Philippe Mathieu
email: philippe.mathieu@univ-lille1.fr

Jean-Paul Delahaye
email: jean-paul.delahaye@univ-lille1.fr

New Winning Strategies for the Iterated Prisoner's Dilemma (Extended Abstract)

Keywords: I.2.11 [Artificial Intelligence]: Distributed Artificial Intelligence-Multiagent systems Algorithms, Experimentation Game theory, group strategy, iterated prisoner's dilemma, IPD, agent's behaviour, memory, opponent identification

INTRODUCTION

In the iterated prisoner's dilemma game, new successful strategies are regularly proposed especially outperforming the well-known tit for tat strategy. New forms of reasoning have also recently been introduced to analyse the game. They lead W. Press and F. Dyson [START_REF] Press | Iterated prisoner's dilemma contains strategies that dominate any evolutionary opponent[END_REF] to a double infinite family of strategies that -theoretically-should all be efficient strategies. We study and confront using severals experimentation the main strategies introduced since the discovery of tit for tat. The iterated prisoner's dilemma is a game that leads to understand various basic truths about social behaviour and how cooperation between entities is established and evolves. Several studies [START_REF] Beaufils | Our meeting with gradual, a good strategy for the iterated prisoner's dilemma[END_REF][START_REF] Press | Iterated prisoner's dilemma contains strategies that dominate any evolutionary opponent[END_REF] have led to consider other strategies than the famous tit for tat. We have begun to make a balance of the situation with the desire to reach clear and as unbiased as possible conclusions. Our method is based on three main ideas, each converging on robust results. (1) Confronting the candidate strategies on the principle of the tournament (mainly for information) and the method of ecological competition which gives results independent from initial conditions. (2) Using sets of strategies in which all strategies of a particular class (eg using the last move of past of each player) are in competition. This method of complete classes [START_REF] Beaufils | Complete classes of strategies for the classical iterated prisoner's dilemma[END_REF] avoids any subjective choice. (3) Taking a phased approach by not trying to find the best of all strategies in absolute terms, but by combining the results of progressive massive confrontation experiments.

Appears in: Proceedings of the 14th International Conference on Autonomous Agents and Multiagent Systems (AA-MAS 2015), Bordini, Elkind, Weiss, Yolum (eds.), May, 4-8, 2015, Istanbul, Turkey.

International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org).

RULES OF THE GAME

The prisoner's dilemma is that accorded to two entities with a choice between cooperation (c) and defection (d) and are remunerated by R points each if each plays c, P points if each plays d and receiving T respectively S points if one plays d and the other c. We describe these rules by writing:

[c, c] -> R + R , [d, d] -> P + P , [d, c] -> T + S
In our experiments with use the classical values T=5, R=3, P=1, S=0 and 1000 rounds for each meeting.

We make a distinction between deterministic strategies and probabilistic strategies (where choices can depend on chance). The study of literature about the dilemma led us to define a set of 17 basic deterministic strategies (including the simplest imaginable strategies). We have added 13 probabilistic strategies mainly taking into account the recent discoveries of Press and Dyson on extortion [START_REF] Press | Iterated prisoner's dilemma contains strategies that dominate any evolutionary opponent[END_REF].

Let us present the set of 17 basic strategies. all c: always cooperates. all d: always defects. tit for tat: cooperates on the first move then plays what its opponent played the previous move. spiteful: (also called grim) cooperates until the opponent defects and thereafter always defects. soft majo: begins by cooperating and cooperates as long as the number of times the opponent has cooperated is greater that or equal to the number of times it has defected; otherwise she defects. hard majo: defects on the first move and defects if the number of defections of the opponent is greater than or equal to the number of times she has cooperated; else she cooperates. per ddc: plays ddc periodically. per ccd: plays ccd periodically. mistrust: (also called suspicious tft) defects on the first move then play what my opponent played the previous move. per cd: plays cd periodically. pavlov: (also called win-stay-loseshift) cooperates on the first move and defects only if both the players did not agree on the previous move. tf2t: cooperates the two first moves, then defects only if the opponent has defected during the two previous moves. hard tft: cooperates the two first moves, then defects only if the opponent has defected one of the two previous moves. slow tft: cooperates the two first moves, then begin to defect after two consecutive defections of its opponent; returns to cooperation after two consecutive cooperations of its opponent. gradual: cooperates on the first move, then defect n times after n th defections of its opponent, and calms down with 2 cooperations [START_REF] Beaufils | Our meeting with gradual, a good strategy for the iterated prisoner's dilemma[END_REF]. prober: plays the sequence d,c,c, then always defects if its opponent has cooperated in the moves 2 and 3; plays as tit_for_tat in other cases. mem2: be-haves like tit for tat : in the first two moves, and then shifts among three strategies all d, tit for tat, tf2t [START_REF] Li | The effect of memory size on the evolutionary stability of strategies in iterated prisoner's dilemma[END_REF].

Memory(X,Y) is the complete class which is the class of all deterministic strategies using my X last moves and the Y last moves of my opponent. In each Memory(X,Y) complete class, all deterministic strategies can be completely described by their "genotype" i.e. a chain of C/D actions to do that begin with the max(X, Y ) first moves i.e. not depending on the past. These starting actions are written in lower case. The list of cases of the past is sorted by lexicographic order on my X last moves (from the older to the newer) followed by my opponent's Y last moves (from the older to the newer).

Our platform has allowed us to compete in tournament and ecological competitions families of 1000 and even 2000 strategies. Our experiments using large complete classes led us to discover four new strategies : winner12 (mem12 ccCDCDDCDD), winner21 (mem21-dcCDCDCDDD), spiteful cc which is classical spiteful but with a cc forced start, tft spiteful which starts with c, then plays tit for tat unless she has been betrayed two times consecutively, in which case she always betrays (plays all d ).

The 17 basic + 4 new strategies : The experiment A involves the 17 basic strategies with these 4 new strategies. It is remarkable that three among the four new introduced strategies are in the 4 first ecological ranking.

All deterministic + 4 new strategies : For this experiment B we add the Memory(1,1) complete class. This leads to a set of 53 strategies (17 + 32 + 4 new). This time the four winners are exactly the same as in the previous experiment B but not exactly in the same order. This result shows the robustness of these four strategies.

All deterministic and probabilistic : This experiment C is built with all the basic deterministic startegies obtained with the 17 initial basic strategies and the Memory(1,1) complete class added with 13 probabilistic strategies coming from [START_REF] Press | Iterated prisoner's dilemma contains strategies that dominate any evolutionary opponent[END_REF] and the four new strategies discovered thanks to the complete classes experiments. This leads to a set of 66 strategies. These experiments show clearly that winner21 seems less robust than the three other stategies.

CONCLUSION

According to the state of the art, we have collected the most well-known interesting strategies. Then we have used the systematic and objective complete classes method to evaluate them. These experiments led us to identify seven efficient and robust strategies: spiteful cc, gradual, win-ner12, tft spiteful, spiteful, mem2, soft majo. We note that they are almost all mixtures of two basic strategies : tit for tat and spiteful. This suggests that tit for tat is not severe enough, that spiteful is a little too much and that finding ways to build hybrids of these two strategies is certainly what gives the best and most robust results. We also note that using information about the past beyond the last move is helpful. Among the seven strategies that our tests put in the head of ranking some of them use the past from the beginning (gradual and soft majo) and all the others use two moves of the past or a little more. This work illustrates the fact that using complete classes of increasingly size will allow to identify increasingly efficient strategies, and provides a broad framework to find new ones.


J.-B Doc

C Vergez

Oscillation regimes produced by an alto saxophone : influence of the control parameters and the bore inharmonicity

The aim of this work is to highlight experimentally how inharmonicity of the bore resonance frequencies of an alto saxophone influence the nature of the oscillation regimes. A variable volume branching from the neck of an alto sax at an appropriate position allows to change the frequency of the first resonance independently from the second. A blowing machine with artificial lips is used to make the saxophone play while controlling independently the control parameters : the blowing pressure and an embouchure parameter. Values of these parameters are estimated experimentally through the measurement of the nonlinear characteristics linking the mean air flow blown into the instrument to the static pressure difference across the reed. Experiments with different values of the control parameters as well as of the inharmonicity produce different kinds of oscillation regimes. These regimes are categorized through the analysis of the pressure signal inside the mouthpiece. The resulting maps demonstrate that the emergence of quasi-periodic regimes, and their extent, depend on the level of inharmonicity, but also on the values of the control parameters. Periodic regimes playable by choosing appropriate values of the control parameters also differ according to the level of inharmonicity, a higher inharmonicity facilitating the emergence of the third register.

I. Introduction

The construction of musical wind instruments requires, for example, drilling side holes and adding a mouthpiece and bell. This may alter the harmonicity of the instrument, which means that the different resonance frequencies deviate from a perfect harmonic series. Inharmonicity of resonance frequencies has a direct influence on the intonation of a musical wind instruments [START_REF] Fletcher | The physics of musical instruments[END_REF] , as well as on the timbre of the sounds produced. Moreover, the inharmonicity of a wind instrument may trigger the production of multiphonics [START_REF] Benade | Fundamentals of musical acoustics[END_REF] , which correspond to a quasi-periodic oscillating regime [START_REF] Gibiat | Phase space representations of acoustical musical signals[END_REF] . Therefore, inharmonicity appears as a key factor to consider when designing musical wind instruments.

Multiphonics can be easily obtained on wind instruments played unconventionally, for instance using fork fingerings or a modified embouchure. These multiphonics are perceived as chords or rolling or beating sounds [START_REF] Backus | Multiphonic tones in the woodwind instruments[END_REF] and are commonly used in Jazz or contemporary music. However, even when the instrument is played in a conventional way, undesirable quasi-periodic regimes may be produced. In that case, craftsmen obviously try to avoid this type of behavior which affects the playability of the instrument.

