Pieter Janssen
email: pieter.janssen@med.kuleuven.

Pieter Vanden Berghe

Sofie Verschueren

Anders Lehmann

Inge Depoortere

Jan Tack

Pieter Vanden Berghe

Jan Tack Affiliations

Role of gastric motility in the control of food intake

Keywords: Stomach and duodenum < Organ-based, Gastric emptying < Topics, Motility < Topics, Obesity gastric accommodation, gastric emptying, migrating motor complex, hunger, appetite

INTRODUCTION

The regulation of food intake relies on a balance between hunger, satiation (the disappearance of hunger during a meal), and satiety (the sensation of satisfaction after a meal that gradually disappears to make way for hunger). These sensations of appetite are the result of complex interactions between central nervous system circuitries and peripheral sensations, which mainly originate from the gastrointestinal tract, the liver 1 , and adipose tissue [START_REF] Ahima | Metabolic actions of adipocyte hormones: focus on adiponectin[END_REF] . Since the gut is the first and main organ in which food is processed it is set to sense meal volume and composition and thus plays a vital role in the regulation of appetite [START_REF] Smith | Neurophysiology of hunger and satiety[END_REF][START_REF] Cummings | Gastrointestinal regulation of food intake[END_REF][START_REF] Maljaars | Review article: the gastrointestinal tract: neuroendocrine regulation of satiety and food intake[END_REF][START_REF] Woods | Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake[END_REF] . For the stomach this central role is illustrated by the efficacy of bariatric surgery: resection or bypass of the stomach results in important and sustained weight loss [START_REF] Torgerson | The Swedish Obese Subjects (SOS) study-rationale and results[END_REF][START_REF] Maggard | Meta-analysis: surgical treatment of obesity[END_REF] .

Appetite regulation by the gastrointestinal tract is mediated through sensation of meal volume and nutrient composition and can be influenced by different factors such as secretion [START_REF] Goetze | The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging[END_REF] and visceral sensitivity [START_REF] Delgado-Aros | Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans[END_REF] but also by gastrointestinal motility. In this review we focus on the role of motility, and more specific gastric motility in the regulation of (solid) food intake through a literature review using the keywords: satiety, satiation and food intake in combination with specific search terms corresponding to the different subdivisions.

GASTRIC INTERDIGESTIVE AND POSTPRANDIAL MOTILITY

Anatomically, the stomach is divided into a fundus, corpus and antrum region, but when it comes to motor function two parts can be distinguished: the proximal an interdigestive and a postprandial motor pattern. During the interdigestive phase, the proximal stomach muscle tone is high while the distal stomach is engaged in a recurrent contraction pattern known as the migrating myoelectrical (or motor) complex (MMC). It has been suggested that the MMC serves to clear the stomach of secretions, debris, and microbes during fasting {Szurszewski, 1981 1001 /id}. Upon food intake the motor pattern of the stomach changes drastically: the proximal stomach relaxes and serves initially as a reservoir. After food intake, a tonic contraction of the proximal stomach pushes the food distally, while the distal stomach mixes and grinds the food by a powerful and regular peristaltic contraction pattern [START_REF] Meyer | Motility of the stomach and the gastroduodenal junction[END_REF] .

This postprandial motor pattern serves three major mechanical stomach functions:

(1) the proximal stomach can act as a reservoir that enables ingestion of a large amount of food without a major intragastric pressure increase, (2) the mechanical aspect of food digestion is started by antral contractions that mix and grind food to smaller particles for further processing by the intestine and (3) tonic and peristaltic contractions generate a steadily controlled flow of food to the duodenum.

The role of gastric motility and its influence on appetite regulation will be discussed in three parts, corresponding to the sequence of events during and after food intake.

During food intake, when gastric emptying, especially of solids, is limited, gastric distension and gastric accommodation play an important function in the regulation of satiation as discussed in the first part. After food intake, when the stomach gradually empties, the role of gastric distension in the determination of appetite decreases and the focus will shift to gastric emptying and intestinal exposure to nutrients. Finally, we will discuss the role of the empty stomach and the MMC in the regulation of hunger signals.

SATIATION DURING FOOD INTAKE

Gastric emptying of a solid meal follows a typical biphasic pattern: during the lag phase, which can take up to 30-60 minutes, solids are redistributed in the stomach and broken down to small particles, less than 1 mm in diameter, which in turn can pass through the pylorus during the emptying phase [START_REF] Meyer | Human postprandial gastric emptying of 1-3-millimeter spheres[END_REF][START_REF] Hellström | The physiology of gastric emptying. Best Practice & Research[END_REF] . Although it is likely that some initial gastric emptying will occur (especially part of the liquid phase of the meal), most of the solid meal will remain in the stomach during food intake [START_REF] Kwiatek | Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI[END_REF] , and sensations from the stomach will play a prominent role in the regulation of satiation.

Satiation signals from the stomach

Gastric mechanosensation is an important factor in the regulation of satiation during food intake. Several authors have demonstrated that distension of the stomach induces a satiating effect: in a magnetic resonance imaging study fullness was found to be related to total gastric volumes for nutrient and non-nutrient meals [START_REF] Marciani | Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI[END_REF] . In healthy volunteers inflation of an intra-gastric balloon induces a range of sensations from fullness and satiation to pain [START_REF] Lee | Differences in the sensorimotor response to distension between the proximal and distal stomach in humans[END_REF] . Furthermore, the presence of an inflated intragastric balloon has been used in the treatment for obesity and was shown to induce premature satiation during a normal meal [START_REF] Rigaud | Gastric distension, hunger and energy intake after balloon implantation in severe obesity[END_REF][START_REF] Nieben | Intragastric balloon as an artificial bezoar for treatment of obesity[END_REF] which were placed in the proximal stomach, indicating an important role for the proximal stomach in generating sensations from the stomach. On the other hand, ultrasound and scintigraphy measurements show a direct correlation between antral volume and the amount of ingested food or administered liquids [START_REF] Darwiche | Correlation between simultaneous scintigraphic and ultrasonographic measurement of gastric emptying in patients with type 1 diabetes mellitus[END_REF][START_REF] Sturm | Energy intake and appetite are related to antral area in healthy young and older subjects[END_REF] , indicating that distal stomach filling is also a determinant of satiation. Most likely, distal and proximal stomach have comparable mechanosensitivity and are both contributing to sensations of satiation and satiety [START_REF] Lee | Differences in the sensorimotor response to distension between the proximal and distal stomach in humans[END_REF] . The presence of a balloon, besides directly distending the proximal stomach, may promote antral distention during food intake and this may contribute to the satiation-enhancing effect.

Gastric distension has been shown to trigger stretch as well as tension mechanosensitive receptors that in turn relay their information via vagal and splanchnic nerves [START_REF] Phillips | Tension and stretch receptors in gastrointestinal smooth muscle: re-evaluating vagal mechanoreceptor electrophysiology[END_REF][START_REF] Sengupta | Gastrointestinal afferents fibers and sensation[END_REF][START_REF] Janig | Neurobiology of visceral afferent neurons: neuroanatomy, functions, organ regulations and sensations[END_REF][START_REF] Grundy | Neuroanatomy of visceral nociception: vagal and splanchnic afferent[END_REF][START_REF] Northway | Weight loss induced by gastric implant in rats. Effects of capsaicin sensory denervation[END_REF] to the hindbrain and several other brain areas [START_REF] Molinari | Cardiovascular effects and c-Fos expression in the rat hindbrain in response to innocuous stomach distension[END_REF][START_REF] Sabbatini | GABAA receptors expression pattern in rat brain following low pressure distension of the stomach[END_REF][START_REF] Van Oudenhove | The role of somatosensory cortical regions in the processing of painful gastric fundic distension: an update of brain imaging findings[END_REF] (Figure 1A). Distension of the proximal stomach in physiological ranges is known to activate a neuronal network in the central nervous system consistent with the 'visceral pain neuromatrix' [START_REF] Vandenbergh | Regional brain activation during proximal stomach distention in humans: A positron emission tomography study[END_REF] . In a recent study from our group, we used positron emission tomography imaging to compare regional brain activity during balloon distension or during intragastric infusion of a nutrient drink. Stepwise gastric balloon distension progressively activated the "visceral pain neuromatrix" (primary & secondary somatosensory cortex, lateral orbitofrontal cortex, insula, anterior cingulate cortex and cerebellum), which was associated with the generation of discomfort and/or pain 31 . In contrast, continuous or stepwise nutrient infusions to equal or higher intragastric volumes induced progressive deactivation of the visceral pain neuromatrix [START_REF] Geeraerts | Different regional brain activity during physiological gastric distension compared to balloon distension: a H(2) (15) O-PET study[END_REF] . We hypothesize that the latter phenomenon is a prerequisite for tolerance of meal volumes in healthy subjects. The difference between gastric balloon distension and nutrient distension might be related to neurohormonal signaling induced by detection There is evidence that gastric distension-induced satiation can also be regulated by gut hormones. Indeed, the satiating effect of gastric distention has been shown to be enhanced by cholecystokinin (CCK) [START_REF] Kissileff | Cholecystokinin and stomach distension combine to reduce food intake in humans[END_REF] . Another example is glucagon-like peptide 1

