Emmanuel Futier

Samir Jaber

Matthias Garot

Marie Vignaud

Yves Panis

Karem Slim

Jean-Christophe Lucet

Gilles Lebuffe

Alexandre Ouattara

Younes El

Effect of oral antimicrobial prophylaxis on surgical site infection after elective colorectal surgery: multicentre, randomised, double blind, placebo controlled trial

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.


Jean-Guillaume Dillinger

Théo Pezel

Charles Fauvel

Clément Delmas

Guillaume Schurtz

Antonin Trimaille

Edouard Gerbaud

Vincent Roule

Jean-Claude Dib

Albert Boccara

Prevalence of psychoactive drug use in patients hospitalized for acute cardiac events: Rationale and design of the ADDICT-ICCU trial, from the Emergency and Acute Cardiovascular Care Working Group and the National College of Cardiologists in Training of the French Society of Cardiology

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.


Maelic Louart

Jean-Christophe Le Lann

Frédéric Le Roy

Abdel Boudraa

Jean-Jacques Szkolnik

HLS-based Accelerated Simulation of Large Scale Cyber-Physical Systems on FPGAs

Keywords: HLS, FPGA, CPS simulation

The design of cyber-physical systems remains challenging because of their highly heterogeneous nature that makes modeling, design and analysis hard. Despite extensive work in model-based approaches, few unified simulation tools are available today for such systems. This paper proposes a simulation strategy that benefits from the characteristics of recent FPGA platforms and advances in the high-level synthesis tools. Our proposal consists in using these tools to build a cyber-physical system simulator running at high-speed on a FPGA; in this view, high-level synthesis is used not only in the traditional prototyping phase of the embedded systems, but also to synthesize its physical environment, which is jointly simulated on the FPGA. Our paper proposes a case study illustrating this approach: the simulation of the automatic identification system required in maritime communications. The simulation executed on the latest FPGA generation is accelerated by a factor x654 compared to software alternatives demonstrating that FPGAs exhibit appealing characteristics for such simulations.

I. INTRODUCTION

As defined in [START_REF] Lee | Introduction to embedded systems: A cyberphysical systems approach[END_REF], a cyber-physical system (CPS) is a tight integration of computation with physical processes. This definition applies at different scales: either at small scale, where such a CPS can be seen as a single embedded system with a physical environment, or at large scale where several embedded systems come into play in a distributed manner. In either cases, simulating such CPSs allows to design more robust embedded systems, by getting a realistic insight of their expected behaviors in a complex environment. However, CPS simulation remains difficult [START_REF] Kim | Cyber-physical systems: A perspective at the centennial[END_REF] because of their intrinsic heterogeneity [START_REF] Fadhlillah | Towards heterogeneous multi-dimensional variability modeling in cyber-physical production systems[END_REF]: the involved models of computation (MoCs) are varied in nature, mixing discrete and continuous phenomena and several temporal and synchronization characteristics. Moreover, such modeling activity requires multi-domain skills dealing with software and hardware components and multiple disciplines (mechanical, electrical and software engineering).

Ptolemy framework [START_REF] Buck | Ptolemy: A framework for simulating and prototyping heterogeneous systems[END_REF], Simulink , Simscape or Modelica are famous tools (and languages) developed to compose, in an hierarchical way, and simulate various models of computation. Pure cosimulation is another technique that allows linking standalone MoC simulators through functional mockup interface buses [START_REF] Gomes | The fmi 3.0 standard interface for clocked and scheduled simulations[END_REF] [START_REF] Saidi | Fast virtual prototyping of cyber-physical systems using systemc and fmi: Adas use case[END_REF] to simulate the behavior of the whole system. Unfortunately, these model-based design approaches make composition complex, model verification difficult [START_REF] Porter | An experimental model-based rapid prototyping environment for high-confidence embedded software[END_REF] and to the best of our knowledge, do not provide immediate This work is supported by Cyber Excellence Center (Brittany region). solution to distribute simulation workloads efficiently and reduce simulation time. In addition, physical timing artifacts such as delays, skews, etc., as well as subtle logical causality errors, are produced because of the simulators connections and the execution models (interrupts, memory access and threads [START_REF] Lee | The problem with threads[END_REF]), which deteriorates the overall simulation confidence [START_REF] Carlsson | Methods for reliable simulation-based plc code verification[END_REF].

We propose to explore an alternative CPS simulation approach. This approach relies on a single model expressed in C++ and resorts too high-level synthesis (HLS) to generate the full CPS simulator executable on a FPGA. Our experiment is inspired by the seminal work of Miller, Vahid, and Givargis on the use of FPGA for digital mockups [START_REF] Miller | Application-specific codesign platform generation for digital mockups in cyber-physical systems[END_REF]. They compiled various physiological models, based on partial differential equations, on an overlay-like structure on FPGA to simulate some human organs behavior (lungs, heart, etc). Such simulations allow to test the reaction of real devices (e.g ventilators, pacemakers) in various conditions. At that time (2011-2014), the capacities of FPGAs in terms of integration were much weaker than today's FPGAs; we demonstrate that we can now simulate both cyber and physical parts on the same FPGA. In this paper, we demonstrate that FPGAs offer a viable platform for full multi-scale CPS prototyping. This method can be considered "agile" because it bypasses a certain number of steps of a classic model-based "waterfall" approach, which is in line with [START_REF] Roy | Waterfall is too slow, let's go agile: Multi-domain coupling for synthesizing automotive cyber-physical systems[END_REF]. A similar method is proposed in literature [START_REF] Sood | Robust design and validation of cyberphysical systems[END_REF], but it does not rely on the combination of FPGA and HLS, and only simulates small scale CPSs.

In the next section, we present our CPS design method. Then we experiment our design method on a case study concerning a maritime communication protocol. We conclude by a discussion and delineate some future work.

II. CPS SIMULATION APPROACH BASED ON FPGA PLUS HLS

Our method comes from three practical observations: the first is the quasi-systematic availability of highly domainspecific C/C++ codes able to simulate behavior parts of almost every CPS (physical, mechanical, chemical phenomena, etc.). These codes are rarely available in model-based specialized languages. The second observation is the growing robustness of HLS tools [START_REF] Lahti | Are we there yet? a study on the state of high-level synthesis[END_REF] able to synthesize hardware code from C++ code. The third is the interesting characteristics of reconfigurable architectures such as recent FPGAs [START_REF] Grimm | The value of fpgas as reconfigurable hardware enabling cyber-physical systems[END_REF]: they offer a high computational power, large amount of resources [START_REF]Xilinx Announces General Availability of VU19P, World's Largest FPGA[END_REF], Fig. 1. Overview of the approach for CPS simulator design parallelism concepts easy to implement, and a native synchronization of computations. Considering these observations, we created a new CPS design method (displayed in Fig. 1) which, from a model expressed in C++, uses HLS to generate the full CPS simulator executable on FPGAs. Note that the functioning of the simulator can be tested thanks to the HLS tool, both at the C level and RTL level.

The method divides the CPS into components: one of them simulates the environment (physical part) and the others emulate the embedded systems (cyber part). The term "emulation" is used when the model under study reproduces a sequence of operations close or even identical to that of the system [START_REF] Mcgregor | The relationship between simulation and emulation[END_REF]. The description of the components behavior is done in C++ and the description of the interactions between components is done using HLS directives. Components are composed by applying the dataflow directive, which implements FIFO or Ping-Pong buffers between components. Computation can be expressed using float, fixed-point and integer with arbitrary precision data types. This method can be only applied to architecture limited to acyclic directed graph. At the macroscopic point of view (component point of view), the Kahn process networks (KPN) MoC is applied [START_REF] Lee | Introduction to embedded systems: A cyberphysical systems approach[END_REF], while, at a microscopic point of view (FPGA logic point of view), the Synchronous Reactive MoC is applied. Fig. 2 illustrates the generic architecture of the resulting synthesized simulators. Note the presence of embedded Piloting, allowing a classical interaction, from the host PC, with such a simulator: start, stop, step-by-step advancement commands. The embedded Piloting allows also to adjust the embedded systems and the simulated environment parameters. The user can, in addition, observe the dynamics of selected signals from the HLS, collected and read back to the host PC (Monitoring). These commands and observations come from interface registers described in a file (in s-expression format) and automatically generated with our Reggae tool [START_REF] Lann | Reggae : FPGA register map VHDL generation[END_REF]. The tool allows to generate a very simple combinatorial glue allowing to interface to the axi stream interface protocol used by the hls tool.