Quasi-periodic regimes have already been studied for organ pipes and flutes 5;6;7 or reed instruments 8;9 . However the emergence of quasi-periodic regimes in musical instruments is still a poorly understood phenomenon. For reed instruments, the paper by Dalmont et al. [START_REF] Dalmont | Some aspects of tuning and clean intonation in reed instruments[END_REF] presents the first experimental evidence that the harmonicity of the resonances may influence the production of quasi-periodic regimes by an alto saxophone. This pioneering work has recently been revisited in a study [START_REF] Doc | A minimal model of a single-reed instrument producing quasi-periodic sounds[END_REF] based on the use of a numerical model of the sound production. This study shows that control parameters set by the player have also a significant influence on the production of quasi-periodic regimes.

The goal of this paper is to highlight experimentally the influence of the harmonicity of the resonances on the sound production by an alto saxophone. The analysis focuses on regimes produced, and questions relative to timbre are ignored. The experiment from Dalmont et al. [START_REF] Dalmont | Some aspects of tuning and clean intonation in reed instruments[END_REF] is carried out again : a piston is added perpendicularly to the neck of the saxophone (see fig. 2(b)) at a location which allows to alter the resonance frequency of the lowest mode without affecting the resonance frequency of the second mode. The inharmonicity of the lowest modes of the instrument can consequently be controlled by the experimenter.

An artificial mouth is used in order to make the saxophone play with two control parameters : the embouchure settings and the blowing pressure (considered independent for this study). These parameters are estimated experimentally according to a model of the acoustical exciter. Sound is recorded for sets of control parameter values, and the nature of the regime is identified through analysis of the signal. These can be represented graphically in maps that allow an easier reading of the experimental data.

Section introduces the experimental device as well as methods used to characterize it. In section , signal processing methods are then presented. Finally, in section , experimental results are presented.

II. Characterization of the experimental device

A. Experimental device

The saxophone used for the experiment is a student model (Yamaha YAS-280), played with a Plasticover reed (force 3) placed on a standard mouthpiece (Yamaha 4C). In order to perform different fingerings, cork pieces are inserted below the corresponding key mechanisms so that the desired keys are maintained closed. Tensioners are also used to keep certain keys closed.

A photo of the experimental device is shown in Figure 1, where the saxophone is laid horizontally in order to be connected to the artificial mouth. The latter is based on a plexiglass box, the inner volume of which is 15cm 3 . The control of air pressure inside the box is carried out through a closed-loop. A real-time dSpace controller drives a servo-valve (placed upstream an air tank) according to the static pressure measured in the box. Specific developments have been necessary to achieve a precise control through time of the pressure in the artificial mouth (technical details are available in [START_REF] Ferrand | High-precision regulation of a pressure controlled artificial mouth : The case of recorder-like musical instruments[END_REF] ). Pressure ramps can therefore be generated in the artificial mouth. Figure 2(a) displays a sketch of the artificial mouth. The mouthpiece of the instrument is connected to the artificial mouth through a rubber seal which ensures air tightness. An artificial lip is pressed against the reed and brings the required damping to avoid squeaks when the instrument is playing. The artificial lip is made with latex tube filled with water through a syringe. Rising the pressure of water increases the bearing force of the lip on the reed, which results in a decreased reed channel opening. The artificial lip is placed around 1cm downstream the tip of the reed (see Figure 2

B. Characterization of the exciter

The mouthpiece and the reed together can be seen as an exciter. According to classical textbooks [START_REF] Chaigne | Acoustics of musical instruments[END_REF] , this system can be characterized through the estimation of two physical quantities : the airflow U through the reed channel and the difference ∆P between the mouth pressure P m and the mouthpiece pressure P . The airflow produced by the reed displacement is ignored in this description. The so-called nonlinear characteristics of the exciter [START_REF] Dalmont | Nonlinear characteristics of single-reed instruments : Quasistatic volume flow and reed opening measurements[END_REF] (noted NLC hereafter), connecting these two quantities can be written :

           U = ζ Z c (P M -∆P ) |∆P | P M sgn (∆P ) if ∆P < P M , (1a)
U = 0 if ∆P > P M , (1b)
where P M is the beating reed pressure, i.e. the minimum pressure difference across the reed to close the reed in the static regime, and ζ the embouchure parameter defined by :

ζ = Z c S 2 ρ P M , (2)
with Z c the characteristic impedance of plane waves inside the resonator, S the cross-section of the instrument input and ρ the density of air. Parameters P M and ζ are estimated experimentally by fitting Eq.(1) onto a measured NLC. Figure 3 displays an example for a given setting of the artificial mouth. Thanks to the measurement, the maximum airflow U max and the corresponding pressure difference P max can be estimated. Considering that P M = 3P max , the embouchure parameter ζ is then obtained through the relation [START_REF] Dalmont | Nonlinear characteristics of single-reed instruments : Quasistatic volume flow and reed opening measurements[END_REF] :

ζ = √ 3 2
U max P max Z c . (3)
The NLC modeled through equation ( 1) is then plotted using the estimated values of P M and ζ. As shown in Figure 3, the measured and the modeled NLC are nearly identical. Moreover, knowing P M allows to evaluate the dimensionless blowing pressure γ, defined as the ratio between the mouth pressure and the reed beating pressure : γ = P m /P M .

For each experiment or for each change in the setting of the experimental mouth, an estimation of ζ and γ parameters is carried out. This allows us to plot the analysis results of the mouthpiece pressure (the different oscillation regimes as explained in section ) on a map representing the control parameters ζ and γ.

C. Characterization of the resonator

The impedance of the alto saxophone is measured with an impedance sensor [START_REF] Macaluso | Trumpt with near perfect harmonicity : Desgin and acoustic results[END_REF] for each fingerings used in the experiment. A cylinder of the same volume as the mouthpiece is placed upstream the instrument. For this study the fingering corresponding to the G note (as read on a score) of the first register (noted hereafter G') is used. A piston is soldered to the neck of the saxophone without affecting the inner geometry of the instrument (see Figure 2(b)). For the G' fingering, this allows to alter the first resonance frequency of the instrument without affecting the other resonances [START_REF] Dalmont | Some aspects of tuning and clean intonation in reed instruments[END_REF] . Therefore, pushing/pulling the piston allows to directly modify the inharmonicity of the instrument. In the following, since the amplitudes of the first two peaks are at least twice as large as those of the upper peaks, we focus on the inharmonicity of the two lowest resonance frequencies f 1 and f 2 defined by ∆f /f = (f 2f 1 )/f 1 . This quantity will be given as a percentage.

Figure 4 presents the dimensionless input impedance of the alto saxophone for the two extreme positions of the piston. When the piston is completely pushed (L p = 0), there is no modification of the air column added and the resonance frequencies are nearly harmonic ∆f /f = 103%. When the piston is completely pulled (L p = 7cm), the volume added to the air column induces an inharmonicity so that ∆f /f = 110%. The input impedance has been measured for different intermediate positions of the piston in order to evaluate the inharmonicity as a function of L p .

III. Data processing

Measurement and analysis of the acoustic pressure inside the mouthpiece of the instrument allows classifying the different oscillation regimes produced. This classification relies on the identification of the instantaneous frequencies and amplitudes in the recorded signals, as explained above.

A. Instantaneous frequencies and amplitudes of the mouthpiece pressure

A spectrogram is first calculated according to the mouthpiece pressure signal. From this, the evolution of instantaneous frequencies and amplitudes are estimated depending on the experimental time-varying parameters (γ, L p or ζ). Practically, the Matlab function findpeaks is used. An additional constraint is imposed on the amplitude of peaks to identified. Thus, only one instantaneous frequency by partial is detected. Figure 5 displays an example. Dotted lines represent the estimated instantaneous frequencies. The main components of the signal are correctly localized on the spectrogram.

B. Classification of the oscillation regimes

An algorithm has been developed to classify the different oscillation regimes according to the instantaneous and amplitude frequencies on each frame of the spectrogram. Three types of oscillation regimes are identified : first of all a static regime (no sound), then a quasi-periodic regime (composed of two incommensurate frequencies) and finally a periodic regime (obviously different playing frequencies are possible). In practice, the instrument does not produce the fourth register. That is why the identification is limited in frequency up to 1000Hz (frequency lower to the one of the 4th harmonic).

The main steps of the algorithm are constructed following this hierarchical order :

• If no instantaneous frequency is detected or if no instantaneous amplitude crosses a user-defined threshold : the regime is classified as static.

• If more than one instantaneous frequency is detected, ratios between each pair of consecutive frequencies are calculated. If at least one of these ratios belongs to the interval [0.7, 1.3], the oscillation regime is classified as quasi-periodic. We can note that the method is configured to calculate a only one instantaneous frequency by harmonic component.

• Otherwise the smallest instantaneous frequency is compared to the frequencies of the expected notes for the fingering considered (mostly the different harmonics of low G). If there is match within 5%, the oscillation regime is classified as periodic.

Figure 5 shows an example of this algorithm output. In this example, a linear increasing ramp of the blowing pressure is carried out, starting below the oscillation threshold. Hence, a static regime is identified during the first 15s of the signal. During the time interval t = [20, 35](s), many non-harmonic frequency components appear on the spectrogram, leading to a classification as a quasi-periodic regime. The rest of the time, a periodic regime is detected and identified as the second register of the instrument (playing frequency 460 Hz), which is correct since the lowest resonance frequency of the saxophone is located around 230 Hz (see Figure 4). However, due to the choice of time step in the spectrogram, errors may occur during transitions between regimes. Indeed, as seen in Figure 5 around t = 35s, register 1 is detected on a few consecutive frames. Inspection by eye of the spectrogram reveals that this is a limitation of the algorithm. However this does not hinder the global reading of the output of the algorithm, i.e., the various regimes produced by the instrument.

IV. Experimental results

A. Nature of the oscillating regimes

In order to illustrate the various types of oscillation regimes studied below, two examples of periodic and quasi-periodic signals recorded inside the mouthpiece of the saxophone are presented here. Both of these signals correspond to notes played by the artificial mouth with a constant blowing pressure.

