Analysis on the mechanical effects induced by beam impedance heating on the HL-LHC target dump injection segmented (TDIS) absorber

The High Luminosity Large Hadron Collider (HL-LHC) Project at CERN calls for increasing beam brightness and intensity. In such a scenario, critical accelerator devices need to be redesigned and rebuilt. Impedance is among the design drivers, since its thermo-mechanical effects could lead to premature device failures. In this context, the current work reports the results of a multiphysics study to assess the electromagnetic and thermo-mechanical behaviour of the Target Dump Injection Segmented (TDIS). It first discusses the outcomes of the impedance analysis performed to characterise the resistive wall and the high order resonant modes (HOMs) trapped in the TDIS structures. Then, their RF-heating effects and the related temperature distribution are considered. Finally, mechanical stresses induced by thermal gradients are studied in order to give a final validation on the design qualit

Precision Oncology, Artificial Intelligence, and Novel Therapeutic Advancements in the Diagnosis, Prevention, and Treatment of Cancer: Highlights from the 59th Irish Association for Cancer Research (IACR) Annual Conference

Advancements in oncology, especially with the era of precision oncology, is resulting in a paradigm shift in cancer care. Indeed, innovative technologies, such as artificial intelligence, are paving the way towards enhanced diagnosis, prevention, and personalised treatments as well as novel drug discoveries. Despite excellent progress, the emergence of resistant cancers has curtailed both the pace and extent to which we can advance. By combining both their understanding of the fundamental biological mechanisms and technological advancements such as artificial intelligence and data science, cancer researchers are now beginning to address this. Together, this will revolutionise cancer care, by enhancing molecular interventions that may aid cancer prevention, inform clinical decision making, and accelerate the development of novel therapeutic drugs. Here, we will discuss the advances and approaches in both artificial intelligence and precision oncology, presented at the 59th Irish Association for Cancer Research annual conference

Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor

Uveal melanoma (UM) is the most common adult eye cancer. UM originates in the iris, ciliary body or choroid (collectively known as the uvea), in the middle layer of the eye. This first or primary UM is treated by targeting cancer cells using ocular radiation implants or by surgical removal of the eye. However, when UM spreads to the liver and other parts of the body, patients have a poor survival prognosis. Unfortunately, there are no effective treatment options for UM that has spread. Our aim is to help identify effective treatments for UM. In our study, we identified that the drug ACY-1215 prevents the growth of cells derived from UM in the eye and a UM that spread to the liver. Our pre-clinical study uncovered a potential treatment approach for advanced UM. Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying molecular mechanisms. A significant (p = 0.0001) dose-dependent reduction in surviving clones of the primary ocular UM cells, Mel270, was observed upon treatment with increasing doses of ACY-1215. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo attenuation of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0001) following 24 h of treatment, and significant apoptosis was triggered in a time- and dose-dependent manner (p < 0.0001). Additionally, ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome profiling, the attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacological inhibition of MITF signaling with ML329 significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and reduced OMM2.5 cells in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of OMM2.5 MUM cells

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation.Comment: Technical Proposa

Platelet-Derived Microparticles From Obese Individuals: Characterization of Number, Size, Proteomics, and Crosstalk With Cancer and Endothelial Cells

Rationale: Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not yet completely clarified.Objectives: We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and non-obese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of (i) genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and (ii) cyclooxygenase (COX)-2 involved in the production of angiogenic and inflammatory mediators.Methods and Results: MPs were obtained from thrombin activated platelets of four obese and their matched non-obese women. MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. MPs from obese women were not different in number but showed increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and three upregulated in MPs obtained from obese vs. non-obese women. A reduction in the proteins of the α-granular membrane and those involved in mitophagy and antioxidant defenses-granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with human colorectal cancer cells (HT29) and human cardiac microvascular endothelial cells (HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. Exclusively MPs from obese women induced COX-2 in HCMEC.Conclusion: Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. MPs from obese individuals presented enhanced capacity to cause changes in the expression of EMT and EndMT marker genes and to induce COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT01581801

The SHiP experiment at the proposed CERN SPS Beam Dump Facility

The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50 m long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400 GeV protons, the experiment aims at profiting from the 4 x 10(19) protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c(2) up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end

Fast simulation of muons produced at the SHiP experiment using generative adversarial networks

This paper presents a fast approach to simulating muons produced in interactions of the SPS proton beams with the target of the SHiP experiment. The SHiP experiment will be able to search for new long-lived particles produced in a 400 GeV/c SPS proton beam dump and which travel distances between fifty metres and tens of kilometers. The SHiP detector needs to operate under ultra-low background conditions and requires large simulated samples of muon induced background processes. Through the use of Generative Adversarial Networks it is possible to emulate the simulation of the interaction of 400 GeV/c proton beams with the SHiP target, an otherwise computationally intensive process. For the simulation requirements of the SHiP experiment, generative networks are capable of approximating the full simulation of the dense fixed target, offering a speed increase by a factor of Script O(106). To evaluate the performance of such an approach, comparisons of the distributions of reconstructed muon momenta in SHiP's spectrometer between samples using the full simulation and samples produced through generative models are presented. The methods discussed in this paper can be generalised and applied to modelling any non-discrete multi-dimensional distribution

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation

The experimental facility for the Search for Hidden Particles at the CERN SPS

The International School for Advanced Studies (SISSA) logo The International School for Advanced Studies (SISSA) logo The following article is OPEN ACCESS The experimental facility for the Search for Hidden Particles at the CERN SPS C. Ahdida44, R. Albanese14,a, A. Alexandrov14, A. Anokhina39, S. Aoki18, G. Arduini44, E. Atkin38, N. Azorskiy29, J.J. Back54, A. Bagulya32Show full author list Published 25 March 2019 • © 2019 CERN Journal of Instrumentation, Volume 14, March 2019 Download Article PDF References Download PDF 543 Total downloads 7 7 total citations on Dimensions. Article has an altmetric score of 1 Turn on MathJax Share this article Share this content via email Share on Facebook Share on Twitter Share on Google+ Share on Mendeley Article information Abstract The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1–3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to Script O(10) GeV/c2 in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background

Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target

The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011 muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27±0.07) × 1011 protons on target was recorded. This amounts to approximatively 1% of a SHiP spill