Neurophysiologic and proteomic investigations of experience-dependent plasticity in the somatosensory cortex of the adult mouse following chronic whisker stimulation

RESUME Les follicules des vibrisses des rongeurs sont représentés sous la forme d'une carte topographique dans le cortex à tonneaux. Lorsque un groupe de vibrisses est coupé pendant plusieurs jours chez un rongeur adulte, en laissant les autres vibrisses intactes, le champ réceptif des neurones du cortex à tonneaux est modifié, ce qui démontre que les cartes corticales sont plastiques. Dans notre étude, une expérience sensorielle a été induite chez une souris adulte se comportant librement en stimulant chroniquement une de ses vibrisses pendant 24h. Par une analyse des potentiels de champ locaux, nous démontrons que les caractéristiques spatiotemporelles du flux d'excitation évoqué par la vibrisse principale (VP) dans la colonne corticale correspondante à la vibrisse stimulée n'est pas altéré. Par contre, l'enregistrement des potentiels d'actions d'un total de 1041 neurones à travers le cortex à tonneaux révèlent plusieurs modifications de l'activité neuronale. L'activité spontanée ainsi que la réponse évoquée par la VP sont déprimées dans la colonne corticale stimulée (nombre moyen de potentiels d'action évoqués par la VP diminue de 25 % et 36% dans la couche IV et les couches II&III). La réponse des neurones à la vibrisse stimulée diminue également dans les colonnes corticales adjacentes, «non-stimulées». La dépression de l'activité spontanée et de la réponse à la VP est localisée à la colonne corticale stimulée. Dans le tonneau stimulé, la première partie de la réponse à la VP n'est pas affaiblie, démontrant que la dépression de la réponse n'est pas due à un phénomène de plasticité sous-corticale ou thalamocorticale. La stimulation chronique d'une vibrisse entraîne une augmentation du nombre de synapses GABAergiques dans la couche IV du tonneau correspondant (Knott et al, 2002). Dès lors, nos résultats suggèrent qu'une augmentation de l'inhibition dans le tonneau stimulé serait à l'origine de la diminution des potentiels d'action évoqués par la vibrisse stimulée et en conséquence de l'amplitude du flux d'excitation vers les couches II&III puis vers les colonnes corticales adjacentes. Toutes les réponses des neurones du tonneau stimulé ne sont pas déprimées. Les réponses des neurones à la vibrisse voisine caudale à VP diminuent dans la couche IV (42%) et dans les couches II&III (52%) mais pas les réponses aux 7 autres vibrisses voisines. Les entrées synaptiques en provenance de la vibrisse caudale pourraient avoir été spécifiquement déprimées en raison d'une décorrélation prolongée entre l'activité évoquée dans les chemins sensoriels relatifs à la vibrisse stimulée et à la vibrisse caudale, spécificité qui découlerait du fait que, parmi les vibrisses voisines à la VP, la vibrisse caudale génère les réponses les plus fortes dans la colonne corticale. Quatre jours après l'arrêt de la stimulation, l'activité neuronale n'est plus déprimée; au contraire, nous observons une potentiation des réponses à la VP dans la couche IV de la colonne corticale stimulée. De plus, nous montrons que l'expression des protéines GLT-1 et GLAST, deux transporteurs astrocytaires du glutamate, est augmentée de ~2.5 fois dans la colonne corticale stimulée, indiquant l'existence d'une «plasticité gliale» et suggérant que les cellules gliales participent activement à l'adaptation du cerveau à l'expérience. ABSTRACT In the barrel cortex, mystacial whisker follicles are represented in the form of a topographie map. The selective removal of a set of whiskers while sparing others for several days in an adult rodent alters receptive field of barrel cortex neurons, demonstrating experience-dependent plasticity of cortical maps. Here sensory experience was altered by chronic stimulation of a whisker for a 24h period in a freely behaving adult mouse. By means of an evoked local field potential analysis, we show that chronic stimulation does not alter the flow of excitation evoked by the principal whisker (PW) in the stimulated barrel column. However, the recording of neuronal firing from a total of 1041 single units throughout the barrel cortex reveals several changes in neuronal activity. Immediately after chronic stimulation, spontaneous activity as well as PW-responses are depressed in the stimulated barrel column (mean number of spikes per PW-deflection decreases by 25% and 36% in layer IV and layers II&III, respectively). Neuronal responses towards the chronically stimulated whisker are also significantly depressed in layers II&III of the adjacent "non-stimulated" barrel' columns. The depression of both spontaneous activity and PW-responses are restricted to the stimulated ban-el column. The earliest time epoch of the PW-response in the stimulated barrel is not depressed, demonstrating that the decrease of cortical responses is not due to subcortical or thalamocortical plasticity. The depression of PW-response in the stimulated barrel correlates with an increase in the number of GABAergic synapses in layer IV (Knott et al., 2002). Therefore, our results suggest that an increase in inhibition within the stimulated barrel may reduce its excitatory output and accordingly the flow of excitation towards layers and the subsequent horizontal spread into adjacent barrel columns. Not all responses of neurons in the stimulated barrel are depressed. Neuronal responses towards the caudal in-row whisker decrease by 42% in layer IV and 52% in layers MM but responses to the other 7 immediate surround whiskers (SWs) are not affected. The synaptic inputs from the SW that elicit the strongest responses in the stimulated barrel may have been specifically depressed following a prolonged period of diminished coherence between neuronal activity evoked in the pathways from the chronically stimulated whisker and from its surrounding in-row whisker. Four days after the cessation of the stimulation, depression of neuronal activity is no longer present; on the contrary, we observe a small but significant potentiation of PW-responses in layer IV of the stimulated barrel column. Moreover we show that the expression of astrocytic glutamate transporters GLT-1 and GLAST proteins were both upregulated by ~2.5 fold in the stimulated barrel column, which indicates that glial cells exhibit experience-dependent functional changes and could actively take part in the adaptation of the cerebral cortex to experience.

