Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.

In silico identification of conserved intercoding sequences in Leishmania genomes: Unraveling putative cis-regulatory elements

In silico analyses of Leishmania spp. genome data are a powerful resource to improve the understanding of these pathogens' biology. Trypanosomatids such as Leishmania spp. have their protein-coding genes grouped in long polycistronic units of functionally unrelated genes. The control of gene expression happens by a variety of posttranscriptional mechanisms. The high degree of synteny among Leishmania species is accompanied by highly conserved coding sequences (CDS) and poorly conserved intercoding untranslated sequences. To identify the elements involved in the control of gene expression, we conducted an in silico investigation to find conserved intercoding sequences (CICS) in the genomes of L major, L infantum, and L braziliensis. We used a combination of computational tools, such as Linux-Shell, PERL and R languages, BLAST, MSPcrunch, SSAKE, and Pred-A-Term algorithms to construct a pipeline which was able to: (i) search for conservation in target-regions, (ii) eliminate CICS redundancy and mask repeat elements, (iii) predict the mRNA's extremities, (iv) analyze the distribution of orthologous genes within the generated LeishCICS-clusters, (v) assign GO terms to the LeishCICS-clusters. and (vi) provide statistical support for the gene-enrichment annotation. We associated the LeishCICS-cluster data, generated at the end of the pipeline, with the expression profile oft. donovani genes during promastigote-amastigote differentiation, as previously evaluated by others (GEO accession: GSE21936). A Pearson's correlation coefficient greater than 0.5 was observed for 730 LeishCICS-clusters containing from 2 to 17 genes. The designed computational pipeline is a useful tool and its application identified potential regulatory cis elements and putative regulons in Leishmania. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis Methodology Applied to a Tunable Patch Filter With Independent Frequency and Bandwidth Control

A new methodology for the synthesis of tunable patch filters is presented. The methodology helps the designer to perform a theoretical analysis of the filter through a coupling matrix that includes the effect of the tuning elements used to tune the filter. This general methodology accounts for any tuning parameter desired and was applied to the design of a tunable dual-mode patch filter with independent control of center frequency and bandwidth (BW). The bandpass filter uses a single triangular resonator with two etched slots that split the fundamental degenerate modes and form the filter passband. Varactor diodes assembled across the slots are used to vary the frequency of each degenerate fundamental mode independently, which is feasible due to the nature of the coupling scheme of the filter. The varactor diode model used in simulations, their assembling, the dc bias configuration, and measured results are presented. The theory results are compared to the simulations and to measurements showing a very good agreement and validating the proposed methodology. The fabricated filter presents an elliptic response with 20% of center frequency tuning range around 3.2 GHz and a fractional BW variation from 4% to 12% with low insertion loss and high power handling with a 1-dB compression point higher than +14.5 dB.

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Abstract Background Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Methods Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Results Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. Conclusions We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.

Model and control of tendon actuated robots

The use of tendons for the transmission of the forces and the movements in robotic devices has been investigated from several researchers all over the world. The interest in this kind of actuation modality is based on the possibility of optimizing the position of the actuators with respect to the moving part of the robot, in the reduced weight, high reliability, simplicity in the mechanic design and, finally, in the reduced cost of the resulting kinematic chain. After a brief discussion about the benefits that the use of tendons can introduce in the motion control of a robotic device, the design and control aspects of the UB Hand 3 anthropomorphic robotic hand are presented. In particular, the tendon-sheaths transmission system adopted in the UB Hand 3 is analyzed and the problem of force control and friction compensation is taken into account. The implementation of a tendon based antagonistic actuated robotic arm is then investigated. With this kind of actuation modality, and by using transmission elements with nonlinear force/compression characteristic, it is possible to achieve simultaneous stiffness and position control, improving in this way the safety of the device during the operation in unknown environments and in the case of interaction with other robots or with humans. The problem of modeling and control of this type of robotic devices is then considered and the stability analysis of proposed controller is reported. At the end, some tools for the realtime simulation of dynamic systems are presented. This realtime simulation environment has been developed with the aim of improving the reliability of the realtime control applications both for rapid prototyping of controllers and as teaching tools for the automatic control courses.

