Clement Morville

Juliane Chaud

Frederic Bolze

Alexandre Specht

C Morville #

J Chaud #

Photolytical reactions for light induced biological effectors release: on the road to the phototherapeutic window

Keywords: Photolysis, Uncaging, Two-photon uncaging, Photon-upconversion, Photopharmacology

Introduction :

Photolabile precursors of biological effectors, also called caged compounds or photocaged compounds, are molecules whose activity or function is masked by chemical modification using a photolabile protecting group (PPG) [START_REF] Brieke | Light-Controlled Tools[END_REF][START_REF] Klán | Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy[END_REF][START_REF] Abou Nakad | Monitoring of uncaging processes by designing photolytical reactions[END_REF][START_REF] Weinstain | Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials[END_REF]. Light excitation of these compounds results in a rapid and specific cleavage of a chemical bond leading to a fast and localized concentration jump of the corresponding biological effectors. This strategy has been successfully used to modify the activities of various biomolecules, including peptides [START_REF] Lin | Activatable cellbiomaterial interfacing with photo-caged peptides[END_REF], proteins [START_REF] Gautier | How to control proteins with light in living systems[END_REF][START_REF] Courtney | Recent advances in the optical control of protein function through genetic code expansion[END_REF], nucleic acids [START_REF] Ruble | Caged oligonucleotides for studying biological systems[END_REF][START_REF] Ikeda | Chemically Caged Nucleic Acids[END_REF], neurotransmitters [START_REF] Paoletti | Optical control of neuronal ion channels and receptors[END_REF], lipids [START_REF] Höglinger | Caged lipids as tools for investigating cellular signaling[END_REF] and many other biological effectors [START_REF] Ankenbruck | Optochemical Control of Biological Processes in Cells and Animals[END_REF] in order to restore their biological functions using light. For biomedical applications, the use of photolytical reactions looks also very attractive for drug release and light controlled drug release has been achieved with PPGs or by using photoactivatable linkers [START_REF] Silva | Light-triggered release of photocaged therapeutics -Where are we now?[END_REF][START_REF] Zhang | Photoactivatable Protherapeutic Nanomedicine for Cancer[END_REF]. The major drawback of most of the PPGs relies on the use of UV irradiation for the uncaging process, which is characterized by low penetration depth in living tissues and important phototoxicity. NIR sensitive PPGs are highly sought after, firstly because in the so-called photo-therapeutical window (between 600 to 1000 nm) light scattering is low and there is little competing absorption from cells or tissues endogenous biomolecules, such as hemoglobin, melanin and even water [START_REF] Weissleder | A clearer vision for in vivo imaging[END_REF]. Secondly, NIR radiation can minimize the photodamage to biological specimens [START_REF] Wäldchen | Light-induced cell damage in live-cell super-resolution microscopy[END_REF]. In the last 20 years, different strategies have been explored to overcome the difficulty that only high energy light can induce photolytical reactions. In this review, the 3 main strategies for designing photoactivatable molecules or systems leading to efficient photolytical reactions using low energy excitation wavelengths will be discussed, with a particular attention for systems working in the photo-therapeutical window. The figure 1 summarizes those 3 strategies from a photophysical point of view.

One-photon visible to NIR sensitive PPGs

One-photon photoinduced reactions using organic PPGs are needed to broadly implement the uncaging strategy for various complex biological applications. The efficiency of a PPG to specifically cleave a chemical bond using classical one-photon excitation (also called uncaging cross-section) is defined as the product of the molar extinction coefficient (e) and the quantum yield of photolytical reaction (fu). In the following paragraphs, we will describe the recent improvement performed on PPGs in the o-nitrobenzyl (NB), o-nitrophenethyl (NPE), coumarinyl, boron-dipyrromethene (BODIPY) and cyanines series. In particular, the most efficient PPGs using visible to far red excitation wavelengths will be described.

o-Nitrobenzyl based PPGs (see scheme 1a for its photolytical reaction pathway) have been the first used PPGs for biological applications [START_REF] Kaplan | Rapid photolytic release of adenosine 5'-triphosphate from a protected analog: utilization by the sodium:potassium pump of human red blood cell ghosts[END_REF][START_REF] Engels | Synthesis, structure, and reactivity of adenosine cyclic 3',5'-phosphatebenzyltriesters[END_REF] and have been extensively applied to control a large number of biological responses using UV excitation [START_REF] Klán | Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy[END_REF] as they can be conjugated to a large number of substrates through an alcohol, amine, phosphate, carbamate, thiol, or carboxylic acid moiety. The optimization of the uncaging efficiency for visible light excitation is extremely challenging since it is difficult to develop efficient red shifted NB PPGs. Indeed, in most cases, NB tailored with extended π-conjugation shows usually a dramatic drop of the uncaging quantum yield [START_REF] Aujard | o-Nitrobenzyl Photolabile Protecting Groups with Red-Shifted Absorption: Syntheses and Uncaging Cross-Sections for One-and Two-Photon Excitation[END_REF]. Recently, several strategies were investigated to induce a bathochromic shift of the NB scaffold absorbance and to allow an efficient photolytic reaction upon one-photon excitation. In 2014, Abe, Katan and Kobayashi developed a dialkyl-dihydronaphthalene NB derivative for the release of glutamate neurotransmitter (1 in scheme 4) [START_REF] Boinapally | Caged Glutamates with π-Extended 1,2-Dihydronaphthalene Chromophore: Design, Synthesis, Two-Photon Absorption Property, and Photochemical Reactivity[END_REF]. This latter compound showed an absorbance maximum around 440 nm and was able to release glutamate with an uncaging efficiency of 60 M -1 cm -1 . In 2016, the group of Ellis-Davies developed a bis-styrylthiophene (BIST) NB derivative with an absorption maximum at 440 nm, and was used to develop a photocleavable caged Ca 2+ chelator (2 in scheme 4) with a high uncaging efficiency of 15180 M -1 cm -1 [START_REF] Agarwal | Calcium Uncaging with Visible Light[END_REF].

In 2012, our group succeeded to design efficient PPGs in the o-nitrophenethyl serie (see scheme 1b for its photolytical reaction pathway). Dialkylamino-biphenyl NPE based PPGs were therefore described for the release of the GABA neurotransmitter (3 in scheme 4) taking advantage of the dialkylamino group which enables functionalization with oligoethylene glycol/carboxylic acid moieties to improve water solubility [START_REF] Donato | Water-Soluble, Donor-Acceptor Biphenyl Derivatives in the 2-(o-Nitrophenyl)propyl Series: Highly Efficient Two-Photon Uncaging of the Neurotransmitter γ-Aminobutyric Acid at λ=800 nm[END_REF]. Those compounds showed an absorbance maximum around 397 nm and were able to release GABA with an uncaging efficiency of 1125 M -1 cm -1 . In 2014, Wombacher introduced a NPE based PPG by introducing an alkyne linkage on the dialkylamino-biphenyl platform for the development of caged gibberellic acid (4 in scheme 4). This modification led to a PPG with a 413 nm absorbance maximum and an uncaging efficiency of 2500 M -1 cm -1 [START_REF] Schelkle | Light-Induced Protein Dimerization by One-and Two-Photon Activation of Gibberellic Acid Derivatives in Living Cells[END_REF].

Coumarin-based PPGs (see scheme 1c for the photolytical reaction pathway) have been recently applied to the release of a large number of biological effectors due to ease of synthesis and their rapid photolytical reactions (in the ns range) [START_REF] Hagen | 7-(Dialkylamino)coumarin-4yl]methyl-Caged Compounds as Ultrafast and Effective Long-Wavelength Phototriggers of 8Bromo-Substituted Cyclic Nucleotides[END_REF]. This scaffold allows to couple a large number of substrates through a carbonate, carbamate, phosphate, pyridine, or carboxylic acid moiety [START_REF] Givens | Applications of p-hydroxyphenacyl (pHP) and coumarin-4-ylmethyl photoremovable protecting groups[END_REF]. In the last seven years, many efforts have been performed to build red shifted 7-(diethylamino)-4-(hydroxymethyl)coumarin (DEAC) PPGs. Therefore, dipolar Donor-Acceptor p-system and quadripolar Donor-Donor p-system have been developed. In 2013, the group of Jullien synthesized a series of such coumarin scaffolds with electron donating group (OMe/ NEt 2 ) at the 7-position and different electron withdrawing groups at 2/3 positions aimed at extending the p-conjugation of the system [START_REF] Fournier | Coumarinylmethyl Caging Groups with Redshifted Absorption[END_REF].

