Boris Berthelot #$
email: boris.berthelot@laas.fr

Jean-Guy Tartarin
email: 2tartarin@laas.fr

Christophe Viallon #

Remy Leblanc $

Hassan Maher

François Boone

GaN MMIC Differential Multi-function Chip for Ka-Band Applications

Keywords: attenuator, Gallium Nitride, Ka-band, MMIC phase shifter, quadrature amplitude modulation (QAM)

High data rate communications have become possible due to improvements in microelectronics, and is based on new topological concepts of architecture. The development of 5G networks using the Ka-band is one of the challenges for new telecommunication systems based on individually controlled active antennas (AESE). The control system is usually developed using silicon processes but this approach does not allow a fully embedded transceiver as the front-end module must be connected to the core-chip module and to its digital control interface. With the GaN power technologies providing high PAE, an interesting issue consists in designing a fully integrated GaN MMIC multifunction chip for highly integrated systems. This work presents, for the first time, a GaN attenuator-phase shifter covering a wide range of frequencies from 30 GHz to 40 GHz. Moreover, this circuit is a balanced version of the attenuator-phase shifter to target an improved linearity and to take full advantage of GaN power amplifiers.

I. INTRODUCTION

The design of attenuator and phase shifter circuits is usually developed in SiGe and CMOS technologies for their high performance and high integration advantages over III-V technologies. Nevertheless, the permissible power level of these circuits does not exceed 20dBm, thus the power gain necessary to compensate interconnections losses quickly become more difficult to reach, especially in the Ka-band. In contrast, III-V technologies can overcome this drawback at the circuit level by making possible a higher integration level when embedded with the power module and switches of the front-end [START_REF] Rieger | A Full-Array-Grid-Compatible Wideband Tx/Rx Multipack Using Multifunctional Chips on GaN and SiGe[END_REF]. Moreover due to their higher permissible power level when using GaN technologies, the required gain of power amplifier is less important. This subsequent solution allows the implementation of a single chip with a full monolithic design, with Serial Input Parallel Output Interface developed on the same chip (i.e. normally-on and normally-off devices to drive the attenuator and phase shifter states) [START_REF]Ommic[END_REF]. Next generation solid state GaN devices offer reduced surface chip for a given output power due to a better drain current, a higher breakdown voltage and junction temperature. Then, the step for phase array systems (used in radar and electronic warfare, but also future telecommunication systems) is to provide these technologies with such embedded attenuator -phase shifter circuits, next designed as 'core-chips' or multi-functions chip (with fully integrated module when enhanced and depletion mode transistors are available). This work is focused on a large bandwidth demonstrator (30 GHz-40 GHz), using a differential structure to improve the linearity of the circuit since this one will be located directly before (or possibly from part to part of) the power amplifier. This work makes use of electrical and EM simulations to secure the design of each cell, and then of the full 11-bit (5 attenuation states, 6 phase-shift states).

Following this introductory paragraph, the second section presents the individual architecture of each cell composing the 11-bit core-chip. Since the initial requirements are stringent (up to 30% bandwidth, inter-stage matching and error functions reduction over the targeted frequency band), the design procedure is presented. The third section presents the measured MMIC chip, digitally controlled by Arduino to set the 2048 states. The constellations associated to a frequency range are discussed in section IV. A conclusion defines the trade-off on the modulation schemes regarding the targeted bandwidth: for a large one (29%), or a reduced one (11%) centered on 35 GHz. Different alternatives of design (single-ended version) are introduced (and discussed in the final version), also considering the linearity of these GaN digitally controlled circuits.

II. CORE-CHIP DESIGN AND SIMULATION

This work has been motivated by the OMMIC corporation in the race of GaN circuits and systems towards high frequencies, and specifically the Ka-band. The portfolio of OMMIC provides the users with many GaN modules, mainly dedicated to power amplifiers, but also robust low-noise amplifiers, and now evolves towards new functions such as core-chips to propose a large variety of circuits that can be embedded on a single chip (featuring overall smaller areas as it overcomes bonding on RF, DC and/or control states).

The stringent specifications are given below:

-bandwidth from 30 GHz to 40 GHz -dynamic attenuation range larger than 15dB -dynamic phase shift between 0°-360° -attenuator and phase shift errors as low as possible (according to the number of used bits as discussed in section III).

Specifically, each cell has to be matched at its input and output port (less than 15 dB); this makes it complicated to accommodate performances (Sij) and matching conditions (Sii) over such initially defined large bandwidth. This issue has been considered as specific keypoint during our design procedure, but will be addressed in another paper.

As previously stated, GaN transistors are excellent options for analog high frequency power modules. However, the large surface area (in comparison with vertically stacked Heterojunction Bipolar Transistors in BiCMOS processes) introduce phase shifts that have to be carefully accounted for.

The core-chip under consideration is composed of 11 different cells, and the fulfillment of the system's specifications needs an objective procedure during the design steps as given below:

1)-Ideal topology analysis (best situation case) using only GaN transistors from OMMIC's design kit D01GH, and lumped elements. The HEMT devices feature 100 nm gate length, with various gate development (number of gate fingers and gate width). Applicability to the targeted frequency band 30-40 GHz and performance/matching management. These simulation results establish minimum achievable errors.

2)-Simulation of the cell using real electrical model of the reactive elements, followed by minimization of errors in the design layout; the sensitivity of non-symmetrical parts of the circuit is considered to lower the common mode conversion.

3)-EM simulations to validate the electrical design and to reduce the risk factor during the design steps when including real elements and lines (same procedure for each of the 11 cells) 4)-Global electrical and EM simulations. The organization of cascaded cells for reduction of errors is also considered (management of mismatch and performances interactions for 11 factorial possible organizations of the 11-bit core-chip). This strategy has been used for single ended design (discussion in section IV).

Examples of ideal topologies are given as an illustration for the 5 attenuators and for the 6 phase shifters in Fig. 1.

The 6-bit phase shifter and 5-bit attenuator is designed for an ultimate target resolution of 5.625° and 0.5dB for this 11-bit configuration. However, as discussed in the next section, this generic Ka-band GaN MMIC core-chip can be used for multipurpose applications, with the knowledge that there is a tradeoff between frequency range and modulation scheme complexity (the larger the frequency band, the lower the quadrature-amplitude modulation complexity). Fig. 2a depicts the simulated constellation of phase and attenuation making use of the 11-cells of the core-chip, centred at 35 GHz. The good global coverage can be appreciated and becomes even more difficult to achieve with increasing frequency band. For balanced S-parameter simulations, the common-mode and differential-mode have been investigated, and prior to any design analysis, the simulation environment has been validated by using two methods; the mathematical formalism can be found in [START_REF] Bockelman | Combined differential and common-mode scattering parameters: theory and simulation[END_REF] and correlates with the simulation setup dedicated to our measurements, based on the application note form Keysight [START_REF]Multiport & Balanced Device Measurement Application Note Series Concepts in Balanced Device Measurements[END_REF]. Moreover, if the targeted phase errors (resp. attenuation errors) must be considered as first order parameters during the design of the phase shifter (resp. attenuator), it must be highlighted the necessity to also consider, in turn, the impact of attenuation (resp. phase) variations for the overall RMS of the core-chip. Fig. 2b presents the RMS errors over the 30 GHz -40 GHz frequency band. A reduced attenuation error is obtained between 33-37 GHz (below 1 dB), while a degradation occurs for the larger frequency band (30-40 GHz) up to 1.5 dB. The constellation from the multi-function chip, as illustrated in Fig. 2, can be used at various frequencies to change the pattern of a multiple-antenna system (such as phase arrays).Such a multi-function circuit can be used to emulate any phase shift and amplitude constellation over a wide frequency band; the control of the switches within the 11-cell module can be achieved by using enhancement depletion technology as provided by the D01GH foundry.

This degraded RMS errors explains the reduced pattern size when increasing the frequency band as explained in the next section. Despite of the phase shift RMS non-centred profile, it can be stated that an advantage is taken from the 6-bit phaseshifter coverage to realize the phase shift and attenuator states according to the desired frequency bandwidth (i.e. 30 GHz-40 GHz 16-states, and 33 GHz-37 GHz 64 states). The MMIC is positioned on an epoxy-PCB secured with an electrically conductive adhesive, the connections between the chip and the PCB bias tracks are ensured by bonding wires. GSGSG probes are used to measure the four port single-ended S-parameter of the MMIC, leading to the extraction of the balanced S-parameters by using the mathematical analysis developed in [START_REF] Bockelman | Combined differential and common-mode scattering parameters: theory and simulation[END_REF]. Measurements are done using the Keysight N5247A four-port PNA-X Microwave Vector Network Analyser. Calibration is performed using SOLT correction method. The phase (resp. attenuator) accuracy is better than 0.5° (resp. 0.1dB) over the considered frequency range.

III. CORE-CHIP MMIC

The digital control of the 11 cells constituting the core-chip (2 transistors per cell) is performed by an Arduino module driven by a computer.