Modulation Techniques for Multi-Phase Converters and Control Strategies for Multi-Phase Electric Drives

The ever-increasing spread of automation in industry puts the electrical engineer in a central role as a promoter of technological development in a sector such as the use of electricity, which is the basis of all the machinery and productive processes. Moreover the spread of drives for motor control and static converters with structures ever more complex, places the electrical engineer to face new challenges whose solution has as critical elements in the implementation of digital control techniques with the requirements of inexpensiveness and efficiency of the final product. The successfully application of solutions using non-conventional static converters awake an increasing interest in science and industry due to the promising opportunities. However, in the same time, new problems emerge whose solution is still under study and debate in the scientific community During the Ph.D. course several themes have been developed that, while obtaining the recent and growing interest of scientific community, have much space for the development of research activity and for industrial applications. The first area of research is related to the control of three phase induction motors with high dynamic performance and the sensorless control in the high speed range. The management of the operation of induction machine without position or speed sensors awakes interest in the industrial world due to the increased reliability and robustness of this solution combined with a lower cost of production and purchase of this technology compared to the others available in the market. During this dissertation control techniques will be proposed which are able to exploit the total dc link voltage and at the same time capable to exploit the maximum torque capability in whole speed range with good dynamic performance. The proposed solution preserves the simplicity of tuning of the regulators. Furthermore, in order to validate the effectiveness of presented solution, it is assessed in terms of performance and complexity and compared to two other algorithm presented in literature. The feasibility of the proposed algorithm is also tested on induction motor drive fed by a matrix converter. Another important research area is connected to the development of technology for vehicular applications. In this field the dynamic performances and the low power consumption is one of most important goals for an effective algorithm. Towards this direction, a control scheme for induction motor that integrates within a coherent solution some of the features that are commonly required to an electric vehicle drive is presented. The main features of the proposed control scheme are the capability to exploit the maximum torque in the whole speed range, a weak dependence on the motor parameters, a good robustness against the variations of the dc-link voltage and, whenever possible, the maximum efficiency. The second part of this dissertation is dedicated to the multi-phase systems. This technology, in fact, is characterized by a number of issues worthy of investigation that make it competitive with other technologies already on the market. Multiphase systems, allow to redistribute power at a higher number of phases, thus making possible the construction of electronic converters which otherwise would be very difficult to achieve due to the limits of present power electronics. Multiphase drives have an intrinsic reliability given by the possibility that a fault of a phase, caused by the possible failure of a component of the converter, can be solved without inefficiency of the machine or application of a pulsating torque. The control of the magnetic field spatial harmonics in the air-gap with order higher than one allows to reduce torque noise and to obtain high torque density motor and multi-motor applications. In one of the next chapters a control scheme able to increase the motor torque by adding a third harmonic component to the air-gap magnetic field will be presented. Above the base speed the control system reduces the motor flux in such a way to ensure the maximum torque capability. The presented analysis considers the drive constrains and shows how these limits modify the motor performance. The multi-motor applications are described by a well-defined number of multiphase machines, having series connected stator windings, with an opportune permutation of the phases these machines can be independently controlled with a single multi-phase inverter. In this dissertation this solution will be presented and an electric drive consisting of two five-phase PM tubular actuators fed by a single five-phase inverter will be presented. Finally the modulation strategies for a multi-phase inverter will be illustrated. The problem of the space vector modulation of multiphase inverters with an odd number of phases is solved in different way. An algorithmic approach and a look-up table solution will be proposed. The inverter output voltage capability will be investigated, showing that the proposed modulation strategy is able to fully exploit the dc input voltage either in sinusoidal or non-sinusoidal operating conditions. All this aspects are considered in the next chapters. In particular, Chapter 1 summarizes the mathematical model of induction motor. The Chapter 2 is a brief state of art on three-phase inverter. Chapter 3 proposes a stator flux vector control for a three- phase induction machine and compares this solution with two other algorithms presented in literature. Furthermore, in the same chapter, a complete electric drive based on matrix converter is presented. In Chapter 4 a control strategy suitable for electric vehicles is illustrated. Chapter 5 describes the mathematical model of multi-phase induction machines whereas chapter 6 analyzes the multi-phase inverter and its modulation strategies. Chapter 7 discusses the minimization of the power losses in IGBT multi-phase inverters with carrier-based pulse width modulation. In Chapter 8 an extended stator flux vector control for a seven-phase induction motor is presented. Chapter 9 concerns the high torque density applications and in Chapter 10 different fault tolerant control strategies are analyzed. Finally, the last chapter presents a positioning multi-motor drive consisting of two PM tubular five-phase actuators fed by a single five-phase inverter.