III. MOTIVATING CASE STUDY

A. AIS Maritime communication system

Our CPS case study consists in a set of vessels that move and exchange radio messages relying on a dedicated maritime protocol named automatic identifying system (AIS). AIS operates on two frequencies at 161.975 MHz and 162.025 MHz on the very high frequency (VHF) band. The sent messages comply with the national marine electronics association (NMEA) 0183 standard. The data rates are 9600 baud. Since 2002, the safety of life at sea agreement of the international maritime organization requires the installation of a class A AIS transponder for international ships over 300 gross tonnage and for passenger ships regardless of their size. This system improves the safety of maritime traffic by allowing the automatic exchange of navigational information (position, identity, port of departure, etc.) between ships. However, this system is vulnerable: the information sent by transponders can be easily falsified or spoofed (for piracy, illegal transport, etc.). This is why spoofing and falsification detection algorithms must be developed and integrated into new generation AIS transponders. The algorithms will be applied to both AIS messages and AIS signals, to detect, for instance, inconsistency in data (AIS messages) or to characterize the transponders radiometric signature (AIS signals).

B. Verification challenges

To develop a reliable system, simulations are required to test a wide range of scenarios reproducing use conditions of the product. However, getting comprehensive test streams from real field measures remains tedious. In our work, to solve this issue, a simulation framework was created to generate a wide variety of synthetic scenarios containing AIS messages and signals. The generated messages can be falsified and spoofed. The simulation framework emulates a variable number of AIS transponders, which communicate with each other in an simulated maritime environment. The simulation runs entirely on hardware, and is synthesized using HLS. An example of the simulation architecture is presented in Fig. 2, where three transponders are communicating. C. Model of the CPS simulated Fig. 3 illustrates the general architecture of our CPS simulator in the same configuration as in Fig. 2. Three types of component are displayed and were modeled. An Emitter that acts as an AIS transponder which, from an NMEA frame (AIS message), sends a modulated AIS signal. A Receiver that acts as a AIS transponder, which only receives AIS signals and demodulates them to extract NMEA frame. Finally, a Channel model simulates the environment to apply some physical laws to the AIS signals. All components are discussed later. The Emitter and the Receiver were the CPS' embedded system and Channel was the CPS' environment. We also represent in Fig. 3 a specific block of piloting and monitoring of the simulation explained above in part II. Every component is modeled by a chain of blocks executed sequentially to the received signal. Note that the architecture is modeled by an directed acyclic graph: the Emitters send AIS signals to the Channel, and the Channel sends the signals to the Receiver.

The simulated signals were not modulated at the carriers frequencies (161.975MHz and 162.025MHz) because the frequencies are to high: FPGA should have huge memory and computation capacities. Thus, we simulated the signal only on baseband at a sample rate equal to 192kHz.

The Emitter component contains eight blocks. First block reads the NMEA frame. The following four blocks transform this frame according to the high-level data link control (HDLC) protocol. HDLC is a level 2 protocol (link layer) of the Open Systems Interconnection model. Each byte is inverted, a checksum is calculated and added at the end of the frame, then a stuffing of bits at 0 is applied to avoid the presence of 6 bits at '1'. Finally a start and end flag is inserted at the beginning and end of the frame. After, a conditioning sequence is added to the frame. Finally, a Non Return to Zero Inverted (NRZI) Coding and Gaussian minimum-shift keying (GMSK) modulation are applied. The signal is not modulated at the carriers frequencies because we only consider the baseband signal.

The Channel component contains four blocks and allows to apply varied environmental effects on the signals sent between the Emitter and Receiver. A first block adds a carrier frequency offset to the signal to characterize Emitter carrier frequency error caused by hardware imperfections. Another block reproduces path loss attenuating the energy of the signal considering the Friis model and the distance between the Emitter and the Receiver. A third block adds a white Gaussian noise to the signal to characterize the propagation noise. The amplitude of the noise is fixed according to the signal-to-noise ratio (SNR) that we want to impose. Finally, a last block sums the signals from every Emitter.

Friis model stipulates that the ratio of received signal power and emitted signal power is given by:

P r P t = G r G t λ 4πR 2 (1)
where P r and P t are respectively the received and transmitted powers. G t and G r are respectively the antenna gains in transmission and reception. λ the wavelength of the working frequency and R the distance separating the emitter from the receiver. We fix antennas gain to G t = G r = 2dBi, as suggested by [START_REF] Mazzarella | A novel anomaly detection approach to identify intentional ais on-off switching[END_REF], and the power of transmitter is P r = 12.5W as defined by AIS standard. Reference [START_REF] Mazzarella | A novel anomaly detection approach to identify intentional ais on-off switching[END_REF] shows that this model is reliable and reproduces the evolution of the energy of the signal up to thirty kilometers.

The Receiver component starts with the computation of the signal energy to detect the effective arrival of an AIS message characterized by a peak of energy. After, it demodulates the AIS signals to extract their NMEA frame. The demodulation is done symmetrically to Emitter. Thus, this component allows to extract AIS information from the signals to applied the algorithms. This receiver prototype is efficient because it extracts AIS message from true baseband signals recorded in the bay of Brest.

D. Hardware synthesis

We experimented our design method presented in Fig. 1. The whole CPS model represented about 5000 lines of C++ code using fixed point and integer with arbitrary precision. Note that some parts of the system are dedicated to pure simulation, while some elements (like our Receiver) can be seen as a viable prototype of a future embedded device. The results of the three components synthesis are presented in Table I. The synthesis target was one of the biggest FPGA proposed in the industry, the Xilinx Ultrascale+ HBM FPGA on a VCU128 board (about 10 6 System logic cells, 3K DSP slices, etc.). The HLS tool was Vitis HLS 2020.2. The occupancy percentage for a simulator with the three components is low (less than 7% for BRAM, DSP, FF, and LUT elements). However, the FPGA platform is not over-sized for such application. Indeed, the testbenches need to simulate synthetic environments with several Emitters moving physically and exchanging AIS messages at the same time. In addition, the simulated environment was too simple to replicate every spoofing and falsification scenario: special geographical maps (presence of islands, etc.) can be used by hackers to spoof AIS. These special geographical maps need high computation capabilities to be simulated. Note that the amounts of resources used by the components Piloting and Monitoring are not displayed in the table I because they are very small and can therefore be ignored.

IV. HIGH-LEVEL SYNTHETIC SCENARIOS

A. Objectives

To illustrate the ability of our simulator to generate ship trajectories that can contain falsified or spoofed messages (but also to prove the functioning of our channel model based on the Friis model), five scenarios were created and observed, and are displayed on Fig. 4 Fig. 4. Simulated trajectories on the FPGA.

Among these scenarios, three reproduce a ship trajectory without falsification or spoofing of AIS messages, and two with falsification and spoofing. The ship 4 on Fig. 4 reproduces the type of spoofed reported in [START_REF] Balduzzi | A security evaluation of ais automated identification system[END_REF]. The ship 5 on Fig. 4 has a falsified trajectory reproducing the type of falsification reported in [START_REF] Katsilieris | Detection of malicious ais position spoofing by exploiting radar information[END_REF]. In this reference, a fishing vessel falsifies its position to fish in a restricted area. For all these trajectories, Channel added white Gaussian noise to the signal to reach a SNR equal to 10dB. To simulate these five scenarios at the same time, five Emitter components were implemented on a single FPGA, in addition to one Channel and one Receiver component.

B. Simulation results and analysis

We compare, in Table II, software's simulation time to hardware's simulation time for the five scenarios presented above. The software was a standard Intel Core I5 processor at 1.7GHz with 16Gb RAM, and the hardware, the FPGA presented above. During every simulation, 1000 messages are received by the Receiver successively from every Emitter. Other simulations, which simulated different trajectories, were done; one required only one Emitter and another ten. The simulation times are displayed in Table II. To run these simulations, Emitter components were added or removed from the FPGA platform, this is why the FPGA usage rate is changing. Considering the results from these three simulations, we predict that the maximum number of Emitters that can be emulated at the same time in the FPGA is 22 because in this case the occupancy percentage of BRAM reaches 98%.

