Chronic infusion of amyloid-β peptide and sustained attention altered α7 nicotinic receptor density in the rat brain

It is already known that progressive degeneration of cholinergic neurons in brain areas such as the hippocampus and the cortex leads to memory deficits, as observed in Alzheimer's disease. This work verified the effects of the infusion of amyloid-beta (A beta) peptide associated to an attentional rehearsal on the density of alpha 7 nicotinic cholinergic receptor (nAChR) in the brain of male Wistar rats. Animals received intracerebroventricular infusion of A beta or vehicle (control - C) and their attention was stimulated weekly (Stimulated A beta group: S-A beta and Stimulated Control group: SC) or not (Non-Stimulated A beta group: N-SA beta and Non-Stimulated Control group: N-SC), using an active avoidance apparatus. Conditioned avoidance responses (CAR) were registered. Chronic infusion of A beta caused a 37% reduction in CAR for N-SA beta. In S-A beta, this reduction was not observed. At the end, brains were extracted and autoradiography for alpha 7 nAChR was conducted using [I-125]-alpha-bungarotoxin. There was an increase in alpha 7 density in hippocampus, cortex and amygdala of SA beta animals, together with the memory preservation. In recent findings from our lab using mice infused with A beta and the alpha 7 antagonist methyllycaconitine, and stimulated weekly in the same apparatus, it was observed that memory maintenance was abolished. So, the increase in alpha 7 density in brain areas related to memory might be related to a participation of this receptor in the long-lasting change in synaptic plasticity, which is important to improve and maintain memory consolidation.

Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1 alpha in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.

Meditation training increases brain efficiency in an attention task

Meditation is a mental training, which involves attention and the ability to maintain focus on a particular object. In this study we have applied a specific attentional task to simply measure the performance of the participants with different levels of meditation experience, rather than evaluating meditation practice per se or task performance during meditation. Our objective was to evaluate the performance of regular meditators and non-meditators during an fMRI adapted Stroop Word-Colour Task (SWCT), which requires attention and impulse control, using a block design paradigm. We selected 20 right-handed regular meditators and 19 non-meditators matched for age, years of education and gender. Participants had to choose the colour (red, blue or green) of single words presented visually in three conditions: congruent, neutral and incongruent. Non-meditators showed greater activity than meditators in the right medial frontal, middle temporal, precentral and postcentral gyri and the lentiform nucleus during the incongruent conditions. No regions were more activated in meditators relative to non-meditators in the same comparison. Non-meditators showed an increased pattern of brain activation relative to regular meditators under the same behavioural performance level. This suggests that meditation training improves efficiency, possibly via improved sustained attention and impulse control. (C) 2011 Elsevier Inc. All rights reserved.

La Real Hacienda y el control del gasto. La Tesorería General en la España del siglo XVIII

[ES] La evolución historiográfica ocurrida en los últimos años en relación con el mundo de las finanzas en general y las Haciendas reales en particular, ha generado grandes cambios en la percepción del interés por el gasto de los Estados. La potenciación del deseo de observar cómo las Monarquías del Antiguo Régimen gestionan la atención a sus necesidades, conlleva aparejada una creciente atención por el estudio de los organismos encargados de dicha actuación. Entre estas instituciones destaca en la España del siglo XVIII la Tesorería Mayor o Tesorería General. Su estudio permite conocer la evolución política de la Monarquía y de su relación con las finanzas privadas desde una perspectiva diferente. Los estudios centrados en la actuación de este organismo, su composición interna, su estructura territorial, los mecanismos de su ordenación contable y, en definitiva, cualquier tipo de actuación ocurrida dentro del ámbito de su gestión son el objeto del presente estudio.

