Karen De La Vega-Hernández

Fabrice Chemla

Franck Ferreira

Olivier Jackowski

Alejandro Pe- Rez-Luna

The stereoselective germylzincation of internal alkynes delivering trisubstituted vinylgermanes is achieved via a radical chain process involving Ph3GeH and Et2Zn with AIBN as initiator. Excellent levels of regiocontrol are observed for non-symmetric (aryl, alkyl)-substituted alkynes, as well as for propargylic alcohols with aryl-, alkyl-, or silyl-substituted alkynes. The germylzincation reaction can be combined in one pot with the Cu(I)-mediated electrophilic substitution of the C(sp 2 )-Zn bond to obtain synthetically challenging tetrasubstituted vinylgermanes.

The increasing demand in germanium-containing compounds also raises considerable interest in the regio-and stereocontrolled preparation of vinylgermanes. [START_REF] Akiyama | For general overviews of the chemistry of vinylgermanes[END_REF] For this, carbon-germanium bond-forming addition reactions to alkynes using hydrogermanes as germanium source are most popular. The regioand stereoselective hydrogermylation of alkynes was disclosed under several conditions, including thermal, sonochemical or microwave activation, 2 transition-metal catalysis, 3 main-group Lewis-acid catalysis, 4 as well as in the presence of radical initiators. 2,3c,5 These methods share however the common intrinsic limitation that they cannot give access to tetrasubstituted or 1,2,2-substituted vinylgermanes which have two substituents distal to the germyl group. 6 Alkyne germylmetalation is attractive in this context, as the newly formed C(sp 2 )-metal bond can serve as linchpin for further functionalization, but remains virtually unexplored: reports on alkyne germylcupration are scarce, [START_REF] Piers | Reaction of (Trimethylgermyl)copper(I)dimethyl Sulfide with Acyl Chlorides: Efficient Syntheses of Functionalized Acyltrimethylgermanes[END_REF][START_REF] Oda | Regioselective Germylcupration of Acetylenes[END_REF] and limited to terminal alkynes. [START_REF] Piers | There is one report on the conjugate addition of (trimethylgermyl)cuprate reagents across alkyl-2-ynoates. The organometallic adducts (allenoates) were not used for further functionalization[END_REF] Moreover, subsequent C(sp 2 )-Cu bond-functionalization is poorly effective or impeded by the reversible character of the addition step. Alkyne germylstannylation was also considered for the same purpose, [START_REF] Kato | Synthesis of Novel Stereodefined Vinylgermanes Bearing an Allyl Group or an Allenyl Group: (E)-2-Aryl-1germylalka-1,4-dienes and (E)-4-Aryl-5-germylpenta-1,2,4-trienes[END_REF] but again only on terminal alkynes and C(sp 2 )-Sn bond-functionalization required an additional synthetic step. To overcome these shortcomings, we recently disclosed the germylzincation reaction of -heteroatom-substituted alkynes relying on their reaction with a hydrogermane and Et2Zn in a radical chain process [START_REF] De La Vega-Hernández | Radical Germylzincation of α-Heteroatom-Substituted Alkynes[END_REF] (Scheme 1). The decisive feature of this new germylmetalation reaction is the possibility to combine it readily in one-pot with a subsequent stereoretentive electrophilic substitution reaction of the created C(sp 2 )-Zn bond. In continuation of this work and given that organogermyl radicals add across various types of C-C triple bonds, we became interested in applying the method with other alkynes. 12 In this Letter, we report the radical germylzincation of internal alkynes, including symmetrical diaryl-and dialkylacetylenes, non-symmetrical (aryl, alkyl)-substituted alkynes, as well as aryl-, alkyl-, or trimethylsilyl-substituted propargylic alcohols. High levels of regio-(where appropriate) and stereocontrol can be achieved through modulation of the operating conditions for germylzincation reactions that can be either trans-or cis-selective depending on the substrate type.

Scheme 1. Radical Germylzincation of Internal Alkynes

We commenced our study by investigating the reaction of diphenylacetylene 1a with a combination of Ph3GeH and Et2Zn (Table 1). Under the operating conditions previously applied for the germylzincation of internal ynamides, i.e. Ph3GeH (1.3 equiv) and Et2Zn (3.0 equiv) in THF at 40 °C (entry 1), after 16 h and following work-up, vinylgermane 3a was obtained with high Zstereoselectivity (Z/E = 88:12), albeit in moderate 49% yield because conversion was not complete (~35-40% unreacted 1a were recovered). Using higher amounts of Ph3GeH (2.0 equiv), adding AIBN (25 mol%) as radical initiator, and operating at 80 °C to ensure decomposition of the latter, made possible to reduce the amount of unreacted 1a to ~20% and allowed for improved results: 67% yield was observed within a much shorter reaction time (1 h), along with a significant enhancement of the stereoselectivity (Z/E = 92:8) (entry 2). Under these conditions, D-labeling confirmed the formation of a vinylzinc intermediate as [ 2 H]-3a was obtained (98% D incorporation) on quenching with ND4Cl (entry 3). Importantly, the critical role played by AIBN here was established through a control experiment: in the same conditions but in the absence of the radical initiator, 3a was detected in amounts lower than 10% (entry 4). Conversely, heating through microwave irradiation instead of an oil-bath (entry 5) or increasing to 50 mol% the amount of AIBN (entry 6) led to full or close-to-full conversion. However, this was not beneficial overall, since the stereoselectivity dropped. In benzene at 100 °C (entries 7 and 8), 88% and 78% yield was achieved with only 10 mol% AIBN, but reversal of stereoselectivity was observed and vinylgermane 3a was delivered in a E/Z ~ 75:25 ratio both upon heating in an oil-bath (for 16 h) or through microwave irradiation (1 h). A similar outcome was observed operating in heptane at 120 °C in the presence of 100 mol% AIBN (entry 9). These results point towards the coexistence of two regimes: a non-equilibrating one which is trans-stereoselective, 13 and an equilibrating one which is (moderately) cis-stereoselective. In line with analogous observations for radical hydrogermylation reactions of terminal alkynes, we surmise that the triphenylgermyl radical is responsible for the isomerization of the -triphenylgermyl vinylzinc intermediates 2a. 5b Accordingly, kinetic selectivity is prevalent for short reaction times and in THF wherein radical chains are short, while thermodynamic selectivity is observed for long reaction times and in benzene or heptane wherein the triphenylgermyl radical-promoted isomerization is facilitated by the existence of longer radical chains. Having identified these two possibilities, we focused on assessing their scope. In THF at 80 °C (Scheme 2), other diarylsubstituted acetylenes also underwent readily trans-selective germylzincation.

