H. N. Werkman

A piece commissioned for COLDFRONT – Singular Vispo :: First Encounters. Artists were asked to talk about their introduction to Visual Poetry and the piece of work that changed the way they saw language

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

MoEDAL - Expanding the LHC's Discovery Frontier

MoEDAL (Monopole and Exotics Detector at the LHC) is the 7th experiment, specifically dedicated to investigating beyond the Standard Model scenarios by searching for highly ionizing particles, such as magnetic monopoles or massive pseudo-stable charged particles and multiply electrically charged particles as messengers of new physics. Sharing the same interaction point as the LHCb experiment, MoEDAL is complementary to the larger ATLAS and CMS experiments, thereby expanding the discovery reach of the LHC. This largely passive detector is comprised of the following subdetectors: A large array of Nuclear Track Detector (NTD) stacks, a magnetic trapping detector (designed to trap both electrically and magnetically charged highly ionizing particles), and a TimePix chip array that monitors particle backgrounds. The MoEDAL Apparatus for Penetrating Particles (MAPP), a new MoEDAL subdetector, is currently being designed and constructed, while the prototype deployed in 2017 is currently being analyzed. The aim of MAPP is to enable MoEDAL to search for fractionally charged particles as well as new long-lived neutrals. The goal of this poster presentation was to summarize the growing physics program ofMoEDAL including MAPP’s search for new fractionally charged particles, introduce the detectors and methodology, as well as present MoEDAL’s latest results on magnetic monopole production at the LHC

Recent Results and Future Plans of the MoEDAL Experiment

The Monopole and Exotics Detector at the LHC (MoEDAL) is a pioneering LHC experiment designed to search for anomalously ionizing messengers of new physics such as magnetic monopoles or massive (pseudo-)stable charged particles. These are predicted to exist in a plethora of models beyond the Standard Model. Deployed at Interaction Point 8 (IP8) along the LHC ring, MoEDAL has taken data at centre-of-mass energies of 8 and 13 TeV. Its ground breaking physics program defines over 40 scenarios that yield potentially revolutionary insights into such foundational questions as: are there extra dimensions or new symmetries; what is the mechanism for the generation of mass; does magnetic charge exist; and what is the nature of dark matter? MoEDAL's purpose is to meet such far-reaching challenges at the frontier of the field. We present a summary of the MoEDAL detector and its latest results on magnetic monopole production at the LHC. Afterwards, progress on the physics program & installation of MoEDAL's Apparatus for the detection of Penetrating Particles (MAPP) subdetector will be discussed

Hydrogen Peroxide as an Oxidiser for Medium-Lift Launch Vehicles: A Performance and Integration Analysis

Cryogenic and semi-cryogenic propellants are the most commonly used liquid propellants for applications in medium-lift launch vehicles. Despite their high performance, the storage requirements for these propellants often lead to complex, heavy, and voluminous structures. The only storable propellant used in medium-lift launch vehicles, UDMH/NTO, comes with its own problems of high toxicity and reduced performance. A promising alternative to this could be storable fuels with highly concentrated hydrogen peroxide (HTP) as an oxidiser. Despite a shorter history of dedicated development, HTP has proved itself an effective oxidiser for in-space applications and small-lift launch vehicles. Therefore, the question could be raised towards the potential of this oxidiser for applications in medium-lift launch vehicles. In this study, the application potential of an HTP-based storable bi-propellant for medium-lift expendable launch vehicles was investigated. To this extent, a large selection of green storable fuels was considered to find the most suitable propellant for this application.Both the integration and compatibility potential of the propellants and the propulsive and mass performance potential were investigated. The integration and compatibility potential were evaluated through a qualitative assessment based on non-performance-related propellant characteristics. Furthermore, eight fuels were subjected to a more detailed assessment covering the criteria of handling toxicity, environmental toxicity, material compatibility, handling and storage, development level, and coolant qualities. RP-1 was found to be the most suitable fuel with respect to the specific criteria, while ethanol, methanol, isooctane, and isopropanol were also found to be promising alternatives. A launch vehicle model was created to evaluate the propulsive and mass potential of twelve fuels proposed based on earlier findings. This model included a propulsion model, a mass and sizing model, and an aerodynamics and trajectory model, which were all connected through a global optimisation model. In terms of propulsive potential, the cryogenic propellant hydrolox was predicted to have a 25% higher vacuum specific impulse than the best-performing HTP-based propellant DMAZ/HTP. In terms of the specific impulse density, kerosene-derivative fuels in combination with HTP were predicted to have a better performance than hydrolox and than that other conventional storable propellant UDMH/NTO. The optimised gross lift-off mass for the launch vehicle concepts employing HTP was found to be 42-61% higher than the gross lift-off mass of Ariane 6 predicted through the model. Separately, the payload capability of the HTP-based launch vehicle concepts was predicted to be at least 38% lower. In both cases, RP-1/HTP was reported to be the HTP-based propellant with the best performance, while DMAZ, isooctane, and isopropanol could be regarded as suitable alternatives. All of these propellants also outperformed UDMH/NTO. Through a sensitivity analysis, it was discovered that up to 270kg additional payload could be taken to GTO upon considering elevated chamber pressures in the HTP-based engine design. In the end, the high potential and promise of HTP were confirmed as it was concluded that increased development efforts towards HTP-based storable bi-propellant rocket engines could not only lead to a promising alternative to cryogenic propellants but could also allow for the complete replacement of toxic hydrazine-derivative fuels.Aerospace Engineerin