IV. TRADE-OFF BETWEEN MODULATION SCHEME AND FREQUENCY-BAND

A) 64-states pattern between 33 GHz and 37 GHz

The pattern presented in Fig. makes use of the complete characterization using the 11-bit facilities (i.e. 2048 states represented by blue dots). Some white regions indicate that the least significant bits do not allow an accurate coverage of the pattern using a full 11-bit definition. Nevertheless, the least significant bits can be used as fine adjusting parameters to match the core-chip coverage according to the desired pattern: Fig. 4 illustrates the possibility to implement a 64-QAM pattern with the designed core-chip (red symbols). This pattern is still efficient between 33 GHz and 37 GHz (i.e. 11% bandwidth), with 18 dB dynamics for the attenuation (by step of 2.4 dB), and 360° coverage (by step of 45°). Fig. 4. Measured core-chip pattern of the GaN-MMIC circuit @ 35 GHz, with evidence of a 64-states pattern (red circles, 8x8 states). This constellation is valid between 33 GHz and 37 GHz. Blue dots are related to the 11-bits pattern featuring 2048 states.

B) 16-states pattern between 30 GHz and 40 GHz

For an increased bandwidth up to almost 30% (still centred at 35 GHz), unsurprisingly the constellation coverage degrades.

Nevertheless, a 4x4 pattern can be used for a 16-states as proposed in Fig. 5. As the area of blue dots (i.e. 2048 states from the 11-bits full characterization of the core-chip) is less patterned than that presented in Fig. 4, the use of least significant bits can help in providing symbols at the vicinity of the red symbols (as illustrated by the dashed circle area for the most critical situations in Fig. 5). The dynamic in attenuation is still of 18 dB at 30 GHz and at 40 GHz (step of 7 dB), while the 360° angle coverage is synthetized by steps of 90°.

C) Comparison with single ended version

Other GaN core-chips have been designed, such as a singleended version, still in the Ka-band and based on a different procedure of design. This design is optimized for reduced RMS errors at 35 GHz, and takes advantage of the organization of the 11-cells to improve the performances of the overall circuit (step 4 from the procedure). This second circuit is currently in fabrication. The simulated constellation at 35 GHz, illustrated in Fig. 6, shows better repartition of phase and attenuation than that presented in Fig. 2a.

D) Linearity

Moreover, linearity simulations and measurements have been performed at 30 GHz, 35 GHz and 40 GHz on the balanced topology depicted in Fig. 3.

From simulation at the device level, compression point features variable output power with the sizing and the biasing of the device, with lowest power simulated at 10 dBm input compression point (common gate configuration, 1 finger of 15 µm gate length). It must be noticed that the topology (serial or shunt device) plays a strong role in the linearity of the circuit (individual cell and final chip). The shunt topology allows higher power levels than what the device can handle alone, like for SPDT series-shunt topologies [START_REF] Nguyen | Wideband high power SPDT and SP3T GaN MMIC switches in low-cost overmolded plastic package[END_REF]. This last point releases constraints on sizing versus power for the transistors from first stages of the core-chip.

From measurements, input power up to 25 dBm is applied to the device in single ended configuration. After calibration steps and with 3 dB correction using the balanced configuration, the linearity is still observed at 30 GHz, 35 GHz and 40 GHz over the power sweep. Thus, we assume that our Ka-band multi-chip circuit can handle input powers higher than Fig. 6. Simulated constellation of 11-bit single ended core-chip at 35 GHz 28 dBm. Dedicated high power (balanced) driver amplifier is needed to verify the linearity limitation of our chip, however the achieved performances are largely above the best results based on SiGe technologies at 20.5 dBm [START_REF] Liu | A Ka-Band Single-Chip SiGe BiCMOS Phased-Array Transmit/Receive Front-End[END_REF].

Finally, this work demonstrates the feasibility of variable multi-symbols patterns up to 30% bandwidth in the Ka-band, with realistic operable settings.

V. CONCLUSION The design of attenuator and phase shifter modules is a key point for new telecommunication or radar applications, as it allows focusing an antenna in a given direction to improve the radio-link budget efficiency, thus allowing the use of higher frequency bands and so the improvement of the data rate. For the first time, this paper demonstrates the feasibility of a MMIC GaN core-chip module that is digitally controlled, over a wide frequency bandwidth up to 30% in the Ka-band. The dynamic is 18 dB in attenuation over 30 GHz and 40 GHz. Measurements have demonstrated that a 64-states pattern can be used from 33 GHz to 37 GHz, while a 16-states pattern still operates for a wider frequency range between 30 GHz and 40 GHz. GaN core-chips can take advantage of the normallyon and normally-off transistor devices to design the digital control circuit of such a system. Then, a fully integrated transceiver module demonstrating high linearity can be developed in the Ka-band using this GaN technology. The integration can largely be improved using these modules for very small surface antennas at such elevated frequencies.

Fig. 1 .

 1 Fig. 1. ideal topologies for Phase Shifters (a)delay line 5,5°, (d)quad-switch 180° and (e)switched filter 11,25°, 22.5°, 45° and 90°) and Attenuators (c)loaded line 0.5dB and 1dB,(b)π-resistive network 2db, 4dB,and 8dB.

Fig. 2 .

 2 Fig. 2. (a) EM simulations of the 11-bits balanced core-chip (2048 states) (b) RMS attenuation and phase errors from 30 GHz to 40 GHz.

  An image of the Ka-band GaN core-chip is depicted in Fig. . The circuit is externally driven: bonding wires are used for electrical connection of the MMIC to an external PCB (gate control biasing). Dedicated software has been developed on an Arduino to set the 2048 different states of the core-chip.

Fig. 3

 3 Fig. 3 Image of the GaN Ka-band Core-chip featuring 11 digitally controlled states (6 phase shifters and 5 attenuators)

Fig 5 .

 5 Fig 5. Measured core-chip pattern of the GaN-MMIC circuit @ 30 GHz, with evidence of a 16-states pattern (red circles, 4x4 states). This pattern is valid between 30 GHz and 40 GHz. Blue dots are related to the 11-bit pattern featuring 2048 states. Red dashed circles feature the area where the symbol still applies for 16-states for critical situations with low availability of blue dots, and without producing error of symbol. Symbols on the right part (360°) are already synthetized on the left part (0°)


Caroline Klingebiel

Yannick Chantran

Rihane Arif-Lusson

Angelica E Ehrenberg

Jonas Östling

Alain Poisson

Valérie Liabeuf

Chantal Agabriel

Joëlle Birnbaum

Françoise Porri

| Yannick Chantran

Anne Sarrat

| Pol

André Apoil

Mylène Vivinus

Lorna Garnier

| Anca

Mirela Chiriac

Davide-Paolo Caimmi

Jean-Luc Bourrain

| Pascal Demoly

| Stéphane Guez

| Franck Boralevi

Bertrand Lovato

Céline Palussière

Sylvie Leroy

Thierry Bourrier

Lisa Giovannini-Chami

Marion Gouitaa

Agnès Aferiat-Derome

Denis Charpin

Tünde Sofalvi

Isabelle Cabon-Boudard

| Yann

Patrick Massabie-Bouchat

| Bernard Hofmann

Nathalie Bonardel

Mireille Dron-Gonzalvez

| Benoît

Ania Carsin

Serge Vivinus

| Bernard Poitevin

Laureline Nicolau

| Geneviève Liautard

Christophe Soler

Soraya Mezouar

Isabella Annesi-Maesano

Jean-Louis Mège

Jonas Lidholm

Joana Vitte
email: jvitte@ap-hm.fr

Allergobionet Networks

Pru p 7 sensitization is a predominant cause of severe, cypress pollen-associated peach allergy

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

tion as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure.

Objective: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France.

Methods: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform.

Results: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests.

Conclusion and Clinical Relevance:

A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

K E Y W O R D S

allergens and epitopes, anaphylaxis, basophil, cypress pollinosis, food allergy, IgE, immunological tests, peamaclein, Pru p 7