(GLP-1), known to reduce food intake in humans [START_REF] Gutzwiller | Glucagon-like peptide-1: a potent regulator of food intake in humans[END_REF] : GLP-1-containing neurons in the nucleus of the solitary tract are activated by gastric distension within the physiological range, suggesting a role for GLP-1 in gastric distension-induced appetite signaling [START_REF] Vrang | Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons[END_REF] .

GLP-1 receptor antagonism in the nucleus tractus solitarius attenuated feeding suppression after gastric distension but not after intraduodenal infusion of a nutrient drink, indicating that central release of GLP-1 and activation of hindbrain GLP-1 receptors mediate specifically gastric satiation signals, while peripheral release of GLP-1, mediated by the L cells in the distal small intestine, is not related to gastric distension [START_REF] Hayes | Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling[END_REF] .

In contrast to mechanosensation, nutrient sensation in the stomach is less likely to be an important factor in the regulation of satiation during food intake: in rats equipped with inflatable cuffs around the pylorus that prevent content from leaving the stomach, infusion of non-nutritive solutions such as saline, results in volumetrically proportionate decreases in food intake and this is as efficacious as infusion with a nutrient solution [START_REF] Phillips | Gastric volume rather than nutrient content inhibits food intake[END_REF][START_REF] Powley | Gastric satiation is volumetric, intestinal satiation is nutritive[END_REF] . In humans, postprandial hunger and satiety were correlated to postprandial gastric volumes, without a significant influence of the nutrient composition (lipids, carbohydrates or proteins) of the meal [START_REF] Goetze | The effect of macronutrients on gastric volume responses and gastric emptying in humans: A magnetic resonance imaging study[END_REF] . Only a few studies have found evidence for a role of nutrient sensation in the stomach: it has been suggested that the pylorus can sense the energy content of food and might play a role in the regulation of the energy load towards the duodenum [START_REF] Hellström | Interactions between gastric emptying and satiety, with special reference to glucagon-like peptide-1[END_REF] . However, most authors agree that distension is the main determinant for gastric sensations of satiation and satiety, and that the stomach does not meaningfully detect the nutrient or caloric composition of a meal [START_REF] Cummings | Gastrointestinal regulation of food intake[END_REF] .

Role of gastric accommodation

In between meals the proximal stomach maintains a high basal muscle tone. This tone is partially due to the myoelectrical properties of the fundus: the resting membrane potential in the fundic muscles is near or above the mechanical threshold 41 . In addition, muscle tone in the proximal stomach is sustained by constant cholinergic input mediated by the vagal nerve [START_REF] Azpiroz | Importance of vagal input in maintaining gastric tone in the dog[END_REF] . Proximal gastric tone decreases during food intake, and this process of active relaxation is mediated by several different (para)sympathetic reflex pathways that have been shown to decrease the contractile cholinergic input and activate the release of nitric oxide [START_REF] Tack | Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans[END_REF] . This reflex, also referred to as gastric accommodation will enhance the storage capacity of the stomach by increasing the compliance of the stomach muscles and thus keeps the intragastric pressure low during food intake [START_REF] Kindt | Impaired gastric accommodation and its role in dyspepsia[END_REF] .

When gastric accommodation is impaired, intragastric pressure will be relatively high during food intake. This has been shown during air insufflation or intra-gastric balloon distension: while in healthy subjects during stomach distension the intragastric pressure increase is minor or stable and does not increase despite further distension, intragastric pressure increase is much more pronounced in patients with impaired gastric accommodation e.g. after vagotomy, patients with Chagas' disease (a tropical parasitic disease characterized by extensive lesions of the myenteric plexus) and patients with functional dyspepsia [START_REF] Ahluwalia | Relaxation responses of the human proximal stomach to distension during fasting and after food[END_REF][START_REF] Jahnberg | Dynamic gastric response to expansion before and after vagotomy[END_REF][START_REF] Oliveira | Impaired gastric accommodation to distension and rapid gastric emptying in patients with Chagas' disease[END_REF][START_REF] Suzuki | Examination of visceral perception and gastric tone by gastric stimulation using air inflation during endoscopy[END_REF] . Increased intragastric pressure is associated with increased postcibal perception [START_REF] Moragas | Relations among intragastric pressure, postcibal perception, and gastric emptying[END_REF] . We recently showed that, during intragastric infusion of a nutrient drink, intragastric pressure is directly correlated to satiation, indicating that intragastric pressure is a determinant of satiation [START_REF] Janssen | Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors[END_REF] .

Whether perception is driven by intragastric pressure, or by another mechanosensitivity modality that is influenced by intragastric pressure, is a matter of controversy [START_REF] Tack | Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention[END_REF][START_REF] Gregersen | Tension receptors: Theoretical construct or fact?[END_REF] . According to the simplified law of Laplace, increased intragastric pressure will be associated with increased wall tension for the same intragastric volume. Studies using isovolumetric and isobaric gastric distensions indicate that gastric wall tension receptors may be most relevant for mediating distension-induced sensation [START_REF] Piessevaux | Perception of changes in wall tension of the proximal stomach in humans[END_REF][START_REF] Carmagnola | Mechanoreceptors of the proximal stomach and perception of gastric distension[END_REF] . In fact, by using a tensostat that keeps an intragastric bag at a constant tension (calculated according to the simplified Laplace's law) it was shown that sensations from the proximal stomach depend on gastric wall tension, whereas intragastric volume and expansion seem less relevant [START_REF] Distrutti | Gastric wall tension determines perception of gastric distention[END_REF] .

Although increased tension by itself can increase sensation, it can also cause redistribution of the food from the proximal stomach to the antrum as shown in imaging studies [START_REF] Troncon | Abnormal intragastric distribution of food during gastric emptying in functional dyspepsia patients[END_REF][START_REF] Gilja | Gastric accommodation assessed by ultrasonography[END_REF] . Since the antrum is less compliant than the proximal stomach it is more sensitive to distension, and increased feelings of fullness and satiation in patients with impaired gastric accommodation can originate from the antrum [START_REF] Sturm | Energy intake and appetite are related to antral area in healthy young and older subjects[END_REF] .

