Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A Randomized Controlled Study.

BACKGROUND: Tinnitus is an often disabling condition for which there is no effective therapy. Current research suggests that tinnitus may develop due to maladaptive plastic changes and altered activity in the auditory and prefrontal cortex. Transcranial direct current stimulation (tDCS) modulates brain activity and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To investigate the efficacy and safety of tDCS in the treatment of chronic subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham-controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex with anode over the prefrontal cortex was investigated in five sessions over five consecutive days. Tinnitus was assessed after the last session on day 5, and at follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale, Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21 sham stimulation. There were no beneficial effects of tDCS on tinnitus as assessed by primary and secondary outcome measures. Effect size assessed with Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: -0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and prefrontal cortices is safe, but does not improve tinnitus. Different tDCS protocols might be beneficial.

Détermination du coût direct lors d'une procédure de cathétérisation d'une angioplastie avec ou sans pose de stent au CHUV

Cette étude consiste à comparer les coûts de deux procédures de dilatation artérielle coronaire (angioplastie par ballonet et angioplastie avec pose de stent) uniquement lors de la phase de cathérisation (et non pas de l'ensemble des coûts du séjour hospitalier). La première partie traite de l'importance de la maladie coronarienne, de ses traitements et des objectifs de l'étude. La deuxième partie explique les éléments et la méthode qui composent le calcul des coûts, illustre les résultats et compare les résultats des deux procédures. La troisième partie analyse les résultats en identifiant quels types de coûts sont à l'origine de la différence du coût total et en explicitant les limites et les compléments nécessaires à l'étude.

Recovery of Hemicelluloses from Wood Hydrolysates by Membrane Filtration

Hemicelluloses are among the most important natural resources that contain polysaccharides. In this study the separation and purification of hemicelluloses from water extraction liquors containing wood hemicelluloses, lignin compounds and monosaccharide by using membrane filtration was investigated. The isolation of the hemicelluloses from the wood hydrolysates was performed in two steps: concentration of high molar mass hemicelluloses by ultrafiltration and separation of low molar mass hemicelluloses from monomeric sugars using tight ultrafiltration membranes. The purification of the retained hemicelluloses was performed by diafiltration. During the filtration experiments, the permeate flux through ultrafiltration and tight ultrafiltration membranes was relatively high. The fouling ability of the used membranes was relatively low. In our experiments, the retention of hemicelluloses using two filtration steps was almost complete. The separation of monosaccharides from hemicelluloses was relatively high and the purification of hemicelluloses by diafiltration was highly efficient. The separation of lignin from hemicelluloses was partially achieved. Diafiltration showed potential to purify retained hemicelluloses from lignin and other organics. The best separation of lignin from hemicelluloses in the first filtration step was obtained using the UC005 membrane. The GE-5 and ETNA01PP membranes showed potential to purify and separate lignin from hemicelluloses. However, the feed solution of the second filtration stages (from different ultrafiltration membranes) affected the permeate flux and the separation of various extracted compounds from hemicelluloses. The GE-5 and ETNA01PP membranes gave the efficient purification of the hemicelluloses when using diafiltration. Separation of degraded xylan from glucomannan (primary spruce hemicelluloses) was also possible using membrane filtration. The best separation was achieved using the GE-5 membrane. The retention of glucomannan was three times higher than xylan retention.

Weight filtration on the cohomology of complex analytic spaces

We extend Deligne's weight filtration to the integer cohomology of complex analytic spaces (endowed with an equivalence class of compactifications). In general, the weight filtration that we obtain is not part of a mixed Hodge structure. Our purely geometric proof is based on cubical descent for resolution of singularities and Poincaré-Verdier duality. Using similar techniques, we introduce the singularity filtration on the cohomology of compactificable analytic spaces. This is a new and natural analytic invariant which does not depend on the equivalence class of compactifications and is related to the weight filtration.

Regulatory framework of local citizen participation: Instruments of Direct and Participative Democracy in the Municipal Field

This article focuses on the analysis of the regulatory framework of citizen participation in the local government, which organises direct and participatory democracy at the local level, and identifies the laws and mechanisms through which the constitutional requirements for participation are accomplished. Mu nicipalities, the authority closest to citizens, are the best level of government since they directly involve civil society in the decision-making process experiencing the scope and appropriateness of the instruments by which it is channeled.