Figure 6(a) displays a periodic pressure signal. Inspecting the waveform reveals the classical Helmholtz motion for saxophones [START_REF] Dalmont | Reed instruments, from small to large amplitude periodic oscillations and the helmholtz motion analogy[END_REF] , while the spectrum confirms the periodicity of the regime with a playing frequency f 1 = 231 Hz (see Figure 6(b)).

Figure 7(a) displays a quasi-periodic regime. The time interval of the figure is large which highlights a -40 low frequency modulation (around f M = 6.8 Hz) of the signal. The corresponding spectrum is shown in Figure 7(b). The envelope modulation in the time domain corresponds to the many spectral components whose frequencies are linear combinations of two inharmonically related frequencies f 1 and f 2 . Indeed the f of each peak in Figure 7(b) can be written as f = nf 1 + mf 2 , where m, n ∈ Z. Two consecutive peaks are always separated by the same frequency f M = 2f 1f 2 . It is worth noting that f 1 is close to the lowest resonance frequency of the saxophone for the G' fingering (see Figure 4). The second frequency f 2 is not directly linked to the second resonance frequency of the saxophone, and is such that the ratio f 2 /f 1 is not an integer.

f1 = 227Hz f2 = 447.2Hz 5f2 -8f1 9f1 -4f2 7f1 -3f2 5f1 -2f2 3f1 -f2 f2 -f1 2f2 -3f1 4f2 -7f1 3f2 -5f1 5f2 -9f1 6f2 -11f1 4f2 -6f1 3f2 -4f1 4f1 -f2 8f1 -3f2 6f1 -2f2 2f2 -2f1 2f1 f2 + f1 3f1 2f2 -f1 5f2 -7f1 4f2 -5f1 3f2 -3f1 5f1 -f2 7f1 -2f2 (b) (a)

B. Maps of the oscillation regimes in the control parameters space

In this section, maps of oscillating regimes (in the control parameter plane (ζ, γ)) are obtained for different inharmonicity values of the instrument. As it has been previously shown [START_REF] Almeida | The clarinet : How blowing pressure, lip force, lip position and reed "hardness" affect pitch, sound level, and spectrum[END_REF] , setting up maps according to various control parameters has the advantage of easing the reading of experimental data. In this study, the measurement of the nonlinear characteristics allows to estimate dimensionless control parameters. This facilitates a better understanding of the range of the control parameters imposed during experimentations.

With the available experimental device, both ζ and L p have to be varied manually (see section ). On the other hand, the blowing pressure and its variation through time are precisely controlled through a PID loop [START_REF] Ferrand | High-precision regulation of a pressure controlled artificial mouth : The case of recorder-like musical instruments[END_REF] . Therefore, to save time and keep a reasonable number of recordings, experiments are carried out with linearly varying blowing pressure : increasing and decreasing ramps, 60s each. These ramps always begin below the oscillation threshold (γ 0.25) and last until the oscillation regime is not willing to change again (γ 0.5). Each time the setting of the artificial mouth is modified, parameters ζ and P M are estimated through the measurement of the NLC (see section ).

Since measurements are carried out with pressure ramps, thresholds at which the various regimes emerge are different when the ramp is increasing or decreasing. This hysteresis is clearly visible in Figure 8 where an example is displayed, for a given setting of the artificial mouth (∆f /f = 110% and ζ = 0.31). However, since the speed of variation of the blowing pressure is low enough (±25Pa/s), the same evolution of oscillation regimes is produced. Since the precise estimation of the bifurcation thresholds is not of interest in this study and for sake of readability, only the analysis corresponding to increasing ramps will be shown below.

Figure 9 displays different maps in the (ζ, γ) space obtained for various inharmonicities. A periodic regime based on the n th register of the instrument is noted Rn, while QP stands for a quasi-periodic regime. Each oscillation regime is tagged with its own color. Each horizontal line corresponds to the output of the identification algorithm (see Part. ). The static (non-oscillating) regime is not plotted for readability. It is worth noting that results lie on a restricted area of the map, since outside this area, no regime change has been observed.

These maps highlight the influence of inharmonicity with respect to the control parameters (ζ and γ). Recall that, the blowing parameter γ is directly linked with the breath pressure. The embouchure parameter ζ is related to the maximum flow through the reed channel. It mainly depends on the geometry of the mouthpiece, the reed mechanical properties, as well as the player's lip force and position on the reed that control the opening. A "tight embouchure" can be viewed as a low value of ζ and a "relaxed embouchure" can be viewed as a high value of ζ. The main conclusions of the analysis of these pictures are gathered below :

• By adjusting the control parameters, periodic oscillation regimes corresponding to the three lowest registers of the instrument are playable, except for an inharmonicity of 105% for which only R1 and R2 are played ;

• Inharmonicity appears to be a key parameter for the production of quasi-periodic regimes. Indeed, above a threshold of inharmonicity (estimated around ∆f /f = 106%), playing quasi-periodic regimes becomes possible ;

• The larger the inharmonicity, the wider the area of quasi-periodicity in the (ζ, γ) plane ;

• In the control parameters space, quasi-periodic regimes occur at the boundary between the different periodic registers ;

• The emergence of R3 or QP when inharmonicity increases comes at the expense of the playability of R1. Indeed, playability of R2 is nearly not altered by the increase of inharmonicity. This is not surprising since pushing/pulling the piston has only an influence on the first resonance frequency ;

• From a quasi-periodic regime, it is possible to get the third (periodic) register by simply modifying the blowing pressure ;

• A jump from the first register to the second requires a greater lip pressure, which corresponds to measurement on real players [START_REF] Ph | An instrumented saxophone mouthpiece and its use to understand how an experienced musician plays[END_REF] .

C. Other ways of triggering quasi-periodicity

Maps presented so far demonstrate that the emergence of quasi-periodic regimes depends on the level of inharmonicity, but also on the values of the control parameters (ζ, γ). It is then interesting to investigate how quasi-periodicity emerges, for instance in the (γ, ∆f /f ) plane, for a given value of ζ. This is done in Figure 10 with ζ = 0.37. This map can be seen as an horizontal slice (at height ζ = 0.37) of a continuum of maps similar to those of Figure 9. The only parameter varying through time is still the blowing pressure γ. It is worth noting that for this experiment, quasi-periodicity occurs for an inharmonicity above ∆f /f = 106% (see Figure 10), as expected when considering Figure 9. Again, when playing crescendo through an increase of the blowing pressure, crossing through a quasi-periodic regime is required to play the third periodic register.

It is also interesting to investigate how quasiperiodicity is triggered when inharmonicity is being varied along time. The experimental device does not allow a computer control of inharmonicicy (see Section ). Thus, the piston is pushed/pulled by hand, and this is done as gently and regularly as possible. Figure 11 displays the spectrogram of the pressure signal when the variation of inharmonicity triggers the bifurcation of the periodic regime towards a quasi-periodic regime (γ = 0.35 and ζ = 0.33 in that experiment). The quasi-periodicity threshold (i.e., the bifurcation) is estimated at ∆f /f = 107%. Before the bifurcation, the inharmonicity increase (through the decrease of the lowest resonance frequency, see Figure 4) causes a decrease in the playing frequency of the first periodic regime R1. This corresponds to mode locking with the first mode [START_REF] Nederveen | Mode locking effects on the playing frequency for fork fingerings on the clarinet[END_REF] . Beyond the bifurcation, the inharmonicity increase causes a rise of the modulation frequency f M , which can be seen in the frequency domain as the increase of the gap between the spectral components of frequencies ±nf 1 ±mf 2 .

In a similar way, quasi-periodicity can also be triggered when the embouchure parameter ζ varies. For this purpose, the water-filled syringe which allows to modify this parameter is pushed/pulled as gently and regularly as possible. Two measurements of the NLC are carried out, at the beginning and at the end of the variation of the syringe position. This allows defining the range of ζ to be explored.

As shown in Figure 12, decreasing ζ allows to undergo a first bifurcation from the first periodic register R1 to a quasi-periodic regime QP, and then a second bifurcation from the quasi-periodic regime to the second periodic register R2. The inverse sequence of bifurcations is observed when ζ decreases. It is also obvious from Figure 12 that the modification of the embouchure parameter ζ allows increasing or decreasing the modulation frequency f M .

D. Practical musical illustrations

The previous results have been obtained for the G' fingering, which is imposed by the additional piston (the position of which on the neck of the saxophone is calculated according to the input impedance of this fingering). However, in order to enlarge the scope of the study, other fingerings are considered in this section. The piston is not used anymore and the inharmonicity is fixed by the instrument and estimated according to the measurement of its input impedance.

A first example is based on the low C fingering (noted C), where nearly all lateral holes are closed. In this case, the inharmonicity of the instrument is ∆f /f = 103% (deduced from the input impedance measurement, the modulus of which is displayed in Figure 13).

For this fingering, Figure 14 displays three pressure signals measured inside the mouthpiece for different values of the embouchure parameter ζ (the blowing pressure is fixed). Figures 14(a These measurements highlight the influence of the peaks amplitude on the oscillation regimes selection. The second register is obtained for all ζ < 0.74 rather than ζ < 0.33 for the G' fingering (when inharmonicity is at the lowest : see Fig. 9(a), and where the amplitude of the second peak is lower than the amplitude of the first : see Fig. 4). Also, quasi-periodic regimes can be produced even for low inharmonicity (∆f /f = 103%). Compared to the quasi-periodicity threshold for the G' fingering (∆f /f = 106%), the amplitude rise of the second resonance mode (see Fig. 13) appears to favor the emergence of quasi-periodicity.

A second example is based on the use of a fork fingering. This consists in playing a low C with one key hole open (right hand forefinger). This particular fingering is often used to play multiphonics. Figure 15 displays the corresponding modulus of the input impedance. It appears that an intermediate, low-amplitude peak, emerges between the main two lowest peaks. This is commonly observed for fork fingerings [START_REF] Nederveen | Mode locking effects on the playing frequency for fork fingerings on the clarinet[END_REF] . Inharmonicity is estimated according to the frequency of the two main peaks and reaches ∆f /f = 115%.