A novel phase variation mechanism in the meningococcus driven by a ligand-responsive repressor and differential spacing of distal promoter elements

Phase variable expression, mediated by high frequency reversible changes in the length of simple sequence repeats, facilitates adaptation of bacterial populations to changing environments and is frequently important in bacterial virulence. Here we elucidate a novel phase variable mechanism for NadA expression, an adhesin and invasin of Neisseria meningitidis. The NadR repressor protein binds to operators flanking the phase variable tract of the nadA promoter gene and contributes to the differential expression levels of phase variant promoters with different numbers of repeats, likely due to different spacing between operators. It is shown that IHF binds between these operators, and may permit looping of the promoter, allowing interaction of NadR at operators located distally or overlapping the promoter. The 4-hydroxyphenylacetic acid, a metabolite of aromatic amino acid catabolism that is secreted in saliva, induces nadA expression by inhibiting the DNA binding activity of the NadR repressor. When induced, only minor differences are evident between NadR-independent transcription levels of promoter phase variants, which are likely due to differential RNA polymerase contacts leading to altered promoter activity. These results suggest that NadA expression is under both stochastic and tight environmental-sensing regulatory control, and both regulations are mediated by the NadR repressor that and may be induced during colonization of the oropharynx where it plays a major role in the successful adhesion and invasion of the mucosa. Hence, simple sequence repeats in promoter regions may be a strategy used by host-adapted bacterial pathogens to randomly switch between expression states that may nonetheless still be induced by appropriate niche-specific signals.

Architectures and design patterns for functional design of logic control and diagnostics in industrial automation