In particular, this research group was able to develop a coumarin analog bearing thiocarbonyl group at the 2position for the uncaging of a non-endogenous Cyclofen-OH gene expression inducer [START_REF] Fournier | A Blue-Absorbing Photolabile Protecting Group for in Vivo Chromatically Orthogonal Photoactivation[END_REF]. This caged compound (5 in scheme 4) showed an absorption maximum at 492 nm with an uncaging efficiency of 58 M -1 cm -1 . Of note, the empty 3d orbital of the sulfur atom of the thiocarbonyl group is expected to enhance the intramolecular charge transfer (ICT) process leading to an increase in the absorbance maximum of this DEAC analog. In 2013, the Ellis-Davies group also modified the DEAC scaffold and introduced a vinyl acrylate function in the 3-position leading to the so called DEAC450 chromophore [START_REF] Olson | Optically Selective Two-Photon Uncaging of Glutamate at 900 nm[END_REF]. This red shifted PPGs was used to liberate glutamic acid (6a in scheme 4) and showed an absorbance maximum at 450 nm with an uncaging efficiency of 16800 M -1 cm -1 . In 2017, the group of Ellis-Davies was able to use this interesting PPG to liberate the GABA neurotransmitter and to effectively reduces the antagonism effect of this later caged-GABA 6b to a very low level by the conjugation of a large and neutral propargyl-[G5]-(OH)32 bis-MPA dendron [START_REF] Richers | Cloaked Caged Compounds: Chemical Probes for Two-Photon Optoneurobiology[END_REF]. In 2016, Katan and Abe groups explored the effect of a Donor-Acceptor system leading to a 7-methoxy-coumarin derivative substituted at the 3 position by a electro withdrawing p-nitrophenyl group, this PPG was able to release benzoic acid (7 in scheme 4) and showed an absorbance maximum at 345 nm with an uncaging efficacity of 2045 M -1 cm -1 [START_REF] Chitose | Design, Synthesis, and Reaction of π-Extended Coumarinbased New Caged Compounds with Two-photon Absorption Character in the Near-IR Region[END_REF]. In 2017, the same group also developed Donor-Donor p-system, therefore the DEAC PPG was modified by an aminophenyl appendage at the 3-position (8 in scheme 4) leading to PPG with an absorption maximum at 407 nm and an uncaging efficiency of 4560 M -1 cm -1 [START_REF] Chitose | Design and Synthesis of a Caged Carboxylic Acid with a Donor-π-Donor Coumarin Structure: One-photon and Two-photon Uncaging Reactions Using Visible and Near-Infrared Lights[END_REF]. In 2018, Zhu's group synthesized DEAC analogues with electron rich styryl appendages in 3-position [START_REF] Lin | Coumarin Photocaging Groups Modified with an Electron-Rich Styryl Moiety at the 3-Position: Long-Wavelength Excitation, Rapid Photolysis, and Photobleaching[END_REF] inducing red shifted absorption maxima at 446 and 515 nm, and uncaging efficiencies up to 8200 and 17500 M -1 cm -1 for 9 and 10 respectively (scheme 4). Of note, the styryl appendage also allowed to produce an unconjugated by-product through an intramolecular reaction on the light generated carbocation (see Scheme 2). This nice improvement lead to the disappearance of the competitive absorption by the photolysis sub-products (sub-product photobleaching). In 2019, the group of Kele introduced modified DEAC PPGs with pyridinium and benzothiazolium heterocycles in 3-position. Compound 11, 12 and 13 showed absorption maxima at 482, 493 and 538 nm respectively with uncaging efficiencies of 260 , 335 and 57 M -1 cm -1 respectively [START_REF] Bojtár | Green-Light Activatable, Water-Soluble Red-Shifted Coumarin Photocages[END_REF]. The same year, the group of Blanchard-Desce also appended Donor-Acceptor p-system at the 3-position of the DEAC PPGs in order to develop caged glycines. The incorporation of respectively a vinylthiazole (14 in scheme 4), a 2vinylbenzo[d]thiazole (15a in scheme 4), an elongated fluorenyl-2-vinylbenzo[d]thiazole (15b in scheme 4), a 2vinylbenzo[d]oxazole (16 in scheme 4) and a 4-vinylbenzo[c] [START_REF] Brieke | Light-Controlled Tools[END_REF][START_REF] Klán | Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy[END_REF][START_REF] Lin | Activatable cellbiomaterial interfacing with photo-caged peptides[END_REF]thiadiazole group (17 in scheme 4) led to absorption maxima at 457, 472, 458, 467 and 472 nm respectively and uncaging efficiencies of 7800, 4000, 18.900, 4500 M -1 cm -1 and below of 600 M -1 cm -1 respectively [START_REF] Klausen | Dual-wavelength efficient two-photon photorelease of glycine by π-extended dipolar coumarins[END_REF].

C4′-dialkylamine-substituted variants of the heptamethine cyanine (see scheme 3 for photolytical reaction pathway) have been reported in 2014, as PPGs by the group of Schnermann [START_REF] Gorka | A Near-IR Uncaging Strategy Based on Cyanine Photochemistry[END_REF]. They demonstrated that cyanine derivatives like compound 18 are able to perform light assisted chemical bond cleavage via a regioselective photooxidative polyene reaction using a 690 nm excitation wavelength. This scaffold was used in combination with a self-immolative linker to uncage a non-endogenous Cyclofen-OH gene expression inducer.

The same year, Urano's group discovered that the well-known BODIPY fluorophore could be used as a PPG and postulate that the bound cleavage was triggered by a photoinduced electron transfer (PeT)-based process [START_REF] Umeda | Boron Dipyrromethene As a Fluorescent Caging Group for Single-Photon Uncaging with Long-Wavelength Visible Light[END_REF]. Classical BODIPYs have an absorption maximum at 502 nm and photocleavage enables the release of phenol function with an uncaging efficiency below to 60 M -1 cm -1 . This research group developed caged histamine using a BODIPY PPG [START_REF] Aujard | o-Nitrobenzyl Photolabile Protecting Groups with Red-Shifted Absorption: Syntheses and Uncaging Cross-Sections for One-and Two-Photon Excitation[END_REF]. In 2015, further studies were described on a meso-methyl-hydroxy-BODIPY (see scheme 1d for photolytical reaction pathway) connected either directly or via a carbamate linker to biological effectors. First, the group of Weinstain developed a cagedp-nitrobenzylamine (20a), a caged-histamine (20b) and a caged dopamine (20c) using a meso-methyl-hydroxy-BODIPY. Compound 20a showed an absorbance maximum at 545 nm and an uncaging efficiency of 7 M -1 cm -1 [START_REF] Rubinstein | meso-Methylhydroxy BODIPY: a scaffold for photolabile protecting groups[END_REF]. Secondly, the group of Winter was able to photorelease acetic acid using the BODIPY derivative 21, and this latter compound showed an absorption maximum at 553 nm with an uncaging efficiency of 117 M -1 cm -1 [START_REF] Goswami | BODIPY-Derived Photoremovable Protecting Groups Unmasked with Green Light[END_REF]. In 2017, Klán, Weinstain and Winter groups were able to dramatically increase BODIPY's uncaging efficiencies by systematic structure-activity relationship studies [START_REF] Slanina | In Search of the Perfect Photocage: Structure-Reactivity Relationships in meso-Methyl BODIPY Photoremovable Protecting Groups[END_REF]. In particular, they demonstrated that iodo-BODIPYs are able to increase the uncaging quantum yield and they introduced the BODIPY caged phenylalanine analog 22. This latter showed an absorption maximum at 537 nm with an uncaging efficiency of 20150 M -1 cm -1 . In 2018, the group of Winter added strong electron-donating groups to a mesomethyl-hydroxy-BODIPY. This red shifted BODIPY derivative was chemically modified by two styryl linkers and benzyl alcohol was used as leaving group via a carbonate linkage. The authors were able to demonstrate that the caged benzyl alcohol 23 had an absorbance maximum at 693 nm with an uncaging efficiency of 73 M -1 cm -1 [START_REF] Peterson | Family of BODIPY Photocages Cleaved by Single Photons of Visible/Near-Infrared Light[END_REF]. BODIPY PPGs exhibit very interesting absorbance wavelengths that now fall in the transparency window enabling more sophisticated biological applications of the uncaging concept. However, the uncaging efficiency need to be improved. Some recent work performed by the group of Peifer, has also pointed out that the uncaging mechanism and his efficiency can be limited in an aqueous environment due to a competitive production of singlet oxygen upon irradiation [START_REF] Rodat | Restricted suitability of BODIPY for caging in biological applications based on singlet oxygen generation[END_REF].

Exciting recent progress, particularly using the Coumarinyl, the BODIPY and the cyanine scaffolds, has extended the uncaging concept in wavelengths well into the visible range, but other strategies are still needed to efficiently cleave a chemical bound in the 650-1000 nm region.

Efficient two-photon sensitive NIR PPGs:

In order to overcome the difficulty that only high energy light can efficiently induce a photolytical reaction, a second strategy based on the use of two-photon induced photolysis was developed during the last 20 years (Figure 1 center). After the first report of two-photon uncaging by the group of Tsien in 1999 [START_REF] Furuta | Brominated 7-hydroxycoumarin-4-ylmethyls: Photolabile protecting groups with biologically useful cross-sections for two photon photolysis[END_REF], this technique has become well established over the last years as an alternative to classical one-photon excitation for triggering PPGs photolysis [START_REF] Bort | From One-Photon to Two-Photon Probes: "Caged" Compounds, Actuators, and Photoswitches[END_REF][START_REF] Piant | -Two-photon uncaging, from neuroscience to materials[END_REF][START_REF] Abe | Design and Synthesis of Two-Photon Responsive Chromophores for Near-Infrared Light-Induced Uncaging Reactions[END_REF]. In Two-Photon Excitation (TPE), a chromophore will not reach an excited state by absorption of one photon with the energy E = hv, but by the simultaneous absorption (within <1 fs) of two photons of half the energy E' = hv/2 (Figure 1b). After excitation, it is assumed that the chromophore, i.e. the PPG, undergoes the same photolytic steps as with conventional one-photon excitation [START_REF] Bort | From One-Photon to Two-Photon Probes: "Caged" Compounds, Actuators, and Photoswitches[END_REF][START_REF] Piant | -Two-photon uncaging, from neuroscience to materials[END_REF][START_REF] Abe | Design and Synthesis of Two-Photon Responsive Chromophores for Near-Infrared Light-Induced Uncaging Reactions[END_REF][START_REF] Ellis-Davies | Two-Photon Uncaging of Glutamate[END_REF]. TPE is based on a non-linear process, and the probability for TPE to occur scales with the squared light intensity. Due to this quadratic dependency, the excitation will be possible only with very high light intensities, out of range of classical sources used for one-photon excitation. This technique indeed requires the use of pulsed (fs range with high peak power in the range of 10 8 W.cm -2 ) focalized lasers, inducing a temporal and spatial concentration of photons reaching the molecules. As a consequence, TPE and can only occur in a very small 3D volume surrounding the focal point of the optical system. This volume can be as small as 1 µm 3 for a tightly focused laser and no excitation occurs outside the focal volume, in contrast to a single photon process were all the light pathway is excited.

The efficiency of a PPG to specifically cleave a chemical bound using two-photon excitation (du) is defined as the product of the two-photon absorption cross section (da expressed in GM) and the uncaging quantum yield of photolytical reaction (fu). In 2001, the first biological application of TP uncaging was reported by Kasai and co-workers using 24 4-Methoxy-7-NitroIndolinyl or MNI caged glutamate (see scheme 1e for photolytical reaction pathway) (δu = 0.06 GM at 730 nm). In particular, they were able to mimic a neurotransmitter's release at single synapse resolution using 730 nm TPE [START_REF] Matsuzaki | Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons[END_REF]. This work initiated the development of specific PPGs with larger molecular two-photon cross-sections.