The map of the oscillation regimes with respect to the control parameters (ζ, γ) is presented in Figure 16. It is worth noting that the range of the parameter ζ is as wide as possible experimentally. This map highlights that playing quasi-periodic sounds is possible on a wide range of the ζ parameter. For this fingering, the inharmonicity is high enough to ease the emergence of quasi-periodic regimes. However the location of these regimes regarding the blowing pressure γ varies significantly with the value of ζ.

On the one hand, for ζ > 0.7, the map shows that quasi-periodic oscillations are often produced between periodic registers 1 and 2 when blowing harder. This is similar to what has been seen above. On the other hand, for ζ < 0.7, describing the map is more complicated. This shows that the fork fingering makes it very difficult to produce oscillation regimes stable on a wide range of control parameters. This is all the more obvious when compared to a regular fingering, as seen in Figure 9(a). This is likely why beginners experience difficulties in selecting a particular regime when playing unconventional fingerings.

V. Discussion and conclusion

Results presented above confirm the observation of the article 10 : inharmonicity is a necessary condition in the production of quasi-periodic regimes with saxophones. However it is not a sufficient condition since the two control parameters which were tested, proved to have a significant influence on the triggering of quasi-periodicity. Complementing what has been stated in article [START_REF] Dalmont | Some aspects of tuning and clean intonation in reed instruments[END_REF] , the control parameters also influence the beating frequency of quasi-periodic oscillations. Indeed, as shown in the figures 11 and 12, the change of control parameters can strongly modify the modulation frequency f M (even if the inharmonicity is constant).

The trends highlighted experimentally in this article are in agreement with the numerical results obtained in a previous work [START_REF] Doc | A minimal model of a single-reed instrument producing quasi-periodic sounds[END_REF] . This numerical study was based on the use of a minimal model of wind instruments, so it is possible to deduce that features neglected in this model are not determining in the production of quasi-periodic regimes (inertia and damping of the reed, resonance modes higher than the third one).

Compared to articles 10;11 , experiments presented in this article highlight other trends in the oscillation regimes production. When inharmonicity is high enough, the production of higher register (unplayable otherwise) is favoured. Also by testing several fingerings, the amplitude of resonance modes appears to be a determining factor in playability of registers. All trends presented in this article are qualitative. This was intended to globally describe how the instrument can produce different oscillation regimes. Many experimental parameters can alter the bifurcation thresholds of the various registers (speed variation of the supply pressure, reed force, composition of artificial reeds, use of vocal-tract support, etc.). Therefore, an interesting work would consist in extending this experimental study in order to obtain more quantitative results. This would allow to study the influence of the control parameters on the bifurcation thresholds of reed instruments.

Fig. 1 -

 1 Fig. 1 -Experimental device (top view).

  (a)). The static pressure inside the artificial mouth as well as the pressure inside the mouthpiece are measured with Endevco pressure sensors (8507C-5 model). A Burkert flowmeter (model 8701) is used to measure the air volume entering the instrument. A National Instrument acquisition module (NI9215 model) digitizes the experimental signals with a sampling frequency of 44kHz, further recorded on a computer.

Fig. 2 -

 2 Fig. 2 -(a) Sketch of the artificial mouth and (b) schematic of the modified saxophone neck. A piston is plugged at 165 mm from the input of the neck. The inner diameter of the piston is 12 mm.

Fig. 3 -

 3 Fig. 3 -(Color online) Measurement of the nonlinear characteristics (NLC) on an alto saxophone (G' fingering) for a given setting of the artificial mouth (ζ 0.45 and P M = 7350 Pa) and comparison with the fitted model. (Eq. (1)).

Fig. 4 -

 4 Fig. 4 -(Color online) Modulus of the dimensionless input impedance of the alto saxophone (G' fingering) for two lengths L p .

Fig. 5 -

 5 Fig. 5 -(Color online) Top : spectrogram of a pressure signal recorded in the mouthpiece for a linearly increasing blowing pressure. Estimated instantaneous frequencies are plotted in dashed lines. Bottom : oscillating regimes labeled using the algorithm developed based on the instantaneous frequencies.

Fig. 6 -

 6 Fig. 6 -(a) Periodic signal in the time domain and spectrum of the mouthpiece pressure (G' fingering, γ = 0.45, ζ = 0.55 and ∆f /f = 103%).

Fig. 7 -

 7 Fig. 7 -(a) Quasi-periodic signal in the time domain and (b) spectrum of the mouthpiece pressure (G' fingering, γ = 0.41, ζ = 0.59 and ∆f /f = 110%).

Fig. 8 -

 8 Fig. 8 -(Color online) Example of identification of the oscillating regimes for a given setting of the experimental device (G' fingering, ∆f /f = 110%, ζ = 0.31). Linearly increasing (continuous line) and decreasing (dashed line) blowing pressure.

Fig. 9 -

 9 Fig. 9 -(Color online) Maps of oscillating regimes in the (γ, ζ) plane for different values of inharmonicity (G' fingering). (a) ∆f /f = 105%, (b) ∆f /f = 106%, (c) ∆f /f = 108% and (d) ∆f /f = 110%. A periodic regime based on the n th register of the instrument is noted Rn, while QP stands for a quasi-periodic regime. Each oscillation regime is represented by a particular color. Each horizontal line corresponds to the output of the identification algorithm.

Fig. 10 -Fig. 11 -Fig. 12 -

 101112 Fig. 10 -(Color online) Map of oscillating regimes in the (γ, ∆f /f ) plane corresponding to the setting ζ = 0.37 (G' fingering). A periodic regime based on the n th register of the instrument is noted Rn, while QP stands for a quasi-periodic regime.

  ) and14(b) show periodic signals corresponding to the first and second register of the instrument respectively.

  Figure 14(c) displays a quasi-periodic signal obtained for another value of the embouchure parameter (ζ = 0.76).

Fig. 13 -

 13 Fig. 13 -Modulus of the dimensionless input impedance of an alto saxophone (low C fingering, ∆f /f = 103%).

1 (Fig. 14 -

 114 Fig. 14 -Mouthpiece pressure signals for different values of the embouchure parameter ζ (low C fingering, γ = 0.42).

Fig. 15 -Fig. 16 -

 1516 Fig. 15 -Modulus of the dimensionless input impedance of an alto saxophone (fork fingering, ∆f /f = 115%).

Acknowledgements

The authors wish to thank Joël Gilbert for his precious advice as well as for the loan of the crook used for the experiments carried out in this article. Also, the authors wish to acknowledge Jean Kergomard for his valuable advice during the preparation of this manuscript. This work has been done in the framework of Labex MEX (ANR-10-LABX-0092) and of the project A*MIDEX (ANR-11-IDEX-0001-02), funded by the French National Research Agency (ANR).


Thierno Tounkara
email: thierno.tounkara@telecom-em.eu

Pierre-Emmanuel Arduin
email: pierre-emmanuel.arduin@dauphine.fr

Contextualizing Knowledge Sharing Strategy: The Case of an International Organization in the area of Development assistance

Keywords: knowledge sharing, knowledge management, information system, organizational culture, strategic alignment

This paper proposes an operational evaluation grid which helps Organizations to determine the perception employees have about the degree of alignment between their Information System (IS) supporting knowledge sharing and different organizational culture contexts. Relying on this perception, Organizations can: (1) analyze barriers to a successful use of information system functionalities for greater efficiency of knowledge sharing and (2) identify appropriate IS functionalities they should invest on to increase the dynamic of knowledge sharing. A case study illustrates the use of our evaluation grid and the implications of this work are finally discussed at the end of this paper.

Introduction

Information systems play an important role in the implementation of knowledge sharing strategies. They act as knowledge flow facilitators and can be used to encourage knowledge sharing which is an important challenge for organizations [START_REF] Liebowitz | Knowledge Retention: Strategies and Solutions[END_REF]. From an Information System perspective, knowledge sharing strategy can be seen as the choice of a set of specific information system functionalities (and associated organizational rules) in order to support knowledge sharing activities.

Successful use of information system functionalities to support knowledge sharing is not only influenced by technical factors, but also by "less rational but highly influential" factors as cultural and organizational contexts [START_REF] Dulipovici | Strategic Alignment and Misalignment of Knowledge Management Systems: A Social Representation Perspective[END_REF][START_REF] Wiewiora | Organizational culture and willingness to share knowledge: A competing values perspective in Australian context[END_REF][START_REF] Leonardi | Knowledge management technology as a stage for strategic self-presentation: Implications for knowledge sharing in organizations[END_REF][START_REF] Alavi | An Empirical Examination of the Influence of Organizational Culture on Knowledge Management Practices[END_REF]. Various studies suggest that cultural and organizational contexts (organizational culture) shape employees' knowledge sharing behaviors and the way they consider information systems to support knowledge sharing [START_REF] Alavi | An Empirical Examination of the Influence of Organizational Culture on Knowledge Management Practices[END_REF][START_REF] Gray | Towards an integrative model of organizational culture and knowledge management[END_REF][START_REF] De Long | Diagnosing cultural barriers to knowledge management[END_REF]. However, few studies have attempted to investigate how cultural and organizational contexts might be associated with the technological choices to support knowledge sharing.

Relying on the "Competing Value Framework" described in §2.2., we propose in this paper an evaluation grid to assess the degree of alignment between Information System (IS) to support knowledge sharing and four organizational culture types. This grid helps identify which one of these four alternatives dominates the present Organization and then helps analyze barriers to a successful use of information system functionalities for greater efficiency of knowledge sharing.

The content of the paper is organized as follows: first, in section 2, we introduce the concept of knowledge and knowledge sharing in the Organization, as we consider it in this research. Then, we explain the reason of the proposed assessment grid and the bases on which it relies. In section 3, a classification of functionalities that may be offered by an information system in order to support knowledge sharing is proposed. Our evaluation grid is then presented as well as the assessment approach. Last, in section 4, we present a case study that illustrates the use of the proposed grid. Discussions and lessons learned from the application of our grid are then described. Finally, our conclusions are presented in section 5.

Literature review

The way we consider knowledge and knowledge sharing in the organization in this work is introduced in the first part of this section. Then, the theoretical bases of the assessment grid proposed are presented in the second part of this section.