Scheme 2. Radical Germylzincation of Aryl-and Alkyl-Substituted Alkynes in THF

a The configuration of each isomer could not be determined unequivocally. The two major isomers had a Z configuration. b AIBN (25 mol%). c Microwave heating. d Yield calculated by 1 H NMR analysis of the crude reaction mixture using butadiene sulfone as internal standard. e Only -regioisomers were detected. Symmetrical diphenylacetylenes 1b-c afforded the corresponding vinylgermanes 3b-c in good yields (66-68%) and high Zselectivity (Z/E ≥ 87:13). In the case of non-symmetrical diarylacetylenes however, the regioselectivity of the process could not be controlled. Illustratively, the germylzincation of diphenylacetylene 1d having both an electron-rich para-OMe-phenyl substituent and an electron-deficient para-CF3-phenyl substituent delivered 3d (in 76% yield) as an / = 50:50 mixture of regioisomers, thus evidencing that an electronic bias of the carbon-carbon triple bond has no influence on the regioselectivity of the addition. The poor regioselectivity observed in the germylzincation of 1e, substituted by a 3-pyridyl group and a phenyl group further confirmed this fact. Here however, the major ( regioisomer of 3e, formed as a single Z diastereomer, was isolated in a decent 57% yield. Dialkyl-substituted acetylenes were also amenable to transgermylzincation in THF at 80 °C (Scheme 2). 14 In the presence of 25 mol% AIBN, the reaction of 4-octyne 4a delivered vinylgermane 5a in 31% yield with Z/E = 93:7. A more satisfactory 58% yield was obtained with 100 mol% AIBN using microwave heating. Here also, fully D-labeled [ 2 H]-5a was recovered on quenching the reaction with ND4Cl, thus confirming the formation of vinylzinc intermediates. Note that the formation of bisgermylated byproduct 6, the structure of which was determined by X-Ray crystallographic analysis, 15 was also detected under these harsher conditions (4% yield). 16 The same protocol was also applied to alkyne 4b having two different alkyl substituents, but louse regiocontrol was observed in spite of the recognizable steric bias, and product 5b was obtained as a mixture of regio-and stereoisomers. Conversely, regiocontrol was not a problem in the case of 1phenyl-1-propyne 7a having substituents different in nature. As for the diaryl-substituted alkynes, 25 mol% AIBN sufficed to achieve a good 66% germylzincation yield. Only the -regioisomers were detected, what can be ascribed to stabilization by the adjacent phenyl group of the vinyl radical intermediate (I (R 1 =Ph), Scheme 1) arising from the triphenylgermyl radical addition. Nevertheless, the isomerization of the E-vinylzinc adduct is more facile and observable to some extent even if full conversion only requires 1 h reaction time. Hence, vinylgermane 8a was obtained as a Z/E = 65:35 mixture of stereoisomers. The structure of E-8a was confirmed by X-ray crystallography. 15 We next surveyed the possibilities offered by operating in heptane at 100 °C (Scheme 3). The reaction of 4-octyne 4a in the presence of 50 mol% AIBN and under microwave irradiation delivered vinylgermane 5a in 52% yield as a Z/E = 75:25 mixture of isomers. Hence, while some isomerization was observed, the process did not seem suitable to steer the reaction towards E-stereoselectivity for this substrate class. In addition, bisgermylated product 6 was formed in 32% yield. As previously observed in THF, non-symmetrical dialkyl-substituted alkyne 4b led to a mixture of regio and stereoisomers. By contrast, with 1-phenyl-1-propyne 7a for which the isomerization occurs more readily, 17 performing the reaction in the presence of 10 mol% AIBN delivered the desired product 8a in excellent 93% yield, with perfect regioselectivity, and remarkable E-stereoselectivity (E/Z = 95:5). No difference was observed using conventional heating (2 h) or microwave irradiation (1 h). Again, D-labeling experiments ascertained that germylzincation was also in these conditions the exclusive reaction pathway accounting for vinylgermane formation. The protocol appears to be general for (alkyl, aryl)-substituted alkynes as, similarly, 1-phenyl-1-butyne 7b afforded vinylgermane 8b in 91% yield and E/Z = 95:5 ratio, with complete control of the regioselectivity. Importantly, no appreciable difference of outcome was noted on running the reaction on a 1 mmol scale.

Scheme 3. Radical Germylzincation of Dialkyl-and (Alkyl, Aryl)-substituted Alkynes in Heptane

a AIBN (50 mol%), microwave heating (1 h). b Microwave heating (1 h). c 94% yield was obtained on a 1 mmol scale (25 mol% AIBN).

We then considered propargylic alcohols (Scheme 4), a synthetically important family of substrates for which we awaited to achieve high levels of regio-and stereocontrol. An O-directing effect allowing for exquisite vicinal-regiocontrol in the addition of triorganostannyl radicals is well documented for radical hydrostannation reactions of propargyloxy dialkylacetylenes with tin hydrides, 18 and we observed similar levels of regioselectivity in a preliminary survey of AIBN-initiated radical hydrogermylation reactions with Ph3GeH. 19 Stereocontrol could be secured through chelate formation (11).

Scheme 4. Radical Germylzincation of Propargylic Alcohols

a For the major -isomer.

Aryl-or alkyl substituted primary (9a, 9c) and secondary (9b, 9d) propargylic alcohols performed well, and germylated alcohols 13a-d were obtained in good-to-high yields, with excellent -regioand Z-stereoselectivity. The methodology was also amenable to the utilization of trimethylsilyl-substituted propargylic alcohol 9e which afforded -trimethylsilyl vinylgermane 13e in 65% yield. Lastly, homopropargylic alcohol 10 was investigated. Here, given that the hydroxy unit is too far away from the alkyne and no regiocontrol is induced in the germyl radical addition, 19,20 a mixture of regioisomers was obtained in -14/-14 = 57:43 ratio and 57% combined yield. Nevertheless, chelate formation remains possible for both regioisomers of the germylzinc adducts -12 and -12 (not shown in the scheme) and allows for almost complete stereocontrol in favor of the Z-isomers of -14 and -14.

In the final part of our study, we established the potential of our new germylzincation procedures to prepare tetrasubstituted vinylgermanes through functionalization in one pot of the C(sp 2 )-Zn bond of the vinylzinc adducts formed. Cu(I)-mediated allylation was performed for each substrate class: tetrasubstituted vinylgermanes 15-18 were obtained from 1a, 4a, 7a and 9b in good-to-excellent yields (58-93%) and with exquisite retention of the geometry of the vinylzinc intermediates (Scheme 5). The configuration of products Z-15 and E-17 was established by Xray crystallography. 15 Scheme 5. Preparation of Tetrasubstituted Vinylgermanes through Alkyne Germylzincation/Cu(I)-Mediated Electrophilic Substitution a AIBN (25 mol%). b AIBN (100 mol%), microwave heating. c 5% of 6 was detected. d AIBN (10 mol%). e Only -regioisomers were detected.

Benzoyl chloride and tributyltin chloride were also competent electrophiles, leading to benzoylated vinylgermane 19 and stannyl vinylgermane 20 as single regio-and stereoisomers. The domino alkyne germylzincation/Cu(I)-mediated stannylation reaction giving 20 is remarkable as it allows for the direct synthesis of these tetrasubstituted 1,2-dimetallated alkenes not accessible through the oxidative addition chemistry of Ge-Sn compounds. 21 In summary, we describe here the germylzincation of internal alkynes by reaction with Ph3GeH and Et2Zn in the presence of AIBN as radical initiator. Upon tuning of the reaction conditions, an array of substrate-types is amenable to germylzincation with high levels of stereoselectivity, including symmetrical diaryl-or dialkylsubstituted acetylenes, non-symmetrical (alkyl, aryl)-substituted acetylenes and propargylic alcohols. Superb regiocontrol is obtained for alkyl-substituted arylacetylenes and propargylic alcohols. As part of this work, we demonstrate the possibility to engage the C(sp 2 )-Zn bond formed in subsequent stereoretentive Cu(I)-mediated electrophilic substitution reactions. This two-step one-pot protocol offers a versatile and modular route to access valuable tetrasubstituted vinylgermanes with substitution patterns that have so far remained synthetically challenging.

Additional data and discussion, experimental details, NMR spectra for new compounds, and X-ray crystal structures for compounds 6, E-8a, Z-15 and E-17 (PDF) * alejandro.perez_luna@sorbonne-universite.fr (12) Terminal alkynes were found to be unsuitable substrates because direct radical hydrogermylation (with Ph3GeH) overrides germylzincation. The feasibility of the approach for conventional internal alkynes was demonstrated in reference 11.

(13) Here, the intermediate vinylradical I (sp-hybridized) is linear and the approach of Et2Zn favored from the less hindered side opposite to the bulky Ph3Ge group. For a similar situation in the case of radical silylzincation reactions, see: Romain, E.; de la Vega-Hernández, K.; Guégan, F.; Sanz García, J.; Fopp, C.; Chemla, F.; Ferreira, F.; Gerard, H.; Jackowski, O.; Halbert, S.; Oestreich, M.; Perez-Luna, A. Radical Silylzincation of (Het)Aryl-Substituted Alkynes and Computational Insights into the Origin of the trans-Stereoselectivity. Adv. Synth. Catal. 2021, in press (DOI: 10.1002/adsc.202001566). ( 14) Here, the intermediate vinylradical I (sp 2 -hybridized) is bent and exists as a rapidly interconverting mixture of Z and E isomers. The reaction of Et2Zn with the Z-isomer, leading to an E-vinylzinc intermediate, is more favorable because the interaction with the bulky Ph3Ge group is avoided. The same stereoselective outcome is observed in radical hydrogermylation reactions of internal alkynes with Ph3GeH, see references 3c and 5a.