Since the two-photon absorption cross-section of a chromophore relies mostly on its molecular structure as well as its environment, many efficient UVA or blue light sensitive PPGs have therefore been embedded within conjugated di-polar, quadrupolar or octopolar architectures in order to improve their two-photon absorption properties for 720 to 950 nm excitations (Sheme 5) [START_REF] Bort | From One-Photon to Two-Photon Probes: "Caged" Compounds, Actuators, and Photoswitches[END_REF][START_REF] Piant | -Two-photon uncaging, from neuroscience to materials[END_REF][START_REF] Abe | Design and Synthesis of Two-Photon Responsive Chromophores for Near-Infrared Light-Induced Uncaging Reactions[END_REF].

In this context, our group developed a new generation of PPGs for the release of carboxylic acids with TP uncaging efficiencies up to 11 GM. Compounds of this new generation have been successfully applied to the photo-controlled release of the neurotransmitters L-glutamate [START_REF] Lovett-Barron | Regulation of neuronal input transformations by tunable dendritic inhibition[END_REF] and GABA [START_REF] Donato | Water-Soluble, Donor-Acceptor Biphenyl Derivatives in the 2-(o-Nitrophenyl)propyl Series: Highly Efficient Two-Photon Uncaging of the Neurotransmitter γ-Aminobutyric Acid at λ=800 nm[END_REF] in intact neuronal tissue at respectively 720 nm and 800 nm using 25 and 3. Starting from these contributions we will focus on the developments in the field of TP uncaging from the last eight years.

The extension of the aromatic system is one of the rational ways to upgrade two-photon properties of a compound. This was remarkably performed in 2014, by Abe, Katan and Kobayashi groups, using a dialkyl-dihydro naphthalene NB derivative for the release of the Glutamate neurotransmitter 1 who showed an important TP uncaging action cross-section of ~ 1.2 GM at 680 nm [START_REF] Boinapally | Caged Glutamates with π-Extended 1,2-Dihydronaphthalene Chromophore: Design, Synthesis, Two-Photon Absorption Property, and Photochemical Reactivity[END_REF]. The same groups were able in 2016 to develop two caged calcium chelator (26a, 26b and 27) with respectively an TP uncaging action cross-section of 16 GM at 740 nm [START_REF] Komori | Design and synthesis of a new chromophore, 2-(4nitrophenyl)benzofuran, for two-photon uncaging using near-IR light[END_REF], 20.7 GM at 740 nm [START_REF] Komori | Design and synthesis of a new chromophore, 2-(4nitrophenyl)benzofuran, for two-photon uncaging using near-IR light[END_REF] and 7.8 GM at 800nm [START_REF] Jakkampudi | Design and Synthesis of a 4-Nitrobromobenzene Derivative Bearing an Ethylene Glycol Tetraacetic Acid Unit for a New Generation of Caged Calcium Compounds with Two-Photon Absorption Properties in the Near-IR Region and Their Application in Vivo[END_REF]. The same year, the group of Ellis-Davies reported the BIST-NB caged Ca 2+ chelator (2) who showed an impressive TP uncaging action cross-section of ~ 80 GM at 775 nm [START_REF] Agarwal | Calcium Uncaging with Visible Light[END_REF].

The two-photon sensitivity of Quinoline PPGs (see scheme 1f for its photolytical reaction pathway) have also been increased in 2014 by the group of Dalko. New quadrupolar species, where two quinolines moieties were directly linked in two different positions, have led to caged acetic acids 28 and 29 reaching respectively δu = 0.07 GM and 0.40 GM at 730 nm [START_REF] Dunkel | Quinoline-derived two-photon sensitive quadrupolar probes[END_REF]. In 2015, the group of Dalko reached a TP uncaging cross-section of δu = 2 GM at 730 nm for compounds 30 by identifying the C5-substituted isomer as a privileged isomer to increase the twophoton sensitivity of 8-dimethylaminoquinoline derivatives [START_REF] Tran | Two-Photon "Caging" Groups: Effect of Position Isomery on the Photorelease Properties of Aminoquinoline-Derived Photolabile Protecting Groups[END_REF]. In 2017, the group of Dalko reported two multipolar Quinoline PPGs with δu values respectively of 0.3 GM at 730 nm 2.3 GM at 730 nm and for compounds 31 [START_REF] Dunkel | Quinoline-Derived Two-Photon-Sensitive Octupolar Probes[END_REF] and 32 [START_REF] Tran | Quinoline-Derived Two-Photon Sensitive Quadrupolar Probes[END_REF]. In 2020, the group of Dore reexplored the 8-cyano-7-hydroxyquinolin-2-ylmethyl (CyHQ) PPG [START_REF] Davis | Substituent Effects on the Sensitivity of a Quinoline Photoremovable Protecting Group to One-and Two-Photon Excitation[END_REF] by introducing several electron withdrawing or donating groups at the C4 position. Compounds 33 a-f were used to mediate an efficient release of homopiperonylic acid with remarkable δu values (up to 2.64 GM) and excellent one photon quantum yields (up to 0.88) [START_REF] Hennig | Two-Photon Excitable Photoremovable Protecting Groups Based on the Quinoline Scaffold for Use in Biology[END_REF].

Coumarinyl PPGs have also been extensively optimized to upgrade their two-photon properties. In 2013, the Ellis-Davies reported the DEAC450 PPGs with a TP uncaging action cross-section of 0.5 GM at 900 nm [START_REF] Olson | Optically Selective Two-Photon Uncaging of Glutamate at 900 nm[END_REF]. Katan and Abe groups reported a 7-methoxycoumarin and DEAC analogs modified respectively with an nitrophenyl or a aminophenyl appendage at the 3-position ( 7 and8). This modification led to a TP uncaging action cross-section of respectively 3.4 GM at 710nm [29] and 1.1 GM at 750 nm [START_REF] Chitose | Design, Synthesis, and Reaction of π-Extended Coumarinbased New Caged Compounds with Two-photon Absorption Character in the Near-IR Region[END_REF]. In 2018, the Zhu group synthesized the DEAC analogue 9 with electron rich styryl appendages at the 3-position [START_REF] Chitose | Design and Synthesis of a Caged Carboxylic Acid with a Donor-π-Donor Coumarin Structure: One-photon and Two-photon Uncaging Reactions Using Visible and Near-Infrared Lights[END_REF]; this latter PPG showed a TP uncaging action cross-section of 39.6 GM at 730 nm. Finally, Kele [START_REF] Lin | Coumarin Photocaging Groups Modified with an Electron-Rich Styryl Moiety at the 3-Position: Long-Wavelength Excitation, Rapid Photolysis, and Photobleaching[END_REF] and Blanchard-Desce [START_REF] Bojtár | Green-Light Activatable, Water-Soluble Red-Shifted Coumarin Photocages[END_REF] groups introduced, in 2019, various donor systems at the 3-position of the DEAC PPGs leading to Coumarinyl PPGs with TP uncaging action cross-section summarized in table 1. In particular, the caged compound 15b showed an unprecedented uncaging action cross-section of 442 GM at 730 nm! In summary, the increase of the two-photon absorption sensitivity by molecular engineering led to highly efficient TP sensitive PPGs (up to 440 GM uncaging cross-section for compound 15b). However, it is extremely difficult to predict how this strategy will influence the uncaging quantum yield [START_REF] Aujard | o-Nitrobenzyl Photolabile Protecting Groups with Red-Shifted Absorption: Syntheses and Uncaging Cross-Sections for One-and Two-Photon Excitation[END_REF][START_REF] Specht | The donor-acceptor biphenyl platform: A versatile chromophore for the engineering of highly efficient two-photon sensitive photoremovable protecting groups[END_REF]. Therefore, a second strategy was described for the rational design of TP sensitive PPGs. This strategy called sensitized uncaging, is based on the use of TP sensitive moieties as an antenna to transfer the light energy to a PPG. It has been reviewed, in 2019, by the group of Blanchard-Desce [START_REF] Klausen | Tandem Systems for Two-Photon Uncaging of Bioactive Molecules[END_REF]; therefore in this review we decide to present only the most efficient systems.

In 2013, a very efficient 2P sensitive modular system was described by Anderson and Blanchard-Desce groups. A pyridinium based PPG (see scheme 1g for his photolytical reaction pathway) able to liberate carboxylic acid functions by photoinduced electron transfer (PeT) was coupled to a symmetric banana-shaped bisethynylfluorene (BEF) (in which the core is extended with substituted anilines via acetylene bridges) TP antenna dye. This complex system led to the synthesis of the caged GABA 34, who showed an important TP uncaging cross-section of 10 GM at 700 nm [START_REF] Korzycka | Two-photon sensitive protecting groups operating via intramolecular electron transfer: uncaging of GABA and tryptophan[END_REF]. In 2016, the group of Blanchard-Desce was able to increase the TP sensitivity of the MNI PPG using a tandem system which a TP absorbing module linked to the PPG via a phosphorous clip, that act together by Forster Resonance Energy Transfer (FRET). This strategy led to a caged acetic acid 35 with a TP uncaging cross-section of 20 GM at 710 nm [START_REF] Diaz | Cooperative Veratryle and Nitroindoline Cages for Two-Photon Uncaging in the NIR[END_REF].

Many PPGs have been reported with increased TP uncaging efficiencies by several organic chemistry groups leading to TP uncaging efficiencies up to 440 GM. However, for biomedical applications two-photon absorption is a time-consuming spot-by-spot process to expose macroscopic materials like tissues or organs [START_REF] Abou Nakad | Monitoring of uncaging processes by designing photolytical reactions[END_REF]. These features have recently stimulated the needs of in situ nanotransducers that can generate UV or visible light with a lowenergy NIR excitation.