Knowledge and knowledge sharing in the organization

In this article, we consider two types of knowledge: explicited, it can be made explicit, it is socially constructed, and it can be supported by information technologies. Individuals, as well as computers are "information processing systems" as said by Hornung (2009) (p. 9). Knowledge sharing strategies focusing on explicited knowledge attempt to increase organizational efficiencies by codifying and reusing knowledge mainly through advanced Information Technologies (Choi and al.2008). tacit, it is not always articulated and cannot always be articulated, relying on [START_REF] Polanyi | Personal Knowledge: Towards a Post Critical Philosophy[END_REF] notably: "we can know more than we can tell". Tacit-oriented knowledge sharing strategies focus on the personalization approach where knowledge is communicated through direct person-to-person contact and through socialization processes (Choi and al.2008).

As highlighted by [START_REF] Davenport | Working Knowledge: How Organizations Manage What They Know[END_REF], knowledge is shared when (1) information is transmitted, (2) information is absorbed, i.e. interpreted into tacit knowledge through an individual cognitive process, and (3) when this piece of tacit knowledge is used, knowledge being linked to the action. For [START_REF] Davenport | Working Knowledge: How Organizations Manage What They Know[END_REF]: "Transfer = Transmission + Absorption (and Use)" (p. 101). Knowledge sharing can then be defined as a process of knowledge transfer, through which an organization maintain complex and ambiguous knowledge and the associated routines (Szulanski 1998).

The "Competing Value Framework" to assess alignment between Information System to support knowledge sharing and Organizational Culture

Formal organizational context (structure and systems, sources of coordination and expertise) and cultural attributes of the organization affect efficiency of knowledge sharing [START_REF] Burgelman | A process model of internal corporate venturing in the diversified major firm[END_REF], Ghoshal and Barlett 1994[START_REF] Wiewiora | Organizational culture and willingness to share knowledge: A competing values perspective in Australian context[END_REF]). [START_REF] Gibson | The antecedents, consequences, and mediating role of organizational ambidexterity[END_REF] referred cultural and organizational contexts (Organizational culture) to the systems, processes, values and beliefs which collectively shape individual-level behaviors in any organization.

Various studies provide evidence to suggest that they are factors influencing knowledge sharing behaviors supported by information systems by shaping patterns and qualities of interactions needed to leverage knowledge among individuals (De long and Fahey 2000, [START_REF] Alavi | An Empirical Examination of the Influence of Organizational Culture on Knowledge Management Practices[END_REF]al. 2006, Gray and[START_REF] Gray | Towards an integrative model of organizational culture and knowledge management[END_REF].

In this article, we explore the choice of appropriate Information System (IS) functionalities in order to support knowledge sharing (these functionalities are an expression of the knowledge sharing strategy of the Organization). We also study how this choice may be influenced by organizational culture, introducing then alignment of IS to support knowledge sharing strategy with organizational culture.

There are many theoretical and methodological frameworks which have been proposed to analyze cultural and organizational contexts [START_REF] Hofstede | Culture's consequences: International differences in work-related values[END_REF][START_REF] Schein | Organizational culture[END_REF][START_REF] Denison | Organizational culture and organizational development: a competing values approach[END_REF][START_REF] Cameron | Diagnosing and Changing Organisational Culture : Based on the Competing Values framework[END_REF].

In our research, we make the choice to use the "Competing Value Framework" (CVF) developed by [START_REF] Cameron | Diagnosing and Changing Organisational Culture : Based on the Competing Values framework[END_REF]. The CVF has been validated in both international and Australian contexts [START_REF] Lamond | The value of Quinn's competing values model in an Australian context[END_REF]. With this framework, Cultural and organizational contexts are assessed relying on two dimensions: internal versus external and stability versus flexibility. These dimensions lead to four cultural and organizational contexts types: Hierarchy, Clan, Adhocracy and Market. In the following, we assimilate "context" to "cultural and organizational context".

It is important to underline that organizations are seldom characterized by a single context type but they tend to develop a dominant context over time in order to adapt themselves to environment changes [START_REF] Cameron | Diagnosing and Changing Organisational Culture : Based on the Competing Values framework[END_REF].

Hierarchy contexts are characterized by an internal orientation (inside the firm) and predictability. Here, the focus is on information management, documentation, expertise, formalization, stability, routines, centralization, continuity and control. Individuals are bounded through internal controls and they are governed by procedures. Principals of stability, formal rules are perceived as the cement of the organization.

In these contexts, there is a strong motivation for individuals to use functionalities for explicited knowledge storage because codification initiatives are encouraged and recognized. Formal communication and expert location functionalities are prioritized because recognition of expertise incites individuals to connect themselves with others and share their knowledge in order to increase their own social capital and then be attractive for assignments in need of their expertise [START_REF] Alavi | An Empirical Examination of the Influence of Organizational Culture on Knowledge Management Practices[END_REF]al. 2006, Rodriguez-Elias 2008).

Clan contexts give importance to the development of a shared understanding and human relationships unless of relying exclusively on formal communication processes. These contexts are characterized by a flexible structure and an internal orientation. Individuals are tied by core values as participation, loyalty and engagement.

Individuals give more importance to communication and collaboration functionalities delivered by the information system to support knowledge sharing.

Adhocracy contexts share the same human values than clan contexts. They emphasize flexibility and external competitive position. Adhocracy contexts give importance to values as innovation, creativity, adaptability and acquisition of external resources. There are values which encourage local initiatives and make possible the emergence of formal and informal communities in the organization.

In adhocracy contexts, the IS is viewed as a vehicle which accelerates innovation via cross-pollination of ideas across communities [START_REF] Alavi | An Empirical Examination of the Influence of Organizational Culture on Knowledge Management Practices[END_REF]) and exploitation of knowledge from the external environment [START_REF] De Long | Diagnosing cultural barriers to knowledge management[END_REF]. Here, it seems relevant to give more importance to environment scanning (from formal and informal sources), storage (of information scanned from sources), communication and collaboration functionalities in the IS supporting knowledge sharing.

Market contexts are characterized by an external orientation (towards the market) and predictability. They emphasize on values such as competitiveness, productivity, goals clarity and efficiency. Individuals are bounded together through goal orientation and competition. Here, there is a tension between values: some of them incite to stability and predictability (controls, clear objectives) and others orient individuals towards an innovation attitude with a market orientation.

It is a state which can lead to divergent use of IS functionalities to support knowledge sharing. Some groups can focus on functionalities supporting knowledge accumulation (codification and storage functionalities) because they are guided by productivity and competition goals. Other groups can give more importance to socialization functionalities (communication, collaboration, and networking) in order to increase their innovation capacity. The Competing Value Framework can help in the design of information systems to support knowledge sharing with features and functionalities fitting to the cultural and organization contexts they are to be embedded in [START_REF] Tounkara | Aligning knowledge sharing strategy with organizational culture[END_REF].

Propositions

The functionalities that may be offered by an information system in order to support knowledge sharing can be grouped into four complementary dimensions. These dimensions are studied in the first part of this section. Our evaluation grid is then presented as well as the assessment approach in the second part of this section.

Classification of Information System functionalities to support knowledge sharing

Many models to support knowledge sharing activities have been proposed [START_REF] Nonaka | The Knowledge-Creating Company: How Japanese Companies Create the Dynamics of Innovation[END_REF], Szulanski 1998[START_REF] Wiig | Knowledge management foundations[END_REF][START_REF] Zack | Managing codified knowledge[END_REF][START_REF] Mcelroy | The knowledge life cycle[END_REF][START_REF] Dalkir | Knowledge Management in Theory and Practice[END_REF][START_REF] Harrison | Knowledge Transfer within Organizations: A Social Network Perspective[END_REF]. Rodriguez-Elias and al. ( 2008) have made a relevant synthesis of knowledge management (KM) main activities involved in knowledge sharing with the two perspectives of tacit and explicited knowledge:

Identification refers to the location of internal and/or external (from the environment) crucial knowledge and knowledge sources. Here, technologies can be useful identify formal sources but also informal sources as experts and communities for example.

Codification deals with formalization of knowledge identified as crucial. It can be difficult for some employees to know how to express their ideas. That is why it is convenient to identify information system functionalities that may facilitate codification of knowledge when possible (Rodriguez-Elias and al. 2008).

Storage activity allows storing and updating explicited knowledge in knowledge repositories. This often requires much work from users to input their explicited knowledge and can lead to the situation where information system (IS) storage functionalities are unused. Providing automatic support at certain stages could reduce users' work.

Diffusion refers to the dissemination, deployment of information source of knowledge. Diffusion of explicited knowledge may be enabled with mechanisms which allow providing information about explicited knowledge that have been stored (search engines, information retrieval systems, etc.). On the other hand, tacit knowledge diffusion can take place in socialization processes, and can be therefore supported by communication and collaboration technologies.

Acquisition activity facilitates for individuals contextualization and interpretation of knowledge (tacit or explicited) to perform an activity, make a decision, etc. However, providing technologies to assist users in this activity can be a challenging job [START_REF] Marwick | Knowledge management technology[END_REF]).

Implementing information system functionalities in order to support knowledge sharing is important but not enough to stimulate their use by individuals in the firm [START_REF] Dulipovici | Strategic Alignment and Misalignment of Knowledge Management Systems: A Social Representation Perspective[END_REF]. Our literature review as much as our industrial fieldworks highlight the fact that cultural and organizational contexts can be successful factors (or barriers) in the use of functionalities designed in order to support knowledge sharing.

Evaluation grid

Relying on the Competing Value Framework described in §2.2., we propose an evaluation grid which focuses on four alternatives that corresponds to four views of alignment between Information System to support knowledge sharing and four organizational culture types, according to the present organization:

IS support for diffusion and acquisition

Respondents have to rate each of these five dimensions by dividing 10 points between the four alternatives (A, B, C and D) depending on how similar the description is to their organization (see appendix 1).