Performance gain is already x183 compared to software simulation for only one Emitter. The speed-up gain was obtained without applying optimization directives to the code of the blocks such as loop unrolling or pipeline, which still leaves a speed-up margin for the FPGA simulation. Only dataflow directive is applied to the code as mentioned in methodology part II. These directives pipeline the components execution. The FPGA acceleration reduces the simulation times from tens of minutes to only 3.14s. Moreover, although the number of components Emitter was increased, the hardware simulation time remained the same: the Emitter components were executed in parallel. This is why for 22 Emitter the performance gain is predicted to be 654. This fact shows the interest of the scalable aspect of FPGAs.

V. DISCUSSION

Our CPS design method is restricted to CPS whose architecture is an directed acyclic graph. Outside this type of architecture, Vitis HLS cannot synthesize systems. For instance, in our application case, the AIS transponders communicate with each other according to the TDMA (Time-division multiple access) method whose architecture is a complete undirected graph with as many nodes as boats. This TDMA method cannot be directly synthesized by Vitis HLS to be simulated on FPGA. Thus, other high-level synthesis tools, allowing actor-based modeling without limit in the complexity of the architecture, using, among others pure dataflow semantics [START_REF] Janneck | Synthesizing hardware from dataflow programs[END_REF], are to be experimented.

VI. CONCLUSION AND FUTURE WORK

In this paper, we proposed the use of FPGA as a simulation platform for complex cyber-physical systems. Our case study focuses on a set of AIS transponders operating in a maritime environment simulated. The progress of HLS tools and the increasing capabilities of FPGAs make such an approach possible. Compared to a pure software simulation, we have shown remarkable performance gains (up to a x654 acceleration factor). The user can interact with the simulator changing the environmental parameters, monitoring the simulation (start, stop, step-by-step) and observing the signals exchanged by the components. We point out some limitations of classical HLS tools, that call for alternatives HLS approaches to be able to simulate a wide range of CPS architectures. Our paper demonstrates that FPGA can be seen as a platform of choice for the integration of multi-domain systems.

Fig. 2 .

 2 Fig. 2. Our proposal: FPGAs as cyber-physical system Simulation platforms.

Fig. 3 .

 3 Fig. 3. Model of the CPS simulated on FPGA.

TABLE I RESOURCES

 I USED BY EACH COMPONENT.

		BRAM	DSP	FF	LUT
	Simulator	293(7%) 66(0%) 30508(1%) 41665(3%)
	Emitter	97	1	8718	16357
	Channel	97	13	1478	4312
	Receiver	99	52	19904	20754

  .

									receiver
		-96.7							ship 1
									ship 2
									ship 3
									ship 4
		-96.8							ship 5
		-96.9
	latitude(°)	-97
		-97.1
		-97.2
		-97.3
		32.5	32.6	32.7	32.8	32.9	33	33.1	33.2
						longitude(°)

TABLE II SIMULATION

 II TIMES OBTAINED ON FPGA AND PROCESSOR.

	Nb. Emitters	Soft.	Hard. Gain FPGA usage
	1	576s	3.14s	183	7%
	5	856s	3.14s	272	24%
	10	1210s 3.14s	386	46%
	22 (pred.)	2050s 3.14s	654	98%


Yizheng Wang
email: yizheng.wang@subatech.in2p3.fr

Thomas Sounalet

A Guertin

Férid Haddad

Nathalie Michel

Etienne Nigron

Electrochemical co-deposition of Ni-Gd2O3 for composite thin targets preparation: production of 155 Tb as a case study

Keywords: electrochemical co-deposition, gadolinium target, cross section measurement, terbium production, stacked-foil technique

In the last years, 155 Tb has attracted enormous interest due to its potential role in theranostics in nuclear medicine. To estimate its production yield, the aim of this study was to develop a method to prepare thin Gd-enriched-containing targets aimed at the 155 Gd(d, 2n) 155 Tb nuclear cross section measurement. To this end, the electrochemical co-deposition method has been chosen to manufacture Ni-Gd2O3 composite targets. Several process parameters that have an impact on the deposit quality, have been investigated to increase the incorporation of Gd mass (up to 3 mg). To validate the concept, seven targets made by natural Gd were irradiated with deuteron beams at the GIP ARRONAX facility cyclotron, with an energy range ranging from 8 MeV to 30 MeV to extract the cross section values by using the stacked-foils method. Results obtained turned out to have great consistency with existing published data thus validating the proposed method. Therefore, an alternative target manufacturing concept aimed at cross section measurement is presented in this work.

Introduction

Theranostics, a new medical approach combining therapy and diagnostic, has become one of the core keywords in recent years in nuclear medicine. Applications of radionuclides have evolved with the development of theranostics, among which the application of Terbium radioisotopes has been mentioned in several articles [START_REF] Cavaier | Terbium Radionuclides for Theranostics Applications: A Focus On MEDICIS-PROMED[END_REF][START_REF] Cleeren | Theranostics studies using 152/149Tb-labeled anti-CXCR4 probes in tumor mice[END_REF][START_REF] Müller | Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application[END_REF][START_REF] Müller | A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α-and β--Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative[END_REF]. As an emitter of Auger electrons and gamma rays, 155 Tb (half-life: 5.32 d) can be applied in Auger therapy as well as single photon emission tomography (SPECT) diagnosis [START_REF] Müller | Future prospects for SPECT imaging using the radiolanthanide terbium-155 -production and preclinical evaluation in tumor-bearing mice[END_REF][START_REF] Nica | Nuclear Data Sheets for A=155[END_REF][START_REF] Webster | Chemical Purification of Terbium-155 from Pseudo-Isobaric Impurities in a Mass Separated Source Produced at CERN[END_REF]. However, applications of 155 Tb are in short supply due to its limited availability. Nowadays, it is mainly produced by high-energy spallation reactions followed by mass separation, which requires rare equipment and high cost [START_REF] Naskar | Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application[END_REF]. Therefore other reaction routes, involving gadolinium targets coupled to light-charged particle beams, are being taken into account to get an increase of 155 Tb supply [START_REF] Duchemin | Deuteron induced Tb-155 production, a theranostic isotope for SPECT imaging and auger therapy[END_REF][START_REF] Formento-Cavaier | New excitation functions for proton induced reactions on natural gadolinium up to 70 MeV with focus on 149Tb production[END_REF][START_REF] Naskar | Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application[END_REF][START_REF] Tárkányi | Activation cross-sections of deuteron induced reactions on natGd up to 50MeV[END_REF]. Enriched Gadolinium targets make it possible through the following reaction routes involving either proton or deuteron beams: 155 Gd(p, n) 155 Tb (threshold energy: 1.61 MeV) or 155 Gd(d,2n) 155 Tb (threshold energy: 3.88 MeV) [START_REF] Koning | TENDL: Complete Nuclear Data Library for Innovative Nuclear Science and Technology[END_REF]. To evaluate the optimal accelerated beam energy ranges, produced contaminants as well as the production yield, reaction cross sections must be determined, first. To this end, high quality and thin Gd-enriched targets are required.

The electrodeposition method to prepare thin targets is often used, as it can be performed with a low cost and simple installation system. In case of Gd target preparation, a critical issue is the redox potential of Gd 3+ /Gd which is very low (E = -2.28 V/SHE) in acid solution [START_REF] Lide | CRC Handbook of Chemistry and Physics[END_REF]. A strong competition with water decomposition is therefore occuring, and good adherence of Gd deposits present in aqueous solution are unattainable under the hydrogen evolution reaction (HER). To overcome such a problem caused, several Gd deposits tests were carried out in organic mediums [START_REF] Gucik | Electrodeposition of Gadolinium Metal from Organic Solvents[END_REF][START_REF] Kovács | Preparation of thin gadolinium samples via electrodeposition for excitation function studies[END_REF][START_REF] Small | Electroreduction of Er3+ in nonaqueous solvents[END_REF], however, they resulted either with too small area (<1.1 cm²) or too fine (<1 µm). In addition, these experiments have strict restrictions on moisture content, which makes them complicated to master. Molten salt mediums were also studied [START_REF] Blessing | Internal irradiation system for excitation function measurement via the stacked-foil technique[END_REF], but this experiment had also many constraints (high temperature, pure argon environment …). It is noteworthy to recall that other methods for thin target preparation, such as HIgh energy VIbrational Powders Plating method (HIVIPP) [START_REF] Skliarova | HIVIPP deposition and characterization of isotopically enriched 48Ti targets for nuclear cross-section measurements[END_REF] or Magnetic Sputtering (MS) [START_REF] Skliarova | Medical Cyclotron Solid Target Preparation by Ultrathick Film Magnetron Sputtering Deposition[END_REF] are available. However, the former method needs a set-up under vacuum and takes considerable time, and the latter requires control of air pressure and temperature.

