Design of a high power production target for the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) project is a proposed general-purpose facility at CERN, dedicated to beam dump and fixed target experiments. In its initial phase, the facility is foreseen to be exploited by the Search for Hidden Particles (SHiP) experiment. Physics requirements call for a pulsed 400 GeV/c proton beam as well as the highest possible number of protons on target (POT) each year of operation, in order to search for feebly interacting particles. The target/dump assembly lies at the heart of the facility, with the aim of safely absorbing the full high intensity Super Proton Synchrotron (SPS) beam, while maximizing the production of charmed and beauty mesons. High-Z materials are required for the target/dump, in order to have the shortest possible absorber and reduce muon background for the downstream experiment. The high average power deposited on target (305 kW) creates a challenge for heat removal. During the BDF facility Comprehensive Design Study (CDS), launched by CERN in 2016, extensive studies have been carried out in order to define and assess the target assembly design. These studies are described in the present contribution, which details the proposed design of the BDF production target, as well as the material selection process and the optimization of the target configuration and beam dilution. One of the specific challenges and novelty of this work is the need to consider new target materials, such as a molybdenum alloy (TZM) as core absorbing material and Ta2.5W as cladding. Thermo-structural and fluid dynamics calculations have been performed to evaluate the reliability of the target and its cooling system under beam operation. In the framework of the target comprehensive design, a preliminary mechanical design of the full target assembly has also been carried out, assessing the feasibility of the whole target system.Comment: 17 pages, 18 figure

Size-advantage of monovalent nanobodies against the macrophage mannose receptor for deep tumor penetration and tumor-associated macrophage targeting

Rationale: Nanobodies (Nbs) have emerged as an elegant alternative to the use of conventional monoclonal antibodies in cancer therapy, but a detailed microscopic insight into the in vivo pharmacokinetics of different Nb formats in tumor-bearers is lacking. This is especially relevant for the recognition and targeting of pro-tumoral tumor-associated macrophages (TAMs), which may be located in less penetrable tumor regions.Methods: We employed anti-Macrophage Mannose Receptor (MMR) Nbs, in a monovalent (m) or bivalent (biv) format, to assess in vivo TAM targeting. Intravital and confocal microscopy were used to analyse the blood clearance rate and targeting kinetics of anti-MMR Nbs in tumor tissue, healthy muscle tissue and liver. Fluorescence Molecular Tomography was applied to confirm anti-MMR Nb accumulation in the primary tumor and in metastatic lesions.Results: Intravital microscopy demonstrated significant differences in the blood clearance rate and macrophage targeting kinetics of (m) and (biv)anti-MMR Nbs, both in tumoral and extra-tumoral tissue. Importantly, (m)anti-MMR Nbs are superior in reaching tissue macrophages, an advantage that is especially prominent in tumor tissue. The administration of a molar excess of unlabelled (biv)anti-MMR Nbs increased the (m)anti-MMR Nb bioavailability and impacted on its macrophage targeting kinetics, preventing their accumulation in extra-tumoral tissue (especially in the liver) but only partially influencing their interaction with TAMs. Finally, anti-MMR Nb administration not only allowed the visualization of TAMs in primary tumors, but also at a distant metastatic site.Conclusions: These data describe, for the first time, a microscopic analysis of (m) and (biv)anti-MMR Nb pharmacokinetics in tumor and healthy tissues. The concepts proposed in this study provide important knowledge for the future use of Nbs as diagnostic and therapeutic agents, especially for the targeting of tumor-infiltrating immune cells.Radiolog

PRELIMINARY THERMAL-HYDRAULIC ANALYSIS OF THE AHTR FUEL ELEMENT

The Advanced High Temperature Reactor (AHTR) is a molten-salt cooled reactor utilizing TRISO particle based fuel plate with graphite matrix. Its fuel type leads to low heavy metal loading which may challenge the desired cycle length and require increasing the core volume and/or reducing the power density. Therefore, tradeoffs are necessary in the core thermal and neutronic design to provide adequate cooling and moderating capability, while preserving the heavy metal loading. The cooling system must be designed to provide efficient heat removal, reducing the total core volume and the maximum fuel temperature. For preliminary analysis of the thermal performance of the system, a MATLAB model of the single coolant channel and fuel plate was developed. The model provides a steady-state characterization of the coolant temperature, velocity and other physical properties, as well as the temperature distribution within the fuel plate. The power density distribution of the plate, both in the axial and transversal directions, was studied in order to determine realistic operating conditions and to evaluate the effects on the temperature distribution. The MATLAB model was then used to perform sensitivity studies on the main parameters of the assembly design: graphite conductivity change due to irradiation and temperature, sleeve thickness, fuel stripe thickness, TRISO particle packing fraction, coolant channel thickness; also, the combined effect of the coolant gap and fuel stripe thickness variation was considered. A RELAP5-3D model of the coolant channel and fuel plate was developed, in order to validate the MATLAB model and provide the capability for transient simulations. A pipe component was selected for the modeling of the coolant channel and a slab heat structure was selected for the fuel plate. A comparison between the MATLAB and RELAP5 model was performed both with a uniform and cosine axial power density distribution, showing that the difference between the two models is mainly due to the discretization of the power profile in the RELAP5 model. An adapted MATLAB model was developed to evaluate the changes between the continuous and the discretized cosine power profile. A RELAP5 model with increased number of axial intervals was tested and a lower error was obtained. The differences between the two models were considered acceptable and the RELAP5 model will be used for implementation in full core simulations

Design of a Helium Passivation System for the Target Vessel of the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) is a proposed general-purpose facility at CERN, dedicated to fixed target and beam dump experiments, currently being developed in the context of the Physics Beyond Colliders program. The design of the facility will allow to host different types of experiments, of which SHiP is planned to be the initial one. The core of the facility is a high-density target/dump absorbing the full intensity of the SPS beam and generating a cascade of particles that are detected downstream the target complex. The target and its shielding blocks are positioned inside a vessel, which is planned to be passivized with helium, in order to reduce the activation of the gas surrounding the target and to extend the operational life of materials and equipment. The passivation system that will be in charge of purifying and circulating the helium is a critical component for the operation of the facility. Fluid dynamics simulations have been performed to study the circulation of the helium through the vessel. A detailed design of the helium passivation system and its main components has been developed

Dataset related to article "Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells"

This record contains data related to the article "Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells". Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancre- atic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor–infiltrating lymphocytes differentially infiltrat- ed PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contri- bute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.This record contains data related to the article "Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells". Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancre- atic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor–infiltrating lymphocytes differentially infiltrat- ed PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contri- bute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.