Dominant characteristics of IS to support knowledge sharing

This dimension brings a global view on the degree of investment on IS codification and storage functionalities, the way knowledge repositories are managed, the type of knowledge diffused through IS, the type of IS communication and collaboration functionalities prioritized and the way they are delivered to individuals (formal/informal, personal/impersonal).

IS support for Identification of knowledge sources

Does the IS offers functionalities to locate internal and or external sources of information/knowledge (it can be formal sources as knowledge repositories but also informal sources as experts and communities)?

IS support for Codification

Is there an important investment on IS functionalities to facilitate codification of knowledge when possible? As examples, we can cite: content management functions, Knowledge elicitation assistance to formalize concepts, tasks, best practices, experiences, etc.

Are individuals strongly encouraged to use IS codification functionalities? Are knowledge codification contribution through IS recognized?

Management of knowledge repositories (storage)

Does the Organization make an important investment on knowledge repositories and functionalities as Information retrieval, Indexation and classification/categorization of explicited knowledge? Do they manage their knowledge repositories in centralized or distributed form? Are there many formal rules for the storage of knowledge contributions?

IS support for knowledge diffusion and acquisition

Does the Organization focus on the diffusion of explicit knowledge, tacit knowledge or both? What type of IS communication and collaboration functionalities are prioritized: formal (as intranets and portals) or informal (informal communities via online chat, online meetings, discussion forums, etc.)? Does the Organization prioritize impersonal channel (knowledge repositories, intranets, portals), personal channel (information push based on individuals interests/profile, online communities, team rooms, etc.) or both?

Case study

The Organization under study is an international actor in the area of development assistance and capacity development. Its role is to help to achieve the eradication of poverty and the reduction of inequalities and exclusion by helping countries to develop policies, leadership skills, partnering abilities, institutional capabilities. This organization works in more than 150 countries.

Its organizational chart is subdivided into three levels:

-Global level with executive offices, Human resources office and Audit office -Regional level with regional bureaus (Africa, Asia and Pacific, Arab States, Europe, Latin America and the Caribbean)

-Local level where are located country offices of each regional bureau Knowledge management (KM) activities are streamlined to coordinate work at the global, regional and local levels and capture the knowledge generated by the country offices. Here, KM activities are important for development work, either directly through externally oriented evidence collection, analysis, knowledge capture, generation and sharing or indirectly by improving organizational effectiveness and efficiency and fostering a culture of learning and sharing.

Data collection

First, a trial survey was conducted using printed questionnaires to assess if the enquiry process and answering could be easily understood and complied with. The respondents confirmed that the questions were easily understandable and the document was easy to fulfill.

Second, the questionnaire was made available to 170 employees at the three organizational levels (Global, regional and local) through a web-based version. They had a two-week survey period to enter their responses and make their comments. An extract of the questionnaire is presented in Appendix 1.

Results and comments

Among the 170 employees targeted, 125 (73%) members have started to complete the questionnaire and 103 (60%) have completed it fully (Table 1). The mean scores collected from the questionnaires are summarized in Table 2. Scores for each dimension are visualized through radar diagrams (Figures 23456) to make interpretations easier. Comments added by respondents (in the questionnaire) help us justify their preferences and also describe the change than can be operated to fit with what they thought was needed.

Figure 2 gives information about the contrast between the global current profile of "IS alignment with organizational culture" and the respondents 'preferred profile.

Figures 3-6 bring more details and precisions about this contrast for others IS dimensions. They highlight two level of strong preference:

-A preference for an "IS alignment with Adhocracy culture" to support expertise identification and knowledge diffusion and acquisition -A preference for an "IS alignment with Market culture" to support knowledge capture, codification and storage

Integrating knowledge networking and knowledge codification functionalities

Figure 2 reproduces the current and global profile of "IS alignment with organizational culture" to support knowledge transfer in contrast with the respondents 'preferred profile for the future. This shows a clear preference to evolve from an "IS alignment with Clan culture" to an "IS co-alignment with Adhocracy and Market cultures" to support knowledge sharing.

Respondents The organization knowledge sharing strategy is people-centered rather than document-centered, with processes and technology being supportive functions. It is an Organization very advanced in the area of "formal networking" and less in the area of "capturing knowledge" with a codification approach. Its use of online communities of practice is recognized as an effective means of sharing.

For respondents, the system of capturing and transferring experiential and organizational knowledge needs to be stronger. New formal processes and IT support to capture tacit knowledge and make it available need to be introduced.

IS to support knowledge sharing can be strengthen with a control approach allowing a regular monitoring of sharing effectiveness. This can be done by building measurable indicators and reporting on how lessons learned and best practices are used to improve organizational activities.

Towards Expertise rosters

Figure 3 shows a preference for an "IS alignment with adhocracy culture" to support identification of knowledge sources. A supportive function for expertise identification (an open wide expertise Roster) can provide universal access for business units to pool of expertise, allow the organization to draw from a pool of qualified practitioners and experts at any time, mobilize staff members to be available for ad-hoc initiatives and virtual projects.

Lessons Learned Database

Figures 4-5 show a preference for an "IS alignment with Market culture" to support knowledge capture, codification and storage. Respondents have given lowest scores for the dimension "IS Support for codification". Knowledge codification takes place under formal, lengthy reports and guidance notes for which the impact is unknown. It is not define a project cycle and IT support to capture lessons and with an aim of reuse, not simply project reporting and closure.

For respondents, the organization must put systems (including but not limited to a searchable lessons learned repository) in place and link them to each other to ensure that throughout their lifecycle, projects will systematically capture, codify and disseminate experiences and lessons to inject them back into project processes. Moreover, indexation, information retrieval and other content management functions to store/classify (in database) and access to these lessons learned must be implemented.

Enhancing knowledge networking and knowledge acquisition capacity

Figure 6 shows a preference for an "IS alignment with adhocracy culture" to support knowledge diffusion and acquisition.

Figure 6: IS support for Diffusion and Acquisition

With Communities of Practices (COPs) and teamworks, the Organization has created a very advanced corporate peer-to-peer platform, connecting practitioners across regions, flattening hierarchies and increasing exchange among employees.

For respondents, the Organization must create further opportunities with public dialogue and crowd-sourcing. IS must support sharing initiatives between the Organization and the public by providing "Online Dialogues" functions and mechanisms for rigorous public feedback to iterate and replicate initiatives that find traction in the marketplace of the international development community.

Teamworks and Communities of Practices can be solidified for consistent knowledge networking by integrating them with various internal and external business knowledge sharing applications that can be built (online consultations, lessons learned databases, expertise location, training facilitation, etc.), the existing central repository of the knowledge products, the intranet, the public website Respondents suggest also that the organization should strengthen its statistical analysis and social network analysis capacities for business intelligence and data-driven decision making, enhancing then its knowledge acquisition and creation capacity.

supporting knowledge sharing with different Organizational culture contexts. Relying on this perception, Organizations can: (1) analyze barriers to a successful use of information system functionalities for greater efficiency of knowledge sharing and (2) identify appropriate IS functionalities they should invest on to increase the dynamic of knowledge sharing.

The case study we have performed in an international Organization in the area of development assistance and capacity development has validated the applicability of the evaluation grid and its utility to make evolve IS functionalities for more efficiency of knowledge sharing.

In this case, the current Information System to support knowledge sharing is perceived by employees as being strongly aligned with a Clan culture. The questionnaire helps identify a clear preference for employees to evolve from an "IS alignment with Clan culture" to an "IS co-alignment with Adhocracy and Market cultures" to support knowledge sharing.

The evaluation grid does not say if changes should be made but only dresses a picture of perceptions and preferences of employees about IS alignment with organizational culture. For changes, larger and deeper analysis must be done to see: whether there is a shared perception of need for change; whether the climate is supportive or not (i.e., encouraging open debate and trust); and whether or not powerful subcultures and countercultures exist.

Figure 1 :

 1 Figure 1: Aligning cultural and organizational contexts with information system to support knowledge sharing

  IS use If many informal communities: Weak use of formal communication/collaboration systems and procedures (as intranets, portals) IS Functionalities to promote -Codification -Storage -Formal Communication Possible barriers for IS use -Heaviness of formal rules for the storage -Managing knowledge repositories in a centralized form (when the context is distributed) IS Functionalities to promote -Environment scanning -Storage -Communication and collaboration Possible barriers for IS use -Imposing specific communication and collaboration tools -Managing knowledge repositories in a centralized form Internal Orientation External Orientation Possible barriers for IS use -Divergent use of IS functionalities: IS must be designed with strong features supporting as well knowledge accumulation (codification and storage) as socialization processes (communication, collaboration, networking) IS Functionalities to promote -Codification and storage -Communication, collaboration, networking

A

  -IS alignment with Hierarchy culture B-IS alignment with Market culture C-IS alignment with Clan culture D-IS alignment with Adhocracy culture This grid helps identify which one of these four alternatives dominates the present organizational IS culture. We use it also to measure what employees would like to see in the Organization, measuring then the desire for change. To assess alignment of IS functionalities supporting knowledge sharing with organizational culture, we consider five dimensions: Dominant characteristics of IS to support knowledge sharing IS support for Identification of knowledge sources IS support for Codification Management of knowledge repositories (IS support for storage)

Figure 2 :

 2 Figure 2: Dominant characteristics of IS to support knowledge sharing

Figure 3 :

 3 Figure 3: IS support for identification of knowledge sources The potential for identification (and management) of expertise is underutilized. The Organization does not analyze what knowledge it needs, and what expertise it therefore needs to develop internally, or import through recruitment for example.

  Figure 4: Is support for codification Figure 5: Management of knowledge repositories

Table 1 :

 1 Respondents

Table 2 :

 2 Summary of mean IS profile scores

Conclusions

The main contribution of this paper is the elaboration of an evaluation grid which helps Organizations to determine the perception employees have about the degree of alignment of their Information system (IS) In completing this questionnaire you are providing a picture of how the Information System (IS) of your organization supports knowledge transfer and the values that characterize it. There are no good or wrong answers as every organization and individual will produce a different set of answers. Just be as accurate as you can.