Electrochemical Characterisation of Filter Media Properties and Their Exploitation in Enhanced Filtration

Streaming potential measurements for the surface charge characterisation of different filter media types and materials were used. The equipment was developed further so that measurements could be taken along the surfaces, and so that tubular membranes could also be measured. The streaming potential proved to be a very useful tool in the charge analysis of both clean and fouled filter media. Adsorption and fouling could be studied, as could flux, as functions of time. A module to determine the membrane potential was also constructed. The results collected from the experiments conducted with these devices were used in the study of the theory of streaming potential as an electrokinetic phenomenon. Several correction factors, which are derived to take into account the surface conductance and the electrokinetic flow in very narrow capillaries, were tested in practice. The surface materials were studied using FTIR and the results compared with those from the streaming potentials. FTIR analysis was also found to be a useful tool in the characterisation of filters, as well as in the fouling studies. Upon examination of the recorded spectra from different depths in a sample it was possible to determine the adsorption sites. The influence of an external electric field on the cross flow microflltration of a binary protein system was investigated using a membrane electroflltration apparatus. The results showed that a significant improvement could be achieved in membrane filtration by using the measured electrochemical properties to help adjust the process conditions.

Position sensorless electrically excited synchronous motor drive for industrial use based on direct flux linkage and torque control

Synchronous machines with an AC converter are used mainly in large drives, for example in ship propulsion drives as well as in rolling mill drives in steel industry. These motors are used because of their high efficiency, high overload capacity and good performance in the field weakening area. Present day drives for electrically excited synchronous motors are equipped with position sensors. Most drives for electrically excited synchronous motors will be equipped with position sensors also in future. This kind of drives with good dynamics are mainly used in metal industry. Drives without a position sensor can be used e.g. in ship propulsion and in large pump and blower drives. Nowadays, these drives are equipped with a position sensor, too. The tendency is to avoid a position sensor if possible, since a sensor reduces the reliability of the drive and increases costs (latter is not very significant for large drives). A new control technique for a synchronous motor drive is a combination of the Direct Flux Linkage Control (DFLC) based on a voltage model and a supervising method (e.g. current model). This combination is called Direct Torque Control method (DTC). In the case of the position sensorless drive, the DTC can be implemented by using other supervising methods that keep the stator flux linkage origin centered. In this thesis, a method for the observation of the drift of the real stator flux linkage in the DTC drive is introduced. It is also shown how this method can be used as a supervising method that keeps the stator flux linkage origin centered in the case of the DTC. In the position sensorless case, a synchronous motor can be started up with the DTC control, when a method for the determination of the initial rotor position presented in this thesis is used. The load characteristics of such a drive are not very good at low rotational speeds. Furthermore, continuous operation at a zero speed and at a low rotational speed is not possible, which is partly due to the problems related to the flux linkage estimate. For operation in a low speed area, a stator current control method based on the DFLC modulator (DMCQ is presented. With the DMCC, it is possible to start up and operate a synchronous motor at a zero speed and at low rotational speeds in general. The DMCC is necessary in situations where high torque (e.g. nominal torque) is required at the starting moment, or if the motor runs several seconds at a zero speed or at a low speed range (up to 2 Hz). The behaviour of the described methods is shown with test results. The test results are presented for the direct flux linkage and torque controlled test drive system with a 14.5 kVA, four pole salient pole synchronous motor with a damper winding and electric excitation. The static accuracy of the drive is verified by measuring the torque in a static load operation, and the dynamics of the drive is proven in load transient tests. The performance of the drive concept presented in this work is sufficient e.g. for ship propulsion and for large pump drives. Furthermore, the developed methods are almost independent of the machine parameters.

Salient Pole Synchronous Machine Modelling in an Industrial Direct Torque Controlled Drive Application