Furthermore, increased tonic pressure exerted by the stomach could increase gastric emptying of liquid but also of solid food [START_REF] Hellström | The physiology of gastric emptying. Best Practice & Research[END_REF][START_REF] Strunz | Effect of intragastric pressure on gastric emptying and secretion[END_REF][START_REF] Collins | Role of the proximal and distal stomach in mixed solid and liquid meal emptying[END_REF] which in turn could influence satiety and food intake [START_REF] Cupples | Physiological regulation of food intake[END_REF] . A number of studies have investigated the importance of gastric accommodation in relation to food intake. Using the barostat it was demonstrated that a subgroup of functional dyspeptic patients has early satiation and weight loss that can be attributed to impaired gastric accommodation [START_REF] Tack | Role of impaired gastric accommodation to a meal in functional dyspepsia[END_REF] . This was confirmed in a later study in which we demonstrated a clear relationship between meal-induced gastric accommodation and caloric intake in healthy volunteers as well as functional dyspeptic patients [START_REF] Tack | Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia[END_REF] . In healthy volunteers we showed that artificially increasing gastric muscle tone (by means of motilin administration or nitric oxide synthase inhibition) also increased meal-induced satiation [START_REF] Tack | Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans[END_REF][START_REF] Cuomo | Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways[END_REF] . In a recent study we demonstrated that in the presence of a balloon blocking gastric outflow, slow ingestion of a liquid meal was able to induce satiation albeit less than in a comparable control situation without pyloric obstruction, indicating, as we have discussed before, that nutrient accumulation in the stomach alone is able to induce a feeling of satiation and that duodenal nutrient exposure adds to feelings of satiation but is not a prerequisite for the occurrence of meal-induced satiation [START_REF] Berghe | Contribution of different triggers to the gastric accommodation reflex in humans[END_REF] . On the other hand, in the same study we showed that gastric accommodation during pyloric outflow obstruction was decreased as compared with the control condition, furthermore supporting the hypothesis that impaired accommodation decreases tolerance of a nutrient load. In addition, the intragastric pressure during nutrient drink ingestion at a constant rate show is significantly correlated to the corresponding satiation scores and the nutrient volume required to induce maximal satiation [START_REF] Janssen | Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation[END_REF] .

Other groups have reported a possible correlation between gastric accommodation and food intake or satiety in binge eating disorder, bulimia nervosa and cancer patients [START_REF] Geliebter | Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder[END_REF][START_REF] Zimmerli | Gastric compliance in bulimia nervosa[END_REF][START_REF] Davis | Early satiety in cancer patients: a common and important but underrecognized symptom[END_REF] . Another observation in favor of such a relationship comes from gastric banding, a frequently-used gastric restrictive bariatric approach for the treatment of suggested that changes in gastric accommodation are responsible [START_REF] De Jong | Weight loss after laparoscopic adjustable gastric banding is not caused by altered gastric emptying[END_REF] .

These findings all indicate that gastric accommodation is an important determinant of food intake, and that impaired gastric accommodation is associated with decreased food intake. The question remains whether this could affect long-term body weight. In patients there are indications that impaired gastric accommodation and weight loss are related e.g. in functional dyspepsia, in some anorexia patients and in cancer patients with loss of appetite [START_REF] Tack | Role of impaired gastric accommodation to a meal in functional dyspepsia[END_REF][START_REF] Davis | Early satiety in cancer patients: a common and important but underrecognized symptom[END_REF] . On the other hand there is hardly any evidence that gastric accommodation is enhanced in obese people. Unfortunately, there is no medication that can selectively impair or enhance gastric accommodation and can be administered over a longer period, and studies that examine the relationship between gastric accommodation and satiation on one hand and body weight on the other hand are lacking.

SATIETY SIGNALING AFTER FOOD INTAKE

During and after food intake (dis)tension of the stomach plays an important role in the determination of appetite. However, after the lag phase of gastric emptying, when the stomach gradually empties into the small intestine, the (dis)tension of the stomach decreases and is therefore likely to play a gradually decreasing role in satiety signaling. The emphasis shifts towards satiety mechanisms that are controlled by the rate of gastric emptying: intestinal exposure of nutrients (Figure 2). molecules (e.g. serotonin (5-HT)), that can act locally or enter the blood stream and work as hormones [START_REF] Cummings | Gastrointestinal regulation of food intake[END_REF][START_REF] Woods | Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake[END_REF] (Figure 1B).

Gut hormones, released in response to gut content, have their peak plasma level at various time points after meal intake: e.g. CCK release peaks early after food intake (within 15 minutes) [START_REF] Boyd | High-fat diet effects on gut motility, hormone, and appetite responses to duodenal lipid in healthy men[END_REF] , whereas PYY reaches its peak plasma level after about 1 hour nuclei which eventually send signals to other brain areas [START_REF] Smith | Neurophysiology of hunger and satiety[END_REF][START_REF] Konturek | Brain-gut axis and its role in the control of food intake[END_REF] . For CCK, GLP-1 and PYY the resulting effect is a well-described increase in satiety [START_REF] Kissileff | Cholecystokinin and stomach distension combine to reduce food intake in humans[END_REF][START_REF] Gutzwiller | Glucagon-like peptide-1: a potent regulator of food intake in humans[END_REF][START_REF] Roux | Peptide YY, appetite and food intake[END_REF] .

When released locally, peptides and small molecules can influence the activation of enteric and (para)sympathetic nerves. 5-HT, for example, is released from enterochromaffin cells and mediates vagal nerve activation via 5-HT 3 receptors [START_REF] Savastano | Intestinal nutrients elicit satiation through concomitant activation of CCK(1) and 5-HT(3) receptors[END_REF] .

Vagal nerves signal to the nucleus tractus solitarius in the hindbrain from which region efferent fibers project to the hypothalamus using the parabrachial nucleus as the main relay. Indeed, administration of the 5-HT 3 receptor agonist mchlorophenylbiguanide can reduce food intake in rats [START_REF] Mazzola-Pomietto | Temperature, food intake, and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats[END_REF] while the 5-HT 3 receptor antagonist ondansetron has been shown to attenuate CCK-induced suppression of food intake in rats [START_REF] Hayes | Cholecystokinin-induced satiety is mediated through interdependent cooperation of CCK-A and 5-HT3 receptors[END_REF] . The role of 5-HT 3 receptors in the control of satiation, however, is less clear: while some groups claim ondansetron by itself does not influence food intake in rats, other groups showed that ondansetron is able to reduce food intake in rats [START_REF] Van Der Hoek | Ondansetron, a selective 5-HT3 receptor antagonist, reduces palatable food consumption in the nondeprived rat[END_REF] and binge-eating behavior in bulimia patients [START_REF] Faris | Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial[END_REF] .

Role of gastric emptying

From a mechanical point of view, gastric emptying of a meal relies on a complex interplay between the major motor patterns of the stomach. Upon food intake, and after an initial relaxation, the proximal stomach propels gastric contents forward by means of a tonic contraction and hereby provides a driving force for gastric emptying.

Simultaneously, peristaltic contractions emerging from the mid-corpus progress in the direction of the antrum, hereby grinding and sieving solid food. This repetitive motor pattern breaks down the food particles, mixes them with juice and forms a second drive that pushes the food content distally. A third mechanical factor in the regulation of gastric emptying is opening and closure of the pyloric sphincter. This narrow highpressure zone closes the stomach during the terminal phase of a peristaltic contraction wave, so that any content from the antrum is prevented from entering into the duodenum during mixing and grinding [START_REF] Tougas | Relation of pyloric motility to pyloric opening and closure in healthy subjects[END_REF] . The relative importance of each of these three mechanical functions depends on the consistency of the food: for liquids the pressure elicited by the proximal stomach and opening of the pylorus will be dominant in the control of gastric emptying, while the peristaltic pump of the antrum is more dominant for solid food [START_REF] Indireshkumar | Relative contributions of "pressure pump" and "peristaltic pump" to gastric emptying[END_REF] . Non-caloric liquids, for instance, empty without lag phase, directly proportional to the gastric volume and in an exponential process.

Solids on the other hand typically empty in a biphasic manner: after a lag-phase where hardly any emptying occurs, gastric emptying rate of the grinded and mixed contents is more or less stable until the stomach is emptied [START_REF] Hellström | The physiology of gastric emptying. Best Practice & Research[END_REF] . The emptying speed of a meal is inversely correlated to its caloric content. Interestingly it has been shown that gastric emptying is independent on the nature of the calories so that a constant delivery of energy to the bowel is maintained [START_REF] Calbet | Role of caloric content on gastric emptying in humans[END_REF] . Besides caloric content, a relationship has been described between gastric emptying rate and the acidity, osmolarity and viscosity of the meal [START_REF] Burks | Regulation of gastric emptying[END_REF][START_REF] Macdonald | Physiological regulation of gastric emptying and glucose absorption[END_REF] . Many of these relationships can be explained by a duodenal-gastric feedback mechanism: exposure of the small intestine to nutrients activates vago-vagal reflex mechanisms and hormonal signals (e.g. GLP-1, PYY and CCK) that modulate gastric emptying [START_REF] Hellström | The physiology of gastric emptying. Best Practice & Research[END_REF][START_REF] Little | Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses[END_REF][START_REF] Sheiner | Gastric motility and emptying in normal and post-vagotomy subjects[END_REF] .