Recently in most of the industrial automation process an ever increasing degree of automation has been observed. This increasing is motivated by the higher requirement of systems with great performance in terms of quality of products/services generated, productivity, efficiency and low costs in the design, realization and maintenance. This trend in the growth of complex automation systems is rapidly spreading over automated manufacturing systems (AMS), where the integration of the mechanical and electronic technology, typical of the Mechatronics, is merging with other technologies such as Informatics and the communication networks. An AMS is a very complex system that can be thought constituted by a set of flexible working stations, one or more transportation systems. To understand how this machine are important in our society let considerate that every day most of us use bottles of water or soda, buy product in box like food or cigarets and so on. Another important consideration from its complexity derive from the fact that the the consortium of machine producers has estimated around 350 types of manufacturing machine. A large number of manufacturing machine industry are presented in Italy and notably packaging machine industry,in particular a great concentration of this kind of industry is located in Bologna area; for this reason the Bologna area is called “packaging valley”. Usually, the various parts of the AMS interact among them in a concurrent and asynchronous way, and coordinate the parts of the machine to obtain a desiderated overall behaviour is an hard task. Often, this is the case in large scale systems, organized in a modular and distributed manner. Even if the success of a modern AMS from a functional and behavioural point of view is still to attribute to the design choices operated in the definition of the mechanical structure and electrical electronic architecture, the system that governs the control of the plant is becoming crucial, because of the large number of duties associated to it. Apart from the activity inherent to the automation of themachine cycles, the supervisory system is called to perform other main functions such as: emulating the behaviour of traditional mechanical members thus allowing a drastic constructive simplification of the machine and a crucial functional flexibility; dynamically adapting the control strategies according to the different productive needs and to the different operational scenarios; obtaining a high quality of the final product through the verification of the correctness of the processing; addressing the operator devoted to themachine to promptly and carefully take the actions devoted to establish or restore the optimal operating conditions; managing in real time information on diagnostics, as a support of the maintenance operations of the machine. The kind of facilities that designers can directly find on themarket, in terms of software component libraries provides in fact an adequate support as regard the implementation of either top-level or bottom-level functionalities, typically pertaining to the domains of user-friendly HMIs, closed-loop regulation and motion control, fieldbus-based interconnection of remote smart devices. What is still lacking is a reference framework comprising a comprehensive set of highly reusable logic control components that, focussing on the cross-cutting functionalities characterizing the automation domain, may help the designers in the process of modelling and structuring their applications according to the specific needs. Historically, the design and verification process for complex automated industrial systems is performed in empirical way, without a clear distinction between functional and technological-implementation concepts and without a systematic method to organically deal with the complete system. Traditionally, in the field of analog and digital control design and verification through formal and simulation tools have been adopted since a long time ago, at least for multivariable and/or nonlinear controllers for complex time-driven dynamics as in the fields of vehicles, aircrafts, robots, electric drives and complex power electronics equipments. Moving to the field of logic control, typical for industrial manufacturing automation, the design and verification process is approached in a completely different way, usually very “unstructured”. No clear distinction between functions and implementations, between functional architectures and technological architectures and platforms is considered. Probably this difference is due to the different “dynamical framework”of logic control with respect to analog/digital control. As a matter of facts, in logic control discrete-events dynamics replace time-driven dynamics; hence most of the formal and mathematical tools of analog/digital control cannot be directly migrated to logic control to enlighten the distinction between functions and implementations. In addition, in the common view of application technicians, logic control design is strictly connected to the adopted implementation technology (relays in the past, software nowadays), leading again to a deep confusion among functional view and technological view. In Industrial automation software engineering, concepts as modularity, encapsulation, composability and reusability are strongly emphasized and profitably realized in the so-calledobject-oriented methodologies. Industrial automation is receiving lately this approach, as testified by some IEC standards IEC 611313, IEC 61499 which have been considered in commercial products only recently. On the other hand, in the scientific and technical literature many contributions have been already proposed to establish a suitable modelling framework for industrial automation. During last years it was possible to note a considerable growth in the exploitation of innovative concepts and technologies from ICT world in industrial automation systems. For what concerns the logic control design, Model Based Design (MBD) is being imported in industrial automation from software engineering field. Another key-point in industrial automated systems is the growth of requirements in terms of availability, reliability and safety for technological systems. In other words, the control system should not only deal with the nominal behaviour, but should also deal with other important duties, such as diagnosis and faults isolations, recovery and safety management. Indeed, together with high performance, in complex systems fault occurrences increase. This is a consequence of the fact that, as it typically occurs in reliable mechatronic systems, in complex systems such as AMS, together with reliable mechanical elements, an increasing number of electronic devices are also present, that are more vulnerable by their own nature. The diagnosis problem and the faults isolation in a generic dynamical system consists in the design of an elaboration unit that, appropriately processing the inputs and outputs of the dynamical system, is also capable of detecting incipient faults on the plant devices, reconfiguring the control system so as to guarantee satisfactory performance. The designer should be able to formally verify the product, certifying that, in its final implementation, it will perform itsrequired function guarantying the desired level of reliability and safety; the next step is that of preventing faults and eventually reconfiguring the control system so that faults are tolerated. On this topic an important improvement to formal verification of logic control, fault diagnosis and fault tolerant control results derive from Discrete Event Systems theory. The aimof this work is to define a design pattern and a control architecture to help the designer of control logic in industrial automated systems. The work starts with a brief discussion on main characteristics and description of industrial automated systems on Chapter 1. In Chapter 2 a survey on the state of the software engineering paradigm applied to industrial automation is discussed. Chapter 3 presentes a architecture for industrial automated systems based on the new concept of Generalized Actuator showing its benefits, while in Chapter 4 this architecture is refined using a novel entity, the Generalized Device in order to have a better reusability and modularity of the control logic. In Chapter 5 a new approach will be present based on Discrete Event Systems for the problemof software formal verification and an active fault tolerant control architecture using online diagnostic. Finally conclusive remarks and some ideas on new directions to explore are given. In Appendix A are briefly reported some concepts and results about Discrete Event Systems which should help the reader in understanding some crucial points in chapter 5; while in Appendix B an overview on the experimental testbed of the Laboratory of Automation of University of Bologna, is reported to validated the approach presented in chapter 3, chapter 4 and chapter 5. In Appendix C some components model used in chapter 5 for formal verification are reported.