Seizure prediction and control in epilepsy

The first part of my thesis presents an overview of the different approaches used in the past two decades in the attempt to forecast epileptic seizure on the basis of intracranial and scalp EEG. Past research could reveal some value of linear and nonlinear algorithms to detect EEG features changing over different phases of the epileptic cycle. However, their exact value for seizure prediction, in terms of sensitivity and specificity, is still discussed and has to be evaluated. In particular, the monitored EEG features may fluctuate with the vigilance state and lead to false alarms. Recently, such a dependency on vigilance states has been reported for some seizure prediction methods, suggesting a reduced reliability. An additional factor limiting application and validation of most seizure-prediction techniques is their computational load. For the first time, the reliability of permutation entropy [PE] was verified in seizure prediction on scalp EEG data, contemporarily controlling for its dependency on different vigilance states. PE was recently introduced as an extremely fast and robust complexity measure for chaotic time series and thus suitable for online application even in portable systems. The capability of PE to distinguish between preictal and interictal state has been demonstrated using Receiver Operating Characteristics (ROC) analysis. Correlation analysis was used to assess dependency of PE on vigilance states. Scalp EEG-Data from two right temporal epileptic lobe (RTLE) patients and from one patient with right frontal lobe epilepsy were analysed. The last patient was included only in the correlation analysis, since no datasets including seizures have been available for him. The ROC analysis showed a good separability of interictal and preictal phases for both RTLE patients, suggesting that PE could be sensitive to EEG modifications, not visible on visual inspection, that might occur well in advance respect to the EEG and clinical onset of seizures. However, the simultaneous assessment of the changes in vigilance showed that: a) all seizures occurred in association with the transition of vigilance states; b) PE was sensitive in detecting different vigilance states, independently of seizure occurrences. Due to the limitations of the datasets, these results cannot rule out the capability of PE to detect preictal states. However, the good separability between pre- and interictal phases might depend exclusively on the coincidence of epileptic seizure onset with a transition from a state of low vigilance to a state of increased vigilance. The finding of a dependency of PE on vigilance state is an original finding, not reported in literature, and suggesting the possibility to classify vigilance states by means of PE in an authomatic and objectic way. The second part of my thesis provides the description of a novel behavioral task based on motor imagery skills, firstly introduced (Bruzzo et al. 2007), in order to study mental simulation of biological and non-biological movement in paranoid schizophrenics (PS). Immediately after the presentation of a real movement, participants had to imagine or re-enact the very same movement. By key release and key press respectively, participants had to indicate when they started and ended the mental simulation or the re-enactment, making it feasible to measure the duration of the simulated or re-enacted movements. The proportional error between duration of the re-enacted/simulated movement and the template movement were compared between different conditions, as well as between PS and healthy subjects. Results revealed a double dissociation between the mechanisms of mental simulation involved in biological and non-biologial movement simulation. While for PS were found large errors for simulation of biological movements, while being more acurate than healthy subjects during simulation of non-biological movements. Healthy subjects showed the opposite relationship, making errors during simulation of non-biological movements, but being most accurate during simulation of non-biological movements. However, the good timing precision during re-enactment of the movements in all conditions and in both groups of participants suggests that perception, memory and attention, as well as motor control processes were not affected. Based upon a long history of literature reporting the existence of psychotic episodes in epileptic patients, a longitudinal study, using a slightly modified behavioral paradigm, was carried out with two RTLE patients, one patient with idiopathic generalized epilepsy and one patient with extratemporal lobe epilepsy. Results provide strong evidence for a possibility to predict upcoming seizures in RTLE patients behaviorally. In the last part of the thesis it has been validated a behavioural strategy based on neurobiofeedback training, to voluntarily control seizures and to reduce there frequency. Three epileptic patients were included in this study. The biofeedback was based on monitoring of slow cortical potentials (SCPs) extracted online from scalp EEG. Patients were trained to produce positive shifts of SCPs. After a training phase patients were monitored for 6 months in order to validate the ability of the learned strategy to reduce seizure frequency. Two of the three refractory epileptic patients recruited for this study showed improvements in self-management and reduction of ictal episodes, even six months after the last training session.

Coordinated Control of Robotic Swarms in Unknown Environments

This thesis gathers the work carried out by the author in the last three years of research and it concerns the study and implementation of algorithms to coordinate and control a swarm of mobile robots moving in unknown environments. In particular, the author's attention is focused on two different approaches in order to solve two different problems. The first algorithm considered in this work deals with the possibility of decomposing a main complex task in many simple subtasks by exploiting the decentralized implementation of the so called \emph{Null Space Behavioral} paradigm. This approach to the problem of merging different subtasks with assigned priority is slightly modified in order to handle critical situations that can be detected when robots are moving through an unknown environment. In fact, issues can occur when one or more robots got stuck in local minima: a smart strategy to avoid deadlock situations is provided by the author and the algorithm is validated by simulative analysis. The second problem deals with the use of concepts borrowed from \emph{graph theory} to control a group differential wheel robots by exploiting the Laplacian solution of the consensus problem. Constraints on the swarm communication topology have been introduced by the use of a range and bearing platform developed at the Distributed Intelligent Systems and Algorithms Laboratory (DISAL), EPFL (Lausanne, CH) where part of author's work has been carried out. The control algorithm is validated by demonstration and simulation analysis and, later, is performed by a team of four robots engaged in a formation mission. To conclude, the capabilities of the algorithm based on the local solution of the consensus problem for differential wheel robots are demonstrated with an application scenario, where nine robots are engaged in a hunting task.