| INTRODUCTION

Fruit and vegetables account for the most common aetiology of food allergies in teenagers and adults. [START_REF] Asero | EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study[END_REF][START_REF] Burney | The prevalence and distribution of food sensitization in European adults[END_REF][START_REF] Fernández-Rivas | Fruit and vegetable allergy[END_REF][START_REF] Sánchez-López | Food allergy in Catalonia: clinical manifestations and its association with airborne allergens[END_REF] Severe reactions are frequent, with fruit and vegetables reported as causative in 5% of all cases of food anaphylaxis in children and adolescents in a range of European countries, [START_REF] Grabenhenrich | Anaphylaxis in children and adolescents: the European Anaphylaxis Registry[END_REF] and confirmed as culprit in 7% of children seeking emergency care at a major Madrid hospital for anaphylaxis-like symptoms. [START_REF] Alvarez-Perea | Anaphylaxis in the pediatric emergency department: analysis of 133 cases after an allergy workup[END_REF] Peach-induced immediate reactions are frequent in pollen-allergic patients and often occur as pollen-food syndromes (PFS). [START_REF] Cuesta-Herranz | Pollen allergy in peach-allergic patients: sensitisation and cross-reactivity to taxonomically unrelated pollens[END_REF][START_REF] Ma | A survey on the management of pollen-food allergy syndrome in allergy practices[END_REF][START_REF] Andersen | Identification of European allergy patterns to the allergen families PR-10, LTP, and profilin from Rosaceae fruits[END_REF] Birch pollen-related PR-10 sensitization underlies most cases of peach-induced oral allergy syndrome (OAS) occurring in temperate climates, while sensitization to non-specific lipid transfer proteins (nsLTPs) is predominant in Mediterranean regions and may induce OAS as well as severe reactions. [START_REF] Asero | EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study[END_REF][START_REF] Sánchez-López | Food allergy in Catalonia: clinical manifestations and its association with airborne allergens[END_REF][START_REF] Andersen | Identification of European allergy patterns to the allergen families PR-10, LTP, and profilin from Rosaceae fruits[END_REF][START_REF] Mastrorilli | Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification[END_REF][START_REF] Gamboa | Two different profiles of peach allergy in the north of Spain[END_REF] In southern Europe, primary food allergies, including peach allergy (PA), may account for up to 96% of food allergy cases. [START_REF] Asero | EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study[END_REF] Sensitization to nsLTPs, either as primary food allergy or as PFS, accounts for most of PA cases in the Mediterranean region. [START_REF] Asero | EpidemAAITO: features of food allergy in Italian adults attending allergy clinics: a multi-centre study[END_REF][START_REF] Asero | The clinical relevance of lipid transfer protein[END_REF][START_REF] Flores | Plant food allergy in patients with pollinosis from the Mediterranean area[END_REF] However, some PA patients have been found to lack sensitization to Pru p 1 (PR-10), Pru p 3 (nsLTP) and Pru p 4 (profilin), despite a convincing clinical history and a strongly positive skin test with fresh peach. [START_REF] Tuppo | Peamaclein -A new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3[END_REF][START_REF] Tenenbaum | Allergie à la pêche avec taux d'IgE spécifiques pêche et allergènes majeurs négatifs ou faiblement positifs[END_REF][START_REF] Klingebiel | Peamacléine Pru p 7: épidémiologie, implications cliniques et place dans le diagnostic moléculaire de l'allergie à la pêche en région méditerranéenne[END_REF] Pru p 7, also referred to as peamaclein, a member of the gibberellin-regulated protein (GRP) family, was described as a novel peach allergen. [START_REF] Tuppo | Peamaclein -A new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3[END_REF] We have previously reported Pru p 7 as a major allergen associated with severe clinical symptoms and strong cypress pollen (CP) sensitization in PA patients from Marseille, southern France. [START_REF] Klingebiel | Peamacléine Pru p 7: épidémiologie, implications cliniques et place dans le diagnostic moléculaire de l'allergie à la pêche en région méditerranéenne[END_REF] As France comprises a wide spectrum of geographic and climatic conditions, including continental, oceanic, Mediterranean and alpine regions, a variety of pollen sensitizations may occur across the country, making a fuller understanding of different pollen-related food allergies particularly relevant. In this study, we set out to further characterize the implications of Pru p 7 sensitization in PA in Mediterranean and non-Mediterranean regions of France.

| ME TH ODS

| Patients

Three hundred sixteen outpatients residing in southern France (42nd to 46th latitude north), seeking allergy work-up for a suspicion of peachinduced food allergy symptoms, were included in this study. Clinical data were collected by means of a standardized questionnaire retrospectively completed by the allergists. Continental, oceanic and Mediterranean climates were represented. Five geographic regions were defined based on cypress and birch pollen counts [START_REF]Le Réseau National de Surveillance Aérobiologique[END_REF] and numbered 1-5 according to ascending order of cypress/birch pollen count ratio: region 1 (Lyon and continental environments), region 2 (Bordeaux and neighbouring Atlantic coastal regions), region 3 (alpine and continental regions including Toulouse and southern Alps), region 4 (Nice and Montpellier regions) and region 5 (Marseille and Var regions, southernmost Mediterranean environments) (Table 1). Each participant's area of residency was categorized as belonging to one of these regions.

| Diagnostic criteria and procedures

Diagnosis of PA was confirmed or rejected according to ICON and EAACI guidelines for food allergy. [START_REF] Burks | ICON: food allergy[END_REF][START_REF] Muraro | EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy[END_REF][START_REF] Werfel | Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens[END_REF] The combination of a convincing clinical history of immediate reaction to peach in the past year, positive skin prick tests (SPT) to peach extract (Stallergènes-Greer, ALK-Abelló) or fresh peach defined as a weal >50% of the positive control, and/or IgE sensitization to peach, formed the basis of a PA diagnosis. [START_REF] Werfel | Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens[END_REF] Convincing clinical history was defined as one or more immediate reaction (s) within 2 hours after peach ingestion, inhalation or direct contact, presenting as acute urticaria or angioedema, contact urticaria, OAS, food-dependent exercise-induced anaphylaxis, laryngeal swelling, immediate vomiting, rhinitis, cough, wheezing, bronchospasm, hypotension or loss of consciousness. The use of peach-specific IgE determination in conjunction with clinical history and peach SPT helped reduce the need for oral food challenge (OFC) as advised. [START_REF] Muraro | Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology[END_REF] Diagnostic OFC was performed according to ICON and EAACI guidelines [START_REF] Burks | ICON: food allergy[END_REF][START_REF] Werfel | Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens[END_REF] and previous PA studies [START_REF] Fernández-Rivas | Fruit and vegetable allergy[END_REF][START_REF] Gamboa | Two different profiles of peach allergy in the north of Spain[END_REF] if negative SPT and IgE results were discordant with clinical history. Patients who had had a life-threatening reaction to peach during the last 12 months did not undergo OFC, in line with current guidelines. [START_REF] Burks | ICON: food allergy[END_REF] A total of 61 patients were subjected to OFC, of whom 41 failed (PA) and 20 passed (peach tolerant, PT).

OFC followed an open protocol, with peach peel and pulp tested separately. After a negative labial challenge test, doses of fresh peach were administered in sequential 20-minute steps, starting the provocation with 1/128 of one fruit (approximately 1 g), then proceeding with 1/64, 1/32, 1/16, 1/8, 1/4 and 1/2 (highest dose approximately 65 g). The OFC was stopped if objective or severe symptoms appeared: erythema, urticaria, sneezing, wheezing, cough, vomiting, severe abdominal pain, hypotension, neurological symptoms or difficulty to breathe. Patients were kept in day-care units at close proximity of an intensive care unit during the challenge procedure and were monitored for 4 hours after ingestion of the last dose of peach. At the end of the diagnostic procedure, patients were categorized as PA or PT.

The diagnostic investigation for other food allergies followed the same steps as that for PA.

| Assessment of clinical severity

The severity of clinical reactions was graded following the recently proposed classification of food allergic and anaphylactic reactions [START_REF] Niggemann | Time for a new grading system for allergic reactions[END_REF][START_REF] Muraro | The urgent need for a harmonized severity scoring system for acute allergic reactions[END_REF] : grade 1 comprising local reactions without systemic involvement: redness, swelling and itching; grade 2 mild to moderate systemic reactions involving distant skin locations, upper airways and/or gastrointestinal symptoms, but without cardiovascular or respiratory involvement: urticaria, angioedema, flush and gastrointestinal symptoms; grade 3 severe systemic reactions with cardiovascular and/or bronchial and laryngeal involvement: wheezing, stridor, objective dyspnoea, tachycardia, lowered blood pressure and shock.

| Ethics statement

Determination of IgE to whole allergen extracts and molecular allergens was part of routine investigations. Patients received written laboratory reports and the study was based on a retrospective review of medical records and laboratory results. In accordance with the Declaration of Helsinki and the French law on research involving humans, ethics committee approval and patient consent were not required for this type of non-interventional study, provided the patients received information and retained the right to oppose to the use of excess serum and anonymized medical data for research purposes. [START_REF] Loi No | 300 du 5 mars 2012[END_REF]25

| IgE antibody measurements

IgE antibodies directed to natural extracts and molecular allergens were measured with the ImmunoCAP ™ assay platform (Thermo Fisher Scientific, Uppsala, Sweden) during the routine diagnostic procedure.

All sera were assayed for IgE to peach, CP, PR-10 protein rPru p 1, nsLTP rPru p 3, profilin rPru p 4, the major and specific CP allergen pectate lyase nCup a 1, and MUXF3, representing cross-reactive carbohydrate determinants (CCD). IgE assays to additional allergen extracts and components were performed according to each patient's history. IgE to natural and recombinant Pru p 7 was measured on excess serum with experimental ImmunoCAP ™ tests. rPru p 1 and rPru p 4 were taken as surrogates for their respective allergen families due to high level of molecular similarity and cross-reactivity. [START_REF] Burney | The prevalence and distribution of food sensitization in European adults[END_REF][START_REF] Kleine-Tebbe | Molecular allergy diagnostics in clinical pratice[END_REF] Pru p 3, the immunodominant nsLTP and a possible primary sensitizer for this allergen family, [START_REF] Asero | The clinical relevance of lipid transfer protein[END_REF][START_REF] Tordesillas | Transport of Pru p 3 across gastrointestinal epitheliuman essential step towards the induction of food allergy?[END_REF] was considered representative of nsLTP sensitization. Specific IgE values exceeding the assay's stated limit of quantitation of 0.10 kU A /L were considered positive. [START_REF] Lambert | The importance of EN ISO 15189 accreditation of allergen-specific IgE determination for reliable in vitro allergy diagnosis[END_REF] For comparison of the experimental ImmunoCAP assay to an independent method for detection of IgE to nPru p 7, a subset of sera were analysed with the multiplexed FABER ® assay (CAAM, Rome, Italy). [START_REF] Alessandri | Diagnosing allergic sensitisations in the third millennium: why clinicians should know allergen molecule structures[END_REF][START_REF] Tuppo | Pomegranate chitinase III: Identification of a new allergen and analysis of sensitization patterns to chitinases[END_REF]

| Preparation of natural and recombinant peach allergens and experimental ImmunoCAP ™ tests

