Closed-loop Identification of an Industrial Extrusion Process

This paper deals with the challenging problem of closed-loop identification for multivariable chemical processes and particularly the estimation of an open-loop plant model for a lab-scale industrial twin-screw extruder used in a powder coatings manufacturing line. The aim is to produce a low order efficient model in order to assist the scaling-up and the model-based control design of the manufacturing process. To achieve this goal, a two-stage indirect approach has been deployed which relies on the a-priori knowledge of the controller parameters in order to extract good estimates of the open-loop dynamics of the underlying process. As input excitation signals we have used multiple single variable step tests at various operating conditions (current industrial practice) carried out manually in order to generate the data-set which captures the dynamics of the extrusion process. In order to increase the efforts for obtaining a suitable plant model, we have employed various identification techniques, such as Prediction Error Methods (PEM) and Subspace Identification Methods (SIM) in order to generate candidate closed-loop models that fit to the original input-output process data. Then, a comparison of the estimated models was performed by means of the mean square error and data fitting criteria in order to select the model that best describes the dynamic behaviour of the extrusion process. Model validation based on closed-loop step responses also used as verification of the results

Spontaneous Group Synchronization of Movements and Respiratory Rhythms

Peer reviewe

Cue properties change timing strategies in group movement synchronisation

To maintain synchrony in group activities, each individual within the group must continuously correct their movements to remain in time with the temporal cues available. Cues might originate from one or more members of the group. Current research suggests that when synchronising movements, individuals optimise their performance in terms of minimising variability of timing errors (asynchronies) between external cues and their own movements. However, the cost of this is an increase in the timing variability of their own movements. Here we investigate whether an individual’s timing strategy changes according to the task, in a group scenario. To investigate this, we employed a novel paradigm that positioned six individuals to form two chains with common origin and termination on the circumference of a circle. We found that participants with access to timing cues from only one other member used a strategy to minimise their asynchrony variance. In contrast, the participant at the common termination of the two chains, who was required to integrate timing cues from two members, used a strategy that minimised movement variability. We conclude that humans are able to flexibly switch timekeeping strategies to maintain task demands and thus optimise the temporal performance of their movements

The choreography of group affiliation

When two people move in synchrony, they become more social. Yet, it is not clear how this effect scales up to larger numbers of people. Does a group need to move in unison to affiliate, in what we term unitary synchrony; or does affiliation arise from distributed coordination, patterns of coupled movements between individual members of a group? We developed choreographic tasks that manipulated movement synchrony without explicitly instructing groups to move in uni- son. Wrist accelerometers measured group movement dynamics and we applied cross recurrence analysis to distinguish the temporal features of emergent unitary synchrony (simultaneous move- ment) and distributed coordination (coupled movement). Participants’ unitary synchrony did not predict pro-social behavior, but their distributed coordination predicted how much they liked each other, how they felt toward their group, and how much they conformed to each other’s opinions. The choreography of affiliation arises from distributed coordination of group movement dynamics

The relationship between gambling event frequency, motor response inhibition, arousal, and dissociative experience

Speed of play has been identified as a key structural characteristic in gambling behaviour, where games involving higher playing speeds enhance the experience of gambling. Of interest in the present study is the consistent finding that games with higher event frequencies are preferred by problem gamblers and are associated with more negative gambling outcomes, such as difficulty quitting the game and increased monetary loss. The present study investigated the impact of gambling speed of play on executive control functioning, focusing on how increased speeds of play impact motor response inhibition, and the potential mediating role arousal and dissociative experience play in this relationship. Fifty regular non-problem gamblers took part in a repeated-measures experiment where they gambled with real money on a simulated slot machine across five speed of play conditions. Response inhibition was measured using an embedded Go/No-Go task, where participants had to withhold motor responses, rather than operating the spin button on the slot machine when a specific colour cue was present. Results indicated that response inhibition performance was significantly worse during faster speeds of play, and that the role of arousal in this relationship was independent of any motor priming affect. The implications of these findings for gambling legislation and gambling harm-minimisation approaches are discussed

Systemic delivery of human parathyroid hormone (1-34) by inhalation / Administration systémique de l'hormone parathyroidienne humaine (1-34) par inhalation