Control of the long-range self-organization of polycyclic aromatic hydrocarbons for device applications

Electronic devices based on organic semiconductors have gained increased attention in nanotechnology, especially applicable to the field of field-effect transistors and photovoltaic. A promising class of materials in this reseach field are polycyclic aromatic hydrocarbons (PAHs). Alkyl substitution of these graphenes results in the selforganization into one-dimensional columnar superstructures and provides solubility and processibility. The nano-phase separation between the π-stacking aromatic cores and the disordered peripheral alkyl chains leads to the formation of thermotropic mesophases. Hexa-peri-hexabenzocoronenes (HBC), as an example for a PAH, exhibits some of the highest values for the charge carrier mobility for mesogens, which makes them promising candidates for electronic devices. Prerequisites for efficient charge carrier transport between electrodes are a high purity of the material to reduce possible trapping sites for charge carriers and a pronounced and defect-free, long-range order. Appropriate processing techniques are required to induce a high degree of aligned structures in the discotic material over macroscopic dimensions. Highly-ordered supramolecular structures of different discotics, in particular, of HBC derivatives have been obtained by solution processing using the zone-casting technique, zone-melting or simple extrusion. Simplicity and fabrication of highly oriented columnar structures over long-range are the most essential advantages of these zone-processing methods. A close relation between the molecular design, self-aggregation and the processing conditions has been revealed. The long-range order achieved by the zone-casting proved to be suitable for field effect transistors (FET).

Spinal cord injury: assessment of autonomic state-dependent control of cardiovascular system and body core temperature

Spinal cord injury (SCI) results not only in paralysis; but it is also associated with a range of autonomic dysregulation that can interfere with cardiovascular, bladder, bowel, temperature, and sexual function. The entity of the autonomic dysfunction is related to the level and severity of injury to descending autonomic (sympathetic) pathways. For many years there was limited awareness of these issues and the attention given to them by the scientific and medical community was scarce. Yet, even if a new system to document the impact of SCI on autonomic function has recently been proposed, the current standard of assessment of SCI (American Spinal Injury Association (ASIA) examination) evaluates motor and sensory pathways, but not severity of injury to autonomic pathways. Beside the severe impact on quality of life, autonomic dysfunction in persons with SCI is associated with increased risk of cardiovascular disease and mortality. Therefore, obtaining information regarding autonomic function in persons with SCI is pivotal and clinical examinations and laboratory evaluations to detect the presence of autonomic dysfunction and quantitate its severity are mandatory. Furthermore, previous studies demonstrated that there is an intimate relationship between the autonomic nervous system and sleep from anatomical, physiological, and neurochemical points of view. Although, even if previous epidemiological studies demonstrated that sleep problems are common in spinal cord injury (SCI), so far only limited polysomnographic (PSG) data are available. Finally, until now, circadian and state dependent autonomic regulation of blood pressure (BP), heart rate (HR) and body core temperature (BcT) were never assessed in SCI patients. Aim of the current study was to establish the association between the autonomic control of the cardiovascular function and thermoregulation, sleep parameters and increased cardiovascular risk in SCI patients.

Analysis of optimal control problems for the incompressible MHD equations and implementation in a finite element multiphysics code

This thesis deals with the study of optimal control problems for the incompressible Magnetohydrodynamics (MHD) equations. Particular attention to these problems arises from several applications in science and engineering, such as fission nuclear reactors with liquid metal coolant and aluminum casting in metallurgy. In such applications it is of great interest to achieve the control on the fluid state variables through the action of the magnetic Lorentz force. In this thesis we investigate a class of boundary optimal control problems, in which the flow is controlled through the boundary conditions of the magnetic field. Due to their complexity, these problems present various challenges in the definition of an adequate solution approach, both from a theoretical and from a computational point of view. In this thesis we propose a new boundary control approach, based on lifting functions of the boundary conditions, which yields both theoretical and numerical advantages. With the introduction of lifting functions, boundary control problems can be formulated as extended distributed problems. We consider a systematic mathematical formulation of these problems in terms of the minimization of a cost functional constrained by the MHD equations. The existence of a solution to the flow equations and to the optimal control problem are shown. The Lagrange multiplier technique is used to derive an optimality system from which candidate solutions for the control problem can be obtained. In order to achieve the numerical solution of this system, a finite element approximation is considered for the discretization together with an appropriate gradient-type algorithm. A finite element object-oriented library has been developed to obtain a parallel and multigrid computational implementation of the optimality system based on a multiphysics approach. Numerical results of two- and three-dimensional computations show that a possible minimum for the control problem can be computed in a robust and accurate manner.

