transfer

The dysferlinopathies comprise a group of untreatable muscle disorders including limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment syndrome, and rigid spine syndrome. As with other forms of muscular dystrophy, adeno-associated virus (AAV) gene transfer is a particularly auspicious treatment strategy, however the size of the DYSF cDNA (6.5 kb) negates packaging into traditional AAV serotypes known to express well in muscle (i.e. rAAV1, 2, 6, 8, 9). Potential advantages of a full cDNA versus a mini-gene include: maintaining structural-functional protein domains, evading protein misfolding, and avoiding novel epitopes that could be immunogenic. AAV5 has demonstrated unique plasticity with regards to packaging capacity and recombination of virions containing homologous regions of cDNA inserts has been implicated in the generation of full-length transcripts. Herein we show for the first time in vivo that homologous recombination following AAV5.DYSF gene transfer leads to the production of full length transcript and protein. Moreover, gene transfer of full-length dysferlin protein in dysferlin deficient mice resulted in expression levels sufficient to correct functional deficits in the diaphragm and importantly in skeletal muscle membrane repair. Intravascular regional gene transfer through the femoral artery produced high levels of transduction and enabled targeting of specific muscle groups affected by the dysferlinopathies setting the stage for potential translation to clinical trials. We provide proof of principle that AAV5 mediated delivery of dysferlin is a highly promising strategy for treatment of dysferlinopathies and has far-reaching implications for the therapeutic delivery of other large genes

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