(15) Crystal structures were deposited at the Cambridge Crystallographic Data Centre with numbers CCDC 2077757 (6), 2077610 (E-8a), 2077611 (Z-15) and 2077612 (E-17) and can be obtained free of charge via www.ccdc.cam.ac.uk.

(16) Product 6 is likely formed following reductive elimination from intermediate vinylzinc derivatives upon exchange of the ethyl ligand on zinc by a triphenylgermyl ligand. Formation of elementary zinc in the reaction media supports this proposal that is reminiscent of an analogous bissilylation pathway reported in the context of alkyne silylzincation reactions, see: Auer, G.; Oestreich, M. Silylzincation of carboncarbon multiple bonds revisited. Chem. Commun. 2006, 49, 311-313. (17) For this specific substrate, Ph3Ge • -promoted isomerization induced by abstraction of allylic hydrogen atoms cannot be excluded, see: Shimoi, M.; Watanabe, T.; Maeda, K.; Curran, D. P.; Taniguchi, T. Radical Trans-Hydroboration of Alkynes with N-heterocyclic Carbene. Angew. Chem. Int. Ed. 2018, 57, 9485-9490. (18) (20) The same lack of regiocontrol is observed for homopropargyloxy functionalities in radical hydrostannation reactions, see: Nativi, C.; Taddei, M. Some Observations on the Stereochemical and Regiochemical Outcome of Hydrostannylation of Substituted Propargylic Alcohols. J. Org. Chem. 1988, 53, 820-826. (21) Pd-catalyzed germylstannation: (terminal alkynes) (a) Senda, Y.; Oguchi, Y.; Terayama, M.; Asai, T.; Nakano, T.; Migita, T. Synthesis of (Z)-1-aryl-2-(germyl)-1-(stannyl)ethenes and the related ethenes, precursors to stereodefined germylethenes, via Pd(dba)2-P(OCH2)3CEt-catalyzed germastannation of acetylenes in THF. J. Organomet. Chem. 2001, 622, 302-308. (non-terminal acetylenic esters) (b) Piers, E.; Skerlj, R. T. J. Regioselective Germyl-Stannylation of ,-Acetylenic Esters. Chem. Soc., Chem. Commun. 1987, 1025-1026.

Table 1 . Germylzincation of Diphenylacetylene (1a)

 1

	entry solvent conditions	AIBN	E	d.r. 3a	yield 3a
				(mol%)		(Z/E) a	(%) b
	1	THF	40 °C, 16 h	-	H	88:12	49 c,d
	2	THF	80 °C, 1 h	25	H	92:8	67 d
	3	THF	80 °C, 1 h	25	D	92:8	71 d
	4	THF	80 °C, 1 h	-	H	>98:2	<10 e
	5	THF	80 °C, f 1 h	25	H	84:16	74
	6	THF	80 °C, 1 h	50	H	80:20	85 e
	7 benzene 100 °C, 16 h	10	H	23:77	88 e
	8 benzene 100 °C, f 1 h	10	H	26:74	78 e
	9 heptane 120 °C, 16 h	100	H	30:70	83 e
	a Determined by 1 H NMR prior to purification. b Isolated yield of
	both diastereomers. c Ph3GeH (1.3 equiv). d Reference 11. e Yield es-
	timated by 1 H NMR analysis of the crude reaction mixture using
	butadiene sulfone as internal standard.

f

Microwave heating.

  Hale, K. J.; Manaviazar, S.; Watson, H. A. The O-Directed Free Radical Hydrostannation of Propargyloxy Dialkyl Acetylenes with Ph3SnH/cat. Et3B. A Refutal of the Stannylvinyl Cation Mechanism. Chem. Rec. 2019, 19, 238-319. (19) See Table S1 in the Supporting Information.

All authors have given approval to the final version of the manuscript.

The authors declare no competing financial interest.

Gilles Clodic (IPCM) and Cédric Przyblski (IPCM) are gratefully acknowledged for HRMS analyses and Jérémy Forté (IPCM) and Geoffrey Gontard (IPCM) for X-Ray crystallographic analysis.


Hung-Ju Lin

Hengyang Xiang

Chenghao Xin

Zhelu Hu

Laurent Billot

Patrick Gredin

Michel Mortier

Zhuoying Chen

Maria-Ujué González

Antonio García- Martín

Lionel Aigouy

Direct Imaging of Fluorescence Enhancement in the Gap between Two Gold Nanodisks

Keywords: Nano-photonics, luminescence enhancement, plasmon resonance, upconversion, near-field optics, dimers

We present an analysis of the optical coupling between two gold nanodisks by near-field fluorescence microscopy. This is achieved by scanning and measuring simultaneously the light emitted by a single Er 3+ /Yb 3+ doped nanocrystal glued at the end of an atomic force microscope tip. The excitation of the nanocrystal was performed at  = 975 nm, via upconversion, and fluorescence was detected in the visible part of the spectrum at  = 550 nm.

For an isolated nanodisk, the near-field presents a two-lobe pattern oriented along the direction of the incident polarization. For two nanodisks with a sizeable separation distance (385 nm), illuminated with the polarization along the interparticle axis, we observe a negative effect of the coupling with a slight decrease of fluorescence in the gap. For smaller gap values (195 nm, 95 nm and 55 nm) a strong increase of fluorescence is observed as well as a reduced spatial localization of the field as the distance decreases. Finally, when the disks touch each other (0 nm), the dipolar-dipolar interaction between them disappears, and no fluorescence enhancement occurs. A new plasmon mode is created, at another wavelength. Our experimental results are in good agreement with numerical simulations of the near-field intensity distribution at the excitation wavelength on the surface of the structures. Combining fluorescence mapping and far-field scattering spectroscopy should be of strong interest to develop bio-chemical sensors based on field enhancement effects.

TEXT

Metallic nanostructures made of gold and silver exhibit extraordinary properties due to the presence of surface plasmon resonances (SPR) [START_REF] Maier | Plasmonics: Fundamentals and Applications[END_REF][START_REF] Schuller | [END_REF][3][4] . These resonances are due to the collective oscillation of electrons on the metal surface and are characterized by a strong absorption and scattering of light. At the local scale, they induce a localization of the electromagnetic field at some specific locations around the nanostructures as well as strong enhancements of the intensity. Numerous applications arise from this field enhancement effect in different domains such as increasing the detection sensitivity for biosensing 3,[5][6][7] , surface enhanced Raman scattering (SERS) 8,9 , or improving the performance of optoelectronic devices [10][11][12] . The intensity of the local fields depends on the nature of the metallic nanoparticles, their shape and their size, and the dielectric environment. Groups of nanoparticles can also lead to an even larger increase of the field enhancement due to the coupling between them. In the case of metallic dimers, if the separation distance is small enough, near-field interaction occur between them and this leads to a strongly enhanced and localized electromagnetic field [13][14][15][16][17][START_REF] Hooshmand | Proc. Nat. Acad. Sci[END_REF] . If the molecules are inserted in the gap, the emission can be enhanced [START_REF] Chekini | [END_REF]20 , either by an increase of the excitation or by an increase of the fluorescence decay rate, or by both effects [21][22][23][24][25][26][27] .