The relation between gastric emptying and appetite is complex and only few studies directly investigated this relationship. Physiological or artificially-induced delay of gastric emptying appears to be linked with increased feelings of satiety and fullness and termination of food intake [START_REF] Wisen | Gastrointestinal motility in obesity[END_REF][START_REF] Hunt | A possible relation between the regulation of gastric emptying and food intake[END_REF][START_REF] Di | Pectin delays gastric emptying and increases satiety in obese subjects[END_REF] . Also, at least a subgroup of patients with anorexia nervosa have markedly delayed gastric emptying, while in some studies obese people were shown to have enhanced gastric emptying [START_REF] Johansson | Relation between body weight and the gastric and intestinal handling of an oral caloric load[END_REF][START_REF] Bergmann | Correlation between echographic gastric emptying and appetite: influence of psyllium[END_REF][START_REF] Dubois | Altered gastric emptying and secretion in primary anorexia nervosa[END_REF] . There is no obvious candidate hormone to explain these findings: leptin, the plasma levels of which directly positively correlate with adiposity, has no major effects on gastric emptying 92 , and circulating ghrelin has been reported to be lower in obese subjects than in healthy controls. Furthermore, in healthy controls a correlation was found between the gastric emptying rate of solids and body surface area and weight [START_REF] Lavigne | Gastric emptying rates of solid food in relation to body size[END_REF] .

It has been suggested that larger intragastric volume and hence increased (dis)tension as a result of delayed gastric emptying is responsible for increased feelings of satiety and delayed return of hunger [START_REF] Wisen | Gastrointestinal motility in obesity[END_REF][START_REF] Geliebter | Gastric distension and gastric capacity in relation to food intake in humans[END_REF] . This interpretation seems to be acknowledged by a study in which a significant correlation was found between ratings of postprandial increase in hunger and the time needed for 90% of the meal to empty. The authors of this latter study also suggested that the reduction of gastric distension may be the determinant factor in the development of hunger after a meal 95 . The interaction between gastric distension, gastric emptying and feelings of appetite was studied in more detail by a series of experiments that combined ultrasound and scintigraphy: satiety and satiation were found to be inversely correlated to gastric emptying, more precisely, a close relationship was found between antral area (and presumably antral distension), satiation and satiety [START_REF] Sturm | Energy intake and appetite are related to antral area in healthy young and older subjects[END_REF][START_REF] Hveem | Scintigraphic measurement of gastric emptying and ultrasonographic assessment of antral area: relation to appetite[END_REF][START_REF] Jones | Relation between postprandial satiation and antral area in normal subjects[END_REF] .

Other studies suggest that not (only) gastric distension is important in the regulation of satiety: in a study in which a concentrated and a diluted meal of 2500 kJ were served to healthy volunteers satiety scores and gastric emptying of solids and liquids did not differ between the meals. A significant correlation however was observed between satiety scores and emptying of the solid fraction in both meals. It was concluded that it is not the volume of the meal that influences satiety but rather the gastric emptying rate of the solid meal fraction of that meal, indicating that gastric emptying of energy and not volume of the ingested meal is the major determinant of satiety [START_REF] Carbonnel | Effect of the energy density of a solid-liquid meal on gastric emptying and satiety[END_REF] . Other studies confirm that feelings of hunger or satiation are dependent on gastric emptying of fat and indeed intestinal exposure to the nutrients [START_REF] Horowitz | The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite[END_REF]100 .

From the findings in the studies above we can conclude that a complex relationship exists between gastric emptying and appetite. We postulate that both gastric (dis)tension and intestinal exposure play a role in the regulation of appetite, but the relative emphasis shifts towards intestinal exposure when the stomach empties.

Interestingly, several anorexigenic hormones such as CCK, PYY, GLP-1 etc. inhibit gastric emptying (and at the same time increase gastric compliance) [START_REF] Hellström | The physiology of gastric emptying. Best Practice & Research[END_REF]101,102 , and these effects on gastric motility can contribute to their effects on satiation.

Return of hunger: role of gastric Phase III contractions

Feelings of hunger have long been associated with contractions of the empty stomach. A little less than 100 years ago Cannon & Washburn described powerful contractions of the empty stomach and showed that they were invariably correlated with hunger pangs that were also perceived as rumbling in the epigastrum 103 . They suggested that the hunger sensation resulted from these contractions. Interestingly, these 'hunger contractions' persisted after vagotomy, indicating that their initiation is independent of the central nervous system 104 . The 'hunger contractions' could later be identified as being part of the MMC. Indeed, when stomach and small intestines are emptied after a meal a very typical myoelectrical and contraction pattern emerges that is characterized by 3-4 phases: phase I is a quiescent period with virtually no contractions, phase II consists of random irregular contractions with low amplitude, Although the association between phase III contractions and hunger pangs was recently confirmed (Figure 3) the underlying mechanism remains unexplained 116 . By means of ultrasound, the typical sensation of rumbling in the epigastrium or 'borborygmia' has been linked to movement of air within the gastric lumen during phase III contractions, possibly from the proximal stomach to the antrum, and in the intestines 117 . This movement of air could explain the rumbling sensation during phase III, however strong contractions in the stomach that can displace air are not exclusively linked to phase III contractions. We recently described that administration of motilin in individuals with an empty stomach induced phase III contractions and associated hunger pangs. Interestingly, antral contractions of a similar amplitude induced by a cholinesterase inhibitor are not associated with hunger, indicating that hunger sensations require a typical phase III pattern or motilin receptor stimulation 118 . Although administration of both motilin and ghrelin are known to induce phase III contractions, only motilin plasma levels fluctuate with the MMC, indicating that motilin is closely related to hunger pangs 119 . Furthermore, while significant correlations were found between motilin, phase III contractions and hunger scores, the best correlation was found between hunger ratings and plasma motilin levels 120 , 120 . These findings indicate that sensation of hunger is closely associated with plasma motilin levels as well as phase III contractions 120 . Whether it is the rise in motilin plasma levels or gastric phase III contractions themselves that trigger the sensation of hunger pangs still remains to be properly investigated. A third option is that the motor and hormonal changes are merely epiphenomena to the hunger pangs but this has not been studied experimentally.

POTENTIAL FOR THERAPEUTIC INTERVENTION

Pharmacological agents

To date there are no drugs on the market that have been developed to modify gastric motility in order to treat over or underweight. However, different drugs that are used to treat obesity have also known effects on gastric motility.

The weight loss effect of the lipase inhibitor orlistat is attributed to the decreased absorption of dietary fat. Interestingly, orlistat does not affect gastric accommodation and meal-induced satiety and, if anything, increases appetite and food consumption 121,122

. The latter effect can be attributed to the decreased postprandial release of GIP, GLP-1, CCK and PYY, furthermore orlistat is known to accelerate gastric emptying, which decreases gastric distention 123 .

Sibutramine is a centrally-acting serotonin and norepinephrine reuptake inhibitor and is used for the treatment of obesity 124 . The anorexigenic effect of sibutramine is thought to be mediated through serotonergic and adrenergic mechanisms in the hypothalamic nuclei that regulate appetite. In overweight patients however sibutramine is known to delay gastric emptying 124 . In a barostat study in dogs, sibutramine increased gastric tone and impaired gastric accommodation to an orally ingested meal 125 . The inhibitory effect of sibutramine on gastric emptying and accommodation may partially explain the reduced food intake with sibutramine in patients with obesity.

The selective cannabinoid receptor antagonist rimonabant was marketed for obesity and its anorectic properties are mediated through decreased food intake (actions on the hypothalamus and the limbic system) and by increasing energy expenditure (increased lipolysis and thermogenesis) 126 . In a barostat study we showed that rimonabant decreased gastric accommodation to a meal, however in the same study, nutrient tolerance during a drinking test was not affected 126 . The effect of rimonabant on gastric emptying in humans is at present unknown, however in rats rimonabant has been shown to reverse the endocannabinoids-induced delay in gastric emptying 127 . Although impaired gastric accommodation and increased gastric emptying could increase satiation, it is unclear whether these effects of rimonabant contribute to its effects on food intake and body weight.