Choice of Optimal MembraneProcesses for Economical Treatment of Paper Machine Clear Filtrate

In this thesis membrane filtration of paper machnie clear filtrate was studied. The aim of the study was to find membrane processes which are able to produce economically water of sufficient purity from paper machine white water or its saveall clarified fractions for reuse in the paper machnie short circulation. Factors affecting membrane fouling in this application were also studied. The thesis gives an overview af experiments done on a laboratory and a pilot scale with several different membranes and membrane modules. The results were judged by the obtained flux, the fouling tendency and the permeate quality assessed with various chemical analyses. It was shown that membrane modules which used a turbulence promotor of some kind gave the highest fluexes. However, the results showed that the greater the reduction in the concentration polarisation layer caused by increased turbulence in the module, the smaller the reductions in measured substances. Out of the micro-, ultra- and nanofiltration membranes tested, only nanofiltration memebranes produced permeate whose quality was very close to that of the chemically treated raw water used as fresh water in most paper mills today and which should thus be well suited for reuse as shower water both in the wire and press section. It was also shown that a one stage nanofiltration process was more effective than processes in which micro- or ultrafiltration was used as pretreatment for nanofiltration. It was generally observed that acidic pH, high organic matter content, the presence of multivalent ions, hydrophobic membrane material and high membrane cutoff increased the fouling tendency of the membranes.

Selective catalytic reduction of nitrogen oxides with ammonia in forced unsteady state reactors - Case based reasoning and mathematical model simulation reasoning