To observe the coupling effects between two metallic dimers, a widely used method is far field scattering or transmission spectroscopy on isolated dimers or on structures arranged in arrays 13,16,17,[28][29][30] . The scattering spectra of two coupled nanoparticles exhibit a red shift of the dipolar resonance compared to the isolated ones. This can be understood by the fact that if we approach two dipoles, i.e. the two nanostructures, the resonance frequency varies due to the dipole-dipole interaction. Other techniques like scattering scanning near-field optical microscopy (SNOM) 31,32 and electron energy loss spectroscopy (EELS) as well as tomographic EELS mapping 33,34 directly showed the light localization in the gap between nanostructures, with a lateral resolution which can be as small as 10 nanometers. Finally, nonlinear far-field imaging techniques like second harmonic generation also evidenced the coupling of plasmons between two nanostructures 35,36 . The intensity of the coupling depends on the distance between the nanostructures. For instance, red shifts of the resonance can be detected if the gap is smaller than approximately 2.5 times the particle diameter 13 . In the case of a nanodisk of 200 nm diameter, this corresponds to a gap of 500 nm. When the distance becomes very small, the electromagnetic field localization and enhancement becomes very high due to the accumulation of charges in the gap, but they start to vanish at very short distances (d < 1 nm), for which the dipolar resonance is inhibited. Finally, when the particles touch each other (d = 0 nm), a new nanostructure is created with other resonances, and new scattering peaks appear at other wavelengths in the near-infrared 15,28 .

In this article, our aim is to explore how the coupling between two gold nanodisks influences the fluorescence emitted by a single nanocrystal. This will be achieved by mapping the fluorescence intensity as a function of the position of the nanocrystal around the disks, for different separation distances between them. Although there are many experimental studies describing the influence of plasmonic structures on fluorescent molecules [START_REF] Chekini | [END_REF][20][21][22][23][24][25][26][27]37 , the direct mapping of the emission intensity or lifetime has only been achieved on simple structures like isolated metallic nanostructures 23,38 . For structures where coupling effects or interactions govern the optical response, many questions are still unanswered. How does the nanocrystal fluorescence evolve as a function of the gap length? How is the fluorescence intensity related to the near-field intensity at the excitation wavelength? Do we observe a total quenching of fluorescence when two coupled structures touch each other? To perform the aforementioned fluorescence mapping, so that we can shed some light on these questions, we use a fluorescent nanocrystal glued at the end of an atomic force microscope (AFM) tip, and measure the emitted light as a function of the tip position around the nanostructures.

To be able to perform quantitative comparisons on series of coupled nanodisks, it is required to use the same tip/nanocrystal for all the samples. Therefore, the nanocrystal has to be robust, durable, and should not present any evidence of photobleaching. Fluoride nanocrystals doped with Er 3+ and Yb 3+ ions nicely satisfy these conditions [38][39][40][41] . In this study, we use NaYF 4 :Er 3+ /Yb 3+ nanocrystals synthetized by hydrothermal route 42,43 . Some details about the synthesis can be found in the supplementary material. Er 3+ /Yb 3+ co-doped materials emit fluorescence at the green ( = 525 nm), the yellowish-green ( = 550 nm) and the red ( = 670 nm) wavelengths in the visible region of the electromagnetic spectrum. It is possible to excite them in the visible with a one-photon excitation and also in the near-infrared by upconversion, for instance at  = 975 nm. This two-photon process is very convenient because the excitation wavelength is well separated from the emission lines and it is easy to get rid of the incident light. We show in Fig. 1 the experimental set-up, a scanning electron microscope (SEM) image of the nanocrystals, their energy band diagram and their fluorescence spectrum. The sample is excited in a transmission mode with a linearly polarized, intensity modulated (f = 330 Hz), laser diode emitting at  EXC = 975 nm. The beam is focused on a 20 µm wide spot and that illuminates both the sample surface and the nanocrystal. The emitted light ( = 550 nm) is collected with a high numerical aperture objective and sent to a photomultiplier tube and a lock-in amplifier synchronized to the laser modulation. The scans are performed in the tapping mode, with the feedback loop disabled, at a constant height (h = 0 nm) above the nanostructures (see Fig 1b). Before studying coupled nanostructures, we measured the fluorescence intensity maps near an isolated gold nanodisk fabricated by electron beam lithography on a glass substrate. The diameter and the thickness of the disk were close to 240 nm and 50 nm respectively. The results are shown in Fig. 2 where the fluorescence maps are composed of two high intensity zones which form two lobes oriented in the direction of the incident polarization of the excitation beam. As shown in Fig. 2(a) and 2(b), when the polarization is rotated by 90°, the lobes also rotate by the same angle. Recently, a complete study on similar structures showed that the fluorescence maps are directly linked to the nearfield intensity near the nanostructure at the excitation wavelength 38 . It was observed that the maximum fluorescence occurred for disk diameters in the 200 -250 nm range and a good agreement was found with numerical simulations. To put forward the role of interactions, we now consider the case of two almost identical nanodisks, where the near-field intensity and the nanocrystal fluorescence depend on the coupling and on the disk separation distance. We characterized five structures of diameter 240 nm and separated, from edge to edge, by d = 385 nm, 195 nm, 95 nm, 55 nm and 0 nm respectively. The chosen diameter for each disk corresponds to that which has the largest local electromagnetic field intensity at the excitation wavelength 38 and the separation distances cover a wide range, from mid-field, where we expect a reduced (but not vanishing) influence of evanescent coupling, to near-field coupling and direct contact. The polarization of the incident light is parallel to the alignment of two nanodisks. In all the experiments, we used the same same tip/nanocrystal, performing the measurements in nearly identical experimental conditions. Let us start with the largest separation distance d = 385 nm, whose experimental fluorescence image and a cross-section are shown in Fig. 3(a) and 3(b) respectively. Even for large this gap, we can see that the fluorescence pattern is not simply the addition of the contribution of two isolated nanodisks. There are four lobes, aligned in the same direction, but the lobes situated in the gap are less intense than the external ones [see Fig. 3(a) and 3(b)]. This shows that, even for this large distance, there is a measurable interaction and the presence of one disk modifies the near-field around the other. This observation agrees with the measurements performed by Su et al 13 and Hooshmand and El-Sayed 18 who observed that the red shift of the resonance due to the coupling between two nanoparticles could be observed when the gap distance is up to 2.5 times larger than the diameter of the particles (in our case, the ratio gap/diameter is 1.6 times smaller than this value). For comparison, we performed rigorous electromagnetic calculations using finite difference time domain (FDTD) method, to obtain the spatial distribution of the near-field intensity (ǁEǁ 2 ) above the disk dimer. To account for the finite fluorescent particle size, the intensity is averaged on a 100 3 nm 3 large cube. The "cube" is scanned in a plane above the disk surface at a constant height of 14 nm. The nearfield intensity map and a cross-section profile along the alignment are shown in Fig. 3(c) and 3(d) respectively. As for the experimental fluorescence maps, four lobes are clearly discernible, oriented along the direction of the incident polarization, the ones located in the gap between the disks being less intense than the external ones. This qualitatively agrees with the experimental results, however the relative intensity of the inner lobes compared to the outer ones is slightly smaller in the fluorescence map than in the simulation. The difference can be explained by several reasons. To simplify the simulation, the average was made on a cube which does not exactly represent the real shape of the nanocrystal, its shape is more or less spherical (see the SEM image in Fig. 1). Also, the nanocrystal is not a pure detector of the electromagnetic field. It is also a light source excited by the near-field, and the emission process (for instance the radiative rate and the emission pattern) can also be influenced by the gold dimer. These effects are not considered in the simulation and would be way too hard to implement. Despite the mentioned differences, the agreement is good enough to consider that the physical role played by the interaction is well captured for this separation distance. In Fig. 4 we show both the experimental fluorescence maps and profiles measured on dimers having a smaller gap (larger interaction) and the corresponding FDTD numerical results. As the gap reduces to d = 195 nm, the inner lobes combine with each other and the resulting intensity becomes larger than the one of the external lobes [Fig. 4(a)]. This is quite the opposite behavior observed for d = 385 nm. Once more, the simulation [Fig. 4(c)] agrees well with the experimental image. When the distance decreases to d = 95 nm, the central lobe becomes yet more intense then the intensity slightly decreases for d = 55 nm. This effect is illustrated in Fig. 4(m) where we plotted the evolution of fluorescence of the central lobe, normalized both by the fluorescence far from the dimer and by the lobe fluorescence of the 385 nm structure. The first normalization allows to get rid of intensity variations when we move the tip from one structure to the others. The second normalization allows to directly compare the evolution of the lobe intensity with numerical simulations. The normalized nearfield intensity of the central lobe deduced from the simulations is also shown, in good agreement with the experiment. For d < 195 nm, we can see that the relative fluorescence is larger than that of an isolated disk of the same dimensions, represented by the horizontal green line in Fig. 4(m). This clearly shows that the association of two particles increases the local enhancement effects compared to a single structure but it also shows that there is a maximum fluorescence intensity observed for d = 95 nm. It is perhaps relevant to recall that the fluorescence experimentally obtained corresponds to an average over the whole of the volume of the fluorescent nanocrystal above the dimers at an average height of 55 nm. It is likely that reducing the integration volume and scanning the surface closer to the gap would give a maximum value for a smaller separation distance. Indeed, in the gap itself, very large enhancements have been calculated for gaps smaller than 5 nm 14,[START_REF] Hooshmand | Proc. Nat. Acad. Sci[END_REF][44][45][46][47] . We are not sensitive to these strong fields here because our tip/nanocrystal is not able to penetrate inside the gap due to its size. Reducing the gap has also an effect on the Full Width at Half Maximum (FWHM) of the central fluorescence lobe. As we can see in Fig. 4(n), as the gap reduces from 195 nm to 55 nm, the FWHM decreases by almost a factor 2 for both the fluorescence and the simulation. This evidences the stronger localization of the electromagnetic field for small separation distances.