L'ostéoporose est une maladie métabolique de l'os caractérisée par une faible masse osseuse et une détérioration structurale du tissu osseux induisant un risque accru de fractures. Les agents antirésorptifs tels que les oestrogènes, les biphosphonates ou la calcitonine diminuent le remodelage osseux en inhibant les ostéoclastes, et préviennent ainsi une future perte osseuse. Cependant, l'architecture et la masse osseuse restent inchangées. Une thérapeutique plus efficace doit inclure la stimulation de nouvelle formation osseuse. Un effet anabolique sur l'os a été démontré après administration sous-cutanée intermittente de faibles doses d'hormone parathyroïdienne. Cette hormone stimule la formation d'os cortical et trabéculaire, et augmente la croissance et la densité osseuses. Son fragment 1-34 N-terminal (PTH) exhibe toute l'activité biologique de la molécule mère et a été lancé sur le marché américain en décembre 2002 sous forme d'injections sous-cutanées pour le traitement de l'ostéoporose post-ménopausique. Un challenge majeur pour la thérapie par PTH consiste à trouver une alternative non-invasive aux injections sous-cutanées quotidiennes. L'administration systémique de macromolécules par inhalation est très attrayante depuis quelques années car un certain nombre de peptides et de protéines sont absorbés plus efficacement par les poumons que par les voies orale, nasale ou transdermique. La voie pulmonaire a été évaluée pour la PTH chez le rat et le singe par instillation intratrachéale et par nébulisation donnant une biodisponibilité de 40% et 29%, respectivement. Cette bonne absorption systémique résulte de caractéristiques physiologiques uniques du poumon : une large surface d'absorption, une barrière étroite vers la circulation sanguine, un flux sanguin élevé, un métabolisme local relativement faible et l'évitement de l'effet de premier passage hépatique. Le but de cette thèse était d'optimiser l'administration systémique de PTH sous forme de poudres sèches. Les inhalateurs à poudre sèche présentent des avantages pour l'administration de peptides via le poumon car ils sont portatifs, faciles d'utilisation, bon-marché, ne contiennent pas de gaz, et peuvent permettre une meilleure stabilité de la formulation grâce à son état sec. Les poudres sèches ont été préparées avec des sucres et des composés endogènes au poumon tels que l'albumine et le dipalmitoylphosphatidylcholine (DPPC) par spray-drying. Nous avons analysé la taille et la densité des particules, les propriétés d'aérosolisation des poudres in vitro, l'intégrité chimique du peptide incorporé ainsi que la stabilité des poudres. L'efficacité de l'absorption systémique du peptide sous forme de poudres sèches de différentes compositions a été évaluée in vivo chez le rat. La tolérance aiguë des poumons aux poudres a également été évaluée in vivo. Afin d'optimiser l'efficacité de la PTH inhalée, nous avons étudié in vivo chez le rat l'impact de la déposition pulmonaire des formulations liquides ou sèches ainsi que l'impact des excipients albumine et DPPC, tous deux présents dans le fluide alvéolaire. Nous avons produit par spray-drying des particules petites (4.5 ± 0.1 µm) et légères (0.039 ± 0.006 g/cm3) optimisées pour leur efficacité d'aérosolisation dans les impacteurs à cascade in vitro. La bonne reproductibilité de la préparation des poudres a été démontrée. La dose émise de poudre en utilisant un inhalateur de type Spinhaler a atteint 91%, la fraction des particules fines s'est élevée jusque 61% et le diamètre aérodynamique expérimental était compris entre 4.0 et 4.5 µm. Le fait de varier le flux d'air entre 30 et 100 L/min n'a pas eu d'impact important sur ces caractéristiques aérodynamiques. La stabilité physique d'une poudre composée de PTH/lactose/DPPC 10:30:60 (p/p) et contenue dans un récipient protégeant de l'humidité a été démontrée pendant 6 mois à des températures de 5° et 25°C. L'intégrité chimique du peptide formulé a été démontrée directeOsteoporosis is a metabolic bone disease characterized by low bone mass and structural deterioration of bone tissue leading to increased risks of fracture. Antiresorptive agents (e.g., estrogens, bisphosphonates, calcitonin) reduce bone remodeling by inhibiting osteoclasts, and thereby prevent further bone loss. However, the architecture and the mass of the bone remain unchanged. A more effective therapeutic approach would involve the stimulation of new bone formation. Anabolic effect on bone has been demonstrated after the intermittent subcutaneous administration of low doses of parathyroid hormone. Parathyroid hormone stimulates new cortical and trabecular bone formation, improves bone growth and density. Its 1 to 34 N-terminal fragment (PTH) exhibits full biological activity and has been launched as a subcutaneous formulation on the US market for the treatment of postmenopausal osteoporosis in December 2002. A major challenge that remains in PTH therapy consists in finding a non-invasive alternative to the daily subcutaneous injections. Systemic delivery of macromolecules by inhalation is attracting considerable attention since a decade because a number of peptides or proteins are more efficiently absorbed from the lung than from the oral, nasal or transdermal routes. The pulmonary route has been evaluated for PTH in rats and monkeys using