The application of forced unsteady-state reactors in case of selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3) is sustained by the fact that favorable temperature and composition distributions which cannot be achieved in any steady-state regime can be obtained by means of unsteady-state operations. In a normal way of operation the low exothermicity of the selective catalytic reduction (SCR) reaction (usually carried out in the range of 280-350°C) is not enough to maintain by itself the chemical reaction. A normal mode of operation usually requires supply of supplementary heat increasing in this way the overall process operation cost. Through forced unsteady-state operation, the main advantage that can be obtained when exothermic reactions take place is the possibility of trapping, beside the ammonia, the moving heat wave inside the catalytic bed. The unsteady state-operation enables the exploitation of the thermal storage capacity of the catalyticbed. The catalytic bed acts as a regenerative heat exchanger allowing auto-thermal behaviour when the adiabatic temperature rise is low. Finding the optimum reactor configuration, employing the most suitable operation model and identifying the reactor behavior are highly important steps in order to configure a proper device for industrial applications. The Reverse Flow Reactor (RFR) - a forced unsteady state reactor - corresponds to the above mentioned characteristics and may be employed as an efficient device for the treatment of dilute pollutant mixtures. As a main disadvantage, beside its advantages, the RFR presents the 'wash out' phenomena. This phenomenon represents emissions of unconverted reactants at every switch of the flow direction. As a consequence our attention was focused on finding an alternative reactor configuration for RFR which is not affected by the incontrollable emissions of unconverted reactants. In this respect the Reactor Network (RN) was investigated. Its configuration consists of several reactors connected in a closed sequence, simulating a moving bed by changing the reactants feeding position. In the RN the flow direction is maintained in the same way ensuring uniformcatalyst exploitation and in the same time the 'wash out' phenomena is annulated. The simulated moving bed (SMB) can operate in transient mode giving practically constant exit concentration and high conversion levels. The main advantage of the reactor network operation is emphasizedby the possibility to obtain auto-thermal behavior with nearly uniformcatalyst utilization. However, the reactor network presents only a small range of switching times which allow to reach and to maintain an ignited state. Even so a proper study of the complex behavior of the RN may give the necessary information to overcome all the difficulties that can appear in the RN operation. The unsteady-state reactors complexity arises from the fact that these reactor types are characterized by short contact times and complex interaction between heat and mass transportphenomena. Such complex interactions can give rise to a remarkable complex dynamic behavior characterized by a set of spatial-temporal patterns, chaotic changes in concentration and traveling waves of heat or chemical reactivity. The main efforts of the current research studies concern the improvement of contact modalities between reactants, the possibility of thermal wave storage inside the reactor and the improvement of the kinetic activity of the catalyst used. Paying attention to the above mentioned aspects is important when higher activity even at low feeding temperatures and low emissions of unconverted reactants are the main operation concerns. Also, the prediction of the reactor pseudo or steady-state performance (regarding the conversion, selectivity and thermal behavior) and the dynamicreactor response during exploitation are important aspects in finding the optimal control strategy for the forced unsteady state catalytic tubular reactors. The design of an adapted reactor requires knowledge about the influence of its operating conditions on the overall process performance and a precise evaluation of the operating parameters rage for which a sustained dynamic behavior is obtained. An apriori estimation of the system parameters result in diminution of the computational efforts. Usually the convergence of unsteady state reactor systems requires integration over hundreds of cycles depending on the initial guess of the parameter values. The investigation of various operation models and thermal transfer strategies give reliable means to obtain recuperative and regenerative devices which are capable to maintain an auto-thermal behavior in case of low exothermic reactions. In the present research work a gradual analysis of the SCR of NOx with ammonia process in forced unsteady-state reactors was realized. The investigation covers the presentationof the general problematic related to the effect of noxious emissions in the environment, the analysis of the suitable catalysts types for the process, the mathematical analysis approach for modeling and finding the system solutions and the experimental investigation of the device found to be more suitable for the present process. In order to gain information about the forced unsteady state reactor design, operation, important system parameters and their values, mathematical description, mathematicalmethod for solving systems of partial differential equations and other specific aspects, in a fast and easy way, and a case based reasoning (CBR) approach has been used. This approach, using the experience of past similarproblems and their adapted solutions, may provide a method for gaining informations and solutions for new problems related to the forced unsteady state reactors technology. As a consequence a CBR system was implemented and a corresponding tool was developed. Further on, grooving up the hypothesis of isothermal operation, the investigation by means of numerical simulation of the feasibility of the SCR of NOx with ammonia in the RFRand in the RN with variable feeding position was realized. The hypothesis of non-isothermal operation was taken into account because in our opinion ifa commercial catalyst is considered, is not possible to modify the chemical activity and its adsorptive capacity to improve the operation butis possible to change the operation regime. In order to identify the most suitable device for the unsteady state reduction of NOx with ammonia, considering the perspective of recuperative and regenerative devices, a comparative analysis of the above mentioned two devices performance was realized. The assumption of isothermal conditions in the beginningof the forced unsteadystate investigation allowed the simplification of the analysis enabling to focus on the impact of the conditions and mode of operation on the dynamic features caused by the trapping of one reactant in the reactor, without considering the impact of thermal effect on overall reactor performance. The non-isothermal system approach has been investigated in order to point out the important influence of the thermal effect on overall reactor performance, studying the possibility of RFR and RN utilization as recuperative and regenerative devices and the possibility of achieving a sustained auto-thermal behavior in case of lowexothermic reaction of SCR of NOx with ammonia and low temperature gasfeeding. Beside the influence of the thermal effect, the influence of the principal operating parameters, as switching time, inlet flow rate and initial catalyst temperature have been stressed. This analysis is important not only because it allows a comparison between the two devices and optimisation of the operation, but also the switching time is the main operating parameter. An appropriate choice of this parameter enables the fulfilment of the process constraints. The level of the conversions achieved, the more uniform temperature profiles, the uniformity ofcatalyst exploitation and the much simpler mode of operation imposed the RN as a much more suitable device for SCR of NOx with ammonia, in usual operation and also in the perspective of control strategy implementation. Theoretical simplified models have also been proposed in order to describe the forced unsteady state reactors performance and to estimate their internal temperature and concentration profiles. The general idea was to extend the study of catalytic reactor dynamics taking into account the perspectives that haven't been analyzed yet. The experimental investigation ofRN revealed a good agreement between the data obtained by model simulation and the ones obtained experimentally.