Separation control by means of oriented DBD plasma actuators: an experimental analysis in a wind tunnel

This thesis provides an experimental analysis of the effectiveness of oriented DBD plasma actuators over a NACA 0015 airfoil at low Reynolds numbers. Tests were performed in partnership with the Department of Electrical Engineering of Bologna University, in the wind tunnel of the Applied Aerodynamics Laboratory of Aerospace Engineering faculty. Lift coefficient measurements were carried out in order to verify how an oriented plasma jet succeeds in prevent boundary layer separation. Both actuators’ chord wise position and plasma jet orientation angle have been investigated to examine which configurations lead to the best results. A particular attention has been paid also to the analysis of results in steady and unsteady plasma actuation. Questa tesi offre un’analisi sperimentale sull’efficacia di attuatori al plasma orientabili, basati su una tecnologia DBD, installati su un profilo alare NACA 0015, a bassi numeri di Reynolds. Le prove sono state condotte in collaborazione con il Dipartimento di Ingegneria Elettrica dell’Università di Bologna, nella galleria del vento del Laboratorio di Aerodinamica Applicata della Facoltà di Ingegneria Aerospaziale di Forlì. Per verificare come un getto orientabile di plasma riesca a prevenire la separazione dello strato limite, sono state eseguite misure sul coefficiente di portanza. Sono state indagate sia la posizione degli attuatori lungo la corda che l’angolo con cui è orientato il getto di plasma, per vedere quali configurazioni conducono ai migliori risultati. Una particolare attenzione è stata riservata all’analisi dei risultati ottenuti con plasma continuo e pulsato.

Nonlinear Control of Magnetically Actuated Spacecraft

The topic of this thesis is the feedback stabilization of the attitude of magnetically actuated spacecraft. The use of magnetic coils is an attractive solution for the generation of control torques on small satellites flying inclined low Earth orbits, since magnetic control systems are characterized by reduced weight and cost, higher reliability, and require less power with respect to other kinds of actuators. At the same time, the possibility of smooth modulation of control torques reduces coupling of the attitude control system with flexible modes, thus preserving pointing precision with respect to the case when pulse-modulated thrusters are used. The principle based on the interaction between the Earth's magnetic field and the magnetic field generated by the set of coils introduces an inherent nonlinearity, because control torques can be delivered only in a plane that is orthogonal to the direction of the geomagnetic field vector. In other words, the system is underactuated, because the rotational degrees of freedom of the spacecraft, modeled as a rigid body, exceed the number of independent control actions. The solution of the control issue for underactuated spacecraft is also interesting in the case of actuator failure, e.g. after the loss of a reaction-wheel in a three-axes stabilized spacecraft with no redundancy. The application of well known control strategies is no longer possible in this case for both regulation and tracking, so that new methods have been suggested for tackling this particular problem. The main contribution of this thesis is to propose continuous time-varying controllers that globally stabilize the attitude of a spacecraft, when magneto-torquers alone are used and when a momentum-wheel supports magnetic control in order to overcome the inherent underactuation. A kinematic maneuver planning scheme, stability analyses, and detailed simulation results are also provided, with new theoretical developments and particular attention toward application considerations.

The role of medial parieto occipital cortex in visuospatial attention and reach planning: electrophysiological studies in human and non-human primates

We usually perform actions in a dynamic environment and changes in the location of a target for an upcoming action require both covert shifts of attention and motor planning update. In this study we tested whether, similarly to oculomotor areas that provide signals for overt and covert attention shifts, covert attention shifts modulate activity in cortical area V6A, which provides a bridge between visual signals and arm-motor control. We performed single cell recordings in monkeys trained to fixate straight-ahead while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention demonstrating that visual, motor, and attentional responses can occur in combination in single neurons of V6A. This modulation in an area primarily involved in visuo-motor transformation for reaching suggests that also reach-related regions could directly contribute in the shifts of spatial attention necessary to plan and control goal-directed arm movements. Moreover, to test whether V6A is causally involved in these processes, we have performed a human study using on-line repetitive transcranial magnetic stimulation over the putative human V6A (pV6A) during an attention and a reaching task requiring covert shifts of attention and reaching movements towards cued targets in space. We demonstrate that the pV6A is causally involved in attention reorienting to target detection and that this process interferes with the execution of reaching movements towards unattended targets. The current findings suggest the direct involvement of the action-related dorso-medial visual stream in attentional processes, and a more specific role of V6A in attention reorienting. Therefore, we propose that attention signals are used by the V6A to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly appears at an unattended location.