In this work, an alternative way called the co-deposition method to obtain Gd containing targets has been therefore explored. This method, which emerged in the 1920s and was improved in the 1960s, has been extensively studied to develop composite materials [START_REF] Lee | Codeposition of micro-and nano-sized SiC particles in the nickel matrix composite coatings obtained by electroplating[END_REF][START_REF] Low | Electrodeposition of composite coatings containing nanoparticles in a metal deposit[END_REF][START_REF] Parida | Synthesis and characterization of Ni-TiO2 composite coatings by electro-co-deposition[END_REF]. The basic principle of this method is to mechanically transport and physically embed target particles mixed in a bath to the growing deposited layer [START_REF] Walsh | A review of the electrodeposition of metal matrix composite coatings by inclusion of particles in a metal layer: an established and diversifying technology[END_REF]. Using this method, Gd atoms are trapped in a metal deposit and avoid most of the difficulties associated with direct Gd electrodeposition. The main advantages of this method are the simple experimental conditions and the target manufacturing duration which is short (30-60 min).

Main goals of this work are to obtain Ni-155 Gd2O3 composite targets via the co-deposition method and to get measurement of the cross sections by using these targets. Gd2O3 has been selected in this experiment because the enriched 155 Gd isotope is easily available in this form. Nickel has been selected as the electroplating matrix metal because the experimental conditions are well known and it is possible to perform it in basic conditions, in which Gd2O3 remains stable. In addition, due to its insolubility in alkaline solution, the Gd2O3 powder can be easily recycled, which greatly improves the material utilization rate which is of particular importance when isotope-enriched materials are used. In this work, proof of concept experiments have been performed using natural gadolinium, due to the high cost of enriched Gd. Influences of main process parameters (i.e., applied potential, concentration of Gd2O3 and stirring speed) on the deposit quality have been studied to validate the optimal experimental procedure. To carry out the experimental measurement, seven of the obtained targets were then irradiated with deuteron beams at the GIP ARRONAX cyclotron, in Nantes [START_REF] Haddad | ARRONAX, a high-energy and high-intensity cyclotron for nuclear medicine[END_REF] in an energy range ranging from 8 MeV up to 30 MeV. The production cross sections have thus been measured and compared with the experimental data available in the literature or world databases (e.g. EXFOR).

Materials and methods

Electrochemical co-deposition study and target preparation

To obtain the Ni-Gd2O3 composite deposits, the following electrolyte was prepared: 0.5 mol/L (NH4)2SO4 + 0.5 mol/L NH4Cl + 0.14 mol/L NiSO4•6H2O + 1 mol/L NH3. These compositions and concentration settings referred to the work of [START_REF] Skitał | Electrodeposition of nickel from alkaline NH4OH/NH4Cl buffer solutions[END_REF]. The final pH of the electrolyte was fixed at 9.8, adjusted by 5 mol/L of NaOH. Insoluble Gd2O3 under powder form (less than 230 mesh size) in basic solution was then added to the solution with a mass varying from 0.1 g to 6.5 g. All chemical products mentioned were provided by Sigma Aldrich. The stirring magnet was used to ensure that the Gd2O3 particles are distributed as evenly as possible in the solution. The stirring speed was set at 100, 300, 400, 600 and 800 rpm.

The co-deposition was carried out in a homemade Teflon cylinder cell containing 35 mL of the electrolyte solution (Fig. 1). A hole with a diameter of 10 mm was on the side of the cylinder to place the working electrode. A sealing film and a stainless steel plate were used to ensure the tightness of the cell and electric connection. For the co-deposition study, the working electrode was a 2.5 cm × 2.5 cm gold foil with a thickness of 50 µm provided by Goodfellow (99.95 % purity). The auxiliary electrode was made of a platinum rod having a diameter of 1 mm. A reference electrode Ag/AgCl/sat KCl was also used during the process. The distance between the working electrode and the auxiliary electrode was set at 1.0 ± 0.1 cm. Experiments of chronopotentiometry and voltammetry were carried out by PGP201 Voltalab Potentiostat/galvanostat. The scanning potential was from -0.1 V/NHE to -1.5 V/NHE for 5 cycles, the scanning speed was 0.05 V/s, and the solution stirring speed was 800 rpm. The applied potential of co-deposition varied from -1.30 V/NHE to -1.04 V/NHE according to voltammetry results. Each experiment was carried out at 30°C and lasted for 1 hour.

Surface morphology and Gd2O3 distribution were observed by JEOL JSM 71OOF scanning electron microscope (SEM) with a magnification of 100×, 1000× and 5000× at 15 kV acceleration voltage. Energy-dispersive X-ray spectroscopy (EDX) coupled to the SEM was also used for investigating the surface chemical composition. The dimension of the region analysis was about 1.1 mm × 0.8 mm at a magnification of 100×. The measuring time was 60 s.

Targets, once characterized, were irradiated for cross section measurements, and after that, dissolved in 10 mL of 12 mol/L HCl for 4 hrs at room temperature. 5 mL of the dissolved solution was taken for the measurement of activity with our High Purity Germanium (HPGe) detector, another 5 mL solution was used for chemical composite analysis with our Thermo Scientific iCAP 6000 Series Inductively Coupled Plasma -Atomic Emission Spectroscopy (ICP-AES) to determine precisely the Gd atomic contents.

Targets irradiations

The ARRONAX cyclotron can accelerate both positive ions (HH + , He ++ ) and negative ions (H -, D -). Protons and alpha particles can be accelerated up to 70 MeV whereas deuteron beams can be accelerated only up to 34 MeV. The irradiation process was carried out at the ARRONAX cyclotron in a typical configuration for stacked-foil experiments [START_REF] Blessing | Internal irradiation system for excitation function measurement via the stacked-foil technique[END_REF]. In these experiments, monitor foils were used to determine the beam flux and degrader foils to adapt the energy of the beam impinging consecutive targets. Titanium foils and nickel foils with a thickness of 15 µm and 20 µm respectively were used as monitors; Aluminum foils with a thickness of 200-800 µm were used as beam energy degraders. All foils mentioned were provided by Goodfellow (99.99 % purity). Foils were placed in air 6 cm downstream the beam output window, made of 50 µm thick Kapton foil. Seven Ni-Gd2O3 composite targets were irradiated in five different experiments (target n°1 and n°2 were irradiated together, target n°4 and n°7 were irradiated together) for 30 min or 60 min by deuteron with an energy range from 8 MeV to 30 MeV. The schematic diagram of one stack for one particular experiment is illustrated in Fig. 2 as an example. The beam parameters used for the irradiation of each target are presented in Table 1. Mean beam intensity was calculated according to the flux measured by monitors. For each experiment, energy in the middle of the thickness of each foil was determined using SRIM software [START_REF] Ziegler | SRIM -The stopping and range of ions in matter[END_REF] and taking into account the beam energy uncertainty (± 0.25 MeV) and energy straggling. Since Gd2O3 particles were uniformly distributed in targets (Fig. 5 (e)), in the SRIM simulation, the target was regarded as to be composed of Gd, O, and Ni three components. The number of atoms of each component and the density of the target were determined according to the ICP-AES analysis results.

Cross section calculation

For a thin target with uniformly distributed Gd2O3, the production cross section for the nat Gd(d, 2n) 155 Tb reaction route at energy 𝐸𝐸, 𝜎𝜎(𝐸𝐸) (mb), can be calculated according to Eq.