The importance of sonographer experience and machine quality with regards to the role of musculoskeletal ultrasound in routine care of rheumatoid arthritis patients.

OBJECTIVES: Regarding recent progress, musculoskeletal ultrasound (US) will probably soon be integrated in standard care of patient with rheumatoid arthritis (RA). However, in daily care, quality of US machines and level of experience of sonographers are varied. We conducted a study to assess reproducibility and feasibility of an US scoring for RA, including US devices of different quality and rheumatologist with various levels of expertise in US as it would be in daily care. METHODS: The Swiss Sonography in Arthritis and Rheumatism (SONAR) group has developed a semi-quantitative score using OMERACT criteria for synovitis and erosion in RA. The score was taught to 108 rheumatologists trained in US. One year after the last workshop, 19 rheumatologists participated in the study. Scans were performed on 6 US machines ranging from low to high quality, each with a different patient. Weighted kappa was calculated for each pair of readers. RESULTS: Overall, the agreement was fair to moderate. Quality of device, experience of the sonographers and practice of the score before the study improved substantially the agreement. Agreement assessed on higher quality machine, among sonographers with good experience in US increased to substantial (median kappa for B-mode and Doppler: 0.64 and 0.41 for erosion). CONCLUSIONS: This study demonstrated feasibility and reproducibility of the Swiss US SONAR score for RA. Our results confirmed importance of the quality of US machine and the training of sonographers for the implementation of US scoring in the routine daily care of RA.

Réhabilitation améliorée après chirurgie--L'ere de la prise en charge optimale du patient chirurgical [Enhanced Recovery After Surgery--optimal management of the surgical patient].

Enhanced Recovery After Surgery (ERAS) is a multimodal, standardized and evidence-based perioperative care pathway. With ERAS, postoperative complications are significantly lowered, and, as a secondary effect, length of hospital stay and health cost are reduced. The patient recovers better and faster allowing to reduce in addition the workload of healthcare providers. Despite the hospital discharge occurs sooner, there is no increased charge of the outpatient care. ERAS can be safely applied to any patient by a tailored approach. The general practitioner plays an essential role in ERAS by assuring the continuity of the information and the follow-up of the patient.

Optimal capital structure: a trade-off model and its empirical testing

In the present research we have set forth a new, simple, Trade-Off model that would allow us to calculate how much debt and, by default, how much equity a company should have, using easily available information and calculating the cost of debt dynamically on the basis of the effect that the capital structure of the company has on the risk of bankruptcy; in an attempt to answer this question. The proposed model has been applied to the companies that make up the Dow Jones Industrial Average (DJIA) in 2007. We have used consolidated financial data from 1996 to 2006, published by Bloomberg. We have used simplex optimization method to find the debt level that maximizes firm value. Then, we compare the estimated debt with real debt of companies using statistical nonparametric Mann-Whitney. The results indicate that 63% of companies do not show a statistically significant difference between the real and the estimated debt.