The interaction between the gold disks is more complex when they are very close to each other, and higher order modes can appear at lower wavelength if d becomes smaller than 1 nm 15,[START_REF] Hooshmand | Proc. Nat. Acad. Sci[END_REF]48 as the electronic cloud influences the dielectric properties of the gap, in a very similar way to the finite size corrections in atomic size conductors back in the 90"s 49 .

Although the local electromagnetic field is very high in the gap for these distances, quantum mechanical effects like electron tunneling can also lead to a decrease of the local enhancement at distances smaller than 0.5 nm 50 . We are not sensitive to these effects with our tip and nanocrystal, but we observed that when the discs contact each other, we do not observe anymore any fluorescence enhancement. This is clearly evident on the fluorescence image and cross-section shown in Fig. 5 where the central lobe disappears and the external ones are barely noticeable. The experiment is, once more, corroborated by our FDTD numerical simulation which shows the very same intensity reduction on the whole structure.

A small increase remains observable in the middle of dark zone (see the cross-sections In Fig. 5), but it apparently comes from the lateral parts of the dimer. The fluorescence (and near-field) map for the touching dimer actually resembles that of a "big" lone disk 38 , and thus we can explain the disappearance of the fluorescence bright spot as caused by the presence of the conductive path between the two disks. Electrons do not oscillate anymore around each disk separately, they can go back and forth between the two disks, which shifts the resonance frequency of the system at another, larger, wavelength, far from the excitation source 28,50 . Therefore, the associated near-field and fluorescence enhancements do not occur anymore. The experiments described here were performed with the incident polarization aligned along the dimer long axis. We also performed experiments with the incident polarization perpendicular to the interparticle axis (see supplementary material). In that case, the two disks behave like isolated structures, with the two lobes positioned on each side of the disks, and the experiments do not exhibit any evidence of coupling between the disks.

In summary, we performed direct mapping of fluorescence enhancement effects between two coupled gold nanodisks. All the experiments were compared to the intensity of the near-field distribution at the excitation wavelength calculated by FDTD. A very good agreement is observed which shows that, for the kind of nanocrystal we used, fluorescence emission is well described by absorption effects. We characterized the transition from well-separated to touching disks. We first showed that even for a large separation distance (385 nm), the fluorescence between two disks is modified compared to isolated structures, and the central The data that support the findings of this study are available from the corresponding author upon reasonable request.

Fig. 1 .

 1 Fig.1. Sketch of the illumination configuration (a) and the scanning mode (b), SEM image of a 100-150 nm large fluorescent NaYF 4 :Er 3+ /Yb 3+ nanocrystals (c), energy band diagram (d) and luminescence spectrum of the nanocrystals. The excitation was performed at  EXC = 975 nm.

Fig. 2

 2 Fig.2 Near-field fluorescence maps (a,b) and cross-sections (c,d) measured when a nanocrystal is scanning an isolated 240 nm-large gold nanodisk. The excitation was performed at  EXC = 975 nm and the luminescence was detected in the 520-550 nm range. The incident polarization of the laser beam is indicated by the arrow. The inset is an SEM picture of the nanodisk.

Fig. 3 .

 3 Fig.3. Experimental fluorescence image (a) and cross-section (b) measured on coupled gold nanodisks with a separation distance d = 385 nm. FDTD simulation (c,d) of the electromagnetic field intensity at the excitation wavelength. The intensity is averaged over a 100 nm large cube and in a plane situated 14 nm above the nanodisk surface. The cross sections are extracted from the images in the direction indicated by the white dash arrow. The incident polarization is parallel to alignment the disks. The inset is a SEM picture of the disks.

Figure 4 .

 4 Figure 4. Experimental fluorescence maps (a,e,i) and cross-section profiles (b,f,j) measured on coupled gold dimers with various separation distances. FDTD simulations (c,g,k) and cross-sections (d,h,l) of the electromagnetic field intensity at the excitation wavelength. The separation distance between the dimers is 195 nm (a,b,c,d), 95 nm (e,f,g,h), 55 nm (i,j,k,l). The cross-sections are taken along the dashed arrows. The insets in (a,e,i) are SEM images of the gold dimers. Experimental fluorescence and calculated near-field relative intensities of the central lobe as a function of the separation distance d (m). The intensities are normalized by the intensities far from the dimers and also by the value for d = 385 nm (reference value). FWHM of the central lobe as a function of the separation distance d (n). In (m), the horizontal green line represents the fluorescence intensity of the lobes for an isolated single disk, extracted from Fig. 2.

Figure 5 .

 5 Figure 5. Experimental fluorescence image (a) and cross-section (b) measured on a structure with touching nanodisks (d = 0 nm); FDTD simulation (c) and cross-section (d) of the electromagnetic field intensity on the structure. The inset in (a) is a SEM image of the dimer.

  lobe is quenched compared to the external one. Then, for smaller separation distances, the fluorescence at central lobes is strongly increased due to the evanescent coupling between the disks. As the disks touch each other, fluorescence is almost totally quenched due to the suppression of the dipole-dipole coupling and the appearance of another plasmon mode, at larger wavelengths as if the dimer were a bigger disk. Combined with far-field extinction or absorption spectroscopy, we think the direct visualization of fluorescence maps near nanostructures can be very interesting to design and optimize sensors based on local field enhancement effects. SUPPLEMENTARY MATERIAL The fabrication of fluorescent nanoparticles, the tip fabrication procedure, and additional near-field fluorescence experiments are shown in the supplementary material.

ACKNOWLEDGMENTS

The authors thank the support from the DIM Nano-K program from "Région Ile de France", from the Idex Paris Sciences & Lettres through the grant ANR-10-IDEX-0001-02 PSL from the CNRS and the CSIC through the Spanish-French program PICS (grant SolarNano #PICS07687 and #PIC2016FR2), and from the Spanish Ministerio de Ciencia e Innovación through grant PID2019-109905GA-C22.