Real-Time Monitoring of the Effect of Tumour-Treating Fields on Cell Division Using Live-Cell Imaging

The effects of electric fields (EFs) on various cell types have been thoroughly studied, and exhibit a well-known regulatory effect on cell processes, implicating their usage in several medical applications. While the specific effect exerted on cells is highly parameter-dependent, the majority of past research has focused primarily on low-frequency alternating fields (<1 kHz) and high-frequency fields (in the order of MHz). However, in recent years, low-intensity (1–3 V/cm) alternating EFs with intermediate frequencies (100–500 kHz) have been of topical interest as clinical treatments for cancerous tumours through their disruption of cell division and the mitotic spindle, which can lead to cell death. These aptly named tumour-treating fields (TTFields) have been approved by the FDA as a treatment modality for several cancers, such as malignant pleural mesothelioma and glioblastoma multiforme, demonstrating remarkable efficacy and a high safety profile. In this work, we report the results of in vitro experiments with HeLa and MCF-10A cells exposed to TTFields for 18 h, imaged in real time using live-cell imaging. Both studied cell lines were exposed to 100 kHz TTFields with a 1-1 duty cycle, which resulted in significant mitotic and cytokinetic arrest. In the experiments with HeLa cells, the effects of the TTFields’ frequency (100 kHz vs. 200 kHz) and duty cycle (1-1 vs. 1-0) were also investigated. Notably, the anti-mitotic effect was stronger in the HeLa cells treated with 100 kHz TTFields. Additionally, it was found that single and two-directional TTFields (oriented orthogonally) exhibit a similar inhibitory effect on HeLa cell division. These results provide real-time evidence of the profound ability of TTFields to hinder the process of cell division by significantly delaying both the mitosis and cytokinesis phases of the cell cycle

Minicharged Particles at Accelerators: Progress and Prospects

Minicharged particles (mCPs), hypothetical free particles with tiny electric charges below the elementary charge, $e$, offer a valuable probe of dark sectors and fundamental physics through several clear experimental signatures. Various models of physics beyond the Standard Model predict the existence of such particles, which could help elucidate the ongoing mysteries regarding electric charge quantization and the nature of dark matter. Moreover, a hypothetical scenario involving a small minicharged subcomponent of dark matter has recently been demonstrated as a viable explanation of the anomaly in the 21 cm hydrogen absorption signal reported by the EDGES collaboration. Although several decades of indirect observations and direct experimental searches for mCPs at particle accelerators have led to severe constraints, a substantial window of the mCP mass\unicode{x2013}mixing parameter space remains unexplored at the energy frontier accessible to current state-of-the-art accelerators, such as the Large Hadron Collider (LHC). Consequently, mCPs have remained topical over the years, and new experimental searches at accelerators have been gaining interest. In this article, we review the theoretical frameworks in which mCPs emerge and their phenomenological implications, the current direct and indirect constraints on mCPs, and the present state of the ongoing and upcoming searches for mCPs at particle accelerators. Additionally, we present the results of an updated study of the projected sensitivity of the recently approved (and relocated) Phase-1 detector of the MoEDAL's Apparatus for Penetrating Particles (MAPP) experiment to Drell\unicode{x2013}Yan pair-produced mCPs at the LHC's Run 3 and the future High-Luminosity LHC.Comment: 20 pages, 5 figures. Paper accepted for publication in the European Physical Journal ST issue titled The MoEDAL-MAPP Experiment \unicode{x2014} The LHC's First Dedicated Search Experiment for BSM Physic