Myc-mediated control of gene transcription in cancer cells

The Myc oncoproteins belong to a family of transcription factors composed by Myc, N-Myc and L-Myc. The most studied components of this family are Myc and N-Myc because their expressions are frequently deregulated in a wide range of cancers. These oncoproteins can act both as activators or repressors of gene transcription. As activators, they heterodimerize with Max (Myc associated X-factor) and the heterodimer recognizes and binds a specific sequence elements (E-Box) onto gene promoters recruiting histone acetylase and inducing transcriptional activation. Myc-mediated transcriptional repression is a quite debated issue. One of the first mechanisms defined for the Myc-mediated transcriptional repression consisted in the interaction of Myc-Max complex Sp1 and/or Miz1 transcription factors already bound to gene promoters. This interaction may interfere with their activation functions by recruiting co-repressors such as Dnmt3 or HDACs. Moreover, in the absence of , Myc may interfere with the Sp1 activation function by direct interaction and subsequent recruitment of HDACs. More recently the Myc/Max complex was also shown to mediate transcriptional repression by direct binding to peculiar E-box. In this study we analyzed the role of Myc overexpression in Osteosarcoma and Neuroblastoma oncogenesis and the mechanisms underling to Myc function. Myc overexpression is known to correlate with chemoresistance in Osteosarcoma cells. We extended this study by demonstrating that c-Myc induces transcription of a panel of ABC drug transporter genes. ABCs are a large family trans-membrane transporter deeply involved in multi drug resistance. Furthermore expression levels of Myc, ABCC1, ABCC4 and ABCF1 were proved to be important prognostic tool to predict conventional therapy failure. N-Myc amplification/overexpression is the most important prognostic factor for Neuroblastoma. Cyclin G2 and Clusterin are two genes often down regulated in neuroblastoma cells. Cyclin G2 is an atypical member of Cyclin family and its expression is associated with terminal differentiation and apoptosis. Moreover it blocks cell cycle progression and induces cell growth arrest. Instead, CLU is a multifunctional protein involved in many physiological and pathological processes. Several lines of evidences support the view that CLU may act as a tumour suppressor in Neuroblastoma. In this thesis I showed that N-Myc represses CCNG2 and CLU transcription by different mechanisms. • N-Myc represses CCNG2 transcription by directly interacting with Sp1 bound in CCNG2 promoter and recruiting HDAC2. Importantly, reactivation of CCNG2 expression through epigenetic drugs partially reduces N-Myc and HDAC2 mediated cell proliferation. • N-Myc/Max complex represses CLU expression by direct binding to a peculiar E-box element on CLU promoter and by recruitment of HDACs and Polycomb Complexes, to the CLU promoter. Overall our findings strongly support the model in which Myc overexpression/amplification may contribute to some aspects of oncogenesis by a dual action: i) transcription activation of genes that confer a multidrug resistant phenotype to cancer cells; ii), transcription repression of genes involved in cell cycle inhibition and cellular differentiation.

Development of control-oriented models of Dual Clutch Transmission systems

A control-oriented model of a Dual Clutch Transmission was developed for real-time Hardware In the Loop (HIL) applications, to support model-based development of the DCT controller. The model is an innovative attempt to reproduce the fast dynamics of the actuation system while maintaining a step size large enough for real-time applications. The model comprehends a detailed physical description of hydraulic circuit, clutches, synchronizers and gears, and simplified vehicle and internal combustion engine sub-models. As the oil circulating in the system has a large bulk modulus, the pressure dynamics are very fast, possibly causing instability in a real-time simulation; the same challenge involves the servo valves dynamics, due to the very small masses of the moving elements. Therefore, the hydraulic circuit model has been modified and simplified without losing physical validity, in order to adapt it to the real-time simulation requirements. The results of offline simulations have been compared to on-board measurements to verify the validity of the developed model, that was then implemented in a HIL system and connected to the TCU (Transmission Control Unit). Several tests have been performed: electrical failure tests on sensors and actuators, hydraulic and mechanical failure tests on hydraulic valves, clutches and synchronizers, and application tests comprehending all the main features of the control performed by the TCU. Being based on physical laws, in every condition the model simulates a plausible reaction of the system. The first intensive use of the HIL application led to the validation of the new safety strategies implemented inside the TCU software. A test automation procedure has been developed to permit the execution of a pattern of tests without the interaction of the user; fully repeatable tests can be performed for non-regression verification, allowing the testing of new software releases in fully automatic mode.