(1):

𝜎𝜎 (𝐸𝐸) = 𝐴𝐴𝐴𝐴𝐴𝐴(𝐸𝐸). 𝐴𝐴 𝐼𝐼 • 𝑁𝑁 𝐴𝐴 . 𝜌𝜌 • 𝛿𝛿𝛿𝛿 • (1 -𝑒𝑒 -𝜆𝜆𝜆𝜆 ) (1)
Where 𝐴𝐴𝐴𝐴𝐴𝐴(𝐸𝐸) (Bq) is the activity of 155 Tb nuclei produced at energy 𝐸𝐸, 𝐴𝐴 (g.mol -1 ) is the molar mass of the target nuclei, 𝐼𝐼 (s -1 ) is the number of projectile per second hitting the target, 𝑁𝑁 𝐴𝐴 is the Avogadro number (at. mol -1 ), ρ is the target material bulk density (g.cm -3 ), 𝛿𝛿𝛿𝛿 is the thickness of the target (cm), 𝜆𝜆 (s -1 ) is the decay constant of 155 Tb and finally, 𝐴𝐴 is the irradiation time. The total Gd atoms in the deposit was calculated according to ICP-AES results obtained from each irradiated target after its dissolution.

For titanium monitors and nickel monitors, using Eq. ( 1), the number of projectile per second I′ of titanium foils or nickel foils were determined by using the reference cross section 𝜎𝜎′(𝐸𝐸′) of the reaction nat Ti(d, x) 48 V [START_REF] Hermanne | Reference cross sections for charged-particle monitor reactions[END_REF] or the reaction nat Ni(d, x) 58(m) Co [START_REF] Amjed | Activation cross-sections of deuteron induced reaction of natural Ni up to 40MeV[END_REF] respectively. The monitor atomic number 𝑁𝑁 ′ was determined by its mass, its atomic mass and the Avogadro constant. The average value of monitors' number of projectile per second 𝐼𝐼′′ was then calculated. Since monitor foils have the same area as targets and are located just behind the target foils, 𝐼𝐼′′ is considered equal to 𝐼𝐼. It can be deduced Eq. [START_REF]8 database, National data center, brookhaven national laboratory[END_REF].

𝜎𝜎 (𝐸𝐸) = 𝐴𝐴𝐴𝐴𝐴𝐴(𝐸𝐸). 𝐴𝐴 𝐼𝐼′′ • 𝑁𝑁 𝐴𝐴 . 𝜌𝜌 • 𝛿𝛿𝛿𝛿 • (1 -𝑒𝑒 -𝜆𝜆𝜆𝜆 ) (2)
Since all parameters in Eq. ( 2) are independent, estimation of cross section uncertainties is based on combined standard uncertainty estimating in ISO guide [START_REF] Iso | Guide to the Expression of Uncertainty in Measurement[END_REF], as the positive square root of the summation of squares of each parameter (Eq.( 3)).

Δσ (E) σ (E) = � � ΔAct (E) Act (E) � 2 + � ΔI′′(E) I′′(E) � 2 + � ΔM M � 2 (3)
The half-life and main γ rays (Nudat 2.8 database, 2021) of 155 Tb, 48 V and 58(m) Co used in this work are presented in Table 2. As indicated in Table 2, the gamma ray energy of 155 Tb that we have chosen is 180.08 keV, which is very close to that of 198m Au (T1/2 = 2.272 d, E = 180.31 keV, Iγ = 0.04%) produced by the gold substrate. This is the reason why the targets were dissolved after irradiation to separate the deposit and the gold substrate. For each target, 5 mL of dissolved solution sample was measured using an HPGe detector 20 h after EOB. Solid titanium monitor foils were measured by the same detector 19 days after EOB [START_REF] Nigron | Is 70Zn(d,x)67Cu the Best Way to Produce 67Cu for Medical Applications[END_REF] to allow the full decay of 48 Sc (T1/2 = 43.67 h, E = 983.526 keV, Iγ = 100.1%) and avoid interferences. Similarly, solid nickel monitor foils were measured 2 months after EOB [START_REF] Hermanne | New measurements and evaluation of database for deuteron induced reaction on Ni up to 50 MeV[END_REF] to avoid interferences of 56 Ni (T1/2 = 6.075 d, E = 811.85 keV, Iγ = 86.0%).All targets and foils were counted with an HPGe detector for 24 hrs. The distance between the sample and the detector was 0 cm for liquid samples (contact) and 19 cm for solid samples. The dead time for liquid samples was between 5 % to 1 % and close to 0 % for solid samples. The Fitzpeak software (Fitzgerald et al., 2009) had been used to determine the EOB activity of 155 Tb (produced in composite targets), 48 V (produced in titanium monitors) and 58(m) Co (produced in nickel monitors). Energy and efficiency calibrations were carried out with a multi-gamma liquid source and a 152 Eu sealed source in the same geometry as the irradiated liquid samples and solid samples respectively.

Results and discussion

Optimization of co-deposition parameters

The main purpose of this work was to obtain a composite target with a high Gd atoms content and the best efficiency thanks to Gd initial amount. From this point of view, the effect of different parameters was studied including applied potential, initial Gd2O3 loading quantity and stirring speed.

Applied potential effects

To choose the potential ranges for a good Ni deposit, voltammetry curves with 5 cycles were performed. All curves of each cycle have the same behavior and Fig. 3 shows the voltammetry curves associated with the fifth cycle of solutions of Ni at 0.14 mol/L and pH equal to 9.8 with 0.8 g or 6.5 g Gd2O3 and without Gd2O3 loading. The solution was stirred by a magnet rod at 300 rpm. An oxidation peak can be observed between -0.4 V/NHE and -0.5 V/NHE, which may be explained by the formation of Ni(OH)2 on the surface of the electrode according to Milosev et al (2007). In the range -1.1 V/NHE to -1.3 V/NHE, the current density is between -10 mA/cm² and -25 mA/cm². The reduction process has also a peak near -1.1 V/NHE, which is probably due to the reduction from Ni(OH)2 to Ni [START_REF] Milošev | Study of Cu-18Ni-20Zn Nickel Silver and other Cu-based alloys in artificial sweat and physiological solution[END_REF]. When the voltage is more negative than -1.3 V/NHE, small fluctuations appear on the curve, which may explain the formation of dendritic structures on the deposits in this voltage range (Fig. 5).

Applied potential effects on average current density, deposit thickness, deposited Gd mass and Gd content fraction are summarized in Table 3. Each of the co-deposition processes lasted 1 hour, with a stirring speed of 300 rpm and a loading of Gd2O3 of 6.5 g. Table 3 shows that when the applied potential is low enough (-1.04 V/NHE), the Gd content in the composite is the highest (8.5 ± 0.6 at.%). However, due to the lower current density (-1.9 ± 0.4 mA/cm²), the thickness of the deposit is limited (3.1 ± 0.4 µm), as a result, the total Gd content is limited (only 1.5 mg of Gd were trapped in the deposit in these conditions). As the applied potential becomes more and more negative, the deposit kinetics increases, although the atomic ratio of Gd in the deposit remains relatively low (around 4 %). In this case, the total Gd quantity trapped in the deposit increases due to the growing thickness of the deposit.

EDX analysis coupled with SEM were also performed to see deposits morphology. Two kinds of particles with different brightness appear on the surface. The EDX analysis (Fig. 4) found the presence of Gd and Ni particles in the deposits, the darker particles were identified as Ni while the lighter particles were identified as Gd2O3. Fig. 5 presents general morphology studies of four deposits under different potentials (from -1.04 V/NHE to -1.30 V/NHE). As can be seen in ( a) and (b) of Fig. 5, with a potential of -1.04 V/NHE, the deposit surface was uneven. This may be because the thickness of the deposit is too thin to smooth the rough surface of the substrate. In addition, under this applied potential condition, the distribution of Gd2O3 particles was not uniform, and some Ni matrix was not covered by Gd2O3. When the potential value was set between -1.16 V/NHE and -1.2 V/NHE (c, d, e and f on Fig. 5), the microscopic surface structures of deposits were very similar. Their surfaces were smoother with more uniform Gd2O3 trapped in the Ni matrix as compared to the previous conditions.

However, when the applied potential was too negative (-1.3 V/NHE), cauliflower-like structures and craters of Ni form on the deposit surface leading to a honeycomb-like overall deposit structure. This morphology is similar to morphologies of Ni or Cu co-deposition in very negative potential [START_REF] Ćirović | Synthesis, structure and properties of nickel-iron-tungsten alloy electrodeposits -part I: Effect of synthesis parameters on chemical composition, microstructure and morphology[END_REF][START_REF] Jović | Electrodeposition of Ni, Co and Ni-Co alloy powders[END_REF][START_REF] Nikolić | Hydrogen Co-deposition Effects on the Structure of Electrodeposited Copper[END_REF].