NIR Upconversion assisted photolysis

NIR to UV (or visible) upconversion (UC) processes have been recently used to assist photolytical reactions. The UC process has been established since the 1960s to generate anti-Stokes shift luminescence [START_REF] Auzel | Upconversion and Anti-Stokes Processes with f and d Ions in Solids[END_REF]. This process relies on the existence of multiple intermediate states to accumulate low-energy excitation photons. Those systems are able to absorb energies from two or more photons subsequently and to generate one emission photon with higher energy. This latter emission can be transferred to a PPG in order to induce a photolytically reaction using low energy excitation (Far red or NIR excitations). UC process can take place in organic and inorganic materials and many high brightness upconversion systems have been reported in nanomaterials [START_REF] Zhou | Upconversion Luminescent Materials: Advances and Applications[END_REF]. The process of UC is mediated by real electronic states, while in TP excitation real intermediate electronic states do not take part. Due to this difference, the TP excitation based on simultaneous interaction of two photons require 5-10 orders of magnitude higher excitation powers but yield more than 5 orders of magnitude lower quantum efficiency in comparison to UC [START_REF] Cohen | Beyond fluorescence[END_REF]. The intermediate states involved in UC must be excited, therefore material systems where these states have relatively long lifetimes will increase the probability of interaction with subsequent photons. This condition is met by quantum systems with parity-forbidden, but partly allowed optical transitions. Therefore lanthanide (Ln) doped materials are most frequently investigated in the context of UC [START_REF] Heer | Highly Efficient Multicolour Upconversion Emission in Transparent Colloids of Lanthanide-Doped NaYF4 Nanocrystals[END_REF][START_REF] Yi | Synthesis, Characterization, and Biological Application of Size-Controlled Nanocrystalline NaYF4:Yb,Er Infrared-to-Visible Up-Conversion Phosphors[END_REF].

In 2010, the group of Branda was able to spectroscopically demonstrate that UC assisted photolysis can be performed on a 3',5'-dialkoxybenzoin PPG using a core-shell lanthanide-doped NaYF4:TmYb nano-particles and an 980 nm excitation (550 W.cm -2 ) [START_REF] Carling | Remote-Control Photorelease of Caged Compounds Using Near-Infrared Light and Upconverting Nanoparticles[END_REF].

In 2012, Lin and Xing groups, have successfully been able to perform an UC assisted photolysis of an onitrobenzyl caged D-luciferin. In this nice work a Tm/Yb co-doped NaYF4 core-shell nanoparticles that have a reduced surface-quenching effect was selected as the platform for the conjugation of D-luciferin using an NB linker (see Figure 2 c). In vivo bioluminescence experiments on mice were performed and strong bioluminescence signals were detected on mice that were injected with the caged D-luciferin/UC nanoparticle conjugate after 1h of 980 nm excitation (at 255 W cm -2 ) [START_REF] Yang | In Vitro and In Vivo Uncaging and Bioluminescence Imaging by Using Photocaged Upconversion Nanoparticles[END_REF].

In 2011, Branda and Zhao groups, were able to use NaYF4:TmYb UCNPs inside micelles formed by onitrobenzyl caged poly(ethylene oxide)-block-polymethacrylate. An UC assisted photolysis (using 980 nm light) was used to cleave the o-nitrobenzyl groups and to convert the polymethacrylate block into an hydrophilic poly-(methacrylic acid), which shifts the hydrophilic hydrophobic balance toward the destabilization of micelles. This system was therefore able to perform a light induced dissociation of the micelles and the release of co-loaded hydrophobic species leading to a nice NIR controlled drug release NP (see Figure 2 a) [START_REF] Yan | Near-Infrared Light-Triggered Dissociation of Block Copolymer Micelles Using Upconverting Nanoparticles[END_REF]. In 2012, the same research groups had described a similar drug release strategy based on NB caged hydrogels. This photosensitive hybrid hydrogel loaded with UCNPs, showed that NIR light (980 nm) can induce a gel-sol transition leading to the release of inactive biomacromolecules entrapped in the hydrogel (see Figure 2 a) [START_REF] Yan | Near Infrared Light Triggered Release of Biomacromolecules from Hydrogels Loaded with Upconversion Nanoparticles[END_REF]. In 2014, Wu and coworker used UCNPs with a mesoporous silica shell to improve the NIR controlled drug release on NP. A mesoporous silica shell was used to release an anticancer drug doxorubicin using NIR light. Therefore, Ru PPGs were drafted onto the NP surfaces. The Ru complexes acted as molecular valves, which prevented drug leakage (see Figure 2 b). Upon NIR irradiation, UC assisted photolysis enabled to release the drug which inhibited cancer cells growth. Of note, this system allowed to use a relatively low 980 nm excitation (0.35 W cm -2 ) [START_REF] He | Ultralow-intensity near-infrared light induces drug delivery by upconverting nanoparticles[END_REF]. In 2013, Zhu and Li were able to release the anticancer drug chlorambucil using a hydrophobic 7-aminocoumarin PPG and a yolk-shell structured NP (coating of the NaLuF4 shell on the NaYF4 :Yb,Tm core) after 980 nm excitation (50 mW cm -2 ) in a living animal model [START_REF] Chien | Near-Infrared Light Photocontrolled Targeting, Bioimaging, and Chemotherapy with Caged Upconversion Nanoparticles in Vitro and in Vivo[END_REF].

In 2013, Su and Yeh groups, were able to use UC assisted photolysis to activate a caged species in order to control cell targeting groups on UCNPs' surfaces. A tumor-homing agent folate was modified with an onitrobenzyl PPG and grafted onto UCNPs. Upon NIR irradiation (980 nm), the UC assisted photolysis allowed folate-conjugated UCNPs to target cancer cells [START_REF] Zhao | Near-Infrared Photoregulated Drug Release in Living Tumor Tissue via Yolk-Shell Upconversion Nanocages[END_REF] leading to a NIR controlled targeting of the NP. This concept was improved in 2014 by Qu and co-workers who introduced UCNPs grafted with photocleavable NB linker bearing an arginine-glycine-aspartic acid (RGD) bioadhesive ligand. This latter UCNP has been successfully used to control cell adhesion using a 980 nm light excitation (2-4 W.cm -2 ) by UC assisted photolysis on an o-nitrobenzyl linker [START_REF] Li | Near-Infrared Upconversion Controls Photocaged Cell Adhesion[END_REF].

Several other UC assisted photolytical reaction using Lanthanide ion-doped inorganic crystals have already been described [START_REF] Chen | Photon Upconversion Lithography: Patterning of Biomaterials Using Near-Infrared Light[END_REF][START_REF] Viger | Low Power Upconverted Near-IR Light for Efficient Polymeric Nanoparticle Degradation and Cargo Release[END_REF][START_REF] Ruggiero | Near infrared photolysis of a Ru polypyridyl complex by upconverting nanoparticles[END_REF][START_REF] Chen | Manipulating pH using near-infrared light assisted by upconverting nanoparticles[END_REF]; but up to date, all those UCNPs still suffer from high power excitation requirement (10 2 -10 -1 W.cm -2 ) and inherently poor UC quantum yields.

Therefore, alternative UC strategies have recently been investigated, particularly using organic chromophore-based systems that achieve efficient triplet-triplet annihilation (TTA)-based UC [START_REF] Askes | Activation of a Photodissociative Ruthenium Complex by Triplet-Triplet Annihilation Upconversion in Liposomes[END_REF][START_REF] Huang | Expanding Anti-Stokes Shifting in Triplet-Triplet Annihilation Upconversion for In Vivo Anticancer Prodrug Activation[END_REF]. Those latter UCNPs should allow to perform efficient photolytical reactions using low power NIR excitations in a near future.

Conclusion :

Photolabile precursors of biological effectors, also known as caged or photocaged compounds, have been extensively used to induce a fast concentration jump of a biological effector by a specific light induced chemical bound cleavage. However most caged compounds absorb light in the 300-400 nm region. The UV region presents several disadvantages, especially for biological applications: 1) high-energy UV light has very limited tissue penetration due to high optical scattering and strong absorbance by endogenous chromophores; 2) UV lead to sample over-heating, 3) UV can cause phototoxic or photoallergic reactions. Visible and especially NIR light looks much more interesting, since it is considerably less harmful to biological materials and can penetrate deeper into tissues, opening the door to new applications of the uncaging concept especially in the field of drug delivery. In this review, 3 strategies leading to photoactivatable molecules or systems with efficient photolytical reactions using red to NIR excitations have been described.

The first strategy is based on the molecular engineering of PPGs leading to a few PPGs activated directly by light of wavelengths above ∼600 nm. In particular Coumarinyl, BODIPY and cyanine scaffolds, have extended the uncaging concept in wavelengths up to 500 nm but the application of this strategy is still limited due to relatively low uncaging efficiencies.

The second strategy is based on the use of two-photon induced photolysis. Several PPGs have been recently developed with extremely efficient TP excitation cross-section for the release of various biological effectors with localized NIR excitation.

Finally, a third strategy, based on the use of indirect photoactivation method was presented. NIR to UV (or visible) upconversion NPs have been recently used to assist photolytical reactions.

We are convinced that all those recent improvements should find significant applications especially in the field of nanomedicine soon [START_REF] Zhao | Remote Light-Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives[END_REF].

N O O N O O O O X O O O O HO + HX N B N F F N B N F F H 2 O N B N F F OH N N O R O O N N O O O R N NO O O R N H NO N X N N OH + HX N O Photosensitizers N O R O X O N O O R X X X X X +

J

  . Chaud, C. Morville, F. Bolze and A. Specht Laboratoire de Conception et Application de Molécules Bioactives, Équipe de Chimie et Neurobiologie Moléculaire, Faculté de Pharmacie, UMR 7199, Université de Strasbourg / CNRS, 74 route du Rhin, 67401 Illkirch-Graffenstaden Cedex, France e-mail: specht@unistra.fr # The first two authors contributed equally

Figure 1 :Scheme 1 :

 11 Figure 1: Simplified Jablonski diagrams for One-photon induced, Two-photon induced and Up-Converted assisted photolysis.

Scheme 2 :Scheme 3 :Scheme 4 :

 234 Scheme 2:Styryl moiety effect on the photolysis mechanism of position 3 modified coumarinyl PPGs.

2 Scheme 5 :

 25 Scheme 5: Chemical structures of TP sensitive PPGs.

Figure 2 :

 2 Figure 2: UC assisted photolysis and major applications in the field of nanomedicine.

Table 1 :

 1 Photophysical and photochemical properties of recently developed caged compounds.

	Two-photon	Solvent
	Uncaging
	efficiency at
	(l/nm)
	GM

Acknowledgements

This work was supported by the Université de Strasbourg (IdEx Grant to A.S.) the CNRS and by Grants from the Agence Nationale de la Recherche (Contract No. ANR-13-JSJV-0009-01 and ANR-18-CE09-0016-01 to A.S.).