DATA AVAILABILITY

AUTHOR INFORMATION

Corresponding Authors

*E-mail: lionel.aigouy@espci.fr


Marion Szadkowski

Catherine Wipf-Scheibel

William Billaud

Cecile Desbiez

Jonathan Gaudin

Gregory Girardot

Patrick Gognalons

Judith Hirsch

Thibaud Jayet

Sylvain

Cécile Desbiez

Grégory Girardot

Sylvain Piry

Loup Rimbaud

Alexandra Schoeny

Eric Verdin

Raphaël Forien

Julien Papaïx

Lionel Roques

Benoît Moury

Karine Berthier

Outside the wild: Risks and mechanisms of host jumps of endive necrotic mosaic potyvirus

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

Host jumps, the acquisition by a parasite of the capacity to infect novel host species, are frequent among plant viruses but still poorly understood. To investigate their mechanisms, we performed an experimental evolution of endive necrotic mosaic virus (ENMV) in five species of the family Asteraceae, including vegetable and ornamental crops, and analysed the incurred genetic changes.

ENMV is mostly confined to wild salsify (Tragopogon pratensis) and occasionally infects lettuce (Lactuca sativa). An ENMV isolate from L. sativa was serially passaged in one of five plant species (either L. sativa, T. pratensis, Calendula arvensis, Zinnia elegans or Cichorium endivia). For each species, six infection cycles were performed, with eight independent experimental replicas. Each of the evolved ENMV populations and the initial isolate were inoculated to the five plant species to measure their pathogenicity.

Changes (gains) in virus pathogenicity were observed in C. arvensis and Z. elegans only. Cross-adaptations between C. arvensis and Z. elegans were also observed. Parallel nonsynonymous substitutions (identical substitutions arising independently) were observed at three nucleotide positions in the VPg cistron of the adapted ENMV populations, and are candidates for the observed pathogenicity changes. Some of these were shared between C. arvensis-and Z. elegans-evolved populations, partly explaining the cross-adaptations.

These results indicate that ENMV is prone to jumping to novel host species, that crossadaptations occur and may be linked to the genetic distance between host species and that these jumps may involve the VPg in a way similar to the breakdown of eIF4E-mediated resistance.


Catherine Macombe
email: catherine.macombe@irstea.fr

And…after? Review of the prospects for food security and agriculture

Keywords:

. In general, authors acknowledge the physical factors to be more compelling for the farther horizon (2100) than for the nearer one (2050). However, the conclusions are not homogenous. For some authors, the adaptation will require more effort in the long term than now (i.e. we can wait). For others, the "adaptation" requires immediate and decisive actions for huge shifts involving agriculture, society and ways of life. The review highlights the rift among scientists, between authors proposing affordable solutions for agriculture and undemanding for the rest of the society, and those authors advocating a paradigm shift and new social structures, to address challenges of food security.

Introduction

"The future will likely look like the pre-industrial era, the only difference being that we will go on with innovation and development of new techniques…compatible with "solar" limits." [START_REF] Servigne | Nourrir l'Europe en temps de crise: vers des systèmes alimentaires résilients. Les Verts Alliance libre européenne au parlement européen[END_REF].

In light of the conference on the general theme of "Action for a sustainable world" the term "Food security" encourages forecasts, with at least three concerns. Food insecurity is a present issue1 , and is likely to worsen in the coming decades, especially in developing countries, where productivity may be reduced three times faster than in developed countries by 2050 (IPCC, 2007;[START_REF] Calzadilla | Climate change impacts on global agriculture[END_REF]. More generally, most scientists think that global food security is threatened by certain ongoing or future changes (identified differently according to the authors). Whatever the point, the issue of food insecurity involves humankind as a whole, because the pace of the exploitation of planet's resources does not allow for selfrenewability. From the Paleolithic to the present day, per capita food energy demand has increased 5-fold [START_REF] Simmons | Changing the face of the earth: culture, environment, history[END_REF].

The other part of the conference's theme "From theory to practice" forces us to examine the practices implemented to strengthen food security orfailing that-encourages us to scan the practical solutions advised by authors, in such a way that we propose a critical review of literature regarding food security linked with agriculture, and the proposed solutions.

Methods

The relationship between food security and agriculture is not straightforward on a local scale. Indeed, it is acknowledged that the conjunction of armed conflicts and climate disasters is the primary cause of malnutrition and food insecurity [START_REF] Fao | The state of food security and nutrition in the World[END_REF]. However, on a world or continental scale, long-term food security is secured only by flourishing and productive agriculture. To enable a direct link between food security and agriculture, we choose to focus our literature review on a wider scale (world, continent or country) only. Moreover, we consider two time-scales: one around the years 2030-2050, and the second around 2080-2100.

Discussions about food security on a large scale depend on the kind of envisioned change. We sort the papers on the following basis: i) no consideration of specific changes; ii) changes are taken into account regarding the physical factors only [via temperature and precipitations only or via other effects of climate change]; iii) changes also relating to economic factors; or iv) social factors. We sort the envisioned solutions in accordance with the required magnitude of disruption of our present way of life.

Results and Discussion

This paragraph sets out the variety of factors taken into account to deal with changes in food security and/or agriculture, the variety of proposed solutions, and the messages delivered for various deadlines, before proposing the final discussion.

a. Consequences of changes in terms of Food Security

The consequences of the changes depend on the nature of the envisioned changes: either continuation of past trends; or considering physical factors only; or dealing also with economic factors; and finally accounting for social factors.

Continuation of past trends

Some authors deal only with the continuation of past trends. This is the case of the report (OECD-FAO, 2017), which envisions the world agricultural yield until the year 2026. The report explicitly states that it does not account for hazards like: "new pests and diseases, [of] increased variability in yields caused by climate change, and uncertainty around policies (page 54)". The authors guess thatin the future-the variability of the factors will remain in the same range of values as in the recent past. Moreover, their modeling forecasts of agricultural yields are determined by the demand side (for food, feed, biofuels, etc.). It is therefore assumed that food insecurity will remain at its present level. Conversely, [START_REF] Godfray | Food security: the challenge of feeding 9 billion people[END_REF] tackle the issue of the necessary strategies to be developed in order to feed 9 billion people in 2050. Nevertheless, as with the former report, they do not consider other changes than world population growth, and its correlated food demand, caused by the attainment of a better standard of living.

Only new physical factors are considered

Other authors account for some physical factors of change, but without considering the economic and social factors. Among them, the models by [START_REF] Lobell | Prioritizing climate change adaptation needs for food security in 2030[END_REF] deal only with the average temperatures and rainfalls envisioned for 2030. They stipulate that the rise in temperatures might be of benefit to the agriculture of some northern regions, and acknowledge that food insecurity will be an issue for some regions, including those already suffering from this scourge. [START_REF] Vincent | Food production and food security[END_REF] reminds us that "the low latitudes are particularly sensitive, because of large negative sensitivity of crop yields to extreme daytime temperatures around 30°C [-]. Production levels of major crops such as wheat, maize, and rice are projected to decline from 2050", which would entail dire consequences for the poor. According to Quasem Al-Amin and Ahmed (2016), climate change is the real food insecurity problem for the developing world, where agricultural production may be reduced by 10-25% by 2080, in the "business-as-usual" scenario. These authors are specifically involved in studying the Malaysian food security by 2065, and account for the damages caused by the yearly average temperature and rainfall fluctuations, the increase in CO 2 emissions, and the feedback on temperatures.

Agronomists could claim that plants are sensitive to extreme temperatures (and not to average ones) (MODEXTREM, 2016), and explain that it would take many years of investment and work to replace tundra with fertile soil (Dalhberg, 1994).

Change dealing with economic factors also [START_REF] Adams | Effects of global climate change on agriculture: an interpretative review[END_REF] present a review of works which consider long-term economic effects of yield losses because of Global Warming (around 2050-2060), in order to discuss the potential patterns in food production and prices. They acknowledge that most studies do not incorporate some impacts "such as changes in the incidence and severity of agricultural pests and diseases and changes in soil erosion". All the same, they state that "few studies consider the effects of changes in the frequencies of extreme events such as droughts and floods, or changes in climatic variability."(page 29). The authors are more interested by the effect of Global Warming upon the economic welfare of the average American citizen, than by food insecurity itself. [START_REF] Calzadilla | Climate change impacts on global agriculture[END_REF] study the effects of Global Warming on agriculture in 2020 and 2050 via water availability. They calculate effects on well-being, including the modifications of international trade. Here also, the link with food insecurity is not straightforward. Because the economic drivers (cheap energy and pervasive externalization of costs)

entailing viability of agro-industrial systems will not last, [START_REF] Clark | The future is organic: but it's more than organic[END_REF] explains the ongoing emergence of novel agro-food systems.