A new method for continuous quality control of nsm cfrp systems

In the last decade the near-surface mounted (NSM) strengthening technique using carbon fibre reinforced polymers (CFRP) has been increasingly used to improve the load carrying capacity of concrete members. Compared to externally bonded reinforcement (EBR), the NSM system presents considerable advantages. This technique consists in the insertion of carbon fibre reinforced polymer laminate strips into pre-cut slits opened in the concrete cover of the elements to be strengthened. CFRP reinforcement is bonded to concrete with an appropriate groove filler, typically epoxy adhesive or cement grout. Up to now, research efforts have been mainly focused on several structural aspects, such as: bond behaviour, flexural and/or shear strengthening effectiveness, and energy dissipation capacity of beam-column joints. In such research works, as well as in field applications, the most widespread adhesives that are used to bond reinforcements to concrete are epoxy resins. It is largely accepted that the performance of the whole application of NSM systems strongly depends on the mechanical properties of the epoxy resins, for which proper curing conditions must be assured. Therefore, the existence of non-destructive methods that allow monitoring the curing process of epoxy resins in the NSM CFRP system is desirable, in view of obtaining continuous information that can provide indication in regard to the effectiveness of curing and the expectable bond behaviour of CFRP/adhesive/concrete systems. The experimental research was developed at the Laboratory of the Structural Division of the Civil Engineering Department of the University of Minho in Guimar\~aes, Portugal (LEST). The main objective was to develop and propose a new method for continuous quality control of the curing of epoxy resins applied in NSM CFRP strengthening systems. This objective is pursued through the adaptation of an existing technique, termed EMM-ARM (Elasticity Modulus Monitoring through Ambient Response Method) that has been developed for monitoring the early stiffness evolution of cement-based materials. The experimental program was composed of two parts: (i) direct pull-out tests on concrete specimens strengthened with NSM CFRP laminate strips were conducted to assess the evolution of bond behaviour between CFRP and concrete since early ages; and, (ii) EMM-ARM tests were carried out for monitoring the progressive stiffness development of the structural adhesive used in CFRP applications. In order to verify the capability of the proposed method for evaluating the elastic modulus of the epoxy, static E-Modulus was determined through tension tests. The results of the two series of tests were then combined and compared to evaluate the possibility of implementation of a new method for the continuous monitoring and quality control of NSM CFRP applications.

Field-free control of magnetism in nanostructured materials probed with high resolution X-ray microscopy

Magnetic memories are a backbone of today's digital data storage technology, where the digital information is stored as the magnetic configuration of nanostructured ferromagnetic bits. Currently, the writing of the digital information on the magnetic memory is carried out with the help of magnetic fields. This approach, while viable, is not optimal due to its intrinsically high energy consumption and relatively poor scalability. For this reason, the research for different mechanisms that can be used to manipulate the magnetic configuration of a material is of interest. In this thesis, the control of the magnetization of different nanostructured materials with field-free mechanisms is investigated. The magnetic configuration of these nanostructured materials was imaged directly with high resolution x-ray magnetic microscopy. rnFirst of all, the control of the magnetic configuration of nanostructured ferromagnetic Heusler compounds by fabricating nanostructures with different geometries was analyzed. Here, it was observed that the magnetic configuration of the nanostructured elements is given by the competition of magneto-crystalline and shape anisotropy. By fabricating elements with different geometries, we could alter the point where these two effects equilibrate, allowing for the possibility to tailor the magnetic configuration of these nanostructured elements to the required necessities.rnThen, the control of the magnetic configuration of Ni nanostructures fabricated on top of a piezoelectric material with the magneto-elastic effect (i.e. by applying a piezoelectric strain to the Ni nanostructures) was investigated. Here, the magneto-elastic coupling effect gives rise to an additional anisotropy contribution, proportional to the strain applied to the magnetic material. For this system, a reproducible and reversible control of the magnetic configuration of the nanostructured Ni elements with the application of an electric field across the piezoelectric material was achieved.rnFinally, the control of the magnetic configuration of La0.7Sr0.3MnO3 (LSMO) nanostructures with spin-polarized currents was studied. Here, the spin-transfer torque effect was employed to achieve the displacement of magnetic domain walls in the LSMO nanostructures. A high spin-transfer torque efficiency was observed for LSMO at low temperatures, and a Joule-heating induced hopping of the magnetic domain walls was observed at room temperatures, allowing for the analysis of the energetics of the domain walls in LSMO.rnThe results presented in this thesis give thus an overview on the different field-free approaches that can be used to manipulate and tailor the magnetization configuration of a nanostructured material to the various technological requirements, opening up novel interesting possibilities for these materials.