Fiat Sylvie

Jérôme Aucan

David Varillon

ReefTEMPS, FAIRs access to Reef ecosystem environmental measurements

  Figure 1. The ReefTEMPS network federates 4 data producers covering in part the South, South West and West Pacific: the Institute of Research for sustainable Development, the Pacific Community, the University of the South Pacific and the University of New Caledonia.

Figure 5 .

 5 Figure 5. Getting Anse Vata (New Caledonia) temperature data in ReefTEMPS : 1/ station metadata, 2/ station location on interactive map (blue spot), 3/ Dataset metadata, 4/ Interactive datagram to preview data, 5/ Download available, 6/ DOI reference, 7/ Data licence, 8/ Data science products as a result.

Figure 2 .

 2 Figure 2. Installation of a sensor by a diver.

Figure 3 .

 3 Figure 3. Underwater sensor.

FigureFigure 9 .

 9 Figure 4. Underwater platform.


Antonella Giacosa

FROM CLASSROOMS TO SCREENS: LESSONS LEARNT IN LECTURERS' AND STUDENTS' EXPERIENCE

Keywords: Higher Education, Distance Learning, Emergency Remote Education, New Normal 1

published or not. The documents may come

INTRODUCTION

In February 2020, a global pandemic caught the world by surprise and forced the whole education system to shift online. Universities had to cope on a massive scale with issues of concern such as the digital divide, the challenging interaction between lecturers and students, the need for new teaching strategies to involve learners and provide them with meaningful experiences [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF]. The system worked, even though the emergency took a toll on both lecturers and students in terms of increased workload, additional responsibilities, emotional burden, and anxieties [START_REF] Bali | Literacies Teachers Need During Covid-19[END_REF]. In September 2020, universities reopened and had to adjust teaching and learning to the changeable and uncertain New Normal: according to the changing regulations, lessons were taught online, in-person and/or streamed. After two semesters of necessary distance learning, it is germane to start analysing coping strategies and attitudes to make meaning of this unprecedented experience and turn a challenge into a possibility of improvement for higher education. A preliminary overview of the literature shows that the Covid-19 has been also an educational emergency (UNESCO, 2020) affecting cohorts of students and teachers regardless of the availability of devices, adequate broadband, and digital skills. The first step to analyse this phenomenon is to understand the nature of this emergency pedagogy. It cannot be considered distance learning, as it was unplanned and relied neither on consolidated models nor on research. Scholars introduced the term Emergency Remote Education (ERE), also called Emergency Remote Teaching (ERT), which is defined as a branch of distance education dealing with the necessary educational response to a crisis [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF]. It involves fully remote teaching solutions for instruction or education that would otherwise be delivered primarily face-to-face and that will return to that format once the crisis or emergency is over [START_REF] Barbour | Understanding Pandemic Pedagogy: Differences Between Emergency Remote, Remote, and Online Teaching[END_REF]. Therefore, the primary goal of ERE is to provide access to education, not to guarantee quality education, as is the case in distance learning. Studies suggest that in a crisis an empathetic approach should be adopted focusing on how learners feel, as caring and supporting them is as crucial as delivering content [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF][START_REF] Bozkurt | Emergency remote teaching in a time of global crisis due to Corona Virus pandemic[END_REF][START_REF] Barbour | Understanding Pandemic Pedagogy: Differences Between Emergency Remote, Remote, and Online Teaching[END_REF] In line with these reflections, several contributions deal with the learner perspectives on the pandemic. On the one hand, they investigate the multiple literacies lecturers and teachers needed to take care of students also emotionally in times of crisis [START_REF] Bali | Literacies Teachers Need During Covid-19[END_REF], and the need to put in place more resources to cope with the digital divide which affected mostly rural areas [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF], UNESCO, 2020). Studies underline that there should be massive efforts in improving the technological infrastructure besides holding good training programs for both students and teachers [START_REF] Farrah | Online learning for EFL students in Palestinian universities during corona pandemic: Advantages, challenges and solutions[END_REF]. On the other hand, surveys highlight not only the challenges but also the opportunities which were perceived by learners. Regarding higher education, for example, studies show that along with difficulties, learners experienced some positive aspects of ERE such as self-paced learning, increased digital literacy, benefits in terms of attending classes from home without the need to commute [START_REF] Yoon | Learning in emergent times: Learner experience and perspectives on ERT in university EFL Courses[END_REF]. The continued use of technology eased the transition for both faculty and students by promoting course continuity and decreasing the cognitive load imposed by the transition [START_REF] Baldock | Overcoming the Challenges of Remote Instruction: Using Mobile Technology to Promote Active Learning[END_REF]. Moreover, familiarity with technology and social media contributed to creating positive remote learning environments, which fostered social presence despite the challenging circumstances (Erickson and Wattiaux, 2020). However, researchers underline that the role of technology should not be overestimated in the analysis of ERE. It is a fundamental tool, but it is not enough to save education and cure all the problems [START_REF] Bozkurt | Emergency remote teaching in a time of global crisis due to Corona Virus pandemic[END_REF]. Attributing the shortcomings of education, inequalities, and barriers solely to ERE obscures the inefficiencies of the usual arrangements in educational systems [START_REF] Murphy | COVID-19 and emergency e-learning: Consequences of the securitization of higher education for post-pandemic pedagogy[END_REF]. Moreover, studies show that in ERE the instructors' attitude affects students' experience and positive perceptions such as individual emotional intelligence and the ability to create a social presence or a positive mindset [START_REF] Cameron-Standerford | The Phenomenon of Moving to Online/Distance Delivery as a Result of COVID-19: Exploring Initial Perceptions of Higher Education Faculty at a Rural Midwestern University[END_REF]. Finally, ERE has reignited the debate about the quality of the classes and the possibility of dramatic consequences on the job market due to online courses [START_REF] Peters | Reimagining the new pedagogical possibilities for universities post-Covid-19[END_REF]. Leaving these controversies aside, it seems fruitful to collect data on lecturers' and students' experiences to identify key aspects to enhance ERE, as it will not be over soon. Campuses have already been closed for public health and safety concerns (for example for the 2003 Sars outbreak or after the hurricane Katrina in 2005); moreover, as the multiple waves of Covid-19 show, the possible need for remote teachingin both emergencies and more planned contexts -must become part of a teacher's skill set, as well as professional development programming for any personnel involved in the instructional mission of colleges and universities [START_REF] Barbour | Understanding Pandemic Pedagogy: Differences Between Emergency Remote, Remote, and Online Teaching[END_REF]. Without being exhaustive, this literature review shows that the learner perspective and the instructor perspectives have been investigated mainly separately, for a short period (the spring semester) and involving respondents from the same university. It seems that a deeper insight into this topic could be achieved by comparing student and lecturer perceptions on ERE and by identifying possible shifts of perception towards ERE in the New Normal involving different universities. To this end, this paper focuses on the educational emergency response which the Italian universities have been providing since the spring of 2020. It draws on an ongoing study that has involved 28 lecturers and 1200 students from 14 Italian universities, who have answered questionnaires on the challenges and opportunities of ERE. Their answers will be analysed to address two research questions: RQ1: what can we learn by comparing lecturers' and students' perceptions of ERE? RQ2: what has changed in lecturers' and students' perceptions after a year? After a brief description of the methodology adopted, this paper will present and discuss the results. Even though it draws on an ongoing study and the results are provisional, this study aims to contribute to the debate on the wisdom learned regarding distance education during the pandemic, which could enhance the digital learning and teaching experience both during a pandemic and under normal circumstances.

METHODOLOGY

To investigate the responses to the educational emergency in Higher Education, 14 Italian universities were randomly selected and their EFL lecturers1 were invited to participate in this study. Thus, since March 2020 28 EFL lecturers from different Italian universities have helped the researcher collect data on online classes in ERE-stage 1 (March-May 2020) and in the ERE-stage 2-the New Normal-(academic year 20-21). Data has been collected through direct observation of online synchronous classes and through two sets of online questionnaires. After observing an online class to gain insight into the instructional context, the researcher sent the lecturer the link to an online questionnaire (lecturer questionnaire) and asked them to invite their students to fill in an online questionnaire (student questionnaire). This survey is part of a wider PhD study investigating ERE in Higher education, but for the purposes of this article, only data referring to questionnaires is reported. Moreover, as it is an ongoing study, data on stage 2 is provisional.

Regarding the lecturer and student questionnaires on stage 1 (Spring 2020), they aim to collect information on how classes were organized and what challenges lecturers and students were facing.

Both surveys are divided into six sections (1. personal digital background, 2. synchronous emergency classes, 3. Asynchronous emergency classes, 4. Communication and interaction, 5. Assessment, 6. Difficulties, challenges and opportunities). The questionnaires concerning stage 2 (the New Normal) aim to collect information on the different ways Italian universities organized EFL classes to comply with restrictions that varied from region to region. The questionnaires are divided into three sections (1. Digital habits, 2. Communication and interaction in online classes 3. Suggestions for improvements in communication and interaction in online classes). Both sets of questionnaires consist of open-ended and closed-questions and Likert-scale-based questions made up of 5 response anchors focusing on quality aspects. The common ground between the two stages of the inquiry is the investigation of strategies to enhance communication and interaction in the video-mediated environment. The answers will be analysed quantitatively and qualitatively to gain insight into the lessons learned on remote education: quantitative data refers to the closed-ended answers, whereas qualitative data is provided by open-ended answers.

RESULTS

ERE-Stage 1 -facing an unprecedented challenge and new opportunities Challenges

Regarding the first research question (RQ1: what can we by comparing lecturers' and students' perceptions of ERE?) both lecturers and students reported that they had difficulties in adjusting to the new setting for several reasons. First, not all the lecturers were adequately equipped and trained to face a massive use of digital tools for teaching and learning. The lecturers stated that they had to improve the internet connection (17%) and to buy a new PC (8%). Students, in turn, had to face an even more challenging situation. Several of them were caught by surprise: universities were shut while a lot of students were visiting their families during the carnival holidays, so they did not have their devices or books with them (40%), could not access university libraries (31%) and to share the PC with other family members (20%) or to use their mobiles (12%) to attend online classes, which was not very convenient. Moreover, they could not rely on adequate broadband and experienced problems with the internet connection (86%), which made it difficult to properly attend classes. Second, some lecturers and students lacked previous experience and training in using digital tools for teaching and learning. Indeed, neither all the lecturers nor all the students were very familiar with educational digital platforms: 62% of the lecturers had never taught online classes before the pandemic and 86% of the students had never attended an online class.