Changes accounting for social factors

Some of the authors quoted above admit that overlooked social factors are important, which are complicating the equation of the Global Warming. "Costs and obstacles to adaptation have also been omitted." (Adams et al., 1998, page 29). To face the compelling changes in agriculture, Quasem Al-Amin and Ahmed (2016) suggest policy measures towards "income stabilization programs due to farmers income loss", because they are aware of the role of social adaptations in the success of agricultural policies. [START_REF] Dahlberg | A transition from agriculture to regenerative food systems[END_REF] notes the growth of income inequalities among the global constraints and threats encountered by modern industrial societies. More specifically for the agricultural sector, the author denounces the historical dispossession of native lands and the subjugation of smallholders, a movement intensified by the technological green revolution, and by the ever-increasing emphasis put on cash crops for export, which have marginalized smallholders and subsistence agriculture. [START_REF] Radanne | Changement climatique et société(s)[END_REF] warns us that the inescapable shift will likely be violent. "We must keep in mind that these transitions can deeply increase economic and social disparity, and that they are often violent" (page 21).

b. Varieties of solutions

The authors suggest various solutions, ranging from (mainly) relying on international trade in agricultural commodities (e.g. [START_REF] Calzadilla | Trade Liberalization and Climate Change: A Computable General Equilibrium Analysis of the Impacts on Global Agriculture[END_REF][START_REF] Adams | Effects of global climate change on agriculture: an interpretative review[END_REF] to a deep shifting in our ways of life.

Changing only agricultural practices

To face the agricultural challenges of the years 2030-2050, [START_REF] Lobell | Prioritizing climate change adaptation needs for food security in 2030[END_REF] guess that "shifting planting dates or switching to an existing crop variety" will not be enough, forcing farmers to "more costly measures including the development of new crop varieties and expansion of irrigation." (Lobell et al., 2008, page 607). [START_REF] Burke | Food security and adaptation to climate change: what do we know?[END_REF] add "water harvesting" and recognize the necessity to set up new institutions to address food production shortfalls. For adapting agriculture to the 2050s-2060s, [START_REF] Adams | Effects of global climate change on agriculture: an interpretative review[END_REF] suggest mitigating responses by increasing fertilizer or water use, and by the adoption of new crop varieties or by "changing planting dates, substituting cultivars or crops, changing irrigation practices, and changing land allocations to crop production, pasture and other uses" (Adams et al., 1998, page 28). [START_REF] Tait | Sustainable development of agricultural systems: competing objectives and critical limits[END_REF] guess that they need to gather stakeholders in order to find sustainable agricultural solutions, and bet on technical innovations, perhaps on a "technical revolution, through biotechnologies" to manage the externalities associated programs due to farmers income loss. They calculated the optimal adoption rate of these measures (whatever the measure), which would be 20% for the Malaysian State. One could comment that since the agricultural system is precisely a system, 20% of spending may be inefficient or also highly efficient, depending on the nature of the adaptations and on their very implementation. For 2050, in the highly-valued journal "Science", [START_REF] Godfray | Food security: the challenge of feeding 9 billion people[END_REF] suggest a catch-all of ideas split in 5 international strategies, and mainly based on the growth of agricultural yields thanks to technologies (ICT, genetically modified crops, cloned animals etc.), waste reduction, decreasing meat consumption, and expanding aquaculture. According to the authors, the whole can be made "sustainable", although they do not explain how.

Modifying food consumption practices

The more extreme proposal is set out in the paper by [START_REF] Denkenberger | Feeding Everyone: Solving the Food Crisis in Event of Global Catastrophes that Kill Crops or Obscure the Sun[END_REF] which envisionsin quantitative mode only-the conversion of the Earth's entire biomass, in order to feed humankind for 5 years, in case of universal catastrophe (sun occultation). Bearing in mind social drivers, the idea is not to explain how to socially manage this conversion, but only to evaluate the quantities of convertible marine and terrestrial calories. More classically, [START_REF] Garnett | Future Demand for Food -Relevance of Land Use and Lifestyles and Relationship with Nutrition, IPCC expert meeting on climate change, food and agriculture[END_REF] proposes a synthesis of many studies, which find that diets with reduced animal product content (meat, eggs, dairy) release less GHGs or are less land use intensive. The lower the meat content, the lower the environmental impacts2 . This is one of the solutions advised by [START_REF] Godfray | Food security: the challenge of feeding 9 billion people[END_REF] but deemed to be the most difficult to undertake-to feed humankind by 2050.

Implementing more radical agricultural solutions entailing social shifts [START_REF] Malézieux | Designing cropping systems from nature[END_REF] highlights the necessity to immediately rethink the management of natural resources, and suggests mimicking natural ecosystems to build new agro-ecosystems. The crucial issue is enhancing the crop diversity, to decrease the dependency on non-renewable resources, and to recreate areas devoted to biodiversity. It is the same for Altieri et al.

moderate negative impact temporarily" only (Altieri et al., 2015, page 1). By 2050, the authors advise setting up polycultures, agroforestry systems, and crop-livestock mixed systems accompanied by organic soil management, water conservation and harvesting, and general enhancement of agrobiodiversity.

In fact, radically new agricultural practices will disrupt societies as a whole. Despite not suggesting radical social changes, [START_REF] Adams | Effects of global climate change on agriculture: an interpretative review[END_REF] are aware of the issue of agricultural structures for the US. They quote the "changes in cultivated acreage by crop, total cultivated acreage, irrigation water consumption, farm employment and other changes in factor demands. The consequences of changes in factor demands on regional or local economies are largely unexplored but are potentially important" (Adams et al., 1998, page 29). Few authors widen the scope to envision the issue of food security and agriculture together. The famous meta-analysis of [START_REF] Badgley | Organic agriculture and the global food supply[END_REF] demonstrates that organic agriculture can contribute significantly to the global food supply without increasing the agricultural land-base. Indeed, long-term yields of both conventional and organic agriculture are comparable, and nitrogen potentially available from fixation by leguminous cover crops is enough to replace the synthetic fertilizers currently in use. [START_REF] Clark | The future is organic: but it's more than organic[END_REF] advocates switching the whole of agriculture towards real organic 3 . She goes even further by suggesting the implementation of novel agro-food systems based on more perennials and less on large-seeded annuals, and emphasizes "local/decentralized food production; seasonal consumption expectations and minimal processed foods." So, the new system will abandon monocrop cultivation. [START_REF] Dahlberg | A transition from agriculture to regenerative food systems[END_REF] calls for a transition from current modes of industrial agricultural production, which will involve "a basic restructuring of the interactions and relationships between natural systems, social systems and technological systems" (Dahlberg, 1994, page 170). The author notes the inefficiency of fossil energy in use in industrial agriculture, where 10 calories of energy are required to deliver 1 food calorie on our dinner plates. He explains that we are unlikely to mobilize the funding which will be necessary to relocate agriculture to the north. He laments the explosion in cattle population because of meat demand, highlights the severity of biodiversity and cultural diversity losses, and reminds us the damage caused by unequal growth. The priority is to maintain and to enhance the "remaining indigenous and traditional food and fiber systems that have demonstrated their regenerative capacities over the centuries" (idem, page 173), then "reforming existing housing and ways of life to make them less resource-and job-dependent" (idem, page 175). Shifts will be required in the evaluative criteria we employ -whether for society at large or for a particular sector like agriculture. The shift -from economic and production criteria-to health criteria is one of the key elements. More recently, [START_REF] Servigne | Nourrir l'Europe en temps de crise: vers des systèmes alimentaires résilients. Les Verts Alliance libre européenne au parlement européen[END_REF] claims that future agriculture will not have to manage food production only, but also to heal the ecosystems functions. Agriculture will be based on renewable energy only (sun and biomass, wind, and methanation) and on cattle and human work also. The author envisions the emergence of multistage agro-ecosystems (e.g. agroforestry), in order to take maximum advantage from solar flux.

c. Different time-scales

What can we say about the influence of the envisioned time-scales upon the delivered message? Few authors venture beyond 2050. Nevertheless, there is a consensus about both ideas that the Global Warming consequences will be much more harmful from 2050, and that unexpected events are increasingly frequent. The messages delivered for the various deadlines are not fundamentally different. In other words, the urgency of the temporal horizon does not affect the nature of the message.

