Fifty years of the CERN Proton Synchrotron : Volume 2

This report sums up in two volumes the first 50 years of operation of the CERN Proton Synchrotron. After an introduction on the genesis of the machine, and a description of its magnet and powering systems, the first volume focuses on some of the many innovations in accelerator physics and instrumentation that it has pioneered, such as transition crossing, RF gymnastics, extractions, phase space tomography, or transverse emittance measurement by wire scanners. The second volume describes the other machines in the PS complex: the proton linear accelerators, the PS Booster, the LEP pre-injector, the heavy-ion linac and accumulator, and the antiproton rings.Comment: 58 pages, published as CERN Yellow Report https://cds.cern.ch/record/1597087?ln=e

Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests

High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study

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

Linac2: The tale of a billion-trillion protons

Linac2, the machine that feeds CERN’s accelerator complex with protons, has entered a well-deserved retirement after 40 years of service

Space Charge Compensation in the Linac4 LEBT for Three Injected Gas Types

The space charge of unbunched, high intensity beams can be compensated by the trapping of charged particles in the potential well of the beam. The source of these secondary charge particles can be the residual gas in the beam line. The effect is important in the Low energy beam transport (LEBT) regions. At CERN’s Linac4, the LEBT transports a pulsed 45keV H^{−} beam, which is compensated by the positive ions, created by collision of the beam with the neutral gas in the beam pipe. The rise time and amount of compensation may be varied by the density of neutral gas and the type of gas used (through the cross-section for ion production and the mass of the resulting ion). In this paper we present measurement results for the transport of the beam at the Linac4 LEBT with the addition of hydrogen, nitrogen and krypton gases into the line, and compare them with simulations of the beam dynamics including the effect of compensating positive ions . The H^{−} beam is provided by a cesiated 2MHz RF ion source with an external solenoidal antenna, operating with 600us pulses at 0.8Hz repetition rate

Dispersion Matching of a Space Charge dominated Beam at Injection into the CERN PS Booster

In order to match the dispersion at injection into the CERN PS Booster, the optics of the injection line was simulated using two different codes (MAD and TRACE). The simulations were benchmarked versus experimental results. The model of the line was then used to re-match the dispersion. Experimental results are presented for different optics of the line. Measurements with varying beam current show the independence of the measured quantity of space-charge effects