Crater structures may be caused by the formation of hydrogen due to hydrogen reduction reaction (Nikolic et al., 2010). There was very little Gd2O3 on the larger cauliflower particles. Gd2O3 particles were gathered in the craters. With the formation of dendritic patterns, these deposits exhibit low adhesion and poor uniformity of Gd2O3, which makes them unsuitable as a target.

Considering both the total Gd quantity obtained in the composite target and the quality of the deposit, -1.2 V/NHE was selected as the best applied potential to prepare the composite target for irradiation experiments.

Gd2O3 loading quantity effects

The comparison between no loading electrolyte and Gd2O3 loading curves (Fig. 3) shows that with the addition of Gd2O3, the current density slightly decreases for the reduction of Ni 2+ , but the slope of the reduction curve remains unchanged. This means that the reduction of Ni 2+ /Ni with Gd2O3 becomes easier without affecting the reaction mechanism. This may be because the absorption of Gd2O3 increases the surface area of the cathode, which in turn provides more nucleation sites for nickel ions [START_REF] Low | Electrodeposition of composite coatings containing nanoparticles in a metal deposit[END_REF]. Through comparison between curves (a) and (b) of Fig. 3, it is found that under the same potential, the greater the Gd2O3 load, the more negative the current density, which also means that more deposits can be obtained. To investigate the effect of Gd2O3 loading, deposit Gd content was analyzed.

Fig. 6 shows the change of the Gd quantity trapped in the deposit as the addition of Gd2O3 increased from 0.1 g to 6.5 g. Experiments were repeated 3 times for each Gd2O3 loading, Fig. 6 presents mean values and standard deviations associated with each Gd2O3 content. The stirring speed was 300 rpm and the applied potential was -1.2 V/NH for all these deposits. The total amount of Gd2O3 trapped in the deposit is positively correlated with the amount of Gd2O3 in the solution (Fig. 6 (a)). Only 0.4 mg Gd is trapped in the deposit for 0.1 g of Gd2O3 loading, while for 6.5 g of Gd2O3 loading, the deposit contains 3.0 mg Gd. The effect of Gd2O3 loading is more obvious when the amount is smaller: when the loading mass increases from 0.1 g to 2.0 g, the trapped mass increases from 0.4 mg to 2.5 mg. The effect of Gd2O3 loading is weakened when its quantity is more than 2.0 g. The change of utilization rate of Gd with the Gd2O3 loading is reported in Fig. 6 (b). When less Gd2O3 is added, the ratio of trapped Gd to the incorporated Gd2O3 is higher. As the Gd2O3 loading increases from 0.1 g to 6.5 g, the incorporation rate of Gd decreases from 0.40 % to 0.04 %. A high incorporation rate is beneficial for cost saving when using enriched Gd oxide. So, a balance must be found to use as little as possible Gd2O3 while ensuring that sufficient Gd is trapped in the deposit.

Stirring speed effects

In the process of co-deposition, the capture of Gd2O3 particles is a mechanical process where charged Ni(NH3)6 2+ and Ni(NH3)5 2+ ions formed by the complexation of NH3 and Ni 2+ could wrap around Gd2O3 particles to form clusters. To achieve this, Gd2O3 clusters that are in suspension in the electrolyte need to pass through the convection layer, diffusion layer and electrical double layer to finally reach the deposited layer [START_REF] Low | Electrodeposition of composite coatings containing nanoparticles in a metal deposit[END_REF]. The effect of stirring is not only to distribute the clusters as evenly as possible in the electrolyte but also to affect the state of the fluid, which will affect the transport of clusters in the convection layer.

The effects of stirring speed on the Gd content of Ni-Gd2O3 deposits can be seen in Fig. 7. Each point in the figure is the average of three repeated experiments, and the error corresponds to the standard deviation. It can be seen that the Gd content increases when the stirring speed increases from 100 rpm to 300 rpm (from 1.4 mg to 3.0 mg), but it decreases when the stirring speed increases further, from 300 rpm to 800 rpm (from 3.0 mg to 1.8 mg).

The low Gd content at lower stirring speed may be explained as a cluster distribution problem: when the stirring speed is too low (100 rpm), the distribution of clusters is not homogeneous, more clusters gather at the bottom of the cell. The low Gd content at high stirring speed may be related to the convection process: when the stirring speed is too high (800 rpm), the electrolyte is in a turbulent state, and the strong hydrodynamic force takes away part of the Gd2O3 particles so that they cannot diffuse into the deposited layer.

From these results, the stirring speed was fixed at 300 rpm for the composite target making.

Cross section results

According to parameter analysis, over 50 targets were fabricated to verify the above optimal experimental conditions (an applied potential of -1.2 V/NHE, a stirring speed of 300 rpm and the addition of 6.5 g of Gd2O3). Then, seven targets were manufactured with a co-deposition duration varied from 10 to 60 min. These targets were irradiated for cross section measurement.

Gd content in targets and measured cross section values are summarized in Table 4.

Fig. 8 shows the comparison of our measured values and existing data in the literature [START_REF] Duchemin | Deuteron induced Tb-155 production, a theranostic isotope for SPECT imaging and auger therapy[END_REF][START_REF] Szelecsényi | Investigation of deuteron-induced reactions on natGd up to 30 MeV: possibility of production of medically relevant 155Tb and 161Tb radioisotopes[END_REF][START_REF] Tárkányi | Activation cross-sections of deuteron induced reactions on natGd up to 50MeV[END_REF]. The figure evidence that despite a low amount of Gd in the deposit, the measurement results of this work are in good agreement with other data, and the experimental errors of this work are similar to the one in the literature data. This confirms that Ni-Gd2O3 composite deposits can be used as targets for the 155 Tb cross section measurement, even in the case of small quantity of Gd (0.4 mg, target n° 2 from Table 4). This indicates that the co-deposition method can be applied to manufacture Gd targets. We also see that even a small amount of Gd2O3 can be efficient to obtain relevant data which is an advantage for future work on enriched 155 Gd2O3 from the point of view of cost.

Conclusion

In this study, we have successfully developed a method to make Ni-Gd2O3 composite thin targets via electrochemical co-deposition. This method allows manufacturing targets that can be used for production cross section measurements. Considering the surface quality and deposited Gd quantity, the optimal condition for the co-deposition to apply are -1.2 V/NHE potential, with a load of 6.5 g Gd2O3 and a stirring speed of the electrolyte equal to 300 rpm. Under these conditions, we can reach a thickness of 14.3 µm after one hour of co-deposition, which contains 3.0 mg of Gd. SEM analysis confirms that the surface of the deposits is flat and the distribution of Gd2O3 is uniform.

The feasibility of cross section measurement through composite targets has been confirmed.

The measured cross section values show great consistency with the data in the literature. This indicates the possibility to use these technique together with enriched gadolinium material to produce thin targets for cross section measurements. 155 Tb production cross sections induced by deuteron and proton reactions on enriched 155 Gd will be measured as the next step. This also opens the possibility to use this technique for thin target preparation in general when electroplating is difficult. Fig. 4 EDX analysis of the chemical composition of the deposits. Applied potential was -1.20 V/NHE, stirring speed was 300 rpm, Gd2O3 loading was 6.5g, Ni 2+ concentration was 0.14 mol/L, pH = 9.8. Gd (d, x)

Figure Captions

Fig. 1

 1 Fig. 1 Schematic diagram of cell structure and electrodes positions used in our experiments:The cell contains 35 mL electrolyte solution. WE refers to the working electrode, AE to the auxiliary electrode, RE to the reference electrode. During the process, a magnetic stirring, a sealing film and a stainless steel plate are also used. Suspended Gd2O3 particles (black dots) were evenly distributed in the electrolyte thanks to the stirring. The schematic diagram is not drawn according to the actual scale.

Fig. 2 Fig. 3

 23 Fig. 2 Schematic diagram of the stack composition used for the experiment where we irradiated target n°4 and n°7. The size and thickness of the foils are not drawn according to the actual scale.

Fig. 5

 5 Fig.5Microscopic images of surface morphology and Gd2O3 distribution of the deposits. Loaded Gd2O3 was 6.5 g, stirring speed was 300 rpm, applied potential was -1.04 V/NHE (a, b), -1.16 V/NHE (c, d), -1.20 V/NHE (e, f), -1.30 V/NHE (g, h).