Natural Pru p 7 was purified from extract of canned peaches by sequential steps of cation exchange, size exclusion and reversed phase chromatography. Bioaffinity adsorption was then performed to eliminate any residual amount of LTPs. Natural Pru p 3 was purified from peach peel extract by affinity chromatography using a monoclonal anti-Pru p 3 antibody, followed by cation exchange chromatography. Recombinant Pru p 7 and Pru p 3 were expressed in Pichia pastoris and purified from culture medium by cation exchange or metal ion affinity chromatography, followed by size exclusion or cation exchange chromatography. Purity, homogeneity and identity of the allergen preparations were verified by SDS-PAGE, analytical size exclusion chromatography, mass spectrometry and immunological activity using ImmunoCAP ™ and serum samples with defined IgE reactivities. All chromatography media and equipment were obtained from GE Healthcare Life Sciences (Uppsala, Sweden). Experimental ImmunoCAP ™ tests were prepared as described. [START_REF] Dewitt | Molecular and immunological characterization of a novel timothy grass (Phleum pratense) pollen allergen, Phl p 11[END_REF]

| IgE competition experiments

Cross-reactivity between Pru p 7 and CP was studied by preincubating serum samples for 2 hours at room temperature either with CP extract (15% w/v final concentration, 42 sera) or with rPru p 7 (100 μg/mL final concentration, 33 sera) prior to measurement of IgE binding to rPru p 7 or CP ImmunoCAP solid phase, respectively.

Percent inhibition was calculated as reduction of IgE binding in comparison with serum samples pre-incubated with buffer alone. Dose-dependent inhibition was performed with four samples. Two samples were incubated with 15% (w/v) CP extract and a 4-fold dilution series thereof, followed by measurement of IgE binding to Pru p 7. Two other samples were instead pre-incubated with rPru p 7 in a 4-fold dilution series from 200 to 0.2 μg/mL, followed by measurement of IgE binding to CP extract. andS2.

| Basophil activation tests

For comparative purposes, sera of six PA subjects with IgE to Pru p 7 by ImmunoCAP were also analysed with the FABER ® assay (CAAM, Rome, Italy) and concordant results were obtained in five of these (83%).

| Pru p 7 sensitization is associated with the severity of reaction and cofactor involvement

| Pru p 7 induces basophil activation in PA patients

The ability of Pru p 7 to activate effector cells was assessed with BAT (Figure 4). S3).

The PT patient's basophils were not activated by any of the extracts or molecular allergens tested (Table S3). Basophil sensitivity to Pru p 7-induced activation was monitored through EC 50 , CD-sens and the lowest activating concentration. Median EC 50 was 0.05 ng/mL (IQR 0.0125-1.25) and median CD-sens was 2000 (IQR 80-8000). EC 50 and the lowest activating concentration were lower in PA patients without cofactor involvement (n = 6) than in those who required a cofactor for reaction to peach (n = 3), with a similar trend for CDsens (Table 3). The ratio of maximal rPru p 7-induced activation to anti-RFcεI-induced activation was close to 1 in both groups.

| IgE to Pru p 7 is associated with and cross-reactive to IgE to cypress pollen

We have previously described a ubiquitous co-sensitization to CP in Pru p 7 sensitized individuals. [START_REF] Klingebiel | Peamacléine Pru p 7: épidémiologie, implications cliniques et place dans le diagnostic moléculaire de l'allergie à la pêche en région méditerranéenne[END_REF] Among the 171 Pru p 7 sensitized subjects in the present study, all but one, who had Pru p 7 IgE at the positivity threshold of the assay (0.10 kU A /L), were also sensitized to CP.

To 5B). The ability of Pru p 7 to inhibit IgE binding to CP extract was negatively correlated to the ratio of IgE to Cup a 1/Pru p 7 (Spearman rho -0.7, CI95 -0.9 to -0.5, P < 0.0001), reflecting the proportion of CP-specific IgE directed to Cup a 1, which is structurally unrelated to Pru p 7.

| Cypress pollen exposure determines regional peach molecular sensitization profiles

Using a multivariate model of CP sensitization including all tested peach allergens as covariates, we found that no peach allergen other than Pru p 7 was significantly associated with CP sensitization (Table S4). The relationship between CP and Pru p 7 sensitization was further assessed by sorting patients by region of residency as described in Methods (Table 1). Ordinal logistic regression models illustrated a strong relationship between the cypress/birch pollen count ratio and the occurrence of sensitization to CP, Pru p 7 or Pru p 1 (Table S5). This relationship was positive for CP and Pru p 7 sensitization (P < 0.0001 and P = 0.0001, respectively), and inverse for Pru p 1 sensitization, a surrogate of Bet v 1 sensitization (P = 0.03).

Further multivariate analysis of CP, Pru p 1 and Pru p 7 sensitizations found independent relationships between these covariates and cypress/birch pollen count ratios, consisting of a quantitative effect of CP exposure associated with higher prevalence of Pru p 7

(P = 0.03) and lower prevalence of Pru p 1 sensitization (P = 0.003) among CP sensitized subjects (Table S5).

| DISCUSSION

We report here that Pru p 7 is a major allergen in PA patients from southern France, in this study showing a prevalence of Pru p 7 sensitization exceeding 60%. In 54% of Pru p 7-sensitized PA patients, there was no concomitant sensitization to other available peach allergens. The occurrence and level of Pru p 7 sensitization were higher in severe PA with peach-induced anaphylactic manifestations, that is grade 3 reactions of the EAACI classification, [START_REF] Muraro | The urgent need for a harmonized severity scoring system for acute allergic reactions[END_REF] at 0.05 ng/L, while median CD-sens was 2000, indicating a biological potency higher than other food allergens. [START_REF] Santos | Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut[END_REF][START_REF] Schwager | Peanut oleosins associated with severe peanut allergy-importance of lipophilic allergens for comprehensive allergy diagnostics[END_REF][START_REF] Franz-Oberdorf | Fra a 1.02 is the most potent isoform of the Bet v 1-like allergen in strawberry fruit[END_REF][START_REF] Martin-Pedraza | Two nonspecific lipid transfer proteins (nsLTPs) from tomato seeds are associated to severe symptoms of tomato-allergic patients[END_REF] In all but one borderline case in this study, Pru p 7 sensitization was associated with CP sensitization. The link between CP and Pru Despite early reports on the association of PA with cypress pollinosis, [START_REF] Hugues | Cross-reactivity between cypress pollen and peach: a report of seven cases[END_REF] the prevalence of cypress-associated peach sensitization and PA is currently unknown. In a cohort of 1280 cypress-sensitized patients from France, 165 (13%) patients had peach sensitization as defined by positive prick-to-prick tests to peach, and 29 of these 165 (18%) had a history of peach-induced symptoms. [START_REF] Caimmi | Epidemiology of cypress pollen allergy in Montpellier[END_REF] In regard to molecular sensitization relevant to peach allergy in our region, preliminary data indicate that 15-25% of cypress pollinosis patients may be Pru p 7 sensitized (unpublished observations). Peach IgE sensitization rates across European countries as reported from the Europrevall cohort peak at 11.9% in Madrid and 13.4% in Zurich. [START_REF] Burney | The prevalence and distribution of food sensitization in European adults[END_REF] Similarly, little is known about allergen(s) other than Pru p 7 potentially involved in the cypress-peach syndrome. [START_REF] Charpin | Cypress pollinosis: from tree to clinic[END_REF] Teams from southern