The role of opioids in the regulation of food intake is complex: in general opioid agonists enhance feeding and opioid antagonists such as naloxone and naltrexone but also the peripherally-restricted antagonist methylnaltrexone decrease feeding 128- 131 but these effects are dependent for example on the treatment duration and whether normal weight, low weight (anorexia patients) or obese volunteers/patients are selected 132 . We recently showed that the peripherally-restricted opioid receptor antagonist methylnaltrexone increased satiation and that this effect on food intake was more pronounced compared to the centrally-acting antagonist naloxone [START_REF] Janssen | Endogenously released opioids mediate meal-induced gastric relaxation via peripheral mu-opioid receptors[END_REF] .

Interestingly, methylnaltrexone impaired gastric accommodation to a meal and this effect was more pronounced than that of naloxone, suggesting that endogenous opioids mediate gastric accommodation and satiation via peripheral mu-opioid receptors. The existence of a peripheral opioid-related mechanism in control of food intake was confirmed in a study in rats, although in the latter study the effect was mediated via potentiation of the effect of leptin 133 .

The effect of sibutramine, rimonabant, naloxone and methylnaltrexone on gastric motility may contribute to their effects on food intake and body weight. However, so far, a contribution of changes in gastric motility to their effects on body weight has not GLP-1 is a well-known regulator of food intake [START_REF] Gutzwiller | Glucagon-like peptide-1: a potent regulator of food intake in humans[END_REF] and is at the same time known to delay gastric emptying, inhibit antral contractility, decrease fasting tone of the proximal stomach and enhance gastric accommodation 102,134,135 . However, GLP-1 is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), which limits its usefulness as a treatment option. Also long-acting GLP-1 analogues exenatide and liraglutide reduce body weight and have been shown to reduce appetite and promote satiety 136,137 .

Although these peptides are known to induce nausea (most likely mediated through central mechanisms) exenatide and liraglutide are also known to slow down gastric emptying. The latter might explain, at least in part, the effect on food intake 138 . So far their effect on gastric accommodation is unknown. The effect of DPP4 inhibitors on body weight is less clear: no or small changes of the body weight have been observed in patients on vildagliptin 139,140 . In concordance, no effects have been observed on gastric emptying, while effects on gastric accommodation have not yet been investigated 141 .

Other drugs used in the treatment of diabetes also affect body weight and gastric function. Pramlintide, an analog of the pancreatic hormone amylin which is used in the management of diabetes mellitus, reduces hunger and food intake in healthy volunteers. Similar effects have been shown in a 6-week study in obese subjects 142 .

The effect of pramlintide on food intake can partly be explained by the fact that it markedly delays gastric empting [143][144][145] .

Intraluminal devices

As discussed previously, inflation of an intragastric balloon induces fullness and satiation [START_REF] Lee | Differences in the sensorimotor response to distension between the proximal and distal stomach in humans[END_REF] . Based on this principle implantation of an intragastric balloon has been used in the treatment of obesity [START_REF] Rigaud | Gastric distension, hunger and energy intake after balloon implantation in severe obesity[END_REF][START_REF] Nieben | Intragastric balloon as an artificial bezoar for treatment of obesity[END_REF] . Although this procedure initially restricts food intake and is able to decrease feelings of hunger, the effect is transient and not associated with lower energy intake or weight loss [START_REF] Rigaud | Gastric distension, hunger and energy intake after balloon implantation in severe obesity[END_REF] .

Adjustable totally implantable intragastric prosthesis (ATIIP) -Endogast® (Districlass Médical S.A., Chaponnay, France) is a new technique for the treatment of morbid obesity 146 . During a minimally invasive procedure an air-filled prosthesis is fixated to the wall of the proximal stomach. The ATIIP induces early satiation and this effect was attributed to impaired gastric accommodation. In a preliminary study 20-40% excess weight loss was achieved in 40 obese patients 146 .

Based on the principles of bariatric surgery but less invasive is the duodenojejunal bypass liner (EndoBarrier® Gastrointestinal Liner, GI Dynamics, Inc, Lexington, MA, USA), an endoscopically placed and removable intestinal liner that creates a duodenojejunal bypass 147,148 . In obese patients 12-23% excess weight loss was achieved after 3 months. This device indicates the importance of the distal gut and the ileal brake in the regulation of body weight. The ileal brake is mediated through release of PYY, GLP-1 and vagal nerve stimulation. Activation of the ileal brake leads to a reduction in hunger and in food intake 149 , but it is uncertain whether this effect results from direct stimulation of central satiety centers in the brain, or if the ileal brake effect on hunger and satiety is achieved indirectly via the delay in gastric emptying. It is most likely that, after activation of the ileal brake, the enhanced gastric

Bariatric surgery

For morbid obese patients bariatric surgery is an effective treatment that induces sufficient and sustained weight loss 150 . Three major types of bariatric surgery are used to treat obese patients: restrictive procedures (e.g. gastric banding, and sleeve gastrectomy), malabsorptive procedures (e.g. jejuno-ileal bypass) and combination restrictive-malabsorptive procedures (e.g. Roux-en-Y gastric and duodenal switch bypass).

With all types of bariatric surgery patients experience not only early satiation while eating but feel satiated longer after the meal. Hence, they eat considerably less as compared to before the operation. The mechanisms responsible for the effects on satiation and satiety are not well understood however there are indications that sensory signals from the upper gastrointestinal tract play a major role.

During the jejuno-ileal bypass procedure a substantial part of the small intestine is bypassed from the alimentary tract and it is believed that malabsorption of nutrients is responsible for the observed weight loss, although an association with delayed gastric emptying and altered gut hormone patterns has been described 151 . Due to the many complications associated with this procedure this type of bariatric surgery is not longer recommended.

Also for sleeve gastrectomy and Roux-en-Y gastric bypass it has been shown that the levels of different (gut) hormones as ghrelin, GLP-1, insulin and PYY are altered after surgery [152][153][154] . These changes in (gut) hormone levels are held responsible for the increased satiation and satiety and are likely caused because food is delivered faster to the duodenum and into the ileum (activating the ileal break as discussed above) after surgery and does not reside in the stomach as it did before surgery 149 .

Increased gastric emptying has indeed been observed after sleeve gastrectomy [START_REF] Vrang | Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons[END_REF][START_REF] Hayes | Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling[END_REF][START_REF] Phillips | Gastric volume rather than nutrient content inhibits food intake[END_REF] and might be caused by the reduced gastric volume which impairs gastric accommodation and leads to increased tension for the same meal volume. This directly increases satiation but also leads to more rapid delivery of the contents to the intestines, and release gut hormones as described above.

CONCLUSION

From a classical point of view gastric motility acts to clear the stomach in between meals, while postprandial motility acts to provide a reservoir for food, mix and grind the food and assures a controlled flow of food to the intestines. In this review we summarized findings that support the role of gastric motility as a key mediator of hunger, satiation and satiety. We showed that gastric accommodation and gastric emptying play an important role in the regulation of gastric (dis)tension and intestinal exposure of nutrients and hence control satiation and satiety. Moreover, phase III contractions are closely correlated with hunger pangs, intense feelings of acute hunger on top of a more tonic sensation of returning hunger. Apart from acute effects on food intake, we described correlations between gastric accommodation, gastric

  of the fundus and the proximal part of the corpus, and the distal stomach consisting of the distal part of the corpus and the antrum. With regard to motility the proximal stomach is characterized by tonic contractions but no slow wave activity, while the distal stomach is characterized by slow wave activity and peristaltic contractions. Two very different motor patterns can be distinguished in the stomach:

  of nutrients further down the gastrointestinal tract, and/or to changes in gastric muscle tone associated with nutrient ingestion.

  obesity: by reducing the size of the proximal stomach early satiation and fullness lead to substantial weight loss. Although the exact mechanism of early satiation and weight loss in gastric banding is incompletely elucidated, it was

  Satiety signals from the intestineAlthough the intestines, like the stomach, are sensitive to distension[START_REF] Azpiroz | Isobaric intestinal distension in humans: sensorial relay and reflex gastric relaxation[END_REF] , most authors agree that sensation of intestinal contents is mainly based on mucosal recognition of luminal content such as osmolarity, lipid content, products of carbohydrate digestion and mucosal mechanical stimulation. Enteroendocrine cells in the mucosa of the small intestine react to different properties of luminal content by releasing a variety of peptides (e.g. CCK, GLP-1, oxyntomodulin and peptide YY (PYY)) and small

72 .