Automotive diesel engine transient operation: modeling, optimization and control

Traditionally, the study of internal combustion engines operation has focused on the steady-state performance. However, the daily driving schedule of automotive engines is inherently related to unsteady conditions. There are various operating conditions experienced by (diesel) engines that can be classified as transient. Besides the variation of the engine operating point, in terms of engine speed and torque, also the warm up phase can be considered as a transient condition. Chapter 2 has to do with this thermal transient condition; more precisely the main issue is the performance of a Selective Catalytic Reduction (SCR) system during cold start and warm up phases of the engine. The proposal of the underlying work is to investigate and identify optimal exhaust line heating strategies, to provide a fast activation of the catalytic reactions on SCR. Chapters 3 and 4 focus the attention on the dynamic behavior of the engine, when considering typical driving conditions. The common approach to dynamic optimization involves the solution of a single optimal-control problem. However, this approach requires the availability of models that are valid throughout the whole engine operating range and actuator ranges. In addition, the result of the optimization is meaningful only if the model is very accurate. Chapter 3 proposes a methodology to circumvent those demanding requirements: an iteration between transient measurements to refine a purpose-built model and a dynamic optimization which is constrained to the model validity region. Moreover all numerical methods required to implement this procedure are presented. Chapter 4 proposes an approach to derive a transient feedforward control system in an automated way. It relies on optimal control theory to solve a dynamic optimization problem for fast transients. From the optimal solutions, the relevant information is extracted and stored in maps spanned by the engine speed and the torque gradient.

Dynamics and control issues of multi-rotor platforms

This thesis deals with the analytic study of dynamics of Multi--Rotor Unmanned Aerial Vehicles. It is conceived to give a set of mathematical instruments apt to the theoretical study and design of these flying machines. The entire work is organized in analogy with classical academic texts about airplane flight dynamics. First, the non--linear equations of motion are defined and all the external actions are modeled, with particular attention to rotors aerodynamics. All the equations are provided in a form, and with personal expedients, to be directly exploitable in a simulation environment. This has requited an answer to questions like the trim of such mathematical systems. All the treatment is developed aiming at the description of different multi--rotor configurations. Then, the linearized equations of motion are derived. The computation of the stability and control derivatives of the linear model is carried out. The study of static and dynamic stability characteristics is, thus, addressed, showing the influence of the various geometric and aerodynamic parameters of the machine and in particular of the rotors. All the theoretic results are finally utilized in two interesting cases. One concerns the design of control systems for attitude stabilization. The linear model permits the tuning of linear controllers gains and the non--linear model allows the numerical testing. The other case is the study of the performances of an innovative configuration of quad--rotor aircraft. With the non--linear model the feasibility of maneuvers impossible for a traditional quad--rotor is assessed. The linear model is applied to the controllability analysis of such an aircraft in case of actuator block.

Motor control system in Parkinson’s disease: a modeling approach

Parkinson’s disease is a neurodegenerative disorder due to the death of the dopaminergic neurons of the substantia nigra of the basal ganglia. The process that leads to these neural alterations is still unknown. Parkinson’s disease affects most of all the motor sphere, with a wide array of impairment such as bradykinesia, akinesia, tremor, postural instability and singular phenomena such as freezing of gait. Moreover, in the last few years the fact that the degeneration in the basal ganglia circuitry induces not only motor but also cognitive alterations, not necessarily implicating dementia, and that dopamine loss induces also further implications due to dopamine-driven synaptic plasticity got more attention. At the present moment, no neuroprotective treatment is available, and even if dopamine-replacement therapies as well as electrical deep brain stimulation are able to improve the life conditions of the patients, they often present side effects on the long term, and cannot recover the neural loss, which instead continues to advance. In the present thesis both motor and cognitive aspects of Parkinson’s disease and basal ganglia circuitry were investigated, at first focusing on Parkinson’s disease sensory and balance issues by means of a new instrumented method based on inertial sensor to provide further information about postural control and postural strategies used to attain balance, then applying this newly developed approach to assess balance control in mild and severe patients, both ON and OFF levodopa replacement. Given the inability of levodopa to recover balance issues and the new physiological findings than underline the importance in Parkinson’s disease of non-dopaminergic neurotransmitters, it was therefore developed an original computational model focusing on acetylcholine, the most promising neurotransmitter according to physiology, and its role in synaptic plasticity. The rationale of this thesis is that a multidisciplinary approach could gain insight into Parkinson’s disease features still unresolved.