France and Spain reported an association of CP and PA in Pru p 3 sensitized patients. [START_REF] Caimmi | Understanding the molecular sensitisation for cypress pollen and peach in the Languedoc-Roussillon area[END_REF][START_REF] Sánchez-López | Cupressus arizonica pollen: a new pollen involved in the lipid transfer protein syndrome?[END_REF] Further, in a series of seven CP and PA patients, all displayed IgE binding to a 45-kDa CP protein, which could be outcompeted by peach extract. [START_REF] Hugues | Cross-reactivity between cypress pollen and peach: a report of seven cases[END_REF] Additionally, certain allergens identified in Japanese cedar (Cryptomeria japonica) pollen, such as Cry j 3 (thaumatin-like protein), CJP-6 (isoflavone-reductase) and CPA-9 (subtilisinlike protease), show sequence identity of 40% or higher with homologues in Rosaceae fruits and other plant foods, suggesting that crossreactions may occur through multiple allergen families. Although cypress trees are typical of Mediterranean regions, Cupressaceae pollen dispersal also affects non-Mediterranean environments, including Central Europe, North America, Mexico and Japan. [START_REF] Charpin | Cypress pollinosis: from tree to clinic[END_REF][START_REF] Panzner | A comprehensive analysis of middle-European molecular sensitisation profiles to pollen allergens[END_REF][START_REF] Inomata | High prevalence of sensitisation to gibberellin-regulated protein (peamaclein) in fruit allergies with negative immunoglobulin E reactivity to Bet v 1 homologs and profilin: clinical pattern, causative fruits and cofactor effect of gibberellin-regulated protein allergy[END_REF][START_REF] Inomata | Gibberellin-regulated protein in Japanese apricot is an allergen cross-reactive to Pru p 7[END_REF][START_REF] Mohanty | Molecular analysis confirms the long-distance transport of Juniperus ashei pollen[END_REF] GRP-related allergy to Rosaceae and Citrus fruits was reported in conjunction with Japanese cedar pollinosis. [START_REF] Inomata | High prevalence of sensitisation to gibberellin-regulated protein (peamaclein) in fruit allergies with negative immunoglobulin E reactivity to Bet v 1 homologs and profilin: clinical pattern, causative fruits and cofactor effect of gibberellin-regulated protein allergy[END_REF][START_REF] Inomata | Gibberellin-regulated protein in Japanese apricot is an allergen cross-reactive to Pru p 7[END_REF][START_REF] Inomata | Identification of gibberellin-regulated protein as a new allergen in orange allergy[END_REF] In south-central United States, mountain cedar (Juniperus ashei) pollen is a major cause of allergic rhinoconjunctivitis. [START_REF] Mohanty | Molecular analysis confirms the long-distance transport of Juniperus ashei pollen[END_REF] Pollinosis to Cupressaceae has been steadily increasing during the past decades, possibly as a result of extended species distribution due to climate change and ability of Cupressaceae pollen to travel over hundreds of kilometres. [START_REF] Charpin | Cypress pollinosis: from tree to clinic[END_REF][START_REF] Fujimura | Spectrum of allergens for Japanese cedar pollinosis and impact of component-resolved diagnosis on allergenspecific immunotherapy[END_REF][START_REF] Mohanty | Molecular analysis confirms the long-distance transport of Juniperus ashei pollen[END_REF] Individuals with Cupressaceae pollinosis who display similar sensitization profiles due to the homology of allergens from different Cupressaceae species 50 might become exposed to previously unencountered, cross-reacting foods, when changing residence regions, travelling overseas, or expanding their consumption of fruits and vegetables as a result of healthy living trends. [START_REF] Skypala | When nutrition and allergy collide: the rise of anaphylaxis to plant foods[END_REF] Indeed, we found that Pru p 7 sensitization was associated with reactions to an array of plant foods, including but not limited to Rosaceae. Members of the GRP family are widely distributed in the plant kingdom, share high levels of sequence identity [START_REF] Tuppo | Peamaclein -A new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3[END_REF][START_REF] Inomata | Identification of gibberellin-regulated protein as a new allergen in orange allergy[END_REF][START_REF] Nahirnak | Snakin/GASA proteins: involvement in hormone crosstalk and redox homeostasis[END_REF] and have been associated with particularly severe food allergic reactions in at least three environments: Italy, [START_REF] Tuppo | Peamaclein -A new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3[END_REF] France [START_REF] Klingebiel | Peamacléine Pru p 7: épidémiologie, implications cliniques et place dans le diagnostic moléculaire de l'allergie à la pêche en région méditerranéenne[END_REF] and Japan. [START_REF] Inomata | Identification of gibberellin-regulated protein as a new allergen in orange allergy[END_REF][START_REF] Inomata | Identification of peamaclein as a marker allergen related to systemic reactions in peach allergy[END_REF] In our cohort, increasing CP exposure and associated Pru p 7 sensitization was related to lower prevalence of PR-10 sensitization even in regions with substantial birch pollen exposure. Conversely, a potential protective effect of birch pollen exposure has been suggested with respect to LTP-related food allergies. [START_REF] Rial | Food allergies caused by allergenic lipid transfer proteins: what is behind the geographic restriction?[END_REF] The pathophysiological background of such interactions between pollen exposure and the resulting host sensitization may bring further insight into the geographic restriction patterns of food allergy.

Specific IgE (kU

Peach allergic

In conclusion, we report here that Pru p 7 sensitization is common in patients allergic to peach, often in the absence of sensitization to other peach allergens. Sensitization to Pru p 7 is invariably associated with CP sensitization and appears to be driven by CP exposure, rather than reflecting a primary food sensitization. Biologically, Pru p 7 was found to be extremely potent, causing basophil activation at sub-picomolar concentrations. Because CP is present in continental as well as Mediterranean environments, and given the world-wide distribution of related Cupressaceae species, Pru p 7 and homologous food proteins may be an important culprit in severe allergic reactions to peach and other plant foods in many regions of the world.

ACKNOWLEDG EMENTS

The Ratio maximal rPru p 7-induced activation/anti-FcεRI (median, range) 1 (0.5-1.8) 1 (0.9-1.8) 0.9 (0.5-1) 0.2

Bold figure denotes statistically significant differences between peach allergic patients experiencing clinical reactions to peach without cofactor intervention and peach allergic patients requiring a cofactor.

Pharma, Mylan, Sanofi, reimbursement for attending a congress from Thermo Fisher Scientific and research grants from the French Society of Allergology. The other authors declare no conflict of interest.

  Basophil activation tests (BAT) were performed with a commercial CD193 (CCR3)/CD63 kit (Bühlmann Laboratories, Hochbuch, Switzerland) in a subset of patients. Peach extract, Mal d 1 (PR-10), Tri a 12 (profilin), and cow's milk extract (Bühlmann Laboratories) and recombinant and natural Pru p 7 and Pru p 3 were used as allergen reagents. Milk extract served as a negative control for foods regularly consumed and tolerated by each tested patient. Extracts T A B L E 1 Geographic and demographic characteristics of the study population

Figure 2 7 [ 1 . 6 - 8 . 5 ]

 271685 Figure2shows the levels of IgE antibody responses to peach, individual peach components, CCD and CP in the PA and PT subjects, illustrating the prominent difference in Pru p 7 sensitization between these groups. Further, Pru p 7 sensitization was more frequent in PA patients who experienced grade 3 reactions (61/78, 78%) than in those who experienced grade 2 (38/59, 64%) or grade 1 (24/61, 39%) reactions, P < 0.0001 (Figure3A). Likewise, the severity of reactions elicited by peach was significantly associated with the concentration of IgE to Pru p 7 (Figure3B). Odds ratio calculation showed that Pru p 7 sensitization was positively and independently related to a higher prevalence of grade 3 reactions (OR [CI95]: 3.7[1.6-8.5]; P = 0.002), and negatively related to grade 1 (OR [CI95]: 0.2 [0.1-0.4]; P < 0.0001). This association remained significant after adjustment for sensitization to other peach allergens and to CP as potential confounding covariates.Cofactor involvement was significantly more frequent in Pru p 7sensitized patients (22/171 vs 7/145, P = 0.01), but eyelid oedema during the allergic reaction was not (15/171 vs 5/145, P = 0.06).

p 7

 7 sensitization was further explored with IgE competition experiments. We found that CP extract could inhibit 80-100% of IgE binding to Pru p 7 in 90% of the 42 sera analysed, whereas Pru p 7 only partly inhibited IgE binding to CP extract. Based on these results and the association between Pru p 7 sensitization and the intensity of CP exposure, we believe that CP acts as a primary sensitizer, eliciting in a proportion of individuals an IgE response that cross-reacts with Pru p 7. A partially characterized 14 kDa CP protein called BP14 has been shown to share a stretch of homology and cross-reactivity with snakin-1 from potato, a protein related to Pru p 7 and other members of the GRP protein family.[START_REF] Senechal | A new allergen family involved in pollen food-associated syndrome: Snakin/gibberellin-regulated proteins[END_REF] In our study, clinical reactions to potato were reported by only two Pru p 7 sensitized patients, one of which was additionally sensitized to Pru p 4. Our data show that Pru p 7 sensitization in PA patients from southern France belongs to the PFS through its association with CP. Similar to other examples of PFS, Pru p 7-induced reactions occur mainly in adolescents and young adults. However, food allergy symptoms are more severe in Pru p 7-related PFS than in previously described examples of PFS.

FF I G U R E 3

 3 I G U R E 2 IgE antibody levels in peach allergic and peach tolerant patients. Levels of IgE to peach and peach components, MUXF3 and cypress pollen in peach allergic (A) and peach tolerant (B) subjects. Horizontal bars indicate median levels among positive (≥0.10 kU A /L) observations. Dotted horizontal lines indicate the 0.10 and 0.35 kU A /L levels. Indicated above the x-axis in each graph are the numbers of sera with IgE <0.10 kU A /L Prevalence and magnitude of Pru p 7 sensitization in relation to the severity of reactions to peach. Prevalence (A) and concentration (B) of IgE to Pru p 7 in patients with mild, moderate or severe reactions to peach. Statistical significance flags for P-value levels: *< 0.05, ** <0.01, *** <0.001. In B, horizontal bars indicate median levels among positive (≥0.10 kU A /L) observations and dotted horizontal lines mark the 0.10 and 0.35 kU A /L levels. Indicated above the x-axis is the number of sera with IgE <0.10 kU A /L

  U R E 4 Dose-response of basophil activation with rPru p 7. Dose-response BAT with rPru p 7 was performed in nine PA patients monosensitized to Pru p 7. A, BAT in individual PA patients without cofactor requirement. B, BAT in individual PA patients with clinical reactions requiring cofactors. The dotted line represents the positivity threshold. The solid line shows the separation between BAT with lowest activating concentrations below or greater than 6.25 pg/mL of rPru p 7

F

  I G U R E 5 Reciprocal IgE inhibition experiments. Sera of peach allergic subjects were pre-incubated with either (A) cypress pollen extract (15% w/v, n = 42) or (B) rPru p 7 (100 μg/mL, n = 33) prior to measurement of IgE binding to rPru p 7 or cypress pollen abstract, respectively, by ImmunoCAP ™ . Resulting degrees of inhibition are expressed as percent reduction of IgE concentration values as compared to measurements performed after preincubation with buffer alone, without inhibitor. Median inhibition is represented as a grey bar at the upper end of each graph