Synchronous motors are used mainly in large drives, for example in ship propulsion systems and in steel factories' rolling mills because of their high efficiency, high overload capacity and good performance in the field weakening range. This, however, requires an extremely good torque control system. A fast torque response and a torque accuracy are basic requirements for such a drive. For large power, high dynamic performance drives the commonly known principle of field oriented vector control has been used solely hitherto, but nowadays it is not the only way to implement such a drive. A new control method Direct Torque Control (DTC) has also emerged. The performance of such a high quality torque control as DTC in dynamically demanding industrial applications is mainly based on the accurate estimate of the various flux linkages' space vectors. Nowadays industrial motor control systems are real time applications with restricted calculation capacity. At the same time the control system requires a simple, fast calculable and reasonably accurate motor model. In this work a method to handle these problems in a Direct Torque Controlled (DTC) salient pole synchronous motor drive is proposed. A motor model which combines the induction law based "voltage model" and motor inductance parameters based "current model" is presented. The voltage model operates as a main model and is calculated at a very fast sampling rate (for example 40 kHz). The stator flux linkage calculated via integration from the stator voltages is corrected using the stator flux linkage computed from the current model. The current model acts as a supervisor that prevents only the motor stator flux linkage from drifting erroneous during longer time intervals. At very low speeds the role of the current model is emphasised but, nevertheless, the voltage model always stays the main model. At higher speeds the function of the current model correction is to act as a stabiliser of the control system. The current model contains a set of inductance parameters which must be known. The validation of the current model in steady state is not self evident. It depends on the accuracy of the saturated value of the inductances. Parameter measurement of the motor model where the supply inverter is used as a measurement signal generator is presented. This so called identification run can be performed prior to delivery or during drive commissioning. A derivation method for the inductance models used for the representation of the saturation effects is proposed. The performance of the electrically excited synchronous motor supplied with the DTC inverter is proven with experimental results. It is shown that it is possible to obtain a good static accuracy of the DTC's torque controller for an electrically excited synchronous motor. The dynamic response is fast and a new operation point is achieved without oscillation. The operation is stable throughout the speed range. The modelling of the magnetising inductance saturation is essential and cross saturation has to be considered as well. The effect of cross saturation is very significant. A DTC inverter can be used as a measuring equipment and the parameters needed for the motor model can be defined by the inverter itself. The main advantage is that the parameters defined are measured in similar magnetic operation conditions and no disagreement between the parameters will exist. The inductance models generated are adequate to meet the requirements of dynamically demanding drives.

Towards integrated operation of membrane bioreactors : effects of aeration on biological and filtration performance

Two experimental studies evaluated the effect of aerobic and membrane aeration changes on sludge properties, biological nutrient removal and filtration processes in a pilot plant membrane bioreactor. The optimal operating conditions were found at an aerobic dissolved oxygen set-point (DO) of 0.5mgO2L-1 and a membrane specific aeration demand (SADm) of 1mh-1, where membrane aeration can be used for nitrification. Under these conditions, a total flow reduction of 42% was achieved (75% energy reduction) without compromising nutrient removal efficiencies, maintaining sludge characteristics and controlled filtration. Below these optimal operating conditions, the nutrient removal efficiency was reduced, increasing 20% for soluble microbial products, 14% for capillarity suction time and reducing a 15% for filterability. Below this DO set-point, fouling increased with a transmembrane pressure 75% higher. SADm below 1mh-1 doubled the values of transmembrane pressure, without recovery after achieving the initial conditions

Intracellular membrane trafficking in Osteoclasts The role of direct Rab protein – Rac 1 interactions in the targeting of intracellular vesicles

Osteoclasts are cells responsible for bone resorption. These cells undergo extensive membrane re-organization during their polarization for bone resorption and form four distinct membrane domains, namely the ruffled border, the basolateral membrane, the sealing zone and the functional secretory domain. The endocytic/biosynthetic pathway and transcytotic route(s) are important for the resorption process, since the endocytic/biosynthetic pathway brings the specific vesicles to the ruffled border whereas the transcytotic flow is believed to transport the degraded bone matrix away from the resorption lacuna to the functional secretory domain. In the present study, we found a new transcytotic route from the functional secretory domain to the ruffled border, which may compensate membrane loss from the ruffled border during the resorption process. We also found that lipid rafts are essential for the ruffled border-targeted late endosomal pathways. A small GTP-binding protein, Rab7, has earlier been shown to regulate the late steps of the endocytic pathway. In bone-resorbing osteoclasts it is involved in the formation of the ruffled border, which displays several features of late endosomal membranes. Here we discovered a new Rab7-interacting protein, Rac1, which is another small GTP-binding protein and binds to the GTP-form of Rab7 in vitro. We demonstrated further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts. In other cell types, such as fibroblast-like cells, this colocalization is mainly perinuclear. Because Rac1 is known to control the actin cytoskeleton through its effectors, we suggest that the Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments, thus enabling endosomal vesicles to switch tracks from microtubules to microfilaments before their fusion to the ruffled border. We then studied the role of Rab-Rac1 interaction in the slow recycling pathway. We revealed that Rac1 also binds directly to Rab11 and to some other but not all Rab-proteins, suggesting that Rab-Rac1 interaction could be a general regulatory mechanism to direct the intracellular vesicles from microtubule mediated transport to actin filament mediated transport and vice versa. On the basis of our results we thus propose a new hypothesis for these GTPases in the regulation of intracellular membrane flow.

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors.