22 research outputs found
A Hybrid In Situ Approach for Cost Efficient Image Database Generation
The visualization of results while the simulation is running is increasingly common in extreme scale computing environments. We present a novel approach for in situ generation of image databases to achieve cost savings on supercomputers. Our approach, a hybrid between traditional inline and in transit techniques, dynamically distributes visualization tasks between simulation nodes and visualization nodes, using probing as a basis to estimate rendering cost. Our hybrid design differs from previous works in that it creates opportunities to minimize idle time from four fundamental types of inefficiency: variability, limited scalability, overhead, and rightsizing. We demonstrate our results by comparing our method against both inline and in transit methods for a variety of configurations, including two simulation codes and a scaling study that goes above 19K cores. Our findings show that our approach is superior in many configurations. As in situ visualization becomes increasingly ubiquitous, we believe our technique could lead to significant amounts of reclaimed cycles on supercomputers.</p
Aspirin commits yeast cells to apoptosis depending on carbon source
The effect of aspirin on the growth of a wild-type Saccharomyces cerevisiae strain (EG103), containing both copper,zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), a strain deficient in MnSOD (EG110) and a strain deficient in CuZnSOD (EG118) was measured in media containing different carbon sources. Aspirin inhibited the fermentative growth of all three strains in glucose medium. It inhibited the non-fermentative growth of the MnSOD-deficient strain very drastically in ethanol medium and had no effect on this strain in glycerol or acetate medium. The non-fermentative growth of the other two strains was not affected by aspirin. The growth inhibition of strain EG110 was associated with early necrosis in glucose medium and late apoptosis in ethanol medium. The apoptosis was preceded by a pronounced loss of cell viability. The growth inhibitory effect of aspirin was not reversed by the antioxidants N-acetylcysteine and vitamin E. Furthermore, aspirin itself appeared to act as an antioxidant until the onset of overt apoptosis, when a moderate increase in the intracellular oxidation level occurred. This suggested that reactive oxygen species probably do not play a primary role in the apoptosis of cells exposed to aspirin.peer-reviewe
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
Who do you love.
Gift of Dr. Mary Jane Esplen.Staged by Dave Bennett [note]Piano vocal ukulele [instrumentation]E flat major [key]Moderato [tempo]Popular song [form/genre]Woman [illustration]Publisher's advertisement on back cover [note
Who do you love? Keep thinking of, there\u27s no wherefores [first line of chorus]
Performance Medium: Piano and Voice (with lyrics