All regions Region 5 Region 4 Region 3 Region 2 Region 1

  vegetables was found in 42 (36%) and to legumes, tree nuts, cereals and seeds in 64 (54%). In 33 (28%) of the PT subjects, no plant food allergy was found (FigureS1). Involvement of a cofactor was reported in 24 (12%) of the PA patients, exercise being the most frequent (n = 19). Among the symptoms experienced, eyelid oedema was reported by 19 (10%) of the PA patients.

	and molecular allergens obtained from Bühlmann Laboratories were
	used at final concentrations of 2.5, 1, 0.5 and 0.05 times the manu-
	facturer's recommended concentration, that is 62.5, 25, 12.5 and
	1.25 ng/mL for peach and milk extracts, and 625, 250, 125 and
	12.5 ng/mL for Mal d 1 and Tri a 12.
	Natural and recombinant Pru p 7 was applied at 11 different
	concentrations, ranging from 0.25 pg/mL to 2.5 μg/mL. Natural and
	recombinant Pru p 3 was applied at final concentrations of 5 ng/
	mL, 50 ng/mL and 2.5 μg/mL. Positive and negative controls (patient
	background, anti-FcεRI and formyl-methionyl-leucyl-phenylalanine)
	were assayed in duplicate at the start and end of the experiment
	for each patient. Analysis was performed with a Canto II flow
	cytometer and FACS Diva software (BD Biosciences, Franklin Lakes,
	NJ). Five hundred basophils or more were analysed for each activa-
	tion condition. Background CD63 expression was lower than 5% in
	all patients, and no non-responder (anti-FcεRI-induced CD63
	expression of 10% or less) was found. BAT was considered positive
	for an allergen concentration if CD63 expression exceeded twice
	the highest background result in each patient. EC 50 , CD-sens and
	the ratio of maximal activation Pru p 7/anti-FcεRI activation were
	calculated as described. 32,33
	Pollen counts (per year and m3)
	Birch	639	69	176	226	1077	1648
	Cypress Spearman's correlation coefficient. Odds ratios were calculated as 11 408 18 782	17 251	4276	9021	7712
	Cypress/birch ratio previously described. 34	18	272	98	19	8	5
	All patients	316	205	27	35	28	21
	Sex ratio (M/F) 3 | RESULTS	0.7	0.8	0.9	0.5	1.0	0.8
	Age (years; median, IQR)	18 (11-33)	17 (11-33)	28 (18-47)	21 (12-32)	16 (10-27)	16 (11-32)
	Peach allergic patients 3.1 | Demographic and food allergy characteristics
	Sample size (number, %) of the study population	198 (63%)	133 (65%)	22 (81%)	20 (57%)	13 (46%)	10 (48%)
	Sex ratio (M/F) A total of 316 patients from the southern part of France were ret-0.8 0.8	1.0	0.5	1.2	0.8
	Age (years; median, IQR) rospectively included in the study, with a median age of 18 years 21 (13-36) 21 (13-36)	32 (21-47)	19 (14-32)	17 (9-31)	16 (13-34)
	Peach tolerant patients
	Sample size (number, %)	118 (37%)	72 (35%)	5 (19%)	15 (43%)	15 (54%)	11 (52%)
	Sex ratio (M/F)	0.7	0.8	0.7	0.4	0.9	0.8
	Age (years; median, IQR)	15 (10-28)	14 (9-26)	15 (13-24)	23 (10-32)	15 (10-25)	17 (10-31)

Regions 1-5 were defined in ascending order of cypress to birch ratio. Outpatients seeking allergy work-up for a history of peach-induced symptoms were included. Peach allergy was confirmed or rejected according to ICON and EAACI guidelines for food allergy.

2.9 | Statistical data analysis

Median and IQR for IgE were calculated for sensitized subjects in each group. GraphPad Prism (version 7, La Jolla, CA), SPSS (version 25, Chicago, IL) and R (version 3.3.2, R Foundation for Statistical

Computing, Vienna, Austria) were used for statistical analyses. Differences with a P value < 0.05 were considered statistically significant. Binomial variables were compared using Fisher's exact test and modelled according to multiple binomial logistic regression models. Ordinal variables (reaction grade and region of residency according to pollen counts) were compared using the asymptotic general independence test and modelled according to multiple ordinal regression models. Continuous variables were compared using Mann-Whitney's test and modelled according to multiple linear regression models. Correlation studies were done by calculating (range 0.13-74) and sex (M/F) ratio 0.7. Subjects were classified according to two diagnostic categories: PA and PT (Table

1

). PA was diagnosed in 198 (63%) patients. Allergy to other fruits (mainly Rosaceae, Citrus and exotic fruits) was found in 157 (79%) of PA patients, while allergy to legumes, tree nuts, cereals and seeds was found in 46 (23%). Among the 118 PT patients, allergy to other fruits or

3.2 |

Pru p 7 sensitization is present in all regions and is higher and more common in PA than PT patients

	Overall, Pru p 7 sensitization was found in 171/316 (54%) patients
	(Table 2). A gradient of Pru p 7 sensitization from north (region 1,
	29% prevalence) to south (region 5, 60% prevalence) was observed,
	P = 0.003 (Figure 1). Pru p 7 sensitization was more frequent in PA
	(123/198, 62%) than in PT (48/118, 41%) patients, P = 0.0002. It
	was positively and independently related to PA (OR [CI95]: 2.5 [1.4-

4.6]; P = 0.003). Apparent monosensitization to Pru p 7, that is without detectable IgE to any of the other tested peach allergens (Pru p 1, Pru p 3, Pru p 4), was more frequent in PA (66/123, 54%) than in PT (8/48, 17%) patients, P < 0.0001. The concentrations of IgE to Pru p 7 were higher in PA than PT patients sensitized to this allergen (median [IQR]: 3.4 [0.5-8.3] vs 0.3 [0.2-0.5] kU A /L; P < 0.0001) (Table

2

). Data on sensitization to other molecular allergens in PA and PT patients are available in Tables

S1

  The test was performed with peach extract, natural and recombinant Pru p 7, available representative molecules for rele-

	vant allergen families: nsLTP (Pru p 3), PR-10 (Mal d 1) and profilin
	(Tri a 12), and a tolerance control allergen, that is cow's milk, in 9 PA
	patients sensitized to Pru p 7 and in one PT, Pru p 7 non-sensitized
	patient with plant food-induced anaphylaxis. Comparable results
	were obtained with the natural and recombinant Pru p 7 and with
	natural and recombinant Pru p 3. All Pru p 7-sensitized patients dis-
	played basophil activation induced by peach extract and Pru p 7 as
	monitored by CD63 membrane expression, but no activation with
	the other allergens tested, nor with cow's milk extract (Table

  [START_REF] Fujimura | Spectrum of allergens for Japanese cedar pollinosis and impact of component-resolved diagnosis on allergenspecific immunotherapy[END_REF]

  Bold figures with asterisks denote statistically significant differences between PA and PT patients. Median and IQR were calculated for samples with Pru p 7 IgE ≥0.10 kU A /L. Statistical significance flags for P-value levels: *< 0.05; **< 0.01; ***< 0.001.

	T A B L E 2 Pru p 7 sensitization by geographic region and peach allergy or tolerance
	rPru p 7 IgE	All regions	Region 5	Region 4	Region 3	Region 2	Region 1
	Peach allergic patients
	Prevalence (number, %)	123 (62%) ***	88 (66%) **	12 (55%)	13 (65%) ***	7 (54%)	3 (30%)
	Median (IQR) (kU A /L)	3.4 (0.5-8.3)	4.1 (0.7-8.6)	2.8 (1.0-10.4)	3.7 (1.1-7.3)	0.2 (0.1-0.6)	0.3 (0.2-0.6)
	Pru p 7 monosensitization	66/123 (54%) ***	49/88 (55%) ***	7/12 (58%)	8/13 (62%)	1/7 (14%)	1/3 (33%)
	Peach tolerant patients
	Prevalence (number, %)	48 (41%) ***	35 (49%) **	4 (80%)	2 (13%)	4 (27%)	3 (27%)
	Median (IQR) (kU A /L)	0.3 (0.2-0.5)	0.3 (0.2-0.7)	0.3 (0.2-0.4)	0.2 (0.2; 0.2)	0.1 (0.1-0.2)	0.2 (0.2-0.4)
	Pru p 7 monosensitization	8/48 (17%) ***	7/35 (20%) ***	0	0	0	1/3 (33%)
	All patients
	Prevalence (number, %)	171 (54%)	123 (60%)	16 (59%)	15 (43%)	11 (39%)	6 (29%)
	Median (IQR) (kU A /L)	1.3 (0.2-6.4)	2.3 (0.3-6.7)	1.2 (0.5-5.1)	3.4 (0.3-6.3)	0.2 (0.1-0.2)	0.2 (0.2-0.5)
	Pru p 7 monosensitization	74/171 (43%)	56/123 (46%)	7/16 (44%)	8/15 (53%)	1/11 (9%)	2/6 (33%)
					F I G U R E 1 Prevalence of Pru p 7
					sensitization in southern France in relation
					to cypress pollen exposure levels. Cypress
					pollen levels: green, low (exposure region
					1); yellow, intermediate (exposure region
					2); orange, high (exposure region 3); red,
					very high (exposure regions 4 and 5). Birch
					pollen exposure follows an inverse gradient
					and is virtually absent in the southernmost
					part defining the region of Marseille (5).
					Pru p 7 sensitization: blue circles:
					sensitized subjects; white circles: non-
					sensitized subjects. The size of each circle
					indicates the number of subjects it
					represents. Small black and white symbols
					indicate sites of pollen counting. Cypress
					pollen map reproduced with permission 17