Authors advocating a societal shift demand strong initiatives as soon as possible, according to the amplitude of the necessary change in mindset.

d. Discussion

When it comes to facing the future challenge of food insecurity, there is a split among the authors between those who suggest affordable solutions that are not demanding for the rest of the society, and others who advocate new social 3 By comparison to North America organic standards.

structures. Some authors are perfectly aware of this debate. [START_REF] Handoh | On the timescales of sustainability and futurability[END_REF] conceptualize two tracks towards solutions: 1) "a consciousness Revolution that leads to mankind's attitude to the environment and to adopting a preindustrial life style"; or ii) "a super energy revolution that leads to full utilization of photovoltaic power generation", to produce sufficient dietary resources to sustain the world population. [START_REF] Tait | Sustainable development of agricultural systems: competing objectives and critical limits[END_REF] explain how the coming changes make it necessary "to initiate fundamental change in the nature of modern farming systems themselves", even if they exclude this possibility at the same time: "However, this may be impossible to achieve under some future scenarios, or at least is likely to take longer to achieve." (Tait and Morris, 2000, page 257). The two competing views have been dubbed the Critical limits view, "which would require future farming systems to accept the ecosystem-imposed limits on the number of people in the world and the lifestyle they can enjoy"; and the Competing Objectives view, which "would balance agricultural sustainability with economic viability, reduction of environmental harm and fulfilling public demands for food and landscape benefits. " (Tait and Morris, 2000, page 247).

For advocates of the "Competing Objectives" views, like [START_REF] Lobell | Climate adaptation as mitigation: the case of agricultural investments[END_REF], the main issue is to know "where to invest?"

to prepare the agriculture of the future, but always in the same framework of mono-varietal and industrialized agriculture.

They do not seem to be aware of the existence of the climate-agriculture-energy nexus, which makes it impossible to change one element without also making the other structurally change. They deal with agriculture as if it were a sector like any other, and in particular like a controllable machine, without understanding the shortcomings of their modellings.

For the supporters of the "Critical Limits" views, it is mandatory to accept the ecosystem-imposed limits, and therefore to change our ways of life, without being nevertheless Malthusian. The major challenge is to demonstrate that there are agricultural systems respecting ecosystem integrity, yet nevertheless as efficientif not more efficient in the long term-as the agro-industrial systems. That is why the core of the scientific work in this view is in favor of agro-ecology and multispecies systems. Indeed, here we find a criterion (if we need only one, here it is) which no doubt differentiates the advocates of the two groups. To reconcile biodiversity and productivity, the advocates of the "Critical Limits" view advocate intercropped systems, mixing different species on the same plot [START_REF] Nair | Managed Multi-strata Tree + Crop Systems: An Agroecological Marvel[END_REF], while the others assumeoften implicitly-that the plots in future agriculture will be monospecific. Indeed, it is a necessary condition for the continuation of agro-industrial practices.

The split line is visible also insofar as the implemented scientific methods are in general different. Indeed, the works carried out by the former group rely on statistical data, on a large scale, because data on the agro-industrial monoculture are already widely available. Conversely, when it comes to designing frugal agro-ecosystems, only sparse and small-scale local monographs are available (with notable exceptions). Even when these monographs are collated [START_REF] Auerbach | Organic agriculture: African experiences in resilience and sustainability[END_REF] it is less easy to envision regional or worldwide forecasts, with the same weight as the authors of the previous group.

The same split is materialized by the way of considering people who are not involved in agricultural sector at the present time. Under the former viewpoint, citizens are considered to be consumers first. In the best case, they are elicited to give their opinion as stakeholders. So, the citizens will be affected because they are expected to become reasonable and to consume less meat, and/or because their purchasing power will be lowered by the rise in food prices. But they are not required to play a more active role in the ongoing change. Under the latter view, the citizens are seen like potential activists of frugal agro-ecosystems, and sometimes, authors hint that citizens will have to be directly involved in the farming work. In this case, the authors advocate a radical structural change, which will disrupt human societies as a whole.

The few factors taken into account (for food security or the future of agriculture) are quite a surprise. Drawing only on the food's energy demand and on production of entropy, [START_REF] Handoh | On the timescales of sustainability and futurability[END_REF] worked out that the sustainability of the human-environment interactions of the present era (called pre-informational and which started in 1960) has an order of duration of 100 to 400 years. In fact, to deal with food security, the contextual evolutions to be accounted for go far beyond world population growth or Global Warming alone. It is quite easy to find works about the future of energy, cities, or globalization. Nevertheless, the future of agriculture in those troubled contexts is rarely dealt with, and moreover rarely taken seriously enough, i.e. placed at the center of the discussion. When will we realize that it is becoming unclear how to feed ourselves? That our time schedule and daily concerns are turning back (as was the case with our ancestors for centuries) first and foremost towards activities directly contributing to nutrition? It is mandatory 4 to make a choice, by recognizing what is a top priority, and what is not.

Conclusions

In general, the supporters of the "Competing Objectives" view acknowledge that the effects of climate change will worsen over time. The supporters of the "Critical Limits" view advocate radical modifications of social structures. They explain the necessity to prepare for the transition as soon as possible, in order to mitigate -as far as possible-the harmful but inevitable effects.

Today, the debate between advocates of human causes of climate change on the one hand, and climate change skeptics on the other hand, seems to be closed. Hence, it is time to decide on another debate, and take up our position. Do we need to follow those who advise adapting the future agriculture with marginal adjustments and technologies whose most obvious advantages are compatibility with the present state of advanced societies? Conversely, should we not keep up with the pace of researchers who urge us to enforce radical changes? They advocate vital changes, which might disrupt the internal organization of our societies, as was the case with the very invention of agriculture...

  with intensive agriculture! Recently, for the Inland Pacific Northwestern region of the US and other equivalent regions,[START_REF] Pan | Integrating Historic Agronomic and Policy Lessons with New Technologies to Drive Farmer Decisions for Farm and Climate: The Case of Inland Pacific Northwestern U.S[END_REF] suggest playing with the agronomic management variables: conservation tillage and residue management, organic carbon (C) and nutrient recycling, refined N management, and crop diversification and intensification, thanks to new cultivars (canola, peas) and ICT sector. Some authors argue for sharing land between land-for-production on the one hand, and land-for-nature on the other, as set out by[START_REF] Tscharntke | Global food security, biodiversity conservation and the future of agricultural intensification[END_REF].Regarding Malaysia in 2065, Quasem Al-Amin and Ahmed (2016) suggest the following options to adapt farms: Irrigation scheduling; Weather and climate information systems; Higher cropping intensity; Diversification of cropping production on irrigated area; Integrated pest management (IPM); Protected cultivation; Post-harvesting technology; Income stabilization

In

2016, the number of under-nourished people in the world was on the rise, as it has been since 2014[START_REF] Fao | The state of food security and nutrition in the World[END_REF].

In descending order the GHG intensity of diets are: no red meat, no meat (vegetarian), no animal products (vegan)[START_REF] Hallström | Environmental impact of dietary change: a systematic review[END_REF][START_REF] Scarborough | Dietary greenhouse gas emissions of meat-eaters, fish-eaters, vegetarians and vegans in the UK[END_REF]