Please rate each of the statements by dividing 10 points between A, B, C and D depending on how similar the description is to your organization. (10 is very similar and 0 is not at all similar to this firm). The total points for each question must equal 10. Rate for both how you feel the firm is now (NOW) and how you think it should be (PREFERRED).

For example, in question 1, assume that you gave 7 points to A, 1 points to B, 2 points to C, and 0 points to D in the 'NOW' column. This would indicate that the Information System of the organization fits predominantly with a hierarchy-culture focusing on information management, documentation, expertise, formalization, stability, routines, centralization, continuity and control. Assume that you gave 2.5 points to each one in the 'PREFERRED' column. This would indicate you would prefer for these Information System attributes to be exactly equal. You may only use four numbers that total 10 in each column.

Here is how you might rate the Information System attributes of your organization 'NOW' and how you might 'PREFER' the Information System to be sometime in the future.

Dominant IS Characteristics for knowledge transfer NOW PREFERRED

A.

The Organization gives importance to functionalities that support knowledge codification/formalization, formal communication and expert location.

B.

The Organization gives importance either to functionalities supporting knowledge accumulation (codification and storage functionalities) to socialization functionalities (communication, collaboration, and networking)

C.

The Organization gives importance to communication and collaboration functionalities to support knowledge sharing.

D.

The Organization gives importance to environment scanning (from formal and informal sources), storage (of information scanned from sources), and communication and collaboration functionalities.

Total


Design of Magnetic Molecularly

During the last decade, nanotechnologies for anticancer drug delivery 1 have been extensively explored, hoping to improve local efficacy and to reduce side effects of chemotherapy. In an ideal targeted drug delivery system, nanomaterials would be directed to the tumor tissue and selectively release therapeutic molecules.

Molecularly imprinted polymers 2 (MIPs), which possess selective affinity and sustained release behavior toward specific biomolecules have found applications in biosensing 3 , drug delivery 4 , bioseparation 5 as well as diagnostics and therapeutics 6

. The biomolecules served as templates during the polymerization of the functional monomer to get the MIP. The advantage in drug delivery of such a system is the possibility to regulate drug release by increasing the residence time of the therapeutic agent within the polymeric matrix, by means of either covalent or non-covalent interactions in specific binding sites. The release of the drug doesn't depend on the swelling degree of the polymer unlike strategy involving a polymer shell.

Magnetic nanoparticles have attracted considerable attention for magnetic targeting 7 and magnetic hyperthermia applications 8 owing to their ability to generate heat when exposed to an alternative magnetic field (AMF) without penetration depth limit. However, heat therapy with magnetic hyperthermia needs a high accumulation of nanoparticles to provide macroscopic therapeutic heating, quite unrealistic with systemic delivery. As a consequence, new strategies were recently envisaged to trigger drug delivery. , liposomes 13 or microgels 14 exhibit an increase of permeability above a defined transition temperature which induces subsequent release of the drugs. Another way to induce the drug delivery is to use hyperthermia to break bonds between magnetic nanoparticles and the drug 15

. That is the case of a recent study where ligands linked to magnetic nanoparticles took benefits from local heating of nanoparticle's surface to release a fluorophore on demand 16 . The weak interactions existing in supramolecular magnetic nanoparticles can also be broken under AMF like J. Cheon and co-workers proposed

17

. This approach is very interesting because it can be performed without macroscopic temperature elevation 18 .

In this study we propose to destabilize the weak interactions existing between the MIP and the drug to trigger the drug release in athermal conditions under AMF. We designed a new magnetic doxorubicin delivery system (Fe 2 O 3 @DOX-MIP) by growing molecularly imprinted polymers from individual iron oxide nanoparticles surface via an acrylic acid monomer (AA) used as polymerization initiator anchored on the surface of Fe 2 O 3 nanoparticles and doxorobucin as template 19 . The DOX release of such functional Fe 2 O 3 @DOX-MIP NPs was investigated in vitro and in living cells under AMF excitation.

Scheme 1. Two-step synthesis of Fe 2 O 3 @DOX-MIP via a subsequent grafting of an acrylic acid compound and the growth of the polymer at 70°C. AMF induces DOX release.

We prepared Fe 2 O 3 @DOX-MIP NPs according to Scheme 1.

The -Fe 2 O 3 NPs (maghemite) were first synthesized through a coprecipitation method, followed by a size sorting process through salt destabilization to get the biggest NPs which are more efficient for magnetic hyperthermia 20 .

TEM analysis shows particles with an average particle diameter (d 0 ) of 11 nm and a polydispersity (of 0.31 (Fig. S1a, ESI †). To stabilize and functionalize the Fe 2 O 3 NPs, an acrylic acid function was anchored by complexation with unsaturated iron ions at the nanoparticle surface. Then, the polymerization could proceed, mixing Fe 2 O 3 -AA nanoparticles with acrylamide as the functional monomer, ethylene glycoldimethacrylate (EGDMA) as the crosslinking agent, azo(bis)isobutyronitrile (AIBN) as the polymerization initiator and doxorubicin (DOX) as the template molecule in ethanol. The deoxygenated mixture was heated for 16h. The final product, consisting of nanoparticles coated by a molecularly imprinted polymer (Fe 2 O 3 @DOX-MIP), was dialyzed during 24 hours, washed several times by magnetic separation and finally dispersed in water. A reference non-imprinted polymer sample (Fe 2 O 3 @NIP) was prepared using the same procedure, but without addition of the template (DOX molecules). It is noteworthy that the polymer layer for Fe 2 O 3 @DOX-MIP nanoparticles (Fig. S1b, ESI †) is too thin to appear on the TEM images, however no morphological change or aggregation is observed due to polymerization process.

The surface chemistry of the Fe 2 O 3 @DOX-MIP was assessed by Fourier transform infrared (FT-IR; Fig. S2,ESI †). The Fe-O stretching peak at ∼586 cm -1 was observed for the two samples, indicating that the composition of Fe 2 O 3 was not changed after polymer coating. The band observed for the Fe 2 O 3 particles at 1385 cm -1 , characteristic of the nitrate ion with D 3h symmetry (ν 3 mode), is not visible after polymerization indicating the surface modification of the particles. The vibration band at 1728 cm -1 (C=O stretching) appears when magnetic nanoparticles were covered with MIP that contains a large number of C=O groups in poly-(acrylamide) units confirming the successful growth of polymer.

Thermogravimetric analysis (TGA) showed that the amount of MIP on Fe 2 O 3 @DOX-MIP was about 70% of the total particle weight, as determined from the significant mass change between 270 and 400°C owing to decomposition of MIP (Fig. S3, ESI †).

The Fe 2 O 3 NPs were found to be covered with MIP after polymerization, as observed by the increase in size (from 31 to 57 nm) using dynamic light scattering (DLS -Fig. S4,ESI †). DLS and zeta potential were measured for both Fe 2 O 3 and Fe 2 O 3 @DOX-MIP NPs versus pH (Fig. S5a Isothermal adsorption experiments were carried out through varying the concentrations of DOX from 20 to 400 µM, with a mixing time of 3 hours (Fig. 1). It was shown that the Q of DOX onto the Fe 2 O 3 @MIP and Fe 2 O 3 @NIP came to equilibrium over 200 µM. The results suggest that the recognition sites on the surface of the Fe 2 O 3 @MIP have better chemical and steric matching with the DOX than Fe 2 O 3 @NIP indicating a non-specific adsorption as the dominant effect and a lower binding affinity of Fe 2 O 3 @NIP. The dissociation constant K d and the maximum binding number (Q max ) were calculated from the Scatchard equation for the prepared polymers (Fig. S7 Fe 2 O 3 and Fe 2 O 3 @DOX-MIP NPs exhibit the same superparamagnetic behavior (Fig. S8,ESI †). More interestingly, the heating capacity also called the Specific Loss Power (SLP) of Fe 2 O 3 and Fe 2 O 3 @DOX-MIP nanoparticles was measured at 335 kHz and 9mT magnetic field. The uncoated NPs exhibit a SLP of 97 W.g -1 in good agreement with theoretical and experimental expectations 20 . For the Fe 2 O 3 @DOX-MIP, a SLP of 67 W.g -1 is obtained with a temperature elevation rate of 0.33°C.s -1 . The SLP decrease may be explained by the appearance of some aggregates after polymerization as observed by DLS. However, the Fe 2 O 3 @DOX-MIP nanoparticles still have an interesting heating capacity if they are submitted to an alternative magnetic field.

To investigate the potential application of Fe 2 O 3 @DOX-MIP for drug delivery, in vitro DOX release studies were monitored in various conditions: in a water bath at human body temperature (37°C) and under AMF (five AMF pulses of 2 minutes with a 30s interval, 335 kHz, 9mT) at 37°C (Fig. 2A and2C). In order to determine the concentration of the DOX binds to the MIP, DOX molecules were extracted in a solvent (ethanol/acetic acid 9:1v/v). Extraction of the template is commonly done with a solvent that promotes the disruption of interactions between the polymer and the template while maintaining the structure of the three-dimensional polymer network 21 . The supernatant was then collected by magnetic separation and analyzed by UV/Vis spectroscopy 1, 2, 3, 4, 6 and 8h after treatment; the materials released 12 µM of DOX after 8h (Fig. 2A). The amount of DOX extracted in acetic acid is used as reference for the calculation of the percentage of drug release (Fig. 2C). Then, samples (Fe 2 O 3 @DOX-MIP NPs, 2 mL, [Fe]=50mM) were periodically placed under AMF at the same time points. Fe 2 O 3 @DOX-MIP NPs submitted to AMF released 7.5 µM of DOX after 8h at 37°C (Figure 2A) whereas a sample left for 8h at 37°C did not show any significant DOX release (15%, Fig. 2B). Therefore the cumulative drug release reaches 60% under AMF. More interestingly for each time point, the drug release is significantly higher when the nanoparticles are submitted to an AMF. To evaluate the imprinting process role in the DOX release under AMF, Fe 2 O 3 @NIP NPs were incubated with DOX (C = 40µM, see supporting information) during 4h, dialyzed during 24h and washed several times by magnetic separation and finally dispersed in water. The final product (Fe 2 O 3 @NIP-DOX, 2mL, [Fe]=50mM, C DOX = 12 µM) was submitted to the same AMF excitation than the Fe 2 O 3 @DOX-MIP NPs. A sample left for 8h at 37°C (Figures 2B and2D) showed a high DOX concentration release (9µM, 73%) and under AMF the same material showed the complete release of the DOX after 8h (11,8 µM, 98%). A burst effect is observed when the DOX is just physically retained in the unprinted polymer shell around the particles. The slight effect observed upon AMF excitation is probably due to a more rapid diffusion of DOX molecules with the temperature elevation in the polymer matrix. These results taking together highlight the importance of the drug interactions with the polymer in the imprinting process to slow the release of the drug from the polymer network. To prove the universality of the imprinted method to other molecules, the same protocol has been carried out with fluorescein and rhodamine (Fig. S9,ESI †). Both imprinted particles exhibit a significant template release after AMF treatment compared to the sample without AMF (respectively 11.8 and 13.6 µM versus 1.9 and 2.3µM).