  authors thank Mr Gérard Kiyici, Ms Isabelle Cleach, Ms Céline

	Chartier, Ms Patricia Blanchard, Mr Simon Pinchemel, Ms Colette
	Mavier for technical assistance; Dr Jean-Luc Fauquert and Dr Michel
	Migueres for insightful advice.
	CONFLI CT OF INTEREST
	AEE, JÖ and JL are employees of Thermo Fisher Scientific. RAL is
	employee of Beckman Coulter. PD has received speaker and consul-
	tancy fees from ALK, Circassia, Stallergènes Greer, Allergopharma,
	Thermo Fisher Scientific, Meda, Menarini and grants from AstraZeneca
	and from MEDA Pharma through CHRUM administration. LGC has
	received reimbursement for attending a symposium and a fee for orga-

nizing education from Thermo Fisher Scientific. PAA has received reimbursement for attending a congress from Thermo Fisher Scientific and a research grant from the French Society of Allergology. YPMB has received speaker fees from Thermo Fisher Scientific, ALK-Abello, Stallergènes. IAM has received research grants from the European Union. JV has received speaker and consultancy fees from Meda

  T A B L E 3 Basophil activation test with rPru p 7 in a sample of peach allergic patients

		All	Without cofactor	With cofactor	P
	Number of subjects	9	6	3
	EC 50 ng/mL (median, range)	0.05 (0.006-6.3)	0.03 (0.006-1.3)	6.3 (0.05-6.3)	0.03
	CD-sens (median, range)	2000 (80-16 000)	5000 (80-16 000)	16 (16-2000)	0.08
	AUC	9990	10 579	8987	0.30
	Lowest activating concentration ng/mL (median, range)	0.006 (0.006-1.3)	0.004 (0.003-1.3)	1.3 (0.01-1.3)	0.048

Funding information

This work was supported by the French Society of Allergology (Société Française d'Allergologie) 2017 through a research grant (JV)


Davide Frey
email: davide.frey@inria.fr

Marc X Makkes
email: m.x.makkes@vu.nl

Pierre-Louis Roman
email: pierre-louis.roman@irisa.fr

Franc ¸ois

Spyros Voulgaris
email: voulgaris@aueb.gr

Dietcoin: Hardening Bitcoin Transaction Verification Process For Mobile Devices

Distributed ledgers are among the most replicated data repositories in the world. They offer data consistency, immutability, and auditability, based on the assumption that each participating node locally verifies their entire content. Although their content, currently extending up to a few hundred gigabytes, can be accommodated by dedicated commodity hard disks, downloading it, processing it, and storing it in general-purpose desktop and laptop computers can prove largely impractical. Even worse, this becomes a prohibitive restriction for smartphones, mobile devices, and resource-constrained IoT devices.

In this demo, we present an implementation of Dietcoin, a Bitcoin protocol extension that allows nodes to perform secure local verification of Bitcoin transactions with small bandwidth and storage requirements. This demo presents and benchmarks the main features of Dietcoin that are important for today's cryptocurrencies and smart contract systems, but are missing in the current state-of-the-art: (i) allowing resource-constrained devices to verify the correctness of selected blocks locally without having to download the complete ledger; (ii) enabling devices to join a blockchain quickly yet securely, dropping bootstrap time from days down to a matter of seconds; (iii) providing a generic solution that can be applied to other distributed ledgers secured with Proof-of-Work.

INTRODUCTION

Within a decade, blockchains have become extremely popular, and have been used to implement several widely-used cryptocurrencies [START_REF] Nakamoto | Bitcoin: A peer-to-peer electronic cash system[END_REF] and smart-contract services [START_REF] Dickerson | Adding concurrency to smart contracts[END_REF][START_REF] Wood | Ethereum: A secure decentralised generalised transaction ledger[END_REF]. A blockchain implements a tamper-proof distributed ledger in which transactions can be recorded in an irrevocable, or probabilistically irrevocable, manner. Recorded transactions are stored in blocks, which are incrementally chained in order to form an append-only list that is synchronized between participants via peer-to-peer exchanges. The security of these chaining mechanisms leverages cryptographic tools and Byzantine agreement mechanisms. Bitcoin, for instance, prevents spam blocks by using computationally costly Proof-of-Work and pairs it with a rule prioritizing the chain with the most aggregated work to ensure convergence on the state of the blockchain. This combination makes it practically infeasible for individual participants to revoke past transactions due to the inconceivable computational costs involved, while it remains possible for any participant to verify the validity of a blockchain's entire history.

Although this verification is possible for any participant, the associated costs are far from trivial. The verifying node must (i) download the entire blockchain and (ii) verify every single block. Downloading an entire blockchain is feasible yet largely impractical, in particular for popular blockchains whose total history size can lie in the order of hundreds of gigabytes. Downloading and processing data of this magnitude is way beyond the capabilities of most resource-limited devices, such as smartphones and IoT devices, which is a major barrier to adoption since these devices are likely to serve as digital wallets for micro-transactions due to their handiness and omnipresence.

The Bitcoin blockchain, for instance, has grown to 200 GiB as of March 2019 (Figure 1), and historically follows an exponential growth despite having a capped block size (which is the subject of vigorous debates). As blockchains are ever-growing structures, the problem can only become more acute. In addition to downloading the blockchain, the verifying node must also check its consistency block by block, a linear process that can take hours on high-end machines and much longer on smartphones.

Assuming average mobile connection bandwidths [START_REF]Measuring mobile broadband performance in the UK: 4G and 3G network performance[END_REF], it takes 30 hours to download the necessary 200 GiB of blocks at 15.1 Mib/s on 4G, and even up to 74 hours at 6.1 Mib/s on 3G. Moreover, verifying the blockchain typically takes longer than downloading it, particularly on computationconstrained devices designed for optimal battery longevity.

The exorbitant price of a full chain verification makes it unrealistic for low-resource devices to implement a blockchain protocol fully. Some blockchain systems, such as Bitcoin, therefore enable nodes to perform varying degrees of verification: full nodes verify everything, while light nodes, known as Secure Payment Verification nodes (SPV nodes) only verify a small fraction of the data (i.e., the block headers).

To protect themselves against counterfeited transactions, full nodes keep track of unspent funds in a structure known as the set of Unspent TransaCTion Outputs (UTXO set). The UTXO set (i.e., the state of the ledger) is aggregated by linearly parsing the entire blockchain (i.e., the list of updates), making it expensive to construct, to exchange (since it weights 2.8 GiB as of March 2019, see Figure 1), and to maintain. This accumulation of costs prevents low-resource devices from relying on the UTXO set. However, since these devices can be used as Bitcoin (mobile) payment terminals, especially in regions with no reliable card-based payment infrastructures, their impaired security, in part due to the current limitations of the Bitcoin protocol, could be significantly improved by harnessing the UTXO set.

In this demo, we show an implementation of the Dietcoin protocol [START_REF] Frey | Bringing secure Bitcoin transactions to your smartphone[END_REF][START_REF] Frey | Dietcoin: shortcutting the Bitcoin verification process for your smartphone[END_REF] with its associated diet nodes that bridge the security gap between full nodes and SPV nodes. The demonstration contains two incremental scenarios to show its efficiency and effectiveness. Scenario 1 shows the initialization phase of a diet node running on a phone. This phase only takes seconds and shows the associated energy, bandwidth, and verification cost of running a diet node on the phone. Scenario 2 shows the diet node perform a transaction verification including showing the aforementioned costs. For both scenarios, a visitor merely needs to either click the "restart" button, to re-initialize and download the blockchain from scratch, or click the "verify transaction" button, to execute a transaction and perform verification. Finally the demo is accompanied by a poster to elaborate on how the verification mechanism works.

The remainder of this paper is organized as follows. Section 2 describes the efficient verification of transactions in the Dietcoin system, Section 3 describes the implementation of Dietcoin, Section 4 discusses the demo scenarios, and finally, Section 5 concludes.

DIETCOIN OVERVIEW

Dietcoin aims at increasing the security of low-resource devices by offering diet nodes that are able to verify the correctness of blocks, as well as subchains of blocks, at a reasonable cost. In short, diet nodes perform secure queries to full nodes for their local replica of the UTXO set and limit their queries to what is required to verify specific blocks.

To that extent, Dietcoin makes three key modifications to Bitcoin: We end this overview by providing in Section 2.4 a few usages enabled by these modifications made to Bitcoin.

Sharding the UTXO set

Full nodes store the UTXOs resulting from each block's transactions into UTXO shards. As the UTXO set evolves with each block, recently modified UTXO shards are stored by full nodes and are available for query by diet nodes who wish to fully verify recent blocks. To maintain small shards, their size is capped such that the average of all shard sizes must not cross a predefined limit M (e.g., 1 KiB).

