Optimization of plasma amplifiers

Plasma amplifiers offer a route to side-step limitations on chirped pulse amplification and generate laser pulses at the power frontier. They compress long pulses by transferring energy to a shorter pulse via the Raman or Brillouin instabilities. We present an extensive kinetic numerical study of the three-dimensional parameter space for the Raman case. Further particle-in-cell simulations find the optimal seed pulse parameters for experimentally relevant constraints. The high-efficiency self-similar behavior is observed only for seeds shorter than the linear Raman growth time. A test case similar to an upcoming experiment at the Laboratory for Laser Energetics is found to maintain good transverse coherence and high-energy efficiency. Effective compression of a 10 kJ , nanosecond-long driver pulse is also demonstrated in a 15-cm-long amplifier

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

Human studies on probiotics and endogenous lactic acid bacteria in the urogenital tract

Every minute of every day more and more children die of diarrheal diseases and women, and girls become infected by HIV An estimated 7,000 women become infected each day. While many valiant efforts are being made to address these issues, until now they have proved to be markedly ineffective. The notion that lactic acid bacteria, formulated into food or dietary supplements, could have a role to play in slowing the morbidity and mortality associated with HIV/AIDS and gastroenteritis, is built upon sound clinical findings and scientific investigations, yet no international efforts have been placed in this approach, to date. We hereby summarize the reasons why such efforts should be made, provide an example of one model being set up in sub-Saharan Africa, and challenge the international community to consider the potential benefits of probiotics, especially for communities not reached by governmental and nongovernmental agencies. Copyright © 2005 by Lippincott Williams & Wilkins

Simulations of efficient Raman amplification into the multipetawatt regime

Contemporary high-power laser systems make use of solid-state laser technology to reach petawatt pulse powers. The breakdown threshold for optical components in these systems, however, demands metre-scale beams. Raman amplification of laser beams promises a breakthrough by the use of much smaller amplifying media, that is, millimetre-diameter plasmas, but so far only 60 GW peak powers have been obtained in the laboratory, far short of the desired multipetawatt regime. Here we show, through the first large-scale multidimensional particle-in-cell simulations of this process, that multipetawatt peak powers can be reached, but only in a narrow parameter window dictated by the growth of plasma instabilities. Raman amplification promises reduced cost and complexity of intense lasers, enabling much greater access to higher-intensity regimes for scientific and industrial applications. Furthermore, we show that this process scales to short wavelengths, enabling compression of X-ray free-electron laser pulses to attosecond duration