Fig. 6

 6 Fig. 6 Effects of Gd2O3 loading on the quantity of Gd trapped Ni-Gd2O3 deposits. (a) mass of Gd in deposits. (b) Percentage of trapped Gd relative to the mass of Gd2O3 incorporated. The stirring speed was 300 rpm, the applied potential was -1.2 V/NHE.

Table 1

 1 Beam parameters of each target foil

	Tables
	Target number Mean beam intensity (nA)	Energy (MeV)	Irradiation time (min)
	1	60.2 ± 4.7		8.7 ± 0.5	30
	2	61.7 ± 4.7		13.2 ± 0.5	60
	3	78.7 ± 6.0		14.2 ± 0.4	60
	4	53.6 ± 4.0		19.5 ± 0.6	30
	5	89.3 ± 6.8		24.0 ± 0.5	60
	6	59.5 ± 4.6		24.4 ± 0.3	30
	7	53.0 ± 4.1		29.5 ± 0.3	30
	Radionuclide Half-life (d)	Eγ (keV)	Iγ (%)
	155 Tb	5.32 (6)	180.08	7.5 (4)
	48 V	15.9735 (25) 983.525	99.98 (4)
	58(m) Co	70.86 (6)	810.7593 (20) 99.450

Table 2

 2 Decay data of detected radionuclides(Nudat 2.8 batabase, 2021).Table 3 Applied potential effects on average current density, deposit thickness, deposited Gd mass and Gd content in composites deposits Table 4 Irradiated Ni-Gd2O3 composite target information and cross section of nat

	Applied potential (V/NHE)	Average current density (mA/cm²) Deposit thickness (µm) Gd quantity (mg)	Gd ratio in the deposit (at.%)
	-1.04	-1.9 ± 0.4	3.1 ± 0.4	1.2 ± 0.3	8.5 ± 0.6
	-1.16	-9.3 ± 0.6	12.2 ± 0.6	1.8 ± 0.1	3.6 ± 0.1
	-1.20	-10.2 ± 0.6	14.3 ± 0.7	3.0 ± 0.4	4.3 ± 0.3
	-1.30	-17.3 ± 0.9	26.5 ± 1.8	8.6 ± 0.6	4.5 ± 0.6
	Target number Gd content (mg)	Energy (MeV)	Cross section 155 Tb(mb)
	1	3.1	8.7 ± 0.5	24.5 ± 1.9
	2	0.4	13.2 ± 0.5	87.8 ± 14.9
	3	1.7	14.2 ± 0.4	104.2 ± 14.4
	4	2.6	19.5 ± 0.6	208.5 ± 15.7
	5	1.8	24.0 ± 0.5	322.7 ± 29.8
	6	2.6	24.4 ± 0.3	362.6 ± 27.9

Acknowledgment

The cyclotron Arronax is supported by CNRS, Inserm, INCa, the Nantes University, the Regional Council of Pays de la Loire, local authorities, the French government and the European Union. This work has been, in part, supported by a grant from the French National Agency for Research called "Investissements d'Avenir", Equipex Arronax-Plus ANR-11-EQPX-0004, Labex IRON ANR-11-LABX-18-01 and ISITE NExT ANR-16-IDEX-007.


José A Piornos

Dimitrios P Balagiannis

| Elisabeth Koussissi

‡ | August Bekkers

Johan Vissenaekens

Bert-Jan Grootes

Eric Brouwer

Jane K Parker
email: j.k.parker@reading.ac.uk|www.reading.ac.uk

Multi-response kinetic modelling of the formation of five Strecker aldehydes during kilning of barley malt to understand the effect of temperature and time on the formation of aroma compounds in malt during the curing stage of kilning, to develop a mechanistic kinetic model for the formation of Strecker aldehydes. to estimate rate constants and activation energies of the reactions defined in the model. Results & Discussion Kilning temperature programmes ▪ Barley is the fourth most important cereal crop in the world; around 30% is used for malt production 1 . ▪ Kilning process conditions (temperature gradient mostly) determine both colour and aroma of barley malts. ▪ This happens during the curing stage of kilning. ▪ Malt characteristic aroma is mainly due to the presence of Strecker aldehydes formed through the Maillard reaction.

The drying stage was kept constant for all experiments.

Isothermal curing stage in order to understand the effect of temperature.

HS-SPME-GC-MS

Malting trials

Experiments carried out in duplicate for each temperature and variety. Samples analysed in duplicate

Quantification of volatile and non-volatile compounds

Multi-response kinetic modelling

90°C 78°C 65°C A C D k 1 k 2 B d[A] dt = -k 1 [A] d[B] dt = -k 1 [B] d[C] dt = k 1 A B -k 2 [C] d[D] dt = k 2 [C] k= k′ • e E a R g 1 T ref - 1 T

How to develop a kinetic model:

1. Propose a model based on the known chemistry of the process. 2. Solve the model. The estimated values for k' and E a will be the ones that make the predicted model fit the observed values the best.

Modify the model (add or remove compounds and steps)

and check whether it improves.

A simple example of a kinetic model:

And the system of differential equations associated: • 'Intermediate 1' represents a pool of reactive intermediates that once they are formed, they react rapidly to other compounds.

• No significant differences were found between spring and winter barleys.

•

  This model can successfully predict the final amount of these important flavour compounds in malt, and in consequence the organoleptic quality of the malt. • It is possible to control the kilning process by manipulating the raw materials and their precursor concentration, as well as the time/temperature kilning profile. An example of the trends for the compounds involved in the formation of 3-methylbutanal ( observed predicted

  , fructose Amino acids: Phe, Trp, Ile, Leu, Met, Tyr, Val, Pro, Glu, Thr, Ala, Gly, Gln, Asn, Asp, Ser, His, Arg, Lys Amadori rearrangement products: fructosyl derivatives of Val, Ile, Leu, Phe, Ala, Gly, Pro Samples Two varieties of barley: the two-row spring variety 'RGT Planet' and six-row winter variety 'Etincel'

•

  There was a clear dependence of the concentration of Strecker aldehydes and curing temperature, with the highest values reached at 90 °C. • The model was based on previous studies about the formation of Strecker aldehydes in other foods 2 .

  on the kinetic rate constants. (*) k 12 , k 13 , k 14 , k 15 , k 1i and k M in kg mmol -1 h -1 ; k 2 and k F in h -1 .•Higher activation energies (steeper slopes in the graph above) mean that a temperature rise brings about larger increases in kinetic rate constants in relation to lower activation energies.• k 2 and k M (degradation of Amadori rearrangement products and 'Intermediate 1', respectively) had higher activation energies Ea than other reactions (steeper slopes);the intermediate compounds degradation rate increased to a larger extend than the degradation rate of the precursors. These intermediates are more sensitive to temperature rises than the precursors in the reaction.

This project has been funded by Heineken Global Supply Chain, BV.


Jose A Piornos

Dimitris P Balagiannis

Elisabeth Koussissi

Eric Brouwer

Jane K Parker

Characterisation of the key aroma compounds in alcoholfree beer base by gas chromatography-olfactometry

The pleasant fruity flavour of lager beers is one of the most appreciated features of these beverages, whereas alcohol-free beers (AFB) also exhibit a flavour reminiscent of wort. Even though several studies have been carried out to characterise the key odorants in different alcoholic beers, there are no similar works for AFB. Hence, the aim of this research is to identify the compounds contributing to the characteristic aroma of AFB. In this work, the volatile fraction of an AFB-base (without added flavourings) was isolated using solvent assisted flavour evaporation (SAFE) and analysed by GC-MS and GC-Olfactometry. Twenty-three odour regions showed odour activity in GC-O experiments, amongst which the most potent were methional, phenylacetaldehyde, 2-methoxyphenol, β-damascenone, 2-phenylacetic acid, 2-phenylethanol, and 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone. The presence of these compounds plays a crucial role in AFB aroma.

Introduction

AFB consumption has increased over the last few years, mainly in response to strict drink driving legislation, medical recommendation or religious grounds, but also due to a growth in health awareness. According to current UK legislation, the description "alcohol-free" may be applied to products containing "an alcoholic strength by volume of not more than 0.05 per cent".