Responses to Central Oxotremorine and Scopolamine Support the Cholinergic Control of Male Mating Behavior in Hamsters

The responses of hamsters to intracranial injections of the cholinergic agonist oxotremorine (OXO) implicate cholinergic mechanisms in the medial preoptic area (MPOA) in the control of male mating behavior. To extend these observations, we ran three studies of responses to cholinergic drugs delivered singly or in combination to the vicinity of the MPOA. The first tested responses to OXO, confirming its ability to reduce the postejaculatory interval. The second complemented the first by examining responses to MPOA microinjections of the cholinergic antagonist scopolamine (SCO). These caused several changes revolving around intromission. These included increases in intromission frequency and ejaculation latency. They also included a change in the patterning of intromissions, marked by continuous strings without the usual separation by dismounts. The final study resembled the others in examining the effects of MPOA injections of OXO and SCO but focused on the ability of each drug to antagonize responses to the other. Most of the responses to OXO and SCO individually replicated earlier findings, though the measures examined here also permitted the description of effects on some noncopulatory sexual behaviors, specifically the male's inspection of the female. However, the most interesting results may be those suggesting asymmetry in the responses to the addition of the second drug: Whereas responses to OXO tended to be antagonized by SCO, OXO was less effective at counteracting responses to SCO. Though the explanation of this asymmetry is not completely clear, it is consistent with previous suggestions of differences in the affinities of these drugs for subtypes of muscarinic receptors. Therefore, it suggests that the cholinergic synapses and circuits controlling distinct elements of male behavior could differ in their dependence on these receptors. Copyright 2013 Elsevier Inc. All rights reserved.

Role of Acetylcholine in Control of Sexual Behavior of Male and Female Mammals

The results of studies using systemic or central applications of cholinergic drugs suggest that acetylcholine makes important contributions to the neurochemical control of male- and female-typical reproductive behaviors. In males, cholinergic control seems largely specific to some elements or aspects of copulatory behavior that can vary significantly across species. Synapses in or near the medial preoptic area represent part of this mechanism, but the entire system appears to extend more widely, perhaps especially to one or more structures flanking some part of the lateral ventricle. In females, the lordosis response that essentially defines sexual receptivity is clearly responsive to cholinergic drugs. The same seems likely to be true of other elements of female sexual behavior, but additional studies will be needed to confirm this. Changes in cholinergic activity may help to mediate estrogenic effects on female sexual behavior. However, estrogen exposure can increase or decrease cholinergic effects, suggesting a relationship that is complex and requires further analysis. Also presently unclear is the localization of the cholinergic effects on female sexual responses. Though periventricular sites again have been implicated, their identity is presently unknown. This review discusses these and other aspects of the central cholinergic systems affecting male and female sexual behaviors. Copyright 2014 Elsevier Inc. All rights reserved.

LOCAL DIGITAL CONTROL OF POWER ELECTRONIC CONVERTERS IN A DC MICROGRID BASED ON A-PRIORI DERIVATION OF SWITCHING SURFACES

In power electronic basedmicrogrids, the computational requirements needed to implement an optimized online control strategy can be prohibitive. The work presented in this dissertation proposes a generalized method of derivation of geometric manifolds in a dc microgrid that is based on the a-priori computation of the optimal reactions and trajectories for classes of events in a dc microgrid. The proposed states are the stored energies in all the energy storage elements of the dc microgrid and power flowing into them. It is anticipated that calculating a large enough set of dissimilar transient scenarios will also span many scenarios not specifically used to develop the surface. These geometric manifolds will then be used as reference surfaces in any type of controller, such as a sliding mode hysteretic controller. The presence of switched power converters in microgrids involve different control actions for different system events. The control of the switch states of the converters is essential for steady state and transient operations. A digital memory look-up based controller that uses a hysteretic sliding mode control strategy is an effective technique to generate the proper switch states for the converters. An example dcmicrogrid with three dc-dc boost converters and resistive loads is considered for this work. The geometric manifolds are successfully generated for transient events, such as step changes in the loads and the sources. The surfaces corresponding to a specific case of step change in the loads are then used as reference surfaces in an EEPROM for experimentally validating the control strategy. The required switch states corresponding to this specific transient scenario are programmed in the EEPROM as a memory table. This controls the switching of the dc-dc boost converters and drives the system states to the reference manifold. In this work, it is shown that this strategy effectively controls the system for a transient condition such as step changes in the loads for the example case.