 72 The time and magnitude of the release is generally dependent on the caloric content and macro-nutrient composition of the meal. Gut hormones exert their action either directly via the bloodstream by leaking through permeable capillaries in the median eminence, and the incomplete blood-brain barrier at the level of the hypothalamic arcuate nucleus, or indirectly via the vagus nerve thereby signaling to the area postrema and the nucleus tractus solitarius in the hindbrain where afferent fibers project to the hypothalamus. In the arcuate nucleus these hormonal signals can in turn activate different populations of orexigenic (neuropeptide Y / agoutirelated peptide neurons, activated by ghrelin) and anorexigenic (proopiomelanocartin/cocaine-and amphetamine-regulated transcript) neurons that modulate amongst others the mediobasal hypothalamic and the paraventricluar

  is a short burst of regular high-amplitude contractions; phase IV represents a short transition period back to the quiescence of phase I {Szurszewski, 1981 1001 /id;Szurszewski, 1969 1325 /id;Itoh, 1981 1327 /id}. Phase III contractions are made up of a group of contractile waves that migrate from the oral to the anal side successively over a constant period, characterized by an interval of 100-150 minutes during fasting. In man, about half of all phase III onsets are located in the stomach and the other half is located in the duodenum. The immediate physiological role of the phase III contractions is believed to provide a pulsatile flow to clear the stomach and small intestines of secretions, debris, and microbes during fasting and let the stomach be ready to receive a next meal. The regulation of phase III contractions and the MMC in general is still not completely resolved. Although there is some evidence that the MMC can be influenced by the CNS, it has been shown to run largely independent of the CNS 107 . It is well-established that the MMC is propagated through the enteric nervous system. Furthermore, there is good evidence that the initiation of the phase III contractions in the stomach might be regulated by gut hormones such as somatostatin and motilin. Indeed, a close relationship between plasma motilin levels and phase III contractions is well-established: plasma motilin concentrations fluctuate during the interdigestive state and peak directly before the occurrence of phase III contractions in the stomach or upper duodenum 108 .Immunoneutralization of circulating motilin suppresses these activity fronts 109,110 and exogenous administration of motilin initiates premature phase III contractions in the stomach in dogs 111,112 and humans 113 . Plasma somatostatin levels are associated with phase III activity fronts in the duodenum and somatostatin infusion can induce intestinal activity fronts114,115 .

  any of the drugs described above and it remains unclear whether the effects on gastric motility are crucial or just an epiphenomenon. More research is needed to investigate directly the link between the effect on gastric motility and decreased food intake and weight loss.

  gastric emptying interacts with a direct stimulation of central satiety centers by hormonal and neural signals, to reduce hunger and energy intake.

  emptying and body weight that indicate that gastric motility can also play a role in the long-term regulation of body weight. Although pharmacological and surgical interventions aimed at reducing weight have sometimes profound effects on gastric is unclear how relevant these changes in gastric motor function are to their effects on appetite and body weight.

Figure 1 .

 1 FIGURES

Figure 2 .Figure 3 .

 23 Figure 2. A hypothetical model of the regulation of satiation, satiety and hunger by

ACKNOWLEGMENTS

Pieter Janssen is a research fellow of the 'Fonds voor Wetenschappelijk onderzoek -Vlaanderen, Belgium'. This work was supported by an FWO grant and a Methusalem grant to Jan Tack, M.D., Ph.D. All of the authors have nothing to disclose.


Ravonimanantsoa N Manda-Vy

Randriamitantsoa P Auguste

Comparison Of The Consumption Of Resources Between HTTP And SIP

Keywords: voip, sip, asterisk, http, apache

Currently, the development of research around VoIP experience a tremendous growth. In the community of open source Asterisk represents a reliable alternative for a lower cost solution. In this same community as the SIP protocol is a supplement to the more asterisk PBX. to share the benefits claimed by proponents of free software co-existence with other Asterisk server is not yet proven. In this context this paper we show a comparison of the use of simplified resource material for the apache server using the HTTP protocol and server that uses the asterisk SIP.

Intorduction

The protocol which dominates the current Internet infrastructure is http. But technological convergence over IP [START_REF] Montoro | A comparative stutdy of VoIP standarts with asterisk[END_REF][2] [START_REF] Shekhar | a comparative study of the Sip and IAX Voip[END_REF]networks leads us to see a large deployment of voice over IP on a global scale thanks to the many proprietary PABX. VoIP in general is from a server and most used in the free software world and the asterisk is most widely used protocol is SIP with Asterisk. But to get a better performance for both protocol and he needed to see what happens in the server ie their resource requirement and more specifically the level of memory consumption. To do so we'll at first briefly describe the environment of our experience, in a second you'll see the experience itself that is the course of the experiment and finally we will deduct from our experience a assumption on our experience.

Methodology

Material .

The server: As a server we used a PC dell optiplex GX 110 with a Pentium III processor and a minimum memory 256Mo

The client:we used a PC dell optiplex GX 110 with a Pentium III processor and a minimum memory 128Mo Software: We used the operating system Debian GNU / Linux[4] that is a computer operating system composed of software packages released as free and open source software especially under the GNU General Public License and other free software licenses.The primary form, Debian GNU/Linux, which uses the Linux kernel and GNU OS tools,[4] is a popular and influential Linux distribution.It is distributed with access to repositories containing thousands of software packages ready for installation and use. For the web server we used Apache. Apache is web server software notable for playing a key role in the initial growth of the World Wide Web.In 2009 it became the first web server software to surpass the 100 million website milestone.Apache was the first viable alternative to the Netscape Communications Corporation web server. For the server we used Asterisk VoIP Asterisk is a software implementation of a telephone private branch exchange (PBX); it was created in 1999 by Mark Spencer of Digium. Like any PBX, it allows attached telephones to make calls to one another, and to connect to other telephone services including the public switched telephone network (PSTN) and Voice over Internet Protocol (VoIP) services. Its name comes from the asterisk symbol, "*". Asterisk is released under a dual license model, using the GNU General Public License (GPL) as a free software license and a proprietary software license to permit licensees to distribute proprietary, unpublished system components. Originally designed for Linux, Asterisk now also runs on a variety of different operating systems including NetBSD, OpenBSD, FreeBSD, Mac OS X, and Solaris. A port to Microsoft Windows is known as AsteriskWin32. And for the evaluation of the consumption in memory we used TOP.The top command is a system monitor tool that produces a frequently-updated list of processes. By default, the processes are ordered by percentage of CPU usage, with only the "top" CPU consumers shown. top shows how much processing power and memory are being used, as well as other information about the running processes. Some versions of top allow extensive customization of the display, such as choice of columns or sorting method. top is useful for system administrators, as it shows which users and processes are consuming the most system resources at any given time.

Conducting the experiment:

At first we run the top command and evaluated the memory used by the operating system. Several parts of the memory is already used for reasons within the system and for different services such as the launch of all deamon. The following figure(Fig. 1) shows the state of our system during the initial phase of our experience. In a second time a customer accesses the apache server in our system and we do the sampling with the top command(Fig. 2) and after sampling it disconnects the client. In the third time we launch a call with a softphone, first you do not pick and we launch the top command (Fig. 3 )and then pick up and watch as it happens(Fig. 4) .