Medical physicists' implication in radiological diagnostic procedures: results after 1 y of experience.

Since January 2008-de facto 2012-medical physics experts (MPEs) are, by law, to be involved in the optimisation process of radiological diagnostic procedures in Switzerland. Computed tomography, fluoroscopy and nuclear medicine imaging units have been assessed for patient exposure and image quality. Large spreads in clinical practice have been observed. For example, the number of scans per abdominal CT examination went from 1 to 9. Fluoroscopy units showed, for the same device settings, dose rate variations up to a factor of 3 to 7. Quantitative image quality for positron emission tomography (PET)/CT examinations varied significantly depending on the local image reconstruction algorithms. Future work will be focused on promoting team cooperation between MPEs, radiologists and radiographers and on implementing task-oriented objective image quality indicators.

Preferred Spatial Frequencies for Human Face Processing Are Associated with Optimal Class Discrimination in the Machine

Psychophysical studies suggest that humans preferentially use a narrow band of low spatial frequencies for face recognition. Here we asked whether artificial face recognition systems have an improved recognition performance at the same spatial frequencies as humans. To this end, we estimated recognition performance over a large database of face images by computing three discriminability measures: Fisher Linear Discriminant Analysis, Non-Parametric Discriminant Analysis, and Mutual Information. In order to address frequency dependence, discriminabilities were measured as a function of (filtered) image size. All three measures revealed a maximum at the same image sizes, where the spatial frequency content corresponds to the psychophysical found frequencies. Our results therefore support the notion that the critical band of spatial frequencies for face recognition in humans and machines follows from inherent properties of face images, and that the use of these frequencies is associated with optimal face recognition performance.

Internationalization of Experience Pro concept

Diplomityö on tehty STTF:lle (Software Technology Transfer Finland), joka pyrkii kansainvälisille markkinoille Experience Pro -tuotekonseptillaan. Kansainvälistyminen on haasteellinen prosessi pk-yritykselle, ja haastetta haluttiin lähestyä strategisella suunnittelulla. Työn tavoitteena oli teoriatiedon ja löydettyjen kansainvälistymisesimerkkien avulla tuottaa STTF:lle kansainvälistymissuunnitelma strategiaan pohjautuen.Kaksi merkittävintä strategista valintaa STTF:n kansainvälistymisessä olivat kohdemaiden ja operaatiomuodon valinnat. Päätökset tehtiin strategisten analyysien perusteella. Analyysien avulla määritettiin myös yrityksen kilpailuedut. Löydettyjä vahvuuksia pyrittiin hyödyntämään myöhemmin kansainvälistymisen osastrategioita rakennettaessa. Tavoitteiden asettaminen ja markkinointi-mix:n kehittäminen olivat keskeisimmät osat markkinoinnin osastrategiassa. Jakelukanavan merkitystä korostettiin STTF:n kansainvälistymisessä ja yhteistyölle pyrittiin luomaan hyvät edellytykset. Strategia konkretisoitiin luomalla operatiiviset suunnitelmat markkinoinnin tukimateriaalien tuottamiseksi ja yhteistyökumppanien etsimiseksi. Markkinatutkimuksen perusteella potentiaaliset kohdemaat Experience Pro -konseptille olivat Australia, Hollanti, Irlanti, Iso-Britannia, Norja, Ruotsi, Saksa ja Tanska. STTF:llä on muutama sopiva vaihtoehtoinen operaatiomuoto valittavanaan riippuen kohdemaasta. Suomen maine vakaana, korkean teknologian maana voidaan nähdä maaetuna STTF:lle ja muita vahvuuksia ovat STTF:n teknologinen osaaminen, tuotteeseen liittyvät palvelut ja henkilökohtaiset kontaktit. SWOT-analyysi paljasti STTF:n heikkouksia voitettaviksi.Tulevaisuudessa STTF voi jatkaa kansainvälistymistään suunnitelman mukaisesti. Tavoitteiden saavuttaminen vaatii sitoutumista, aktiivista yhteistyökumppanien etsimistä ja jatkuvaa prosessien kehittämistä vastaamaan kansainvälisten markkinoiden vaatimuksia.