The lecturers explored the technology on their own (58%), asked their colleagues (54%), and the elearning centre for help (38%). Adjusting to the new teaching setting took a toll on the lecturers in terms of stress and increased workload: only 4% were happy to follow the guidelines and 13% felt they were forced to record their classes even if they were not comfortable with it. Moreover, live classes were not easy to handle. On the one hand, the preparation was time-consuming (51%), because they were not familiar with technology (35%), had to change their slides (22%), to find new ways of teaching (44%), and reorganise the course schedule (35%). On the other hand, live classes could be stressful since they were afraid of connection problems (48%), of not being able to carry on with lesson (39%) or of not being able to help students 35%; the fact that students kept their cameras off made feel as if they were talking into the empty (35%).

The students had difficulties getting organised (55%), also because they had no clear ideas about how exams would be done (60%), could not study with their classmates as usual (28%), the material provided was not adequate (19%), they were not able to attend the courses (18%) and reaching out to lecturers was not easy (10%). Finally, 45% stated they felt not ready to take the exams and 24% had the feeling of wasting their time.

Opportunities

Despite the difficulties, both lecturers and students reported an increase in their digital skills: data shows that the perceived familiarity with technology increased by 25% among students and 30% among lecturers. Moreover, data shows a sense of satisfaction with the educational response. Lecturers were able to respond effectively to the educational emergency: even if 17% felt their lessons were not as effective as face-to-face classes and had to lower their expectations (17%), 96% felt they were useful and 90% felt happy with the content delivered during the lesson. It is relevant that 35% think their online live lessons, after all, were better than your usual face-to-face classes. This data is confirmed by the students' opinion about online classes: 84% of students think they were useful, lessons were easy to follow (69% was able to follow and take notes, 14% to make up for skipped classes,31% watched the recording even if they had attended the lessons, 33% because of connection problems, 66% to understand better). The lecturers' satisfaction with online classes was partly due to the increase in attendance (40%) and active participation (50%). 14% of the students attended the classes they were not able to attend in person. Regarding active participation, 80% of the students wrote their questions in the chat either not interrupt or to avoid being heard or recorded while speaking in English, whereas only 14% did not dare to ask questions. Furthermore, classes could be more flexible: lecturers could vary the length of the lesson according to students' needs (32%) and easily opt for additional classes without the problem of booking a classroom (27%). Students, in turn, could benefit from recorded classes (91%): on the one hand, they watched the recording of classes they had attended to understand better. On the other hand, they watched video-lessons recorded by other lecturers because either they were curious (55%) or their lecturers did not provide them (26%).

ERE-Stage 2 How lessons learned during the spring 2020 affected the New Normal

Concerning the second research question (RQ2: what has changed in lecturers' and students' perceptions after a year?), the answers to the second questionnaire for the lecturers and the students will be analyzed. Although the data collection is not completed yet and the results are provisional, some differences from the first stage of the pandemic can be highlighted. First, universities capitalized on the flexibility experienced in the first stage of the pandemic and introduced a new option: the hybrid, or dual courses, which were taught in class for a limited number of students and streamed for students at home. They were experienced by 31% of our respondents, who had to prepare lessons suitable for both an online class and an in-person class. Moreover, they complained it was difficult to keep an eye on the chat and to give clarifications to students from home and in the classroom. Despite the challenges, the so-called hybrid classes showed both lecturers and students another option for higher education which they had not experienced before. Lecturers reported that they got accustomed to the new setting and some of them even like having students in the classroom and students from home as they could have different kinds of feedback. On the whole, the level of satisfaction with online classes has increased by 10% in the lectures' group: all the respondents feel more satisfied with their classes if compared to last year. If they seem to appreciate their progress in managing online classes, still they show some concern about interactivity. While 75% are satisfied with the interaction in online classes if compared to in-person classes, 25% is not, which means that there is still room for improvement. The need for improvement in interaction can be noticed also in students' perceptions: even if the majority of them are satisfied with the level of interaction in online classes, 28% of them are not. Broadly speaking, the lecturers defined the atmosphere of online classes as cooperative (75%), supportive (75%), friendly (62%), safe (38%), formal (31%), anonymous (6%). The lecturers' positive opinion is in line with students' answers, even if some differences arise. If students deemed the atmosphere of their online classes friendly (57%), cooperative (47%), supportive (31%) and safe (26%), they also felt it was formal (31%) and anonymous (29%).

Discussion

This study shows that the first wave of the pandemic challenged lecturers and students in many respects, as is highlighted also in other studies on ERE [START_REF] Bali | Literacies Teachers Need During Covid-19[END_REF][START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF]. Even though this study draws on a relatively small number of respondents belonging to the same field (EFL), it has involved lecturers from different universities to have an overview on how Italian lecturers and students relate to ERE. By comparing lecturers' and students' answers, some common challenges can be identified such as the availability of devices, adequate broadband, which were issues of concern in Italian universities for both the groups of respondents. Therefore, in line with other studies on the pandemic, this paper argues that investments in infrastructures are needed to provide students and lecturers with adequate broadband to teach and attend online lessons (UNESCO, 2020, [START_REF] Barbour | Understanding Pandemic Pedagogy: Differences Between Emergency Remote, Remote, and Online Teaching[END_REF]. This would tackle one of the causes of discomfort reported by both students and lecturers, who taught classes having to cope with connection problems (theirs and their students') and felt anxious about the delivery of the lesson and the possibility for students to properly follow.

Apart from technical problems due to poor connection and the availability of devices, both lecturers and students were affected by the lack of training and familiarity with online teaching and learning, which are considered issues of concern also in other studies on ERE. Studies referring to ERE in colleges where technology was already embedded in the teaching and learning practices show that better technologically trained and equipped lecturers and students have more satisfying experiences [START_REF] Cameron-Standerford | The Phenomenon of Moving to Online/Distance Delivery as a Result of COVID-19: Exploring Initial Perceptions of Higher Education Faculty at a Rural Midwestern University[END_REF]. This correlation is confirmed by the preliminary data on the New normal: the increase in digital literacy perceived at the end of the first wave of the pandemic may have contributed to the increase in the lecturers' satisfaction with their online course, who stated to be more satisfied if compared to the previous academic year. However, even though they seem to have capitalized on their previous experience, felt better prepared and more at ease to deal with online lessons, they could benefit from a specific training to be ready to teach online in future if necessary. As was highlighted in other studies on ERE, the educational response was quick and effective despite the technical and emotional difficulties. Both the lecturers and students participating in this study were overall satisfied with ERE and appreciated some opportunities they experienced such as flexibility and self-paced studies, the various options of teaching and learning relating to asynchronous classes, increased attendance. Moreover, ERE revealed new ways of providing higher education such as streamed online classes, which could also be recorded and available on the course page for students who want to watch the lesson again or catch up on a missed class. Therefore, also under normal circumstances, in-person classes could be streamed and recorded to allow more students to attend according to their needs. This paper does not argue that streamed or recorded lessons could fully replace in-person classes or increase the size of university classes as was feared in the debate about distance education. What seems relevant is that students could be given the possibility either to attend in person or from home and /or to watch the recording to understand better or to catch up on a missed class. Providing students with more options could prove to positively affect the whole society in the long run: this could make universities more affordable, more inclusive and could contribute to increasing the percentage of the population owning a higher education degree without detriment to in-person classes. Further research and clear policies are needed to regulate this matter because hybrid or dual teaching is demanding, requires proper training and a clear student/teacher ratio. Our respondents mentioned several difficulties relating to online courses and lecturers cannot be expected to deal with bigger numbers of students, as students attending from home need more help and support from the lecturers if compared to in-person classes.

As underlined in the literature review, technology is a powerful tool, but it is not the only element to be considered and invest in. The social presence and the emotional support provided by lecturers are key aspects to successful teaching and learning [START_REF] Bozkurt | Emergency remote teaching in a time of global crisis due to Corona Virus pandemic[END_REF]. During the first wave of the pandemic, some lecturers felt uneasy and as if they were talking in the empty, whereas students complained about the difficulties in reaching out to their lecturers. In the New Normal lecturers neither complained about lack of communication nor mentioned anxieties regarding online classes, which shows that they got accustomed to the new instructional setting. Moreover, they described the atmosphere of their online classes in positive terms. Indeed, paradoxically online classes can be more informal and friendly than in-person classes and can also encourage shy students to participate more actively, for example by writing in the chat [START_REF] Luporini | Implementing an online English linguistics course during the Covid-19 emergency in Italy: Teacher's and students' perspectives[END_REF]. However, data does not show an increase in interaction, which calls for more action on ways to increase students' participation in online classes. By the way, this is an issue of concern for Higher Education which had already been identified before the pandemic and became more visible in ERE. Thus, further research on ways to make online class more interactive should be carried out to improve higher education (in a pandemic and under normal circumstances).

Regarding the outcomes of this paper, it can be noticed that comparing students' with lecturers' perceptions, as suggested in the first research question, could be the first step to change the narrative of ERE as a failure. Along with the undeniable challenges and difficulties, both lecturers and students had on the whole a positive experience of ERE, which increased their digital literacy and broadened their horizons about the opportunities. Leaving aside the concerns for possible negative effects on the quality of education and the job market, ERE showed that universities could be more affordable, inclusive, and open to students' various needs.

Concerning the second research question about the changes in the new Normal, it can be noticed that lecturers have become more open and flexible towards online teaching. Their comments suggest that online classes can be engaging, motivating and interactive, provided that they master the technology. Even if the atmosphere has become more informal and cooperative, still a relevant number of students perceive online classes as anonymous. At this point, the legitimate question arises as the labels ERE and ERT can still apply to this academic year. On the one hand, they do, as the New Normal has been characterised by uncertain and changeable circumstances which require planning and flexibility but cannot rely on consolidated models and training. On the other hand, it can be noticed that both the lecturers' attitude towards online classes has become more positive, even though some issues of concern such as interactivity are still relevant and need to be addressed in further and more extensive research. It would be interesting to plan studies to monitor their perceptions in the long term when the emergency is over.