Results and commentary Results:

According to simulations, the phase initila mamoire free 22220ko is then connected when the client http free memory becomes 7348ko ie an http client consomne 14872ko memory and if we therefore multiplied the number of client server may stop responding. when initiating the call from a softphone free memory is 21980ko (this when the other end does not answer yet) then when it picks up the free memory becomes 21,740 which means that even if the customer lifts the receiver called the initiation of a SIP call consomne already resource at the server and the client called to consumption picks up in the memory increases. ramarque: the level of free memory 22220ko spent during the initial 21980ko during the launch of the appeal is to say that the memory occupied by a non-call pick up is 240ko. Then when the called party has picked up the level of memory is increased from 21980ko to 21740ko ie that Emmis's call with a second client occupies the same memory that the caller 240ko so if a call is has 480ko memory used and this we can deduce that the memory used(Mu) during a call 2nK Sip it with K = 240ko

Mu=2nK

(1)

conclusion

We have presented experimental results obtained during the simulation of a VoIP call and also the comparison with the http protocol. The different figures and results showed us that the http protocol consomne lot of memory compared to SIP, but a call sip Equival has a double connection to the server. It should be noted that the increase of the call can sip unanswered generated also a saturation of the mathematical model proposed mémoire.Le would then determine the number of calls made in relation to the size of memory used by the server.

  Fig. 1

Fig. 2

 2 Fig. 2

Fig. 3

 3 Fig. 3

Fig. 4

 4 Fig. 4


Marcus Dejardin
email: marcus.dejardin@fundp.ac.be

D Audretsch

O Falck

Entrepreneurship and Rent-Seeking Behavior *

Keywords: JEL-classification: L26, D70, O10, O40 entrepreneurship, rent-seeking, economic development

published or not. The documents may come   L'archive ouverte pluridisciplinaire

Entrepreneurship is now pervasively recognized in economic theory for its contribution in carrying innovation into the economic process and, consequently, in feeding economic growth [START_REF] Aghion | A model of growth through creative destruction[END_REF][START_REF] Carree | The impact of entrepreneurship on economic growth[END_REF]. Ceteris paribus, different entrepreneurial endowments may explain different rhythms of growth between nations. Among the theoretical discussions of the several conditions entering the ceteris paribus assumption, one appears tremendously fruitful. It relates to the allocation of the entrepreneurial resources between more or less socially productive activities. All activities in a maximizing economy are not equally conducive to production and economic growth. Some can even affect growth negatively. The idea is linked with the concept of rent-seeking behavior. The connections between entrepreneurship and rent-seeking behavior constitute the topic of this chapter.

Having defined the general framework and employed concepts, we shall discuss the allocation of entrepreneurs between different types of economic projects (in other words, between innovative entrepreneurship and rent-seeking), as well as the explicative factors of this allocation. A dynamic set-up follows where interactions between project categories and relations to growth are scanned. We conclude by briefly examining some policy implications.

Introducing entrepreneurship and rent-seeking behavior

Assuming that the individual arbitrage between different remunerative occupations ends up, in all cases, in the development of socially productive activities, the economy is sketched as a strict income economy. Maximizing individuals exploit their skills as best they can. Moreover, in a perfectly competitive economy, private and social benefits coincide. Now, let us introduce an activity that is remunerated by transfers. We note that, by definition, transfers do not imply a productive counterpart. Transfers result in the possibility that distortions between private and collective interests may occur. This distortion is undoubtedly effective when rent-seeking is involved when compared with the classical competitive benchmark model. That is, the actual net effects of rent-seeking (whether positive or negative) is a matter of concern since optimal allocation and dynamic efficiency of the economy are not taken for granted, as suggested later on.

Although Tullock introduced the basic argument corresponding to rent-seeking behavior to public choice theory in 1967, the term 'rent-seeking' was not coined until Krueger published 'Political Economy of the Rent-Seeking Society' in the American Economic Review in 1974 (see [START_REF] Tullock | The origin rent-seeking concept[END_REF]. According to its most common and widespread definition, rent-seeking (behavior) refers to 'the socially costly pursuit of wealth transfers' (Tollison, 1997, p. 506). Rent-seekers' private returns result from redistribution of wealth and not from wealth creation [START_REF] Murphy | The allocation of talent: implications for growth[END_REF].

The rent at stake here is to be distinguished from entrepreneurial creation of rents: rents due to better use of resources, arising from specific assets or technology, securable (by patents, for example) but limited in time from the pressure of competitors and progress [START_REF] Douhan | The political economy of entrepreneurship[END_REF]; see also [START_REF] Alvarez | Entrepreneurial rents and the theory of the firm[END_REF]Douhan and Henrekson, 2008a).

On the other hand, Tollison's definition of rent-seeking allows for an expression of social opportunity costs in terms of resources diversion to, or following, the rent-seeking activity. Examples of rent-seeking include corruption, stealing, bribery, as well as seeking abusive judicial compensation or protection-seeking with the express purpose of limiting economic competition and promoting particular interest. Rent-seeking can originate from both the public and private sectors.

For the connection between entrepreneurship and growth, the occurrence of unproductive but remunerated activities means that not only are projects with socially positive or negative impacts in competition, but also that there is a direct potential diversion of entrepreneurial talents. For this diversion to take place, it is assumed that the skills and abilities required by entrepreneurship and by rent-seeking correspond.

Following these introductory considerations, at least two remarks can be formulated that are considered as important additions. The first refers to public action and public services. The economic rationale for public intervention refers generally to market failures, magnificent evidence-jigging from economic reality and questioning the benchmark of the perfectly competitive model.1 Public services are generally financed by transfers. That being the case, transfers are not a sufficient condition for defining rentseeking. Public services are not included in rent-seeking given their socially productive contribution. We note further that, while a discussion of the redistribution role of the state is outside the framework of this chapter, things may appear differently if we look at legal institutions that organize productive activities, as they might, for example, create rent-seeking behaviors by limiting competition.

The second remark concerns the entrepreneurial initiatives and goes back to the entrepreneurial creation of rents through innovation. Through innovation, the entrepreneur seeks to create a monopoly position, from which he will derive overprofit. In the Schumpeterian model, this position is necessary as it motivates the innovation activity. However, it is temporary, as competition will quickly reduce this position in favor of a new monopoly created by a new innovation. The institutional framework of competition is of primary importance. In this case, a dynamic assessment of the entire process will justify the existence of an abnormal profit, as it will distinguish its positive net contribution to the social benefit2 .

Rent-seeking behavior thus defined, as well as the general framework of this chapter, we address in the following discussion the allocation of talents between socially productive entrepreneurship and rent-seeking or unproductive activities.

Explaining the allocation of talents

Attempting to explain the allocation of talents implies considering a variety of arguments explaining individual arbitrage between distinct remunerative activities. Together with relative remunerations, institutions or non-pecuniary factors may also play a role. According to Murphy et al. (1991, p. 506), 'talent goes into activities with the highest private returns, which need not have the highest social returns'. These authors assume increasing returns on talent. In other words, the greater the ability of an individual, the greater his private benefits will be. Because the exercise of talent is physically limited (by the period of human activity in a day), talented individuals tend to invest themselves and their abilities in reward-maximizing occupations. It follows that their occupational choice is almost directly determined by the size of the market, the compensation contract (rewards on talent application) and the technology.

Furthermore, the allocation of talent can be linked with both institutional context and non-pecuniary explicative factors. The legal framework and its effective use define a propitious environment for entrepreneurship and, contrarily, for rent-seeking behavior. Property rights, the conditions of their application, and the respect of these rights, joined with governance and fiscal organization, appear to be crucial factors. They contribute particularly and decisively to determine compensation schemes. Information is also important as it determines the efficiency of allocation and how far it is possible to link talents' application and its social and economic results [START_REF] Baumol | Entrepreneurship: productive, unproductive, and destructive[END_REF][START_REF] Baumol | Entrepreneurship, management, and the structure of payoffs[END_REF][START_REF] Murphy | The allocation of talent: implications for growth[END_REF][START_REF] Acemoglu | Reward structures and the allocation of talent[END_REF][START_REF] Mohtadi | Democracy, rent-seeking, public spending and growth[END_REF][START_REF] Gradstein | Governance and growth[END_REF][START_REF] Corchón | Forms of governance and the size of rent-seeking[END_REF].

Social esteem may play a role. The question therefore becomes how much entrepreneurship is socially valued over other less socially productive occupations (see the seminal [START_REF] Baumol | Entrepreneurship: productive, unproductive, and destructive[END_REF][START_REF] Baumol | Entrepreneurship, management, and the structure of payoffs[END_REF]. Finally, entrepreneurs or rent-seekers may influence, by voting or lobbying, political organization and political decisions. The idea is that the political equilibrium, responding to one or another group's interests, will make decisions favoring its maintenance [START_REF] Acemoglu | Reward structures and the allocation of talent[END_REF]. Regarding this last argument, we point out that the innovative entrepreneur would be strongly inclined, when in a (temporary) monopoly position, to adopt rent-seeking behavior.

