On-Orbit Compressor Technology Program

A synopsis of the On-Orbit Compressor Technology Program is presented. The objective is the exploration of compressor technology applicable for use by the Space Station Fluid Management System, Space Station Propulsion System, and related on-orbit fluid transfer systems. The approach is to extend the current state-of-the-art in natural gas compressor technology to the unique requirements of high-pressure, low-flow, small, light, and low-power devices for on-orbit applications. This technology is adapted to seven on-orbit conceptual designs and one prototype is developed and tested

The impact of variable sea ice roughness on changes in Arctic Ocean surface stress: a model study

The Arctic sea ice cover is thinning and retreating, causing changes in surface roughness that in turn modify the momentum flux from the atmosphere through the ice into the ocean. New model simulations comprising variable sea ice drag coefficients for both the air and water interface demonstrate that the heterogeneity in sea ice surface roughness significantly impacts the spatial distribution and trends of ocean surface stress during the last decades. Simulations with constant sea ice drag coefficients as used in most climate models show an increase in annual mean ocean surface stress (0.003 N/m2 per decade, 4.6%) due to the reduction of ice thickness leading to a weakening of the ice and accelerated ice drift. In contrast, with variable drag coefficients our simulations show annual mean ocean surface stress is declining at a rate of -0.002 N/m2 per decade (3.1%) over the period 1980-2013 because of a significant reduction in surface roughness associated with an increasingly thinner and younger sea ice cover. The effectiveness of sea ice in transferring momentum does not only depend on its resistive strength against the wind forcing but is also set by its top and bottom surface roughness varying with ice types and ice conditions. This reveals the need to account for sea ice surface roughness variations in climate simulations in order to correctly represent the implications of sea ice loss under global warming

Processes controlling surface, bottom and lateral melt of Arctic sea ice in a state of the art sea ice model

We present a modelling study of processes controlling the summer melt of the Arctic sea ice cover. We perform a sensitivity study and focus our interest on the thermodynamics at the ice–atmosphere and ice–ocean interfaces. We use the Los Alamos community sea ice model CICE, and additionally implement and test three new parametrization schemes: (i) a prognostic mixed layer; (ii) a three equation boundary condition for the salt and heat flux at the ice–ocean interface; and (iii) a new lateral melt parametrization. Recent additions to the CICE model are also tested, including explicit melt ponds, a form drag parametrization and a halodynamic brine drainage scheme. The various sea ice parametrizations tested in this sensitivity study introduce a wide spread in the simulated sea ice characteristics. For each simulation, the total melt is decomposed into its surface, bottom and lateral melt components to assess the processes driving melt and how this varies regionally and temporally. Because this study quantifies the relative importance of several processes in driving the summer melt of sea ice, this work can serve as a guide for future research priorities

Sea ice concentration data produced from a simulation with the sea ice model CICE-CPOM-2019, including a prognostic floe size distribution model to study the Marginal Ice Zone

Monthly mean sea ice concentration output from CICE-CPOM-2019, a stand-alone (fully forced) dynamic-thermodynamic sea ice model, based on CICE model version 5.1.2, but with an added prognostic floe-size distribution, prognostic melt pond model, elastic anisotropic plastic rheology, and a prognostic ocean mixed layer. Details on the forcing and full references concerning the modifications made to the original CICE model can be found in the Readme file

Sea ice formation in a coupled climate model including grease ice

Sea ice formation processes occur on sub‐grid scales and the detailed physics describing the processes are therefore not generally represented in climate models. One likely consequence of this is the premature closing of areas of open water in model simulations, which may result in a misrepresentation of heat and gas exchange between the ocean and atmosphere. This work demonstrates the implementation of a more realistic model of sea ice formation, introducing grease ice as a wind‐ and oceanic‐ stress‐dependant intermediary state between water and new sea ice. We use the fully coupled land‐atmosphere‐ocean‐ sea ice model, HadGEM3‐GC3.1 and perform a three member ensemble with the new grease ice scheme from 1964 to 2013. Comparing our sea ice results with the existing ensemble without grease ice formation shows an increase in sea ice thickness and volume in the Arctic. In the Antarctic, including grease ice processes results in large local changes to both simulated sea ice concentration and thickness, but no change to the total area or volume

Use of a beta-lactam graded challenge process for inpatients with self-reported penicillin allergies at an academic medical center

BackgroundThe Antimicrobial Stewardship Program (ASP) at Nebraska Medicine collaborated with a board-certified allergist to develop a penicillin allergy guidance document for treating inpatients with self-reported allergy. This guidance contains an algorithm for evaluating and safely challenging penicillin-allergic patients with beta-lactams without inpatient allergy consults being available.MethodsFollowing multi-disciplinary review, an order set for beta-lactam graded challenges (GC) was implemented in 2018. This contains recommended monitoring and detailed medication orders to challenge patients with various beta-lactam agents. Inpatient orders for GC from 3/2018–6/2022 were retrospectively reviewed to evaluate ordering characteristics, outcomes of the challenge, and whether documentation of the allergy history was updated. All beta-lactam challenges administered to inpatients were included, and descriptive statistics were performed.ResultsOverall, 157 GC were administered; 13 with oral amoxicillin and 144 with intravenous (IV) beta-lactams. Ceftriaxone accounted for the most challenges (43%). All oral challenges were recommended by an Infectious Diseases consult service, as were a majority of IV challenges (60%). Less than one in five were administered in an ICU (19%). Almost all (n = 150, 96%) were tolerated without any adverse event. There was one reaction (1%) of hives and six (4%) involving a rash, none of which had persistent effects. Allergy information was updated in the electronic health record after 92% of the challenges.ConclusionBoth intravenous and oral beta-lactam graded challenges were implemented successfully in a hospital without a regular inpatient allergy consult service. They were well-tolerated, administered primarily in non-ICU settings, and were often ordered by non-specialist services. In patients with a self-reported penicillin allergy, these results demonstrate the utility and safety of a broadly adopted beta-lactam GC process

A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka: sea ice data compilation and model differences

The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations

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