To show the crucial role of the magnetic core in the drug release process Fe 2 O 3 NPs were dissolved in HCl and after separation of the polymer from the acidic solution by ultracentrifugation, in vitro DOX release studies were monitored at 37°C under AMF. After 8h, the DOX release concentration is insignificant (1.5µM, Fig. S10,ESI †) confirming the importance of the magnetic core in the drug delivery system. As nanoparticles preferentially accumulate at the tumour site thanks to the Enhanced Permeability and Retention effect (EPR effect), using Fe 2 O 3 @DOX-MIP as drug delivery system could be useful in AMF-induced drug delivery applications. To evaluate the temperature effect on the drug-release profile, Fe 2 O 3 @DOX-MIP nanoparticles were heated at different temperatures (water bath) during 4 hours and supernatants were analyzed after magnetic separation (Fig. S11, ESI †). The DOX concentration released after a bulk heating during 4h at 37°C is of the order of 1.2 µM which is three times lower than the amount of DOX released after 4 hours with AMF pulse at each time point (5.6 µM, Fig. 1A,ESI †) at the same temperature. The maximum of DOX release reached under AMF (7.5 µM) is obtained for a temperature of 60°C whereas macroscopic temperature elevation measured during AMF experiments is only of 3°C (Fig. S12,ESI †). Therefore, we can conclude that the effect of AMF is due to a high temperature gradient from the nanoparticle surface, this gradient is restricted to the environment close to the periphery of the nanoparticle, thus leading to localized heating. The effect of this localized heating on the drug release may be explained by the destabilization of the weak interactions (hydrogen bonds) existing between the DOX and the MIP.

DOX release was then tested in cancer cells, with a view to future therapeutic application. Fe 2 O 3 @DOX-MIP nanoparticles were very efficiently captured by cancer cells (PC-3), with an iron load per cell of 10 pg, when incubation (2-hours) was performed at [Fe]=2 mM (see also the uptake curve in Fig. S13). This [Fe]=2mM concentration corresponds to a maximal DOX release on µmolar range (Fig. 2A). DOX was clearly associated to the tumor cells on confocal microscopy images (Fig. 3A), and cross-sectional images of the cells (Fig. 3B and Fig. S14, ESI †) demonstrate unambiguously its intracellular localization, sequestered inside intracellular endosome-like compartments.

These Fe 2 O 3 @DOX-MIP nanoparticles internalization did not induce cancer cell death (Fig. 3C), demonstrating that when bonded to the MIP (and thus the nanoparticles), DOX is inactive. By contrast, after AMF application (at 700 kHz, 25 mT), cancer cell viability was affected, with cell viability reduced to 60% after 1h30 treatment (Fig. 3C). It is very important to emphasize here that this AMF-induced cancer cell death was achieved in athermal conditions. Indeed, during the AMF exposure, the cell medium was maintaining at a 37°C temperature (See Fig. S15, ESI † for the temperature monitoring during treatment). This is in agreement with the control experiment where cells loaded with the same amount of iron (10 pg per cell) but without DOX (incubation with Fe 2 O 3 @citrate nanoparticles, with same magnetic core as Fe 2 O 3 @DOX-MIP nanoparticles) didn't suffer any mortality. Also worth noticing, the same levels of cell deaths were found when free DOX was incubated with the cancer cells for 2 hours at concentration in the range 0.5-2 µM (Fig. 3D), corresponding remarkably to the concentration which could be AMF released by the Fe 2 O 3 @DOX-MIP incubated with the cells. Taken together, these cellular experiments support the DOX release under AMF application evidenced in solution, and demonstrate the possibility of initiating a chemotherapeutic treatment via an athermal magnetic hyperthermia strategy. This remote magnetic activation of doxorubicin is particularly promising to limit the adverse effects of chemotherapy on bystander tissues. In summary, we reported the synthesis of an innovative magnetic delivery nanoplatform for triggered cancer therapy showing active control over drug release by using local effect of hyperthermia. Our material, wich combines the controlled drug release ability of non thermosensitive Molecularly Imprinted Polymers (MIP) with magnetic properties of iron oxide, allows the control release of doxorubicin. Upon AMF exposure, the hydrogen bonds between the MIP and the DOX are broken and the molecule is released without any significant heating of the medium. This strategy is efficient both in vitro and in living cells. These nanomaterials offer great promise for the doxorubicin release under magnetic field and moreover we think that this approach will be easily expanded to other polymers, targeting molecules or drugs. The use of Magnetic Molecularly Imprinted Polymers for drug delivery under alternative magnetic field (AMF) is a major advance in the development of multifunctional targeted drug delivery nanotechnologies and may become important theranostic tools in nanomedicine.

Notes and references ‡ We kindly acknowledge Delphine Talbot for the ATG characterization of the nanomaterials. We also thank Aude Michel and Sandra Casale for the TEM pictures.

  delivery nanomaterial for triggered cancer therapy showing active control over drug release by using alternative magnetic field is proposed. In vitro and in living cells release of doxorubicin (DOX) were investigated and showed a massive DOX release upon alternative magnetic field without temperature elevation of the medium.

  and S5b, ESI †). The hydrodynamic diameter of Fe 2 O 3 @DOX-MIP particles is constant on the whole pH range according to their constant zeta potential (-27 mV). As the poly(acrylamide) is non pH sensitive, this result is in agreement with the effective surface modification of the Fe 2 O 3 NPs with the polymer coating. Kinetic adsorption tests (Fig. S6, ESI †) onto the Fe 2 O 3 @DOX-MIP after DOX extraction (named Fe 2 O 3 @MIP) and Fe 2 O 3 @ NIP were performed by measuring the adsorption of DOX at regular intervals from 5 to 120 min with the same initial concentration of DOX (400 µM). The adsorption capacity (Q) of DOX onto the Fe 2 O 3 @MIP has a fast adsorption profile within 20 min, and then slows down gradually. After 20 min, the adsorption has almost reached equilibrium. Compared to other surface imprinting technologies for DOX, the adsorption equilibrium time of the Fe 2 O 3 @MIP is similar 18 .

  , ESI †). The respective K d and Q max values are 35.6 µmol g -1 and 3.4µM for the Fe 2 O 3 @DOX-MIP and 12.5 µmol g -1 and 100µM for the Fe 2 O 3 @DOX-NIP. The difference in DOX binding affinity to the MIP and NIP clearly indicated the role of the imprinting process in the formation of specific binding sites.

FeFig. 1

 1 Fig. 1 Adsorption isotherms of Fe 2 O 3 @MIP (black) and Fe 2 O 3 @NIP (red) toward Doxorubicin. Adsorption conditions: V = 5 mL, m MIPs = m NIPs = 20mg, T = 25 °C, t = 3h .

Fig. 2

 2 Fig. 2 Cumulative DOX release in µmol/L and in percent versus time of Fe 2 O 3 @DOX-MIP (A) and (B) and Fe 2 O 3 @NIP-DOX nanoparticles (C) and (D) ([Fe]=50 mM) (a) after acid treatment, (b) at 37°C without magnetic field and (c) under AMF (335 kHz, 9mT).

Fig. 3 (

 3 Fig.3 (A,B): Cancer cells (PC-3) internalization of the Fe 2 O 3 @DOX-MIP nanoparticles (2-hours incubation at [Fe]=2 mM). DOX is detected in the green channel (excitation at 488 nm, emission at 561 nm). Nuclei and cell membranes are stained by DAPI (A) in blue and PKH26 (A,B) in red, respectively. Z reconstructions (B) identify DOX inside the cells. (C): Viability of cancer cells labelled with Fe 2 O 3 @DOX-MIP after exposure to the alternative magnetic field (AMF at 700 kHz, 25 mT) for 0min (No AMF), 30min, 1h30, and 2h30 compared to the control experiment (cancer cells labelled with Fe 2 O 3 nanoparticles, at the same cellular iron dose, and exposed to the same conditions of AMF). The overall temperature during treatment was 37.,5 °C for both conditions. (D) Treatment of the cancer cells with free doxorubicin (DOX) incubated for 2 hours from 0.5 to 50 µM. Cell viability (normalized by control cells) was measured 24 hours after the incubation, in the exact same conditions as the ones used for Fe 2 O 3 @DOX-MIP after AMF treatment.In summary, we reported the synthesis of an innovative magnetic delivery nanoplatform for triggered cancer therapy showing active control over drug release by using local effect of hyperthermia. Our material, wich combines the controlled drug release ability of non thermosensitive Molecularly Imprinted Polymers (MIP) with magnetic properties of iron oxide, allows the control release of doxorubicin. Upon AMF exposure, the hydrogen bonds between the MIP and the DOX are broken and the molecule is released without any significant heating of the medium. This strategy is efficient both in vitro and in living cells. These nanomaterials offer great promise for the doxorubicin release under magnetic field and moreover we think that this approach will be easily expanded to other polymers, targeting molecules or drugs. The use of Magnetic Molecularly Imprinted Polymers for drug delivery under alternative magnetic field (AMF) is a major advance in the development of multifunctional targeted drug delivery