intratracheal instillation or nebulization and the absolute bioavailabilities were 40% and 29%, respectively. Efficient systemic absorption results from unique physiological features of the lung: the large absorptive surface area, the very thin diffusion path to the bloodstream, the elevated blood flow, the relatively low metabolic activity locally as well as the avoidance of first-pass hepatic metabolism. The aim of this thesis was to optimize the systemic delivery of PTH using inhalation dry powders. Dry powder inhalers present advantages for peptide delivery to the lung as they are portable, easy to operate, inexpensive, propellant-free, and could show improved stability of the formulation as a result of the dry state. We prepared powders with sugars and compounds endogenous to the lung such as albumin and dipalmitoylphosphatidylcholine (DPPC) by spray-drying, and analyzed their particle size and density, their aerosolization properties in vitro, the chemical integrity of the peptide incorporated as well as their stability. We assessed in vivo in the rat the efficacy for systemic absorption of dry powders of PTH made of different composition and examined the tolerability of the rat lung to powder insufflation. In order to optimize the effectiveness of inhaled PTH, we assessed in vivo in rats the impact on pulmonary absorption of the site of lung deposition of the formulation, and of new factors as the use of the excipients albumin and DPPC, both abundant component of lung surfactant, and the physical state of the formulation, solution or powder. We produced small (4.5 ± 0.1 µm) porous (0.039 ± 0.006 g/cm3) particles by spray-drying optimized in terms of aerosolization efficiency in cascade impactors in vitro. Good reproducibility of the dry powder preparation was demonstrated. The emitted dose using a Spinhaler inhaler device reached 91%, the fine particle fraction up to 61% and the experimental mass median aerodynamic diameter was comprised between 4.0 to 4.5 µm. Varying the airflow rate from 30 to 100 L/min had limited influence on the aerodynamic behavior of the aerosols. The physical stability of a powder composed of PTH/lactose/DPPC 10:30:60 (w/w/w), stored in a container protecting from humidity, was demonstrated until 6 months at 5°C and 25°C. The chemical integrity of the formulated peptide was demonstrated directly after spray-drying but not over time as 15% and 21% decrease in PTH content were measured after 6 months at 5° and 25°C, respectively. This pattern of degradation was similar as the one obtained with the neat peptide. A pharmacokinetic study was performed in rats after subcutaneous and intravenous injection of PTH and after intratracheal insufflation of two types of dry powders, one composed of PTH/albumin/lactose/DPPC 1:30:10:60 and the other of PTH/lactose/DPPC 10:30:60. The absolute PTH bioavailability was 21% after intratracheal administration of the powder containing albumin. Equilibrium dialysis revealed 71 to 78% binding of PTH to albumin and the withdrawal of albumin from the powder increased the absolute bioavailability after inhalation from 21 to 34%, showing that binding to formulated albumin significantly decreased absorption to the systemic circulation. No acute inflammation appeared in the lung up to 48 h after a single inhalation. The absolute bioavailability of PTH was also assessed after several methods of instillation of PTH solutions with and without DPPC, followed or not by insufflation of an air-bolus. Deposition in the trachea, peripheral and central lobe sections was assessed after tissue grinding using albumin-biotin as a marker. Instillation using a precise microsyringe followed by an air-bolus and using spray-instillation, followed or not by an air-bolus, yielded a PTH bioavailability of 37, 16 and 10%, and a peripheral to central (P/C) zones ratio of 0.52, 0.39, and 0.30, respectively. As insufflation of the powder free from albumin resulted in a bioavailability of 34%, in spite of a P/C ratio of only 0.12, the high absorption was explained to result from an impact of the excipient DPPC. This was confirmed by the increase in bioavailability to 65% after instillation with the microsyringe of a PTH/DPPC suspension. In conclusion, a mode of administration that favors peripheral deposition, the avoidance of albumin in the formulation and/or the use of DPPC dramatically promoted PTH absorption.Thèse de doctorat en sciences pharmaceutiques (FARM 3) -- UCL, 200

Closed-Loop Identification with an Unstable or Non-minimum Phase Controller

In many practical cases, the identification of a system is done in closed loop with some controller. In this paper, we show that the internal stability of the resulting model, in closed loop with the same controller, is not always guaranteed if this controller is unstable and/or nonminimum phase, and that the classical closed-loop prediction-error identification methods present different properties regarding this stability issue. With some of these methods, closed-loop instability of the identified model is actually guaranteed. This is a serious drawback if this model is to be used for the design of a new controller. We give guidelines to avoid the emergence of this instability problem; these guidelines concern both the experiment design and the choice of the identification method