Entrepreneurship and rent-seeking in motion

The interaction between entrepreneurship and rent-seeking is an interesting question to examine. Formalized models show that multiple equilibria -an equilibrium being defined by an entrepreneur share in the population and a rate of growth -may exist [START_REF] Murphy | Why is rent-seeking so costly to growth?[END_REF][START_REF] Acemoglu | Reward structures and the allocation of talent[END_REF]Mehlum et al., 2003aMehlum et al., , 2003b)). Readers interested in model developments may consult the above references. To give a brief overview, we note that results may be derived from the specification of two functions, both with negative slopes, and consequently the potential for multiple intersections. Because it places burdens on entrepreneurial rewards, rent-seeking negatively affects entrepreneurship. Moreover, given competition in the rent-seeking sector itself, 3 rent-seeking rewards will depend negatively on the number of rent-seekers. [START_REF] Baland | Rent-seeking and resource booms[END_REF] formalize the effect of entrepreneurial activities on rent-seeking. Their model applies to an economy with import licenses. The production of direct substitutes by local entrepreneurs tends to limit the rents obtained by importers. Results suggest the existence of multiple equilibria. Additionally, these authors discuss the effect of an exogenous resource boom such as an increase in income resulting from an increase in the world price of exports. In their model, the result, more entrepreneurship or more rent-seeking, depends on the importance of the proportion of entrepreneurs and rentseekers in the population preceding the shock. [START_REF] Lane | Power, growth, and the voracity effect[END_REF] initiate an important and often connected literature with the introduction of the 'voracity effect', which is 'a more than proportional increase in aggregate redistribution in response to an increase in the raw rate of return ' (p. 226). Recent contributions, also related to the 'natural resource curse', include those by [START_REF] Torvik | Natural resources, rent seeking and welfare[END_REF], [START_REF] Mehlum | Institutions and the resource curse[END_REF], [START_REF] Perroni | Entrepreneurial drain under moral hazard: A highyield sector curse?[END_REF], and [START_REF] Do | Trade, inequality, and the political economy of institutions[END_REF]. For the sake of illustration, [START_REF] Tornell | The voracity effect[END_REF] analyze the consequences of windfall gains in a two-sector economy. The first sector can be taxed, the second cannot. Moreover, the first sector uses more efficient technology than the second. Weak legal and political institutions as well as the existence of powerful lobbies characterize the economy. Each tries to support their own interests in an effort to increase their share of the national wealth through additional transfers. This leads to higher tax rates, where they can be applied, i.e. in the first sector. This provokes the reallocation of production factors toward the non-taxed and less productive sector. The result, the so-called voracity effect, is that a positive exogenous shock is followed by a more than proportional increase in transfers and a decline in growth.

Rent-seeking behavior may affect entrepreneurial activities and innovation. Several contributions can be found modeling the relationships. Recent contributions include Acemoglu and Robinson (2006a), and [START_REF] Chaudhry | Do Governments Suppress Growth?: Institutions, Rent-Seeking, and Innovation Blocking in a Model of Schumpeterian Growth[END_REF]. A simple, nonformalized but clear-cut discussion of the problem is proposed by Murphy et al. (1993, pp. 412-13). These authors suggest that rent-seeking, whether from private or public origins, can undoubtedly jeopardize the profits of established productive sectors. The innovation sector, however, might be described as the reserved hunting ground of public rent-seeking. In particular, their arguments rely on the nature of innovation. While the project develops, the innovative entrepreneur is confronted with legal and environmental constraints. Innovation may need production permits, licenses, dispensations, as well as amendment to local zoning regulations. This results in demand for government intervention and provides opportunities for corruption. Moreover, the socially unproductive transfers that corruption implies may inhibit some innovative activity, given that innovators may not have equal lobbying power compared to that of established firms, or the same financial resources to pay bribes. To avoid expropriation, important funds are then consumed instead of invested. The ex post existence of rentseeking should increase project risk and effective cost. The authors mention, following these arguments, that the negative effects of rent-seeking could be limited if the rentseeker became a stakeholder in the innovation project. In the long run, rent-seekers should be interested in such involvement. This idea can be generalized as: rent-seeking, by jeopardizing current entrepreneurial profits, limits its future transfer opportunities. See Mehlum et al. (2003b).

The interaction between entrepreneurship and rent-seeking can generate multiple equilibria that correspond to an allocation of talents and an economic growth rate. Starting from a dynamic extension of his basic model, [START_REF] Acemoglu | Reward structures and the allocation of talent[END_REF] discusses the history dependence of an economy. 4 Past and current allocation of talents influences the future structure of rewards. Given historical circumstances (particularly describing successive states of determining factors and allocation), the economy can be locked in low or high steady-state equilibrium. The extremes are high rent-seeking with low growth rate versus highly active and socially productive entrepreneurship with high growth rate. Under these circumstances, for economies trapped in inferior equilibrium, it seems that only an exogenous shock will have any positive and sustainable effect.

That being the case, if rent-seeking affects innovation and economic growth, the actual net effects of rent-seeking are not always as clear as the above cited literature on rentseeking suggests. One may expect the effects to be obviously negative. But rent-seeking should also be discussed in comparison with a reference situation that could be far from the benchmark of the perfectly competitive model. In some circumstances -for a reference situation that is not the first best but could be more comparable with the actual situation of a given jurisdiction, the net effects could be positive, as has been suggested by some authors [START_REF] Samuels | A critique of rent-seeking theory[END_REF][START_REF] Douhan | The political economy of entrepreneurship[END_REF]. Distorted allocation may render rent-seeking necessary to attain greater efficiency. For example, accepting the rent-seeking behavior of some official (or even taking it as an opportunity) and bearing the cost of bribery may sometimes be the only way for an entrepreneur to make concrete efficiency-enhancing innovation. Both from a private and a social viewpoint, efficiency gains can be greater than the rent-seeking costs -and achieving the new situation would be impossible without accepting rent-seeking.

Entrepreneurship, rent-seeking and public policy

The allocation of entrepreneurial supply between socially productive and unproductive, or rent-seeking, projects relies on an arbitrage. The result contributes to determining economic growth. In contrast to entrepreneurial supply, which is ultimately explained by the distribution of skills and abilities in the population and on which it is difficult to intervene, the allocation presents some opportunities for public actions [START_REF] Baumol | Entrepreneurship: productive, unproductive, and destructive[END_REF][START_REF] Baumol | Entrepreneurship, management, and the structure of payoffs[END_REF][START_REF] Naudé | Entrepreneurship in Economic Development[END_REF]. It could, for example, take the form of (additional) fiscal measures in favor of innovation rewards. Another way could consist in (heavier) penalties on socially unproductive activities. [START_REF] Dutz | Entrepreneurship, access policy and economic development: lessons from industrial organization[END_REF], referring more particularly to economies that are developing or in transition, and [START_REF] Minniti | The role of government policy on entrepreneurial activity: productive, unproductive, or destructive?[END_REF] stress the primordial role that could be played by governments in creating (or reinforcing) institutions that foster entrepreneurship. An emphasis on better institutions and regulation can be included in a more general framework helping to define entrepreneurial policy guidelines (see [START_REF] Audretsch | Explaining entrepreneurship and the role of policy: a framework[END_REF]).

Observation of reality would not only lead to point market failures but state failures as well, as public choice theorists would note.

On this question, see[START_REF] Buchanan | Rent seeking and profit seeking[END_REF].

Acemoglu (1995, p. 29) discusses the case when barriers to entry in rent-seeking activities are established by insiders.

Also see some more recent contributions:[START_REF] Acemoglu | Institutions as the fundamental cause of long-run growth[END_REF],Acemoglu and Robinson (2006b),Douhan and Henrekson (2008b).

Acknowledgment:

The author thanks Jean-Marie Baland, Pierre Perrin, Margaret Main, Michel Mignolet and Adam Lederer for comments on earlier versions.