These beers usually exhibit a flavour reminiscent of wort. Recent literature shows that Strecker aldehydes, particularly 2-methylbutanal, 3-methylbutanal and methional, are responsible for the negative attributes associated with AFB flavour [1], and these compounds are also present in barley malt [2]. These aldehydes have exceptionally low odour thresholds (1.25 μg/L, 0.6 μg/L and 0.25 μg/L for 2-methylbutanal, 3-methylbutanal and methional, respectively [3]) and impart potent worty, malty aromas even at very low concentrations.

Although worty aroma of AFB has been related to Strecker aldehydes [1], there is no information in literature about the possible contribution of other odour-active compounds to the overall aroma of AFB. Sensomic methodology has been employed to identify the key odorants in different beers, such as pale lager [4] and wheat beers [5]. In the latter example, the authors found more than 30 odorants contributing to the characteristic aroma of wheat beer, Strecker aldehydes being amongst them. The aim of this study was to identify a more complete set of odour-active volatile compounds present in AFB by means of Sensomic methodology.

Experimental

Materials

An alcohol-free beer-base (AFB-base), without any external flavour added, was brewed, bottled and pasteurised in Heineken's pilot brewery (Zoeterwoude, The Netherlands) in January 2016 following a standard cold-contact fermentation procedure (brewing conditions not specified). Diethyl ether and saturated alkane standards were purchased from Sigma (Dorset, UK).

Isolation of the volatile fraction

For the isolation of volatiles from the AFB-base, the procedure described by Langos et al. was employed with slight modifications [5]. Briefly, 1 kg of sample was extracted with redistilled diethyl ether (250 mL  4). The organic phase was dried over anhydrous Na2SO4 and filtered before concentration using a Vigreux distillation column (60 cm, 1 cm i.d.) at 40 °C until a final volume of approximately 100 mL was reached. To separate the non-volatile materials from the extract, this was submitted to a high-vacuum distillation process known as solvent assisted flavour evaporation (SAFE) technique (evaporation at 25 °C and 10 -5 Pa). The distillate was fractioned into an acidic and a basic/neutral fraction using NaHCO3 0.5 M solution (60 mL  3). After washing with 30 mL of a saturated NaCl solution three times, the organic layer was kept for further treatment (basic organic extract). In parallel, the basic aqueous phase was acidified to pH 2.25±0.10 by adding HCl solution (10 M or 1 M) and extracted using redistilled diethyl ether (60 mL  3) and the extracts combined (acidic organic extract). Both basic and acidic organic extracts were concentrated using a Kuderna-Danish concentrator at 45 °C (final volume ~400 µL for each extract). The concentrated aroma extracts were kept at -80 °C until use.

Gas chromatography analyses of concentrated aroma extracts

In order to identify odour-active compounds in the concentrated aroma extracts, these were analysed by GC-Olfactometry (GC-O) using a 5890 Series II gas chromatograph (Hewlett Packard, Waldbronn, Germany) provided with an FID detector held at 250 °C. A sample (2 μL) was injected and two capillaries with different polarities were employed: Rxi®-5 Sil MS capillary (30 m, 0.25 mm i.d., 1.0 µm df) non-polar column and a Stabilwax®-DA (30 m, 0.25 mm i.d., 0.25 µm df) polar column, both from Restek (Bellefonte, Pennsylvania, USA). The temperature gradients were set as follows: 40 °C for 2 min, then a rise of 5 °C/min up to 200°C and 15 °C/min from 200 °C to 300 °C, and then held for 19 min for the non-polar column; 40 °C for 2 min, then rise of 4 °C/min up to 200 °C, then from 200 °C up to 250 °C at 15 °C/min, and then held for 15 min for the polar column. Helium was used as a carrier gas (2 mL/min). The sample was split 1:1 at the end of the column, followed by two untreated silica-fused capillaries of the same dimensions (1 m, 0.32 mm i.d.). An ODO II sniffing port (SGE, Ringwood, Victoria, Australia), where the flow was diluted with a moist make up gas, was utilised. Every sample was analysed by at least 3 assessors in duplicate. The assessors scored the intensity of the aromas perceived on a scale from 1 ("very weak") to 10 ("very strong"). These results were reported as the modified frequency, defined as MF(%)=[F(%)•I(%)] 1/2 , where F(%) is the detection frequency and I(%) is the average intensity expressed as the percentage of the maximum intensity [6].

The concentrated aroma extracts were also analysed by GC-MS using equivalent capillaries and chromatographic conditions as used for the GC-O analyses. The instrument employed for these analyses was a gas chromatograph model 7890A coupled to a 5975C inert XL EI/CI MSD triple axis mass spectroscopy detector and a 7683B Series autosampler (Agilent Technologies, Santa Clara, CA, USA). The carrier gas was helium at a flow rate of 1mL/min. Mass spectra were recorded in the electron-impact mode at an ionisation voltage of 70 eV and source temperature of 200 °C.

Results and discussion

The sensomic approach was applied for the identification of key odorants in alcoholfree beer. Recently, this methodology has been applied to identify key flavour compounds in a wide variety of foodstuff and beverages, such as hazelnuts [7] and rapeseed oil [8]. For this reason, concentrated aroma extracts (basic and acidic fractions) were prepared from AFB-base using the methodology described previously [5]. These extracts from the AFB-base were sniffed by GC-O on columns of different polarity and mass spectra were obtained from GC-MS analyses. Twenty-three odour regions were found in total in both basic and acidic fractions from the AFB-base. Table 1 shows the most active odour regions found in the SAFE extracts. Amongst them, the highest MF values corresponded to 2-methoxyphenol, β-damascenone, 5-ethyl-3-hydroxy-4-methyl-2(5H)-furanone, 2-phenylacetic acid, 2-phenylethanol and the Strecker aldehydes methional and phenylacetaldehyde. The presence of these compounds might explain the honey-like, worty aroma of alcohol-free beers brewed by cold contact fermentation. Moreover, two Strecker aldehydes were found to be important: 2-methylbutanal and 3-methylbutanal. These two, along with methional, have been previously reported as contributors to malty and worty aromas in alcohol-free beers [1,2].

Similar work has been carried out in other beers, such as wheat beer [5] and pale lager beer [4], where higher alcohols and esters were found to be main contributors to the overall aroma. Examples of these are ethyl hexanoate, ethyl butanoate, 3-methylbutyl acetate, and 3-methyl-1-butanol. In our case, no fruity esters were detected by GC-O. This was associated with the mild conditions for cold contact fermentation process, where yeast was not active enough to synthesise esters throughout the Ehrlich pathway [9]. Butanedione, also found in this study, has been reported as an off-flavour in lager beers [START_REF] Dresel | Springer Handbook of Odor[END_REF].

Moreover, in this study we used an alcohol-free beer "base" which was prepared without the addition of external flavours which provide the desirable fruity note which is not generated during cold contact fermentation. The addition of external flavours to commercial alcohol-free beers is common practice of brewers to improve the flavour of AFB.

We conclude that the information generated from this study will help in the identification of the less desirable worty notes in alcohol-free beers. Further quantitative and sensory analysis will elucidate the actual role of the key odorants in the overall aroma of these beverages.

a

  Odour perceived at the sniffing port of the GC-O. b Compounds were identified by comparison of their mass spectrum and LRI on two columns with those of authentic standards, and confirmed by detection in the extract by GC-MS c Fraction where the compound was found: basic/neutral (b) or acidic (a). d MF(%)=[F(%)•I(%)] 1/2 , where F(%) is the detection frequency and I(%) is the average intensity expressed as the percentage of the maximum intensity *Tentative identification based on odour description and LRI.

Table 1 :

 1 Odour regions and attributed compounds found by GC-Olfactometry (n=3 in duplicate) in acidic and/or basic fractions of a SAFE extract of an alcohol-free beer-base

		LRI
	Rxi-5	Stabil-wax	Odour quality a	Odorant b	Fn c	%MF d
	579	1000	cream, butter	butanedione	b	80
	648	950	malty, cocoa	3-methylbutanal	a	65
	664	1429	vinegar	acetic acid	a	76
	680	950	cocoa	2-methylbutanal	b	60
	725	1225	banana, alcoholic	3-methyl-1-butanol	b,a	44
	845	1609	cheese	butanoic acid	a	76
	886	1646	cheese, rancid	3-methylbutanoic acid


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