CONCLUSIONS

After two semesters spent coping with a changeable and uncertain situation, it can be noticed that there are also positive outcomes. First, lecturers seem more aware of their students' needs and keener on experimenting with alternatives to traditional teaching. Second, students and lecturers have experienced a more inclusive higher education, appreciate being offered different options to attend lessons, have become more autonomous and feel they can organize themselves better.

The outcomes described in this study cannot be generalized as the sample of respondents is relatively small and may be positively biased toward online classes, since they accepted to be observed while teaching. However, by comparing lecturers' to students' perceptions this study shows that ERE cannot be simply dismissed as a second rate teaching and learning experience. Data shows that it is high time we changed the narrative of digital education which cannot be perceived as a per se flawed experience anymore. Further and more extensive research is needed to investigate possible ways of integrating the flexibility experienced in ERE in future higher education. Moreover, even though this study has involved EFL lecturers, it has not dealt with aspects typical of second language acquisition such as interaction in the foreign language, which should be specifically addressed in studies on ERE.

In conclusion, since quality education (inclusive, equitable and promoting lifelong learning) is one the goals of the ambitious Agenda 2030 (Un General assembly, 2015), we should capitalize on the wisdom learned during the various phases of the pandemic and embrace the changes to improve higher education [START_REF] Peters | Reimagining the new pedagogical possibilities for universities post-Covid-19[END_REF].

In this article, the term "EFL lecturers" refers both to lettori, who teach English classes, and lecturers of English Linguistics.

ACKNOWLEDGEMENTS

This paper and the research behind it would not have been possible without the help of Prof. Pulcini (Università di Torino), Prof. Santini (Università degli Studi di Genova), Prof. Pedrazzini and Prof. Nava (Università di Milano), Prof. Castello (Università di Padova), Prof. Peruzzo (Università Ca' Foscari), Prof. Luporini (Università di Bologna), Prof. Cecconi (Università di Firenze), Prof. Gatto (Università di Bari), Prof. Cavalieri (Università di Napoli), Prof. Brett (Università di Sassari), Prof. Denti (Università di Cagliari), Prof. Caimotto (Università di Torino), Prof. Demata (Università di Torino), Prof. Lukasic (Università di Torino-University of Slupsku), Prof. Molino (Università di Torino), Prof. Piovaz (Università di Torino), Prof. Restaldi (Università di Torino), Prof. Salusso (Università di Torino), Prof. Triki (Università di Torino), Prof. Vecchiato (Università di Torino), Prof. Degano (Università Roma Tre), Prof. Miles A. (Università di Palermo), Prof. Varuzza (Università Ca' Foscari), Prof. Miles S.(Università Ca' Foscari), Prof. Titmarsh (Università Ca' Foscari), Prof. Sawisza (Università di Torino), Prof. Dorrity (Università di Torino).


Antonella Giacosa

Daniela Salusso

Maria Carmela Zaccone

USING OERS IN EMERGENCY DISTANCE LANGUAGE LEARNING: A CASE STUDY

Keywords: Learner autonomy, Distance learning, OER, ERE, Second language learning, Language skills

whether they are published or not. The documents may come

INTRODUCTION

Due to the Covid-19 outbreak in the spring of 2020, lecturers and students had to adjust to a new instructional setting almost overnight: on the one hand, lecturers had to adapt the activities and contents planned for in-person classes to online classes; on the other hand, students could not rely on constant exposure and immediate feedback and had to learn more autonomously. However, the University had already launched a series of open online courses in the academic year 2018-2019 with the Start@Unito project. In particular, the Department of Foreign Languages already offered 6 first-year undergraduate modules in Modern Languages (French, German, English, Portuguese, Russian, Spanish), aimed at both prospective students and first-year university students. Start@Unito has been extensively studied as a form of OER to bridge over the passage from secondary to higher education: first, it has proved useful as a chance for secondary school teachers to broaden their horizons and to help students acquire the key competences (knowledge, abilities and attitudes) to become aware global citizens (Marchisio et al., 2019a). Secondly, it has been studied as a way to train lecturers to update their digital skills and to approach online teaching [START_REF] Marchisio | Instructional Design to "train the trainers": the Start@unito Project at the University of Turin[END_REF]. From both perspectives, studies focus on Start@unito as a useful tool to help teachers provide quality activities and reliable ready-to-use materials to enhance the effectiveness of their lessons. As shown by previous studies, the educational experience lecturers and students have had during the waves of the Covid outbreak can be described as Emergency Remote Education (ERE), a branch of distance education referring to the sudden, unplanned, and temporary transition of in-person classes onto digital platforms [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF]. UNESCO (2020b) encouraged implementation of OERs to support learning and knowledge worldwide during the pandemic. Actually, OERs had already been identified as an effective means of building open and inclusive knowledge societies and to achieving the objectives of the United Nations Sustainable Development Goals regarding education (UNESCO 2020a, [START_REF] Ossiannilsson | From Open Educational Resources to Open Educational Practices, in Distances et médiations des savoirs[END_REF]. A survey on ERE in different countries investigated the challenges and the integration of OERs into the educational response to the crisis (Ossianilsson et al., 2020). The investigation focuses on the employment OERs (Open Education Resources) and OEPs (Open Education Practices) during the Covid-19 crisis, indicating that there are still gaps in the effort to move from awareness raising about OERs to OEPs, that is a changed mindset, attitudes, and values regarding a culture of openness. The link between OERs and flexible, self-paced learning had already been identified before the pandemic [START_REF] Huang | Guidance on Open Educational Practices during School Mooc2Move Conference on[END_REF][START_REF] Ossiannilsson | From Open Educational Resources to Open Educational Practices, in Distances et médiations des savoirs[END_REF]. When the need for flexible, self-paced and self-directed learning became urgent, OERs were bound to come into play. Studies on ERE show that self-paced learning played a relevant role potentially making it a more learner-centred approach [START_REF] Benson | Teaching and researching autonomy in language learning[END_REF] than traditional teaching. Indeed, studies show that opportunities offered by ERE, such as the massive use of asynchronous classes, rely on and subsequently promote learner autonomy, which is an essential skill for both academic and life-long learning [START_REF] Amin | EFL students' preferences on digital platforms during emergency remote teaching: Video Conference, LMS, or Messenger Application?[END_REF], as suggested also by [START_REF] Benson | Teaching and researching autonomy in language learning[END_REF][START_REF] Pekkanli Egel | Learner autonomy in the language classroom: from teacher dependency to learner independency[END_REF] well before the pandemic outbreak. Before being monopolized by issues related to the pandemic, studies on language teaching focused on enhancing learner autonomy and control over the language learning process particularly in Higher Education (HE) [START_REF] Littlemore | Learner autonomy, self-instruction and new technologies in language learning: Current theory and practice in higher education in Europe[END_REF]. More specifically, technologies had been investigated in CALL research (Computer-Assisted Language Learning) concerning learner autonomy and self-directed learning. New technologies have the potential to increase learner autonomy in the 4 different skills (for example, reading and writing emails, listening and speaking in videoconferencing and help learners develop critical thinking skills as they have to evaluate and select information [START_REF] Littlemore | Learner autonomy, self-instruction and new technologies in language learning: Current theory and practice in higher education in Europe[END_REF][START_REF] Little | Language learner autonomy: Rethinking language teaching[END_REF]. Interestingly, the OER topic is reported as one of the least investigated ones in studies on CALL [START_REF] Gillespie | CALL research: Where are we now?[END_REF][START_REF]OER use in intermediate language instruction: a case study[END_REF], even though it is a way to provide teachers with reliable, ready-to-use material to meet students' needs under normal circumstances and even more during an emergency. To this end, the present paper aims to understand if and how the Start@unito Open Education Resources (OERs) have been integrated into Emergency Remote Education [START_REF] Bozkurt | A global outlook to the interruption of education due to COVID-19 pandemic: Navigating in a time of uncertainty and crisis[END_REF] to promote learner autonomy in achieving the required level in the 4 linguistic competences (listening, reading, speaking, writing). In line with other studies on ERE and adopting a learner-centred approach, a survey was carried. The research questions addressed in this case study are: RQ1 To what extent have OERs been integrated into second language courses during the pandemic regarding the four language skills? RQ2: What role could OERs play in enabling autonomous language learning in student and lecturer perceptions? This paper provides reflections on possible ways of integrating OERs with ERE. First, the methodology of data collection and analysis will be explained, secondly data will be discussed and finally, data-driven reflections will be provided to shed light on useful tools for lecturers and students to cope with possible future emergencies.

METHODOLOGY

This case study draws on data collected on language courses taught at the Department of Foreign Languages and Literatures of the University of Turin, which had the opportunity to rely on OER courses provided by the platform Start@unito. As shown in the literature review, Start@unito itself was an interesting and almost unique experiment in Italy of possible integration of OER resources into second language teaching. Therefore, it is relevant to investigate how and to what extent its resources were used in ERE. This could shed light on weak and strong points of OER current practices, so that possible improvements regarding the integration of OERs in language teaching can be envisaged. The originality of this study relies on the perspective adopted, which narrows down on a specific issue of concern for second language teaching and investigates the use of OERs in different waves of the pandemic, so that medium-term shifts in teaching practices can be identified. Moreover, it adopts a comparative approach by dealing with more than one second language, which makes it different from other studies on ERE. Data was collected through questionnaires which were sent in May 2020 to second-language experts teaching at the university of Turin; more specifically, the languages involved are English, German, French, Spanish, Portuguese and Russian. The respondents to both questionnaires teach Spanish (31%), English (25%), German (25%), French (6%), Russian (6%) and Portuguese (6%). The percentages of the students who answered are the following: 97.7 % Spanish and 3.3% Portuguese students for the first questionnaire; 64% Spanish, 25% French, 7.1% Russian, 3,6 Portuguese for the second one. The lecturer questionnaire is divided into 3 sections investigating how courses were taught during the pandemic and how Start@Unito resources were used before and during the Covid-19 emergency. The student questionnaire is divided into two parts focusing on their experience using OERs regarding the four skills during ERE. Data was updated through a follow-up questionnaire in February 2021 to investigate possible changes in the integration of OERs in their courses during the academic year 2020-21, which was taught online from the beginning. Both students and lecturers' questionnaires were anonymous and consisted of closed-ended, open-ended questions and Likert-scale-based questions made up of 5 or 10 response anchors asking the respondents to evaluate the quality of the resources in question with the aim of improving linguistic competences. Each questionnaire took approximately 15 minutes to complete. Data from the answers to closed-ended questions were analyzed quantitatively, whereas open comments elicited through open-ended questions were considered qualitative data, providing a better understanding of the respondents' perceptions.