The sharding policy uses the first k bits of each UTXO to determine the UTXO shard it belongs to. Since the first 32 bytes of a UTXO is the SHA-256 transaction hash it references, using the first k bits for indexing resembles random indexing. This particular indexing results in shards of theoretical homogeneous sizes. Each full node locally increments k when the cap M is crossed, which doubles the number of shards and halves the average shard size in the process.

Committing the UTXO set into blocks

In addition to UTXO shards, full nodes also maintain a Merkle tree to enable diet nodes to verify the integrity of said shards. The root of that tree is committed into blocks and is subject to verification, hence is rejectable, by each validating node. A miner committing an erroneous UTXO Merkle root is at risk of seeing his block rejected and consequently losing the rewards that come with it.

Since UTXOs are indexed by their first k bits, there are 2 k shards at all times which results in a complete UTXO Merkle tree with 2 k leaves all at the same height. Because only a subset of all UTXO shards are modified when a block is added to the chain, only a subset of the UTXO Merkle tree leaves are modified, while the vast majority of the tree remains unchanged. Using shards makes the UTXO Merkle tree updatable in-place and enables diet nodes to keep unchanged sections of the tree in a cache to further reduce their bandwidth consumption.

To ensure a smooth adoption, Dietcoin must fit within the existing Bitcoin consensus rules. The commitment is therefore stored in a transaction output that Bitcoin nodes ignore. Although the Dietcoin protocol is compatible with the Bitcoin protocol, the UTXO set is stored differently. Diet nodes must then connect to full nodes running Dietcoin to obtain the needed UTXO shards.

Enabling block and subchain verification

Thanks to sharding the UTXO set and committing its Merkle root into blocks, diet nodes are able to securely query UTXO shards to verify the correctness of blocks' transactions. However, diet nodes must also be able to verify the correctness of the now committed UTXO Merkle root.

As depicted in Figure 2, a diet node can verify the UTXO Merkle root of block B k by acquiring (i) the UTXO Merkle root stored in block B k-1 , (ii) all the UTXO shards modified in B k and (iii) the partial UTXO Merkle tree needed to ensure the integrity of all the downloaded shards. Once the integrity of each UTXO shard has been verified, the diet node updates its copies of the UTXO shards by removing from them all the UTXOs spent in B k , and by adding all the UTXOs created in B k . This operation is similar to the one performed by full nodes, the only difference is that diet nodes do not have to possess the shards that are not needed to verify the transactions in B k . After updating the shards, the diet node updates, in turn, their corresponding leaves in the UTXO Merkle tree as well as all their parent nodes in the tree. The root of the now updated Merkle tree should be equal to the value committed in B k , provided the block is correct, which completes the full verification of block B k including both its transactions and UTXO Merkle root.

This block verifying process can be iterated towards the next blocks, by relying on the trust that the diet node has in the verified UTXO Merkle root in block B k . Dietcoin, therefore, can be used to verify both individual blocks and subchains of blocks. Assuming a subchain of blocks (e.g., 6 blocks 1 ), a diet node can increase its trust in B k by ver-1 https://bitcoin.org/en/payment-processing-guide# verifying-payment ifying the correctness of the subchain (B k-+1 , ..., B k ) to ensure that none of these blocks have been counterfeited. While a block is already costly to create for an attacker, a subchain of blocks is exponentially more costly to counterfeit [START_REF] Kiffer | A Better Method to Analyze Blockchain Consistency[END_REF]; verifying that they are all correct can exponentially increase the trust a diet node has in B k therefore drawing its trust in B k much closer to that of a full node.

Dietcoin usages

The main usage enabled by Dietcoin, which is the one presented in this demo, is to enable low-resource devices to verify the correctness of individual blocks and subchains of blocks.

As second usage, Dietcoin enables low-resource devices to check the inclusion of specific UTXOs into the UTXO set, even if these UTXOs were created in old transactions. Diet nodes can infer from a UTXO the shard it should belong to, and query another node for that specific shard at any point in time. This usage allows low-resource devices to ensure that (i) specific transactions have been committed into the blockchain, and that (ii) their UTXOs are still spendable and have not been stolen.

Finally, full nodes too can benefit from Dietcoin as they can quickly bootstrap into functioning verifying nodes thanks to the UTXO set commitment. Full nodes can skip the verification of most blocks, choose to download all the UTXO shards at a point in time and only verify the correctness of the blocks that are part of the, possibly long, head of the blockchain. Alternatively, full nodes can start their bootstrap by first downloading all the UTXO shards forming the most recent UTXO set, then parse the entire blockchain backwards. Doing so enables them to quickly verify new blocks, while verifying the chain in the background.

Both UTXO proof of inclusion and fast bootstrapping full node have been presented in other non peer-reviewed proposals made by the Bitcoin community [START_REF] Bryan | Protocol-Level Pruning[END_REF], but these proposals however do not enable affordable subchain verification.

IMPLEMENTATION

The experimental setup for Dietcoin is designed to produce data that is as realistic as possible. To this end, Dietcoin (i) is deployed in a realistic environment, (ii) is based on a mature open-source code, and (iii) uses a large and real dataset. We chose to extend the de facto standard Bitcoin java library bitcoinj2 with the features of Dietcoin to have diet nodes executable on Android smartphones. We use the Bitcoin blockchain as a large public dataset and we have the actual blocks replayed to the diet node.

The software architecture for the demonstration is separated into three components (Figure 3 (right)). A Bitcoin full node (using bitcoin-core 3 ) serves as a verified store for the blockchain and as an interface to the outer network. A Dietcoin replayer is used as a middleman: it fetches blocks from the Bitcoin full node, enriches them with the UTXO Merkle root, locally stores the UTXO shards and UTXO Merkle tree, and interacts with the diet node. Finally, the diet node deployed and monitored on an Android smartphone makes all its queries to the Dietcoin replayer as it would to a regular Dietcoin full node.

DEMONSTRATION

The demonstration of Dietcoin is performed on several devices which include a Raspberry PI 3+, the smartphones LG Nexus 5, LG Nexus 5X, and Huawei Nexus 6P accompanied by a Monsoon power monitor and a laptop that displays system statistics from these devices. The demonstration contains two scenarios, which are paired with a poster illustrating the workings of Dietcoin. The first scenario shows the difference in bootstrap time of a diet node compared to that of a Bitcoin full node and a Bitcoin SPV node. The second scenario shows the resource consumption impact of performing a transaction on the IoT device. Demo GUI. Figure 3 (left) shows a screenshot of the demo GUI. The GUI is part of a device monitor that collects data from the demonstration resource-constrained device and displays it to the user. The statistics depicted on the GUI are system load over a 5 minutes window, current CPU load, current storage usage used for the blockchain, the power consumption of a device in mAh, and network usage in Mib/s. In addition, but not shown in Figure 3, are the accumulated network usage as well as the total processing time of each implementation. Users can select different devices and can compare different clients. Demo Dataset. The demonstration uses the ever growing full Bitcoin blockchain which is 200 GiB big as of March 2019. The Bitcoin blockchain contains over 10 years of public data since its launch in January 2009 and is comprised of 567,000 blocks and 391,200,000 transactions. Demo Scenarios. This demo provides two scenarios to showcase the main properties of Dietcoin. Scenario 1 : a bootstrapping comparison between a Bitcoin full node, a Bitcoin SPV node, and a diet node. In this scenario, users can initiate all types of clients, i.e., remove all previously downloaded data, and start from the genesis Bitcoin block. The statistics of the device is reset on startup, and is depicted as shown in Figure 3. Users can change the time frame of the statistics to get an overview of the involved computational, network, and system costs. Scenario 2 : transaction costs comparison between a full Bitcoin node, a Bitcoin SPV node, and a diet node. Users can press a button that, after bootstrapping, verifies a specific transaction which can be selected from a list. After pressing the "verify transaction" button, the system verifies that the selected transaction is valid, i.e., by requesting the UTXO Merkle tree from a replayer/full node. Users can directly see what the network, storage, and computational costs for verifying a transaction are.

CONCLUSION

In this demo, we demonstrate through Dietcoin the benefits of sharding the state of the distributed ledger of Bitcoin and making it available for other nodes to query. This demo allows the audience to securely interact with the Bitcoin cryptocurrency without having to suffer through the costly requirement of downloading the entire ledger.

Figure 1 :

 1 Figure 1: The size of both the Bitcoin blockchain and of its UTXO set have increased sixfold over the past four years.

Figure 2 :

 2 Figure2: The UTXO set is updated at every block validation. For a counterfeited block to be validated by diet nodes, a malicious miner has to forge at least two consecutive blocks: the first block B k-1 containing a fake UTXO Merkle root of UTXO k-1 , and the second block B k spending fake coins validated by the fake UTXO k-1 .

Figure 3 :

 3 Figure 3: The demo showing real-time system statistics of a diet node performing a transaction verification within the Bitcoin blockchain replaying setup.

https://github.com/bitcoinj/bitcoinj

Acknowledgments

This work has been partially funded by the Region of Brittany, France, by the Doctoral school of the University of Brittany Loire (UBL), by the French National Research Agency (ANR) projects SocioPlug under contract ANR-13-INFR-0003 and OBrowser under contract ANR-16-CE25-0005, by the Dutch SIDN Fonds contract 172027 and by the Dutch Organisation for Scientific Research (NWO) under contract 629.009.014.