RESULTS

RQ1 To what extent have OERs been integrated into second language courses during the pandemic regarding the four language skills? Generally speaking, data show that the increased workload was an issue of concern for 88% of the lecturers, as students were more demanding and had additional needs, such as the need for information, feedback, human contact and human relationship with their teachers. There is no significant difference depending on the language taught. As data shows, feedback and correction was an issue of concern for 44% of the respondents and lesson planning and preparation of materials was mentioned by 50% of the sample. When the same question was asked to the student sample on a Likert scale from 1 to 5, they answered as follows: 43.3% said the workload was comparable to that of the in-person lessons, 12,5% answered that they had not noticed any increase, and only 6.3 stated that there had been a remarkable increase. From the lecturer perspective, effective and ready-to-use open-source materials could have played a key role. However, 56% of the respondents reported that they never used them and 13% that they rarely used them, whereas only 19% used them sometimes and 13% used them often. Although 88% of the students reported an increased workload, only 44% used the Start@unito OERs. If we consider the different languages, only Russian and English did not use the Start@unito resources at all (concerning English, this may be partly explained by noticing that the Start@unito course was a linguistics course rather than a language course). There are no substantial differences among the other languages. We asked the students why they used the Start@unito platform, giving them different options: 53.6% of them used Start@unito to review the subjects covered during the lesson, 25% to carry out tasks proposed by the lecturer, and 17.9% did not use the platform at all. Moreover, 25% of the students stated that the Start@unito OERs entirely replaced the in-person language course, while 32.1% used the available resources to prepare for the final exam. In addition, 78.1% of the students reported using Start@unito resources to study, while 21.9% also used other platforms. Narrowing the analysis on the lecturers who used open online resources (44% of the sample), data show that 50% of them followed the department guidelines, 33% decided autonomously and 17% agreed on what to do with colleagues. By contrast, lecturers who did not use the Start@unito OERs stated either that they were not aware of their existence (13%), or that they preferred their own materials (13%) or that using them was time-consuming (7%) or that they did not have the right credentials to access them (7%). However, in those cases where the Start@unito resources were used, data show that they were successfully integrated with ERE. With reference to the activities that benefited the most from the use of online open resources, listening and reading were chosen by 57% of lecturers, writing was chosen by 42% and speaking by 29%. Out of 16 respondents, only 2 used the Start@unito resources in their classes (listening, reading, speaking, writing) to introduce or consolidate topics that they had dealt with in their online lessons. As far as the different languages are concerned, German lecturers used them to improve all 4 skills; Spanish and Portuguese lecturers used them for speaking activities; English and Russian lecturers did not use them at all. Regarding the integration of the Start@unito OERs into second language courses, data concerning the first semester of the academic year 20-21 do not show any relevant increase. The second questionnaire shows that 88% of the respondents did not use the Start@unito resources because they preferred using materials tailored on their students' needs (50%) or taken from the study book (21%); in addition, some lecturers did not consider them relevant for the course (29%), or they did not know about their availability (28%). If compared to the spring 2020, it seems that the number of lecturers who used Start@unito resources in the winter term has decreased. Analysing the data with reference to the different languages, it can be noticed that the German and the French lecturers opted for selfprepared materials because Start@unito resources were not relevant for their courses. The percentages of students who availed themselves only of Start@unito resources and those who used also different materials remain the same.

RQ2: What role could OERs play in encouraging autonomous language learning in student and lecturer perceptions?

Out of 16 lecturers, only 6 respondents expressed their opinion on the usefulness of Start@unito resources during the pandemic, stating that they provided students with deeper knowledge (6), motivation (1), self-evaluation (2); indeed, the exercises with keys or automated feedback proved particularly useful. Drawing on their one-year experience of ERE, our respondents identified some needed improvements concerning OERs, stating that OERs should provide students with selfevaluation and self-study materials. In addition, they think that students should be supported to be able to engage in activities involving digital skills such as video-making. All these activities should ideally be designed to promote learner autonomy. Among the few students who reported using OERs autonomously, 87.5% employed exclusively materials already available on the Start@unito platform, while only 12.5% (students of Spanish, English and Portuguese) used other applications to improve their language skills (Youtube, Duolinguo, radio apps). The second questionnaire reveals a slight improvement in the use of external tools to support their learning. To be more precise, 33% of the students reported using Youtube, web pages, Duolingo, Bab.la, Udemy. The Start@unito OERs lacked specific resources aimed at improving students' speaking skills. To solve this problem, it appears that students made use of external resources: 46.9% utilized language learning applications, 37.5% applications of linguistic exchange with native speakers, while a small percentage opted for a personal tutor, self-corrected or automatically corrected exercises, or simply chose to wait until in-person classes resumed. Furthermore, we asked students to compare OERbased automatically corrected exercises with traditional exercises carried out in the classroom and corrected by the teacher: 59.4% found them equivalent, 31.3% easier, while 9.4% found them more difficult. One of the aims of our questionnaires was understanding whether using OERs could, at least partially, solve the problem of the lack of interaction. We asked them to evaluate their competences on a scale from 1 to 10 (1 being the minimum and 10 the maximum levels of competence) after the online course. The results show that:

-writing: 22.6% answered 5 and 22,6% 6 -speaking: 25.8% answered 6 and 40.7% gave an answer in the range from 1 to 5 -listening: 22.6% answered 7 while 25.8% 8 -reading comprehension: 25.8% answered 8. Overall, the level of competence acquired by the students at the end of the course can be regarded as satisfactory for listening and reading and not satisfactory for speaking and writing. In light of the students' previous answers, we asked them if the lack of interaction had influenced their final evaluation (we used a Likert scale from 1 to 5 where 1 stands for not at all influenced and 5 very influenced): 3.7% answered not at all influenced, 44.4% not very influenced, 33% was neutral, 7.4% very influenced, 11.1% very much influenced.

CONCLUSIONS

In the present study we have asked ourselves how Open Educational Resources (OERs) have been integrated with distance teaching during the pandemic. Given the increased workload for both lecturers and students, we expected the Start@unito resources to be employed extensively. The results show that regardless of the language taught, lecturers resorted to the existing OERs only marginally. Although there is a general agreement on the importance of integrating OERs into ERE, a practice encouraged also by the UNESCO document on inclusive education (UNESCO 2020 b), our study demonstrates that having ready and available resources is not enough to use them in open educational practices (OEP). Start@unito courses, for example, originally had a different purpose, in that they were specifically designed for those students wishing to study autonomously (such as students in their last year of high school, working students, students who live far away from the university headquarters) or to promote inclusive education using computer-assisted technology for language learning (CALL). Moreover, Start@unito courses were designed to be self-sufficient and selfcontained. Hence the difficulty in adapting these resources into ERE practices. Regarding the 4 basic language skills, our data show that the Start@unito OERs were used mainly to improve listening and reading and less when it came to speaking and writing. The latter, in fact, require personalized feedback which falls outside the scope of Start@unito courses. In the evaluation of their competences, students stressed the importance of face-to-face time with the lecturer and immediate feedback to improve their speaking and writing skills respectively. In fact, this problem was solved by using the Webex platform where lecturers held synchronous lessons trying to increase student talking time, and writings were either corrected collectively during such lessons or individually via email. Conversely, the OERs available on Start@unito proved to be a valuable asset to integrate into lessons for reading and listening comprehension. The reason why not many lecturers decided to use them is twofold: first, as said before, the courses were designed to be self-sufficient and the resources were often consequential and "rigid" in their structure; second, not all lecturers were familiar with the Start@unito resources, as the project was still in its infancy when the pandemic started. Moreover, the Start@unito resources were used mainly for self-correction and self-study by those students who were already autonomous learners or wished to take a step towards becoming one. Another critical point regarding OERs lies in the need for personalization of contents and activities, highlighted by both lecturers and students. When asked about the level of difficulty of the exercises proposed on Start@unito, the answers given by students are equally distributed between "easy" and "difficult". This shows one of the limits of using OERs for language learning: not all learners have the same linguistic level, therefore the one-size-fits-all approach is often not feasible. Focusing now on our second research question, namely using OERs to promote learner autonomy, a key factor seems to be the possibility to provide students with automated feedback. Appropriate feedback is essential to keep motivation and self-efficacy alive and to guide students in their path towards learning and self-learning, thus facilitating the teacher's work. The necessity to give feedback to the students was identified as the main cause of the increased workload for lecturers, which the students, in turn, confirmed. Already in the first questionnaire, students' comments the lack of interaction with the lecturer and of resources with automatic correction to prepare them for final exams. At the same time, lecturers also stressed the need for OERs that foster learning autonomy and activities that provide students with feedback. It seems, then, that future research should go in the direction of creating resources that promote learner autonomy, so that teachers may truly take on the role of facilitators and so that distance education may become fertile soil for good educational practices. To conclude, the first limitation of this study is the small number of replies received from both students and lecturers, although the answers are in line with the general trends, we noticed throughout the implementation of ERE. Secondly, the data collected shed light on the need for common policies and guidelines shared with all the teachers of a department. Finally, distance learning opened the door to the extensive use of technology in teaching and learning foreign languages. The Covid-19 emergency made it clear that we need to find new teaching and learning strategies to replace traditional teachercentred lessons. This is even truer when it comes to language students, since languages are constantly evolving and there is no such thing as knowing a language without constant training and autonomous learning. A further area of future investigation is teacher training on how to use OERs and integrate them in a flexible teaching practice in order to meet students' needs and face unpredictable circumstances more efficiently.

ACKNOWLEDGEMENTS

Foremost, we would like to express our gratitude to all the lecturers and students who took the time to participate in our survey. Our sincere thanks also go to the DELTA (Digital Education for Learning and Teaching Advances) research group of the Department of Mathematics of the University of Turin, who coordinated the Start@unito project.